⚙

Pathophysiology

4

Severe Thyroid Hormone Deficiency

Myxedema is the severe end of hypothyroidism, with reduced thyroid hormone signaling causing systemic slowing of metabolism and, in decompensated cases, altered mental status, hypothermia, and multiple organ-system abnormalities.

Thyroid follicular cell link

Response to thyroid hormone link ↓ DECREASED Thyroid hormone metabolic process link ↓ DECREASED

Downstream

Respiratory And Cardiovascular Decompensation Severe hypothyroidism drives multisystem respiratory and cardiovascular decompensation in myxedema coma.

Cutaneous Myxedema Thyroid hormone dysregulation affects skin homeostasis and contributes to cutaneous myxedema manifestations.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"life‑threatening expression of severe hypothyroidism, with patients showing"

This review directly links myxedema coma to severe hypothyroidism with multisystem clinical decompensation.

Respiratory And Cardiovascular Decompensation

Profound hypothyroidism can reduce ventilatory drive and cardiac output, contributing to hypoventilation, hypoxemia or hypercarbia, bradycardia, hypotension, serous effusions, and coma.

Response to thyroid hormone link ↓ DECREASED

Downstream

ADH-Mediated Water Retention Low cardiac output and hypovolemia stimulate ADH release, impairing free water excretion.

Coma Respiratory decompensation can progress through hypercarbia and CNS depression to coma.

Bradycardia Cardiovascular depression in myxedema coma includes bradycardia.

Pericardial Effusion Cardiovascular involvement in myxedema coma includes pericardial fluid accumulation.

Hypoventilation Reduced ventilatory drive produces hypoventilation with hypercarbia.

Hypotension In-hospital hypotension is part of the severe decompensated presentation and predicts mortality.

Show evidence (2 references)

PMID:31237256 SUPPORT Human Clinical

"via a common pathway of respiratory decompensation with carbon dioxide narcosis"

This supports respiratory decompensation as a major pathway from severe hypothyroidism to coma.

PMID:31237256 SUPPORT Human Clinical

"Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."

This supports cardiovascular depression and effusions as downstream mechanisms in myxedema coma.

ADH-Mediated Water Retention

Decreased cardiac output and hypovolemia can stimulate ADH release, reducing free water excretion and contributing to hyponatremia in myxedema coma.

Downstream

Hyponatremia ADH-mediated water retention contributes directly to low sodium in myxedema coma.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Decreased cardiac output and hypovolemia sensed by baroreceptors may lead to a stimulation of antidiuretic hormone (ADH) release, further contributing to hyponatremia and impaired free water excretion."

This directly supports ADH-mediated water retention as a mechanism contributing to hyponatremia.

Cutaneous Myxedema

Severe thyroid hormone dysregulation affects skin homeostasis and can produce diffuse non-pitting edema and thickened skin. The cutaneous mechanism is modeled as abnormal aminoglycan and hyaluronan metabolism in the skin.

Skin fibroblast link Keratinocyte link

Extracellular matrix organization link ⚠ ABNORMAL Glycosaminoglycan metabolic process link ⚠ ABNORMAL Hyaluronan metabolic process link ⚠ ABNORMAL

Downstream

Non-pitting Edema Cutaneous myxedema produces non-pitting edema of the face, hands, and feet.

Dry Skin Cutaneous involvement includes dry, scaly skin.

Macroglossia Tissue edema in myxedema can include macroglossia.

Sparse Hair Hair thinning or sparse body hair is part of the skin and appendage involvement in myxedema coma.

Show evidence (1 reference)

PMID:37251685 PARTIAL Human Clinical

"Specifically, skin is considered an important target organ in which the"

This thyroid dermatology review supports skin as a thyroid hormone target organ, consistent with cutaneous myxedema manifestations.

⬡

Pathograph

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Phenotypes

12

Cardiovascular 2

Bradycardia Bradycardia (HP:0001662)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."

This supports bradycardia as a cardiovascular finding in myxedema coma.

Hypotension Hypotension (HP:0002615)

Show evidence (1 reference)

PMID:35945394 SUPPORT Human Clinical

"in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality."

This identifies in-hospital hypotension as a clinically important feature associated with mortality in myxedema crisis.

Digestive 1

Constipation Constipation (HP:0002019)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"The effects of such profound hypothyroidism on the gastrointestinal tract will include complaints of anorexia and constipation, and reduced motility, gastric atony, paralytic ileus and megacolon are not unusual."

This supports constipation and reduced gastrointestinal motility in profound hypothyroidism.

Integument 2

Dry Skin Dry skin (HP:0000958)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."

This supports dry skin as a physical finding of myxedema coma.

Sparse Hair Sparse hair (HP:0008070)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."

This directly supports thinning or sparse body hair as a myxedema coma physical finding.

Nervous System 1

Coma Coma (HP:0001259)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"the most dramatic aspect of the presentation is the coma per se which typically evolves from initial lethargy, then progressing to a history of increased sleeping throughout the day"

This supports coma as a decompensated manifestation of severe hypothyroidism.

Other 6

Non-pitting Edema Non-pitting edema (HP:6000507)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."

This explicitly describes non-pitting edema among physical examination findings in myxedema coma.

Hypothermia Hypothermia (HP:0002045)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"In the pre-comatose state, the typical clinical findings include hypothermia, decreased mentation, generalized edema and the usual hallmarks of profound hypothyroidism."

This identifies hypothermia as a typical finding in the pre-comatose state of myxedema coma.

Macroglossia

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."

This directly lists macroglossia among physical examination findings in myxedema coma.

Delayed Deep Tendon Reflexes Reduced tendon reflexes (HP:0001315)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."

This directly lists delayed deep tendon reflexes as a physical examination finding in myxedema coma.

Pericardial Effusion Pericardial effusion (HP:0001698)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."

This supports pericardial effusion as part of the cardiovascular involvement in myxedema coma.

Hypoventilation Hypoventilation (HP:0002791)

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Even in the absence of pulmonary infection, there will be hypoxemia and hypercarbia secondary to a reduced ventilatory drive triggered by hypercapnia that forms the basis for respiratory depression."

Reduced ventilatory drive with hypercarbia supports hypoventilation in myxedema coma.

💊

Treatments

5

Intravenous Thyroid Hormone Replacement

Action: Pharmacotherapy NCIT:C15986

Agent: levothyroxine ↗ liothyronine ↗

ICU management centers on rapid thyroid hormone replacement, often with intravenous levothyroxine and selected use of liothyronine.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Recently published guidelines for treatment of hypothyroidism and myxedema coma by the American Thyroid Association (13) emphasize individualizing dosage based upon age, weight, and cardiac status, suggesting the initial use of intravenous T4 in a dose of 200–400 μg with a lower dose given to..."

This supports guideline-based intravenous T4 replacement for myxedema coma, with dosing individualized by patient risk.

Empiric Hydrocortisone

Action: Pharmacotherapy NCIT:C15986

Agent: hydrocortisone ↗

Empiric corticosteroid coverage is considered while adrenal insufficiency is evaluated, particularly before or during thyroid hormone replacement.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"As recommended above, a baseline plasma cortisol having been drawn, the patient’s vascular stability may be enhanced by administration of empiric corticosteroid administration, e.g., 50–100 mg hydrocortisone intravenously."

This supports empiric intravenous hydrocortisone during acute myxedema coma management.

Oral Levothyroxine When Intravenous Levothyroxine Is Unavailable

Action: Pharmacotherapy NCIT:C15986

Agent: levothyroxine ↗

Oral levothyroxine has been reported as an alternative when intravenous levothyroxine is unavailable, but this is based on observational evidence.

Show evidence (1 reference)

PMID:33777819 PARTIAL Human Clinical

"Oral LT4 is an effective treatment option for myxedema coma when"

This supports oral levothyroxine as a fallback option in settings where intravenous levothyroxine cannot be obtained.

Mechanical Ventilatory Support

Action: mechanical ventilation Ontology label: artificial respiration MAXO:0000503

Mechanical ventilation or other artificial respiratory support may be required when impaired ventilation progresses toward ventilatory failure.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"To ensure adequate ventilation, mechanical means often must be employed with careful monitoring blood oxygen and carbon dioxide levels."

This directly supports mechanical ventilatory support during myxedema coma management.

Hyponatremia Correction

Severe hyponatremia is corrected carefully with monitored hypertonic saline when sodium is below 120 mEq/L, with otherwise normal or mixed saline/glucose support.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Low blood sodium is likely to be playing a major role in any lethargy, disorientation or coma when present and must be corrected."

This directly supports electrolyte correction as supportive management for myxedema coma.

🌍

Environmental Factors

2

Cold Exposure

Cold weather can precipitate decompensation from hypothyroidism to myxedema coma.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Severely cold weather is only one of many possible precipitating factors that may convert the clinical status of the patient from hypothyroidism to myxedema coma."

The review identifies severe cold weather as a precipitating factor for myxedema coma.

Medication-Related Respiratory Suppression

Sedatives and related medications can precipitate myxedema coma by suppressing respiration.

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Medications that can precipitate myxedema coma include sedatives, analgesics, antidepressants, hypnotics, antipsychotics, and anesthetic drugs via a shared mechanism of the tendency to suppress respiration."

This supports medication-related respiratory suppression as a precipitating factor.

🔬

Biochemical Markers

4

Free T4 (Decreased)

Context: Myxedema coma

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"FT4 levels will be low and can be almost undetectable, while TSH levels have varied widely in reported cases of myxedema coma."

Low free T4 supports profound thyroid hormone deficiency in myxedema coma.

TSH (Variable)

Context: Myxedema coma, including primary and central hypothyroidism

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"FT4 levels will be low and can be almost undetectable, while TSH levels have varied widely in reported cases of myxedema coma."

TSH varies depending on whether hypothyroidism is primary or central, so it is not by itself diagnostic.

Hyponatremia (Present)

Context: Myxedema coma

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Other laboratory test abnormalities can include low blood glucose, low sodium and chloride levels, high total and ionized calcium, and mild renal failure with elevations in blood urea nitrogen (BUN) and creatinine."

Low sodium supports hyponatremia as a laboratory abnormality in myxedema coma.

Hypoglycemia (Present)

Context: Myxedema coma

Show evidence (1 reference)

PMID:31237256 SUPPORT Human Clinical

"Other laboratory test abnormalities can include low blood glucose, low sodium and chloride levels, high total and ionized calcium, and mild renal failure with elevations in blood urea nitrogen (BUN) and creatinine."

Low blood glucose supports hypoglycemia as a laboratory abnormality in myxedema coma.

{ }

Source YAML

click to show

name: Myxedema
creation_date: "2026-05-07T23:30:13Z"
updated_date: "2026-05-08T00:01:47Z"
category: Complex
disease_term:
  preferred_term: myxedema
  term:
    id: MONDO:0009718
    label: myxedema
parents:
- Endocrine Disease
- Hypothyroidism
epidemiology:
- name: High inpatient mortality in myxedema crisis cohort
  description: Combined single-center cohort mortality estimate and mortality predictors for myxedema crisis.
  mean_range: "60.9"
  unit: percentage
  factors:
  - Female sex
  - Mechanical ventilation
  - In-hospital hypotension
  - High qSOFA score
  evidence:
  - reference: PMID:35945394
    reference_title: Utility of myxedema score as a predictor of mortality in myxedema coma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall mortality was 60.9%. On comparative analysis among survivors and non-survivors, female gender (OR 20.4, p value 0.018), need for mechanical ventilation (OR16.4, p value 0.009), in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality."
    explanation: This cohort provides a direct mortality estimate and identifies several predictors of death in myxedema crisis.
- name: COVID-era myxedema coma incidence increase
  description: Single-center case series reporting increased incidence during and after the COVID-19 pandemic and cohort mortality.
  mean_range: "27.2"
  unit: percentage mortality
  factors:
  - COVID-19 pandemic-era health care access constraints
  - Inadequately treated hypothyroidism
  evidence:
  - reference: PMID:38967885
    reference_title: "Increased incidence of myxedema coma during the COVID-19 pandemic and in the post pandemic era: a single-center case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The mortality rate in this cohort was 27.2%. In conclusion, the increase of the incidence of MC, which is a life-threatening complication of inadequately treated hypothyroidism, during the COVID-19 pandemic, when resources were limited, and in the post-pandemic era, underlines the importance of adequate communication with patients and of long-term availability of primary"
    explanation: This case series directly supports both mortality and increased incidence of myxedema coma during the COVID-19 and post-pandemic period.
pathophysiology:
- name: Severe Thyroid Hormone Deficiency
  description: >
    Myxedema is the severe end of hypothyroidism, with reduced thyroid hormone
    signaling causing systemic slowing of metabolism and, in decompensated cases,
    altered mental status, hypothermia, and multiple organ-system abnormalities.
  biological_processes:
  - preferred_term: Response to thyroid hormone
    term:
      id: GO:0097066
      label: response to thyroid hormone
    modifier: DECREASED
  - preferred_term: Thyroid hormone metabolic process
    term:
      id: GO:0042403
      label: thyroid hormone metabolic process
    modifier: DECREASED
  cell_types:
  - preferred_term: Thyroid follicular cell
    term:
      id: CL:0002258
      label: thyroid follicular cell
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "life‑threatening expression of severe hypothyroidism, with patients showing"
    explanation: This review directly links myxedema coma to severe hypothyroidism
      with multisystem clinical decompensation.
  downstream:
  - target: Respiratory And Cardiovascular Decompensation
    causal_link_type: DIRECT
    description: Severe hypothyroidism drives multisystem respiratory and cardiovascular decompensation in myxedema coma.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Manifestations of myxedema coma like those of thyroid storm reflect multisystem decompensation."
      explanation: This directly supports connecting severe thyroid hormone deficiency to multisystem decompensation.
  - target: Cutaneous Myxedema
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Thyroid hormone effects on skin homeostasis
    description: Thyroid hormone dysregulation affects skin homeostasis and contributes to cutaneous myxedema manifestations.
    evidence:
    - reference: PMID:37251685
      reference_title: Dermatologic manifestations of thyroid disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Thyroid hormone is considered one of the key regulatory hormones for skin homeostasis."
      explanation: This supports a causal branch from thyroid hormone dysregulation to skin pathology.
- name: Respiratory And Cardiovascular Decompensation
  description: >
    Profound hypothyroidism can reduce ventilatory drive and cardiac output,
    contributing to hypoventilation, hypoxemia or hypercarbia, bradycardia,
    hypotension, serous effusions, and coma.
  biological_processes:
  - preferred_term: Response to thyroid hormone
    term:
      id: GO:0097066
      label: response to thyroid hormone
    modifier: DECREASED
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "via a common pathway of respiratory decompensation with carbon dioxide narcosis"
    explanation: This supports respiratory decompensation as a major pathway
      from severe hypothyroidism to coma.
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."
    explanation: This supports cardiovascular depression and effusions as
      downstream mechanisms in myxedema coma.
  downstream:
  - target: ADH-Mediated Water Retention
    causal_link_type: DIRECT
    description: Low cardiac output and hypovolemia stimulate ADH release, impairing free water excretion.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Decreased cardiac output and hypovolemia sensed by baroreceptors may lead to a stimulation of antidiuretic hormone (ADH) release, further contributing to hyponatremia and impaired free water excretion."
      explanation: This directly supports the ADH-mediated hyponatremia mechanism downstream of cardiovascular decompensation.
  - target: Coma
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Carbon dioxide narcosis
    - Progressive central nervous system depression
    description: Respiratory decompensation can progress through hypercarbia and CNS depression to coma.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "In the presence of pneumonia, the downhill process is accelerated and torpor with slowed respiration coupled with airway obstruction from peri-laryngeal edema and the large tongue lead to progressive depression of the central nervous system and coma."
      explanation: This supports coma as a downstream consequence of respiratory decompensation in severe myxedema.
  - target: Bradycardia
    causal_link_type: DIRECT
    description: Cardiovascular depression in myxedema coma includes bradycardia.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."
      explanation: This supports bradycardia downstream of cardiovascular decompensation.
  - target: Pericardial Effusion
    causal_link_type: DIRECT
    description: Cardiovascular involvement in myxedema coma includes pericardial fluid accumulation.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."
      explanation: This supports pericardial effusion downstream of cardiovascular decompensation.
  - target: Hypoventilation
    causal_link_type: DIRECT
    description: Reduced ventilatory drive produces hypoventilation with hypercarbia.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Even in the absence of pulmonary infection, there will be hypoxemia and hypercarbia secondary to a reduced ventilatory drive triggered by hypercapnia that forms the basis for respiratory depression."
      explanation: This supports hypoventilation downstream of respiratory decompensation.
  - target: Hypotension
    causal_link_type: DIRECT
    description: In-hospital hypotension is part of the severe decompensated presentation and predicts mortality.
    evidence:
    - reference: PMID:35945394
      reference_title: Utility of myxedema score as a predictor of mortality in myxedema coma.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality."
      explanation: This supports hypotension as a clinically important downstream decompensation marker.
- name: ADH-Mediated Water Retention
  description: >
    Decreased cardiac output and hypovolemia can stimulate ADH release, reducing
    free water excretion and contributing to hyponatremia in myxedema coma.
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Decreased cardiac output and hypovolemia sensed by baroreceptors may lead to a stimulation of antidiuretic hormone (ADH) release, further contributing to hyponatremia and impaired free water excretion."
    explanation: This directly supports ADH-mediated water retention as a mechanism contributing to hyponatremia.
  downstream:
  - target: Hyponatremia
    causal_link_type: DIRECT
    description: ADH-mediated water retention contributes directly to low sodium in myxedema coma.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Decreased cardiac output and hypovolemia sensed by baroreceptors may lead to a stimulation of antidiuretic hormone (ADH) release, further contributing to hyponatremia and impaired free water excretion."
      explanation: This links the ADH mechanism to the hyponatremia biochemical finding.
- name: Cutaneous Myxedema
  description: >
    Severe thyroid hormone dysregulation affects skin homeostasis and can produce
    diffuse non-pitting edema and thickened skin. The cutaneous mechanism is
    modeled as abnormal aminoglycan and hyaluronan metabolism in the skin.
  biological_processes:
  - preferred_term: Extracellular matrix organization
    term:
      id: GO:0030198
      label: extracellular matrix organization
    modifier: ABNORMAL
  - preferred_term: Glycosaminoglycan metabolic process
    term:
      id: GO:0006022
      label: aminoglycan metabolic process
    modifier: ABNORMAL
  - preferred_term: Hyaluronan metabolic process
    term:
      id: GO:0030212
      label: hyaluronan metabolic process
    modifier: ABNORMAL
  cell_types:
  - preferred_term: Skin fibroblast
    term:
      id: CL:0002620
      label: skin fibroblast
  - preferred_term: Keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  evidence:
  - reference: PMID:37251685
    reference_title: Dermatologic manifestations of thyroid disease.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Specifically, skin is considered an important target organ in which the"
    explanation: This thyroid dermatology review supports skin as a thyroid
      hormone target organ, consistent with cutaneous myxedema manifestations.
  downstream:
  - target: Non-pitting Edema
    causal_link_type: DIRECT
    description: Cutaneous myxedema produces non-pitting edema of the face, hands, and feet.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
      explanation: This directly supports non-pitting edema as a cutaneous consequence.
  - target: Dry Skin
    causal_link_type: DIRECT
    description: Cutaneous involvement includes dry, scaly skin.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
      explanation: This directly supports dry skin as a cutaneous consequence.
  - target: Macroglossia
    causal_link_type: DIRECT
    description: Tissue edema in myxedema can include macroglossia.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
      explanation: This directly supports macroglossia as a downstream physical finding.
  - target: Sparse Hair
    causal_link_type: DIRECT
    description: Hair thinning or sparse body hair is part of the skin and appendage involvement in myxedema coma.
    evidence:
    - reference: PMID:31237256
      reference_title: Thyroid emergencies.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
      explanation: This directly supports sparse hair as a skin-appendage consequence.
phenotypes:
- name: Non-pitting Edema
  category: Dermatological
  phenotype_term:
    preferred_term: Non-pitting edema
    term:
      id: HP:6000507
      label: Non-pitting edema
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
    explanation: This explicitly describes non-pitting edema among physical
      examination findings in myxedema coma.
- name: Dry Skin
  category: Dermatological
  phenotype_term:
    preferred_term: Dry skin
    term:
      id: HP:0000958
      label: Dry skin
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
    explanation: This supports dry skin as a physical finding of myxedema coma.
- name: Hypothermia
  category: Systemic
  phenotype_term:
    preferred_term: Hypothermia
    term:
      id: HP:0002045
      label: Hypothermia
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In the pre-comatose state, the typical clinical findings include hypothermia, decreased mentation, generalized edema and the usual hallmarks of profound hypothyroidism."
    explanation: This identifies hypothermia as a typical finding in the
      pre-comatose state of myxedema coma.
- name: Coma
  category: Neurological
  phenotype_term:
    preferred_term: Coma
    term:
      id: HP:0001259
      label: Coma
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the most dramatic aspect of the presentation is the coma per se which typically evolves from initial lethargy, then progressing to a history of increased sleeping throughout the day"
    explanation: This supports coma as a decompensated manifestation of severe
      hypothyroidism.
- name: Macroglossia
  category: Craniofacial
  phenotype_term:
    preferred_term: Macroglossia
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
    explanation: This directly lists macroglossia among physical examination findings in myxedema coma.
- name: Delayed Deep Tendon Reflexes
  category: Neurological
  phenotype_term:
    preferred_term: Delayed deep tendon reflexes
    term:
      id: HP:0001315
      label: Reduced tendon reflexes
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
    explanation: This directly lists delayed deep tendon reflexes as a physical examination finding in myxedema coma.
- name: Sparse Hair
  category: Dermatological
  phenotype_term:
    preferred_term: Sparse body hair
    term:
      id: HP:0008070
      label: Sparse hair
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On physical examination there will be dry, scaly skin, nonpitting edema of the faces, hands, and feet, macroglossia, delayed deep tendon reflexes, and thinning or sparse body hair."
    explanation: This directly supports thinning or sparse body hair as a myxedema coma physical finding.
- name: Bradycardia
  category: Cardiovascular
  phenotype_term:
    preferred_term: Bradycardia
    term:
      id: HP:0001662
      label: Bradycardia
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."
    explanation: This supports bradycardia as a cardiovascular finding in
      myxedema coma.
- name: Pericardial Effusion
  category: Cardiovascular
  phenotype_term:
    preferred_term: Pericardial effusion
    term:
      id: HP:0001698
      label: Pericardial effusion
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Findings in the cardiovascular system include pericardial effusion, cardiomegaly, bradycardia, and reduced ejection fraction and cardiac output due to decreased cardiac contractility."
    explanation: This supports pericardial effusion as part of the cardiovascular
      involvement in myxedema coma.
- name: Hypoventilation
  category: Respiratory
  phenotype_term:
    preferred_term: Hypoventilation
    term:
      id: HP:0002791
      label: Hypoventilation
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Even in the absence of pulmonary infection, there will be hypoxemia and hypercarbia secondary to a reduced ventilatory drive triggered by hypercapnia that forms the basis for respiratory depression."
    explanation: Reduced ventilatory drive with hypercarbia supports
      hypoventilation in myxedema coma.
- name: Hypotension
  category: Cardiovascular
  phenotype_term:
    preferred_term: Hypotension
    term:
      id: HP:0002615
      label: Hypotension
  evidence:
  - reference: PMID:35945394
    reference_title: Utility of myxedema score as a predictor of mortality in myxedema coma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality."
    explanation: This identifies in-hospital hypotension as a clinically important feature associated with mortality in myxedema crisis.
- name: Constipation
  category: Gastrointestinal
  phenotype_term:
    preferred_term: Constipation
    term:
      id: HP:0002019
      label: Constipation
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The effects of such profound hypothyroidism on the gastrointestinal tract will include complaints of anorexia and constipation, and reduced motility, gastric atony, paralytic ileus and megacolon are not unusual."
    explanation: This supports constipation and reduced gastrointestinal
      motility in profound hypothyroidism.
biochemical:
- name: Free T4
  presence: Decreased
  context: Myxedema coma
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "FT4 levels will be low and can be almost undetectable, while TSH levels have varied widely in reported cases of myxedema coma."
    explanation: Low free T4 supports profound thyroid hormone deficiency in
      myxedema coma.
- name: TSH
  presence: Variable
  context: Myxedema coma, including primary and central hypothyroidism
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "FT4 levels will be low and can be almost undetectable, while TSH levels have varied widely in reported cases of myxedema coma."
    explanation: TSH varies depending on whether hypothyroidism is primary or
      central, so it is not by itself diagnostic.
- name: Hyponatremia
  presence: Present
  context: Myxedema coma
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Other laboratory test abnormalities can include low blood glucose, low sodium and chloride levels, high total and ionized calcium, and mild renal failure with elevations in blood urea nitrogen (BUN) and creatinine."
    explanation: Low sodium supports hyponatremia as a laboratory abnormality in
      myxedema coma.
- name: Hypoglycemia
  presence: Present
  context: Myxedema coma
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Other laboratory test abnormalities can include low blood glucose, low sodium and chloride levels, high total and ionized calcium, and mild renal failure with elevations in blood urea nitrogen (BUN) and creatinine."
    explanation: Low blood glucose supports hypoglycemia as a laboratory
      abnormality in myxedema coma.
environmental:
- name: Cold Exposure
  notes: Cold weather can precipitate decompensation from hypothyroidism to myxedema coma.
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Severely cold weather is only one of many possible precipitating factors that may convert the clinical status of the patient from hypothyroidism to myxedema coma."
    explanation: The review identifies severe cold weather as a precipitating
      factor for myxedema coma.
- name: Medication-Related Respiratory Suppression
  notes: Sedatives and related medications can precipitate myxedema coma by suppressing respiration.
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Medications that can precipitate myxedema coma include sedatives, analgesics, antidepressants, hypnotics, antipsychotics, and anesthetic drugs via a shared mechanism of the tendency to suppress respiration."
    explanation: This supports medication-related respiratory suppression as a
      precipitating factor.
treatments:
- name: Intravenous Thyroid Hormone Replacement
  description: >
    ICU management centers on rapid thyroid hormone replacement, often with
    intravenous levothyroxine and selected use of liothyronine.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: levothyroxine
      term:
        id: CHEBI:18332
        label: L-thyroxine
    - preferred_term: liothyronine
      term:
        id: CHEBI:18258
        label: 3,3',5-triiodo-L-thyronine
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Recently published guidelines for treatment of hypothyroidism and myxedema coma by the American Thyroid Association (13) emphasize individualizing dosage based upon age, weight, and cardiac status, suggesting the initial use of intravenous T4 in a dose of 200–400 μg with a lower dose given to older patients or those with cardiac disease."
    explanation: This supports guideline-based intravenous T4 replacement for
      myxedema coma, with dosing individualized by patient risk.
- name: Empiric Hydrocortisone
  description: >
    Empiric corticosteroid coverage is considered while adrenal insufficiency is
    evaluated, particularly before or during thyroid hormone replacement.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: hydrocortisone
      term:
        id: CHEBI:17650
        label: cortisol
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "As recommended above, a baseline plasma cortisol having been drawn, the patient’s vascular stability may be enhanced by administration of empiric corticosteroid administration, e.g., 50–100 mg hydrocortisone intravenously."
    explanation: This supports empiric intravenous hydrocortisone during acute
      myxedema coma management.
- name: Oral Levothyroxine When Intravenous Levothyroxine Is Unavailable
  description: >
    Oral levothyroxine has been reported as an alternative when intravenous
    levothyroxine is unavailable, but this is based on observational evidence.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: levothyroxine
      term:
        id: CHEBI:18332
        label: L-thyroxine
  evidence:
  - reference: PMID:33777819
    reference_title: "Oral Levothyroxine is an Effective Option for Myxedema Coma: A Single-Centre Experience."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Oral LT4 is an effective treatment option for myxedema coma when"
    explanation: This supports oral levothyroxine as a fallback option in
      settings where intravenous levothyroxine cannot be obtained.
- name: Mechanical Ventilatory Support
  description: >
    Mechanical ventilation or other artificial respiratory support may be
    required when impaired ventilation progresses toward ventilatory failure.
  treatment_term:
    preferred_term: mechanical ventilation
    term:
      id: MAXO:0000503
      label: artificial respiration
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To ensure adequate ventilation, mechanical means often must be employed with careful monitoring blood oxygen and carbon dioxide levels."
    explanation: This directly supports mechanical ventilatory support during myxedema coma management.
- name: Hyponatremia Correction
  description: >
    Severe hyponatremia is corrected carefully with monitored hypertonic saline
    when sodium is below 120 mEq/L, with otherwise normal or mixed saline/glucose
    support.
  evidence:
  - reference: PMID:31237256
    reference_title: Thyroid emergencies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Low blood sodium is likely to be playing a major role in any lethargy, disorientation or coma when present and must be corrected."
    explanation: This directly supports electrolyte correction as supportive management for myxedema coma.
review_notes: >
  Myxedema is curated here as severe hypothyroidism and its decompensated
  myxedema coma/crisis presentation. Pretibial myxedema is treated as a distinct
  Graves-associated dermopathy and was not folded into this page.
datasets: []

📚

References & Deep Research

Deep Research

1

Falcon ▸

Disease Characteristics Research Template

Edison Scientific Literature 39 citations 2026-05-07T19:44:16.352170

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

Disease Name: Myxedema
MONDO ID: (if available)
Category: Complex

Research Objectives

Please provide a comprehensive research report on Myxedema covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

What is the disease? Provide a concise overview.
What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
What are the common synonyms and alternative names?
Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
Risk Factors:

Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Genetic risk factors (causal variants, susceptibility loci, modifier genes)
Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
Protective Factors:

Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Genetic protective factors (protective variants, modifier alleles)
Environmental protective factors (diet, lifestyle, exposures that reduce risk)
Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Pathogenic Variants:
Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
Variant type/class (missense, frameshift, nonsense, splice-site, structural)
Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
Functional consequences (loss of function, gain of function, dominant negative)
Modifier Genes: Genes that modify disease severity or expression
Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

Search first: CDC databases, WHO, PubMed, NHANES
Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

Search first: PubMed, Gene Ontology, Reactome
Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Molecular Profiling (if available):
Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
Advanced Technologies (if applicable):
Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

Organ Level:
Primary organs directly affected
Secondary organ involvement (complications, secondary effects)
Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Tissue and Cell Level:
Specific tissue types affected (epithelial, connective, muscle, nervous)
Specific cell populations targeted (with Cell Ontology terms)

Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Subcellular Level:
Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Localization:
Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

Onset:
Typical age of onset (congenital, pediatric, adult, geriatric)
Onset pattern (acute, subacute, chronic, insidious)

Search first: OMIM, Orphanet, HPO, PubMed
Progression:
Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
Progression rate (rapid, slow, variable)
Disease course pattern (episodic, relapsing-remitting, progressive, stable)
Disease duration (self-limited, chronic lifelong)

Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Patterns:
Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

Epidemiology:
Prevalence (cases per 100,000 at given time)
Incidence (new cases per 100,000 per year)

Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
For Genetic Etiology:
Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
Population Demographics:
Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
Geographic distribution of specific variants
Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

Clinical Tests:
Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
Genetic Testing:

Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
Overview of recommended genetic testing approach
Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
FISH > Search first: ClinVar, cytogenetics databases, PubMed
Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
Omics-Based Diagnostics (if applicable):
RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
Clinical Criteria:
Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
Screening:
Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

Survival and Mortality:
Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
Morbidity and Function:
Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
Disease Course:
Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
Prediction:
Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

Pharmacotherapy:
Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
Advanced Therapeutics:
Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
Surgical and Interventional:
Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
Supportive and Rehabilitative:
Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
Experimental:
Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
Treatment Outcomes:
Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
Treatment Strategy:
Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

Prevention Levels:
Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
Immunization: Vaccine strategies (if applicable)

Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Screening and Early Detection:
Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
Behavioral Interventions: Lifestyle modifications to reduce risk

Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Counseling: Genetic counseling (risk assessment, family planning guidance)

Search first: NSGC resources, ACMG guidelines, GeneReviews
Public Health:
Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
Prophylaxis: Preventive medications or procedures

Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

Taxonomy: Species affected (with NCBI Taxon identifiers)

Search first: NCBI Taxonomy
Breed: Specific breeds affected (with VBO identifiers if applicable)

Search first: VBO (Vertebrate Breed Ontology)
Gene: Orthologous genes in other species (with NCBI Gene IDs)

Search first: NCBI Gene
Natural Disease:
Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
Comparative Biology:
Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
Transmission (if applicable):
Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

Model Types:
Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
Genetic Models:
Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
Model Characteristics:
Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
Applications:
Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
Resources:
Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

Cite primary literature (PMID preferred) for all mechanistic and clinical claims
Prioritize recent reviews and landmark papers
Include direct quotes from abstracts where possible to support key statements
Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Comprehensive Disease Characteristics Report: Myxedema (incl. Myxedema Coma)

Target disease

Disease name: Myxedema (clinical syndrome of severe hypothyroidism with characteristic non‑pitting edema) and myxedema coma (decompensated, life‑threatening severe hypothyroidism). (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)

Note on scope and terminology: Contemporary reviews emphasize that “myxedema coma” is a misnomer because mental status can range from lethargy to coma; some authors prefer “myxedema crisis.” (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)

Key identifiers (ICD/MeSH/MONDO/OMIM/Orphanet): Not reliably extractable from the currently retrieved sources in this run; therefore not reported here (no evidence to cite).

Common synonyms/related terms (usage varies by context): - Generalized myxedema (diffuse, non‑pitting edema/skin thickening in severe hypothyroidism) (bonino2023pediatricmyxedemadue pages 1-2, cohen2023dermatologicmanifestationsof pages 2-3) - Myxedema coma / hypothyroid coma / myxedema crisis (severe decompensation) (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2) - Pretibial myxedema / thyroid dermopathy (localized mucin deposition classically associated with Graves disease; distinct from generalized myxedema) (cohen2023dermatologicmanifestationsof pages 2-3, demirkesen2015skinmanifestationsof pages 4-6)

Data provenance: This report uses aggregated evidence from peer‑reviewed reviews, cohorts, case series, and a national administrative database study; it is not derived from a single-patient EHR. (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2, sokołowski2024increasedincidenceof pages 2-4, hashmi2023weekendhospitaladmissions pages 4-9)

1. Disease information (overview)

Myxedema (generalized) is a manifestation of severe hypothyroidism characterized by non‑focal thickening/induration of skin and subcutaneous tissues due to increased deposition of connective tissue constituents (glycosaminoglycans/mucin) with water retention. (bonino2023pediatricmyxedemadue pages 1-2, cohen2023dermatologicmanifestationsof pages 2-3)

Myxedema coma is the extreme decompensated state of profound hypothyroidism with altered mentation and multisystem organ dysfunction, requiring ICU‑level care. (ylli2019thyroidemergencies pages 3-4, hwang2014treatmentofendocrine pages 6-9)

2. Etiology

2.1 Primary causal factors

Underlying cause: myxedema/myxedema coma generally arises from longstanding severe hypothyroidism (usually primary; less commonly central) with failure of compensatory mechanisms. (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2, sokołowski2024increasedincidenceof pages 2-4)

Evidence (recent case series): In a 2015–2023 Polish center cohort (n=11), 9 patients had primary hypothyroidism and 2 had central hypothyroidism; most cases were due to severe hypothyroidism from therapy non‑compliance, with 2 (18%) de novo diagnoses. (sokołowski2024increasedincidenceof pages 2-4)

2.2 Risk factors and triggers (myxedema coma)

Frequently reported precipitants include: - Infection (pneumonia, sepsis) (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2) - Cold exposure and winter seasonality (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2) - Stroke/CVA, heart failure, trauma, GI bleeding, and sedatives/other medications (chaudhary2023utilityofmyxedema pages 1-2, garg2020handbookofinpatient pages 57-62)

Medication-related risk: Reviews highlight medications that may contribute to thyroid dysfunction/critical illness interpretation, including amiodarone (iodine-rich) and iodinated contrast, among others; amiodarone is noted in the hypothyroidism/ICU setting. (garg2020handbookofinpatient pages 57-62)

2.3 Protective factors

No directly evidenced genetic or environmental protective factors were identified in the retrieved sources. Prevention is implied through consistent hypothyroidism treatment adherence and healthcare access (see Section 13). (sokołowski2024increasedincidenceof pages 2-4)

2.4 Gene–environment interactions

Not specifically addressed in the retrieved evidence.

3. Phenotypes (clinical & laboratory) with ontology suggestions

3.1 Generalized myxedema (severe hypothyroidism)

Core phenotype: diffuse/non‑focal, non‑pitting edema and skin thickening/induration. (bonino2023pediatricmyxedemadue pages 1-2, cohen2023dermatologicmanifestationsof pages 2-3)

HPO suggestions (examples): - Nonpitting edema (HP:0100651) - Facial edema (HP:0000282) - Periorbital edema (HP:0000284) - Xerosis (dry skin) (HP:0000958) - Hypothermia (HP:0002045) (in severe decompensation) (bonino2023pediatricmyxedemadue pages 1-2)

Systemic involvement examples: pericardial effusion reported in pediatric severe hypothyroidism with myxedema (up to 12 mm in a case). (bonino2023pediatricmyxedemadue pages 1-2)

3.2 Myxedema coma (decompensated severe hypothyroidism)

Typical clinical features: - Altered mental status (lethargy → coma) (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2) - Hypothermia (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2) - Bradycardia and low cardiac output/hypotension (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2) - Hypoventilation with hypoxemia/hypercarbia; possible airway obstruction from macroglossia/peri‑laryngeal edema (ylli2019thyroidemergencies pages 3-4) - Serous effusions (pleural/pericardial), ascites (ylli2019thyroidemergencies pages 3-4)

Laboratory abnormalities (commonly reported): - Very low free T4 (often near undetectable) with variable TSH (including patterns consistent with central hypothyroidism) (ylli2019thyroidemergencies pages 3-4, sokołowski2024increasedincidenceof pages 2-4) - Hyponatremia, hypoglycemia, and renal dysfunction (elevated BUN/creatinine) may occur (ylli2019thyroidemergencies pages 3-4)

Quantitative thresholds used in a large cohort (operational definitions): - Hypothermia ≤35°C; hypotension <90/60 mmHg; bradycardia <60 bpm; hyponatremia <135 mEq/L; hypoglycemia ≤60 mg/dL; hypoxemia SatO2 <88% or PaO2 <55 mmHg. (chaudhary2023utilityofmyxedema pages 1-2)

HPO suggestions (examples): - Abnormality of consciousness (HP:0001251) - Hypothermia (HP:0002045) - Bradycardia (HP:0001662) - Hypotension (HP:0002615) - Hyponatremia (HP:0002902) - Hypoglycemia (HP:0001943) - Hypoventilation (HP:0002791) - Hypercapnia (HP:0012418) - Hypoxemia (HP:0012418/HP:0002093 context-dependent)

Course: Cases cluster in winter and are commonly precipitated by acute stressors; delayed recognition is common due to nonspecific presentation. (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)

Quality-of-life impact: Not quantified in retrieved sources; however, severe hypothyroid manifestations can impair daily function and, in coma, lead to critical illness requiring organ support. (ylli2019thyroidemergencies pages 3-4, hwang2014treatmentofendocrine pages 6-9)

4. Genetic / molecular information

Causal genes/variants: Myxedema is typically not a monogenic disorder; it is a clinical syndrome resulting from thyroid hormone deficiency. No causal gene/variant evidence was retrieved for this run.

Autoimmune context: For localized pretibial myxedema (thyroid dermopathy), thyrotropin receptor antibodies are implicated in some literature; older evidence suggests TRAb elevated in ~50% of pretibial myxedema cases (not specific to generalized myxedema). (anuradha2015pretibialmyxedemain pages 3-4)

5. Environmental information

Cold exposure and winter seasonality are repeatedly cited as triggers for decompensation (myxedema coma), consistent with environmental stress interacting with reduced thermogenesis in severe hypothyroidism. (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)

Medication exposures: ICU/geriatric review highlights exposures relevant to thyroid dysfunction (e.g., amiodarone; iodinated contrast) in critically ill older adults. (garg2020handbookofinpatient pages 57-62)

6. Mechanism / pathophysiology

6.1 Generalized myxedema (severe hypothyroidism)

Current understanding (skin/interstitium): - Major accumulating GAG in myxedema is hyaluronic acid. (cohen2023dermatologicmanifestationsof pages 1-2) - Generalized myxedema is attributed to altered dermal mucopolysaccharides (GAGs) and increased dermal water content, producing cool, pale skin. (cohen2023dermatologicmanifestationsof pages 2-3) - Mechanisms proposed include increased protein extravasation and relatively slow lymphatic drainage, contributing to interstitial swelling. (cohen2023dermatologicmanifestationsof pages 18-18)

Cell types: Dermal fibroblasts and epidermal keratinocytes are thyroid-hormone responsive; thyroid hormones stimulate keratinocyte and fibroblast growth and influence hyaluronate synthesis/barrier formation. (cohen2023dermatologicmanifestationsof pages 1-2)

Histopathologic correlates (esp. thyroid dermopathy/pretibial form): mucin/GAG deposition separating dermal collagen bundles; Alcian blue pH 2.5 and colloidal iron staining highlight mucin. (cohen2023dermatologicmanifestationsof pages 3-4, demirkesen2015skinmanifestationsof pages 4-6)

GO biological process suggestions (examples): - Glycosaminoglycan metabolic process (GO:0006022) - Extracellular matrix organization (GO:0030198) - Hyaluronan metabolic process (GO:0030212) - Regulation of fibroblast proliferation (GO:0048146)

Cell Ontology suggestions: - Dermal fibroblast (CL:0002553, broadly “fibroblast” CL:0000057) - Keratinocyte (CL:0000312) (cohen2023dermatologicmanifestationsof pages 1-2)

UBERON suggestions: - Skin (UBERON:0002097) - Dermis (UBERON:0002067) - Epidermis (UBERON:0001003)

6.2 Myxedema coma (systemic decompensation)

Myxedema coma represents multisystem failure from profound thyroid hormone deficiency. Key downstream physiological effects described include hypoventilation with hypoxemia/hypercarbia, cardiovascular depression (bradycardia/low output), and serous effusions. (ylli2019thyroidemergencies pages 3-4)

A major clinical pathophysiology consideration is possible coexisting adrenal insufficiency; thyroid hormone replacement can increase cortisol metabolism and precipitate adrenal crisis, motivating empiric stress-dose glucocorticoids. (hwang2014treatmentofendocrine pages 6-9)

7. Anatomical structures affected

Primary systems: endocrine (thyroid axis), skin/subcutis, cardiovascular and respiratory systems, CNS. (ylli2019thyroidemergencies pages 3-4, cohen2023dermatologicmanifestationsof pages 1-2)

Organ/tissue involvement (examples): - Skin/dermis (GAG/mucin deposition and edema) (cohen2023dermatologicmanifestationsof pages 1-2, cohen2023dermatologicmanifestationsof pages 2-3) - Heart/pericardium (pericardial effusion; low output) (ylli2019thyroidemergencies pages 3-4, bonino2023pediatricmyxedemadue pages 1-2) - Lungs/pleura (hypoventilation; pleural effusions) (ylli2019thyroidemergencies pages 3-4)

8. Temporal development

Onset: generalized myxedema typically develops insidiously with progressive hypothyroidism; myxedema coma often emerges acutely/subacutely in the setting of a precipitating factor (infection, cold exposure, etc.). (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)

Course: Myxedema coma is rare but high risk and requires urgent intervention; delayed diagnosis is common because symptoms can resemble sepsis/metabolic encephalopathy. (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)

9. Inheritance and population

Inheritance pattern: Not applicable as a primary inherited disease entity (clinical syndrome secondary to thyroid hormone deficiency).

Epidemiology (myxedema coma): - A recent U.S. National Inpatient Sample (NIS) analysis (2016–2020) identified 5,095 myxedema coma hospitalizations with overall inpatient mortality 11.60%. (hashmi2023weekendhospitaladmissions pages 4-9, hashmi2023weekendhospitaladmissions pages 1-4) - In that NIS study, mortality increased from 6.76% (2016) to 13.36% (2020), and weekend admissions had higher mortality: 13.11% weekend vs 8.38% weekday, adjusted OR 1.91. (hashmi2023weekendhospitaladmissions pages 4-9, hashmi2023weekendhospitaladmissions pages 1-4) - A 2015–2023 single-center Polish series (n=11) reported mortality 27.2% and suggested a marked rise in cases during/post‑COVID era (1 case in 2015–2019 vs 10 cases after pandemic onset). (sokołowski2024increasedincidenceof pages 2-4)

Sex/age: Reviews describe predominance in older adults and women (e.g., mean age 77 in one cited series; ~two-thirds women in review discussion). (ylli2019thyroidemergencies pages 3-4)

10. Diagnostics

10.1 Clinical diagnosis and scoring

Because presentation is nonspecific, scoring systems support structured diagnosis.

Popoveniuc (myxedema coma) score thresholds: cumulative score ≥60 correlates with myxedema coma; 45–59 indicates overt hypothyroidism with increased risk; ≤25 unlikely in some summaries. (ylli2019thyroidemergencies pages 3-4, aguirre2026fromthepopoveniuc pages 5-6)

A 2024 case series used a point-based score including neurologic status (e.g., coma/seizures), cardiovascular, respiratory, GI, and metabolic parameters; the paper restated that 60+ is highly suggestive/diagnostic; 25–59 suggests risk. (sokołowski2024increasedincidenceof pages 2-4)

10.2 Laboratory tests

Recommended initial tests include thyroid function tests (TSH, free T4 ± T3) and metabolic panels, plus baseline/random cortisol prior to thyroid replacement where feasible (do not delay treatment). (garg2020handbookofinpatient pages 62-66)

10.3 Differential diagnosis

Nonspecific features overlap with sepsis, metabolic encephalopathy, and other causes of coma/shock; the diagnostic scoring approach and thyroid labs are used to support recognition in ambiguous cases. (ylli2019thyroidemergencies pages 3-4, hwang2014treatmentofendocrine pages 6-9)

11. Outcome / prognosis

11.1 Mortality

Cohort mortality remains high; in one large single-center cohort spanning 1999–2020, mortality was 60.9%. (chaudhary2023utilityofmyxedema pages 1-2)
National inpatient mortality in the U.S. NIS analysis (2016–2020) was 11.6% overall, with worsening trend through 2020. (hashmi2023weekendhospitaladmissions pages 4-9, hashmi2023weekendhospitaladmissions pages 1-4)

11.2 Prognostic factors

A 1999–2020 cohort analysis found higher mortality associated with: - Higher myxedema score (see below) - Need for mechanical ventilation - In-hospital hypotension - Higher qSOFA score - Female sex (in that cohort). (chaudhary2023utilityofmyxedema pages 1-2)

Myxedema score and mortality: myxedema score >90 associated with significantly higher mortality; >110 associated with 100% mortality in that cohort. (chaudhary2023utilityofmyxedema pages 1-2)

12. Treatment

12.1 Core treatment principles (ICU emergency)

Myxedema coma management consists of rapid thyroid hormone replacement, empiric stress-dose glucocorticoids, and aggressive supportive care (airway/ventilation, hemodynamic support, cautious rewarming, correction of metabolic derangements, and treatment of precipitating factors including infection). (ylli2019thyroidemergencies pages 3-4, garg2020handbookofinpatient pages 62-66)

12.2 Thyroid hormone replacement (dosing patterns in retrieved sources)

IV levothyroxine (LT4) regimen (summarized guidance): - Loading 200–400 mcg IV, followed by 50–100 mcg IV daily. (lundholm2025myxedemacomadiagnostic pages 1-2, garg2020handbookofinpatient pages 62-66)

Liothyronine (LT3) adjunct (selected cases / controversial): - 5–20 mcg IV once, then 2.5–10 mcg IV q8h, with lower doses for older adults or cardiac disease. (lundholm2025myxedemacomadiagnostic pages 1-2, garg2020handbookofinpatient pages 62-66)

12.3 Glucocorticoids

Stress-dose hydrocortisone recommended prior to/during thyroid hormone replacement, due to adrenal insufficiency risk: - Hydrocortisone 50–100 mg IV every 6–8 hours (and similar stress regimens). (garg2020handbookofinpatient pages 62-66)

12.4 Real-world implementation when IV LT4 is unavailable (oral/liquid LT4)

Oral LT4 single-center experience: 14 patients treated with an oral LT4 regimen including 300–500 mcg loading followed by taper over several days; 13/14 survived. (rajendran2021orallevothyroxineis pages 2-3)

Protocol figure (oral LT4): A published algorithm stratifies loading dose by coronary disease and LVEF and integrates baseline cortisol‑guided hydrocortisone. (rajendran2021orallevothyroxineis media 1ba7db35)

12.5 MAXO (Medical Action Ontology) suggestions

Thyroid hormone replacement therapy (MAXO term suggestion: levothyroxine therapy / thyroid hormone replacement)
Glucocorticoid therapy (stress-dose hydrocortisone)
Mechanical ventilation
Vasopressor therapy
Passive rewarming
Antibiotic therapy (when infection suspected)
Electrolyte correction (e.g., hyponatremia management). (ylli2019thyroidemergencies pages 3-4, garg2020handbookofinpatient pages 62-66)

13. Prevention

Evidence in the retrieved sources supports prevention strategies focused on preventing progression of hypothyroidism to decompensation: - Medication adherence and long-term follow-up: A 2024 case series attributed most cases to therapy non-compliance and emphasized maintaining healthcare access/communication, particularly during resource-limited periods (e.g., COVID-19 era). (sokołowski2024increasedincidenceof pages 2-4) - Risk reduction for triggers: vigilance for infection/cold exposure in high-risk patients (older adults with severe hypothyroidism). (ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)

14. Other species / natural disease

No cross-species naturally occurring myxedema or zoonotic information was retrieved in this run.

15. Model organisms

No model organism evidence specific to myxedema/myxedema coma was retrieved in this run.

Recent developments and latest research highlights (prioritizing 2023–2024)

Myxedema score as a mortality predictor (2023): A Journal of Endocrinological Investigation cohort study evaluated the Popoveniuc-derived myxedema score as a predictor of mortality and identified high-risk cutpoints (MS>90; MS>110). (chaudhary2023utilityofmyxedema pages 1-2)
COVID-era access/implementation effects (2024): A single-center case series reported increased myxedema coma incidence during/post-pandemic and documented use of oral (often liquid) LT4 due to lack of parenteral LT4. (sokołowski2024increasedincidenceof pages 2-4)
Dermatologic mechanistic synthesis (2023): A Frontiers in Endocrinology review summarized modern mechanistic understanding of thyroid-related skin disease, emphasizing hyaluronic-acid/GAG accumulation and the roles of fibroblasts/keratinocytes and lymphatic/vascular factors in myxedema. (cohen2023dermatologicmanifestationsof pages 1-2, cohen2023dermatologicmanifestationsof pages 3-4)

Evidence table (selected quantitative and protocol data)

Topic	Key data	Population/setting	Source (first author year, journal)	URL	Citation ID (pqac-...)
Epidemiology/incidence	Myxedema coma incidence reported as “as low as 1.08 per million people per year.”	Emergency medicine educational review summarizing epidemiology	Namespetra 2025, JETem	https://doi.org/10.21980/j8vm0j	(mansoor2025myxedemacomaas pages 4-5)
Mortality	Historical mortality described as 25–60%; in one 1999–2020 cohort, mortality was 60.9%.	Single-center cohort of myxedema crisis/coma patients	Chaudhary 2023, Journal of Endocrinological Investigation	https://doi.org/10.1007/s40618-022-01884-6	(chaudhary2023utilityofmyxedema pages 1-2)
Mortality	Cohort mortality was 27.2%.	Single-center Krakow case series, 11 patients treated 2015–2023	Sokołowski 2024, Internal and Emergency Medicine	https://doi.org/10.1007/s11739-024-03690-9	(sokołowski2024increasedincidenceof pages 2-4)
Mortality trend / weekend effect	NIS study identified 5,095 myxedema coma hospitalizations (2016–2020); overall mortality 11.60%; weekend mortality 13.11% vs weekday 8.38%; adjusted OR for weekend admission 1.91 (95% CI 1.18–3.10), p=0.009.	U.S. National Inpatient Sample	Hashmi 2023, Research Square preprint	https://doi.org/10.21203/rs.3.rs-3085786/v1	(hashmi2023weekendhospitaladmissions pages 4-9, hashmi2023weekendhospitaladmissions pages 1-4)
Mortality trend over time	Overall mortality increased from 6.76% in 2016 to 13.36% in 2020 (p=0.014).	U.S. National Inpatient Sample, 2016–2020	Hashmi 2023, Research Square preprint	https://doi.org/10.21203/rs.3.rs-3085786/v1	(hashmi2023weekendhospitaladmissions pages 4-9, hashmi2023weekendhospitaladmissions pages 1-4)
Diagnostic scoring cutoffs	Popoveniuc-style score: ≥60 highly suggestive/diagnostic; 25–59 suggests risk for myxedema coma.	Review/guideline summaries and case series using diagnostic score	Ylli 2021, Polish Archives of Internal Medicine; Sokołowski 2024, Internal and Emergency Medicine	https://doi.org/10.20452/pamw.14876 ; https://doi.org/10.1007/s11739-024-03690-9	(ylli2019thyroidemergencies pages 3-4, sokołowski2024increasedincidenceof pages 2-4)
Mortality predictors by score	Myxedema score >90 associated with significantly higher mortality; score >110 associated with 100% mortality.	Single-center cohort, 1999–2020	Chaudhary 2023, Journal of Endocrinological Investigation	https://doi.org/10.1007/s40618-022-01884-6	(chaudhary2023utilityofmyxedema pages 1-2)
Other prognostic factors	Female sex, need for mechanical ventilation, in-hospital hypotension, and high qSOFA predicted mortality.	Single-center cohort, 1999–2020	Chaudhary 2023, Journal of Endocrinological Investigation	https://doi.org/10.1007/s40618-022-01884-6	(chaudhary2023utilityofmyxedema pages 1-2)
Key precipitants	Common precipitants include infection (especially pneumonia/sepsis), cold exposure, CVA/stroke, CHF, GI bleeding, trauma, sedatives; winter predominance noted.	Reviews and cohort studies of myxedema coma	Ylli 2021, Polish Archives of Internal Medicine; Chaudhary 2023, Journal of Endocrinological Investigation	https://doi.org/10.20452/pamw.14876 ; https://doi.org/10.1007/s40618-022-01884-6	(ylli2019thyroidemergencies pages 3-4, chaudhary2023utilityofmyxedema pages 1-2)
COVID-era incidence change	At one center, 1 case occurred in 2015–2019 versus 10 cases after the start of the COVID-19 pandemic through 2023.	Single-center Krakow case series	Sokołowski 2024, Internal and Emergency Medicine	https://doi.org/10.1007/s11739-024-03690-9	(sokołowski2024increasedincidenceof pages 2-4)
Etiology in recent case series	2/11 (18%) had de novo hypothyroidism; 9/11 had severe hypothyroidism due to therapy non-compliance; 9 primary and 2 central hypothyroidism.	Single-center Krakow case series	Sokołowski 2024, Internal and Emergency Medicine	https://doi.org/10.1007/s11739-024-03690-9	(sokołowski2024increasedincidenceof pages 2-4)
Key labs	Very low FT4 (often almost undetectable) with variable TSH; possible hypoglycemia, hyponatremia, low chloride, hypercalcemia, mild renal failure (elevated BUN/creatinine).	Review of thyroid emergencies	Ylli 2021, Polish Archives of Internal Medicine	https://doi.org/10.20452/pamw.14876	(ylli2019thyroidemergencies pages 3-4)
Key labs / cohort thresholds	Defined thresholds used in cohort: hypothermia ≤35°C, hypotension <90/60 mmHg, bradycardia <60 bpm, hyponatremia <135 mEq/L, hypoglycemia ≤60 mg/dL, hypoxemia SatO2 <88% or PaO2 <55 mmHg.	Single-center cohort, 1999–2020	Chaudhary 2023, Journal of Endocrinological Investigation	https://doi.org/10.1007/s40618-022-01884-6	(chaudhary2023utilityofmyxedema pages 1-2)
Treatment doses	Recommended IV levothyroxine loading 200–400 mcg, then 50–100 mcg IV daily; consider IV liothyronine 5–20 mcg once then 2.5–10 mcg q8h; hydrocortisone 100 mg q8h or 50–100 mg every 6–8 h before/during thyroid replacement.	Guideline/review summaries	Lundholm 2025, Evidence to Action: Official Journal of MDCalc; Garg 2020, Handbook of Inpatient Endocrinology	https://doi.org/10.65357/001c.153938 ; https://doi.org/10.1007/978-3-030-38976-5	(lundholm2025myxedemacomadiagnostic pages 1-2, garg2020handbookofinpatient pages 62-66)
Supportive care protocol	ICU admission; do not wait for labs; broad-spectrum antibiotics if infection suspected; assisted ventilation/intubation as needed; passive rewarming; fluids/vasopressors for hypotension; correction of hyponatremia/hypoglycemia.	Review/guideline summaries	Ylli 2021, Polish Archives of Internal Medicine; Garg 2020, Handbook of Inpatient Endocrinology	https://doi.org/10.20452/pamw.14876 ; https://doi.org/10.1007/978-3-030-38976-5	(ylli2019thyroidemergencies pages 3-4, garg2020handbookofinpatient pages 62-66)
Oral LT4 protocol alternative	Oral LT4 regimen in 14 patients: loading dose 300–500 mcg followed by taper over 3–5 days; 13/14 survived.	Single-center retrospective observational study where IV LT4 unavailable	Rajendran 2021, European Thyroid Journal	https://doi.org/10.1159/000507855	(rajendran2021orallevothyroxineis pages 2-3)
Oral LT4 protocol details	Algorithm stratified by cardiac status: no CAD, LD 500 mcg; CAD with normal LVEF, LD 300–400 mcg; CAD with LVEF <60%, LD 250–300 mcg; check FT4 every alternate day; if cortisol <15 mcg/dL give hydrocortisone 50–100 mg IV stat then q8h.	Figure 1 protocol for oral LT4 in myxedema coma	Rajendran 2021, European Thyroid Journal	https://doi.org/10.1159/000507855	(rajendran2021orallevothyroxineis pages 2-3, rajendran2021orallevothyroxineis media 1ba7db35)
Alternative non-IV implementation	Due to lack of parenteral levothyroxine, recent Polish series used oral, mostly liquid, levothyroxine.	Single-center Krakow case series	Sokołowski 2024, Internal and Emergency Medicine	https://doi.org/10.1007/s11739-024-03690-9	(sokołowski2024increasedincidenceof pages 2-4)

Table: This table compiles evidence-backed quantitative findings and practical treatment protocol details for myxedema coma from the gathered literature. It highlights incidence, mortality, diagnostic score cutoffs, prognostic markers, common precipitants, laboratory abnormalities, and both IV and oral levothyroxine treatment approaches.

Visual evidence: oral levothyroxine protocol

The following cited figure provides a practical, published algorithm for oral levothyroxine dosing and cortisol-guided hydrocortisone use in myxedema coma when IV LT4 is unavailable. (rajendran2021orallevothyroxineis media 1ba7db35)

Notes on evidence gaps and PMIDs

Several key retrieved items are peer‑reviewed but the tool-extracted metadata did not include PMIDs; thus, this report cannot provide PMID‑keyed citations without risking fabrication. URLs and DOIs are provided where available in the sources above.
Dedicated interventional clinical trials for myxedema coma were not identified in the retrieved ClinicalTrials.gov search results; available trials largely address hypothyroidism broadly rather than myxedema coma specifically. (clinical trials retrieved; no relevant myxedema-coma interventional trials identified in evidence)

References

(ylli2019thyroidemergencies pages 3-4): D. Ylli, J. Klubo-Gwiezdzinska, and L. Wartofsky. Thyroid emergencies. Polish archives of internal medicine, 129:526-534, Jun 2021. URL: https://doi.org/10.20452/pamw.14876, doi:10.20452/pamw.14876. This article has 21 citations.
(chaudhary2023utilityofmyxedema pages 1-2): S. Chaudhary, L. Das, Nikhil Sharma, N. Sachdeva, A. Bhansali, and P. Dutta. Utility of myxedema score as a predictor of mortality in myxedema coma. Journal of Endocrinological Investigation, 46:59-65, Aug 2023. URL: https://doi.org/10.1007/s40618-022-01884-6, doi:10.1007/s40618-022-01884-6. This article has 19 citations and is from a peer-reviewed journal.
(bonino2023pediatricmyxedemadue pages 1-2): Elisa Bonino, Patrizia Matarazzo, Raffaele Buganza, Gerdi Tuli, Jessica Munarin, Claudia Bondone, and Luisa de Sanctis. Pediatric myxedema due to autoimmune hypothyroidism: a rare complication of a common disorder. Children, 10:614, Mar 2023. URL: https://doi.org/10.3390/children10040614, doi:10.3390/children10040614. This article has 3 citations.
(cohen2023dermatologicmanifestationsof pages 2-3): Benjamin Cohen, Adam Cadesky, and Shuchie Jaggi. Dermatologic manifestations of thyroid disease: a literature review. Frontiers in Endocrinology, May 2023. URL: https://doi.org/10.3389/fendo.2023.1167890, doi:10.3389/fendo.2023.1167890. This article has 63 citations.
(demirkesen2015skinmanifestationsof pages 4-6): Cuyan Demirkesen. Skin manifestations of endocrine diseases. Turk patoloji dergisi, 31 Suppl 1:145-54, Jan 2015. URL: https://doi.org/10.5146/tjpath.2015.01321, doi:10.5146/tjpath.2015.01321. This article has 24 citations.
(sokołowski2024increasedincidenceof pages 2-4): Grzegorz Sokołowski, Katica Bajuk Studen, Marta Opalinska, Karolina Wegrzyn, Marcin Motyka, Aleksandra Gilis-Januszewska, and Alicja Hubalewska-Dydejczyk. Increased incidence of myxedema coma during the covid-19 pandemic and in the post pandemic era: a single-center case series. Internal and Emergency Medicine, 19:1921-1928, Jul 2024. URL: https://doi.org/10.1007/s11739-024-03690-9, doi:10.1007/s11739-024-03690-9. This article has 2 citations and is from a peer-reviewed journal.
(hashmi2023weekendhospitaladmissions pages 4-9): Mariam Hashmi, Zubair Hassan Bodla, Fatima Niaz, Umer Farooq, Christopher L. Bray, and Peters Okonoboh. Weekend hospital admissions for myxedema coma linked to higher mortality rates: an insight from national inpatient sample from 2016 to 2020. Jun 2023. URL: https://doi.org/10.21203/rs.3.rs-3085786/v1, doi:10.21203/rs.3.rs-3085786/v1.
(hwang2014treatmentofendocrine pages 6-9): Janice J. Hwang and David Y. Hwang. Treatment of endocrine disorders in the neuroscience intensive care unit. Current Treatment Options in Neurology, 16:1-15, Jan 2014. URL: https://doi.org/10.1007/s11940-013-0271-4, doi:10.1007/s11940-013-0271-4. This article has 24 citations and is from a peer-reviewed journal.
(garg2020handbookofinpatient pages 57-62): RK Garg. Handbook of Inpatient Endocrinology. Springer International Publishing, Jan 2020. URL: https://doi.org/10.1007/978-3-030-38976-5, doi:10.1007/978-3-030-38976-5.
(anuradha2015pretibialmyxedemain pages 3-4): KB Anuradha and K Prasad. Pretibial myxedema in hypothyroidism-a clinical paradox. Unknown journal, 2015.
(cohen2023dermatologicmanifestationsof pages 1-2): Benjamin Cohen, Adam Cadesky, and Shuchie Jaggi. Dermatologic manifestations of thyroid disease: a literature review. Frontiers in Endocrinology, May 2023. URL: https://doi.org/10.3389/fendo.2023.1167890, doi:10.3389/fendo.2023.1167890. This article has 63 citations.
(cohen2023dermatologicmanifestationsof pages 18-18): Benjamin Cohen, Adam Cadesky, and Shuchie Jaggi. Dermatologic manifestations of thyroid disease: a literature review. Frontiers in Endocrinology, May 2023. URL: https://doi.org/10.3389/fendo.2023.1167890, doi:10.3389/fendo.2023.1167890. This article has 63 citations.
(cohen2023dermatologicmanifestationsof pages 3-4): Benjamin Cohen, Adam Cadesky, and Shuchie Jaggi. Dermatologic manifestations of thyroid disease: a literature review. Frontiers in Endocrinology, May 2023. URL: https://doi.org/10.3389/fendo.2023.1167890, doi:10.3389/fendo.2023.1167890. This article has 63 citations.
(hashmi2023weekendhospitaladmissions pages 1-4): Mariam Hashmi, Zubair Hassan Bodla, Fatima Niaz, Umer Farooq, Christopher L. Bray, and Peters Okonoboh. Weekend hospital admissions for myxedema coma linked to higher mortality rates: an insight from national inpatient sample from 2016 to 2020. Jun 2023. URL: https://doi.org/10.21203/rs.3.rs-3085786/v1, doi:10.21203/rs.3.rs-3085786/v1.
(aguirre2026fromthepopoveniuc pages 5-6): Rodolfo A Valerio Aguirre, Karla C Ocaña Martinez, Erick U Martinez Rodriguez, Taide I Cabrera López, and Jonathan G Gonzalez Mena. From the popoveniuc score to therapeutic protocols: a comprehensive review of myxedema coma. Cureus, Jan 2026. URL: https://doi.org/10.7759/cureus.101023, doi:10.7759/cureus.101023. This article has 0 citations.
(garg2020handbookofinpatient pages 62-66): RK Garg. Handbook of Inpatient Endocrinology. Springer International Publishing, Jan 2020. URL: https://doi.org/10.1007/978-3-030-38976-5, doi:10.1007/978-3-030-38976-5.
(lundholm2025myxedemacomadiagnostic pages 1-2): Michelle D. Lundholm. Myxedema coma diagnostic score. Evidence to Action: Official Journal of MDCalc, Dec 2025. URL: https://doi.org/10.65357/001c.153938, doi:10.65357/001c.153938. This article has 0 citations.
(rajendran2021orallevothyroxineis pages 2-3): Arjun Rajendran, Nisha Bhavani, Vasantha Nair, Praveen V. Pavithran, V. Usha Menon, and Harish Kumar. Oral levothyroxine is an effective option for myxedema coma: a single-centre experience. European Thyroid Journal, 10:52-58, Jun 2021. URL: https://doi.org/10.1159/000507855, doi:10.1159/000507855. This article has 38 citations and is from a peer-reviewed journal.
(rajendran2021orallevothyroxineis media 1ba7db35): Arjun Rajendran, Nisha Bhavani, Vasantha Nair, Praveen V. Pavithran, V. Usha Menon, and Harish Kumar. Oral levothyroxine is an effective option for myxedema coma: a single-centre experience. European Thyroid Journal, 10:52-58, Jun 2021. URL: https://doi.org/10.1159/000507855, doi:10.1159/000507855. This article has 38 citations and is from a peer-reviewed journal.
(mansoor2025myxedemacomaas pages 4-5): Rabia Mansoor, Maheen Iqbal, Tushaar Kakkar, Aymen Bader, and Taha Elsahy. Myxedema coma as the initial presentation of undiagnosed hypothyroidism: a rare but reversible emergency. Cureus, Dec 2025. URL: https://doi.org/10.7759/cureus.98621, doi:10.7759/cureus.98621. This article has 0 citations.

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Pathophysiology

Pathograph

Phenotypes

Treatments

Environmental Factors

Biochemical Markers

Source YAML

References & Deep Research

Deep Research

Disease Characteristics Research Template

Target Disease

Research Objectives

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Citation Requirements

Output Format

Comprehensive Disease Characteristics Report: Myxedema (incl. Myxedema Coma)

Target disease

1. Disease information (overview)

2. Etiology

2.1 Primary causal factors

2.2 Risk factors and triggers (myxedema coma)

2.3 Protective factors

2.4 Gene–environment interactions

3. Phenotypes (clinical & laboratory) with ontology suggestions

3.1 Generalized myxedema (severe hypothyroidism)

3.2 Myxedema coma (decompensated severe hypothyroidism)

4. Genetic / molecular information

5. Environmental information

6. Mechanism / pathophysiology

6.1 Generalized myxedema (severe hypothyroidism)

6.2 Myxedema coma (systemic decompensation)

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

10. Diagnostics

10.1 Clinical diagnosis and scoring

10.2 Laboratory tests

10.3 Differential diagnosis

11. Outcome / prognosis

11.1 Mortality

11.2 Prognostic factors

12. Treatment

12.1 Core treatment principles (ICU emergency)

12.2 Thyroid hormone replacement (dosing patterns in retrieved sources)

12.3 Glucocorticoids

12.4 Real-world implementation when IV LT4 is unavailable (oral/liquid LT4)

12.5 MAXO (Medical Action Ontology) suggestions

13. Prevention

14. Other species / natural disease

15. Model organisms

Recent developments and latest research highlights (prioritizing 2023–2024)

Evidence table (selected quantitative and protocol data)

Visual evidence: oral levothyroxine protocol

Notes on evidence gaps and PMIDs