Cushing's Syndrome

Complex MONDO:0018912 Endocrine Disorders Adrenal Gland Diseases
0
Mappings
0
Definitions
0
Inheritance
3
Pathophysiology
0
Histopathology
7
Phenotypes
0
Pathograph
0
Genes
4
Treatments
0
Subtypes
0
Differentials
0
Datasets
0
Trials
0
Models
⚙

Pathophysiology

3
Chronic Cortisol Excess
Cushing's syndrome results from prolonged exposure to excess glucocorticoids, either exogenous (iatrogenic from corticosteroid therapy) or endogenous (from pituitary adenomas secreting ACTH, adrenal tumors, or ectopic ACTH production). Elevated cortisol causes widespread metabolic, immunologic, and cardiovascular effects.
glucocorticoid secreting cell link
glucocorticoid secretion link
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology."
This review confirms the fundamental pathophysiology of Cushing's syndrome as prolonged cortisol excess.
Hypothalamic-Pituitary-Adrenal Axis Dysregulation
In endogenous Cushing's, the normal negative feedback regulation of cortisol on the HPA axis is disrupted. ACTH-dependent forms involve autonomous ACTH secretion from pituitary or ectopic sources, while ACTH-independent forms involve autonomous adrenal cortisol production bypassing normal regulation.
corticotroph link
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production."
This confirms that ACTH-secreting pituitary tumors are the most common cause of endogenous Cushing's, representing HPA axis dysregulation.
Metabolic Consequences of Hypercortisolism
Chronic cortisol excess induces insulin resistance, hepatic gluconeogenesis, protein catabolism in muscle and skin, redistribution of adipose tissue to central deposits, and altered lipid metabolism, leading to the characteristic phenotypic features of the syndrome.
response to glucocorticoid link
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders."
This confirms the metabolic consequences including hyperglycemia, protein catabolism, and weight gain.
●

Phenotypes

7
Blood 1
Easy Bruising Bruising susceptibility (HP:0000978)
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae"
Easy bruising is confirmed as a characteristic skin change.
Cardiovascular 1
Hypertension Hypertension (HP:0000822)
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition"
This confirms hypertension as a characteristic metabolic manifestation.
Integument 1
Purple Striae Striae distensae (HP:0001065)
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae"
This confirms purple striae as a characteristic skin manifestation.
Metabolism 1
Glucose Intolerance Glucose intolerance (HP:0001952)
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders."
Hyperglycemia from cortisol-induced insulin resistance is a key feature.
Musculoskeletal 2
Proximal Muscle Weakness Proximal muscle weakness (HP:0003701)
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders."
Protein catabolism from cortisol excess causes proximal muscle weakness and myopathy.
Osteoporosis Osteoporosis (HP:0000939)
Growth 1
Central Obesity Truncal obesity (HP:0001956)
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs."
This confirms central obesity with excess fat in the face, back of neck (buffalo hump), and visceral organs.
💊

Treatments

4
Surgical Resection
Action: surgical procedure MAXO:0000004
First-line treatment for most endogenous Cushing's syndrome: transsphenoidal surgery for pituitary adenomas (Cushing's disease), adrenalectomy for adrenal tumors, or resection of ectopic ACTH-secreting tumors.
Show evidence (1 reference)
PMID:37432427 SUPPORT
"Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production"
Surgery is confirmed as the first-line treatment for endogenous Cushing's syndrome.
Medical Therapy
Action: pharmacotherapy MAXO:0000058
Steroidogenesis inhibitors (ketoconazole, metyrapone, osilodrostat) or glucocorticoid receptor antagonists (mifepristone) to control hypercortisolism when surgery is not possible or has failed.
Show evidence (1 reference)
PMID:37432427 SUPPORT
"medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers"
Multiple medication classes are used for hypercortisolism management.
Radiation Therapy
Action: radiation therapy MAXO:0000014
Pituitary radiation (conventional or stereotactic radiosurgery) for persistent or recurrent Cushing's disease after unsuccessful surgery.
Show evidence (1 reference)
PMID:37432427 SUPPORT
"For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate."
Radiation therapy is confirmed as an option for refractory cases.
Bilateral Adrenalectomy
Action: adrenalectomy MAXO:0001030
Definitive treatment option for patients with persistent hypercortisolism, resulting in permanent adrenal insufficiency requiring lifelong hormone replacement.
Show evidence (1 reference)
PMID:37432427 SUPPORT
"For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate."
Bilateral adrenalectomy is confirmed as a treatment for refractory cases.
{ }

Source YAML

click to show 
name: Cushing's Syndrome
creation_date: '2026-01-09T07:21:01Z'
updated_date: '2026-01-09T07:21:01Z'
category: Complex
disease_term:
  preferred_term: Cushing syndrome
  term:
    id: MONDO:0018912
    label: Cushing syndrome
parents:
- Endocrine Disorders
- Adrenal Gland Diseases
pathophysiology:
- name: Chronic Cortisol Excess
  description: >
    Cushing's syndrome results from prolonged exposure to excess glucocorticoids,
    either exogenous (iatrogenic from corticosteroid therapy) or endogenous (from
    pituitary adenomas secreting ACTH, adrenal tumors, or ectopic ACTH production).
    Elevated cortisol causes widespread metabolic, immunologic, and cardiovascular
    effects.
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology."
    explanation: "This review confirms the fundamental pathophysiology of Cushing's syndrome as prolonged cortisol excess."
  biological_processes:
  - preferred_term: glucocorticoid secretion
    term:
      id: GO:0035933
      label: glucocorticoid secretion
  cell_types:
  - preferred_term: glucocorticoid secreting cell
    term:
      id: CL:0000460
      label: glucocorticoid secreting cell
- name: Hypothalamic-Pituitary-Adrenal Axis Dysregulation
  description: >
    In endogenous Cushing's, the normal negative feedback regulation of cortisol
    on the HPA axis is disrupted. ACTH-dependent forms involve autonomous ACTH
    secretion from pituitary or ectopic sources, while ACTH-independent forms
    involve autonomous adrenal cortisol production bypassing normal regulation.
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production."
    explanation: "This confirms that ACTH-secreting pituitary tumors are the most common cause of endogenous Cushing's, representing HPA axis dysregulation."
  cell_types:
  - preferred_term: corticotroph
    term:
      id: CL:0002309
      label: corticotroph
- name: Metabolic Consequences of Hypercortisolism
  description: >
    Chronic cortisol excess induces insulin resistance, hepatic gluconeogenesis,
    protein catabolism in muscle and skin, redistribution of adipose tissue to
    central deposits, and altered lipid metabolism, leading to the characteristic
    phenotypic features of the syndrome.
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders."
    explanation: "This confirms the metabolic consequences including hyperglycemia, protein catabolism, and weight gain."
  biological_processes:
  - preferred_term: response to glucocorticoid
    term:
      id: GO:0051384
      label: response to glucocorticoid
phenotypes:
- name: Central Obesity
  description: >
    Preferential fat deposition in the trunk, face (moon facies), and dorsocervical
    area (buffalo hump) with relative sparing of the extremities, characteristic
    of hypercortisolism.
  phenotype_term:
    preferred_term: truncal obesity
    term:
      id: HP:0001956
      label: Truncal obesity
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs."
    explanation: "This confirms central obesity with excess fat in the face, back of neck (buffalo hump), and visceral organs."
- name: Purple Striae
  description: >
    Wide (greater than 1 cm), violaceous stretch marks, typically on the abdomen,
    thighs, and upper arms, resulting from cortisol-induced collagen breakdown
    and skin thinning.
  phenotype_term:
    preferred_term: striae distensae
    term:
      id: HP:0001065
      label: Striae distensae
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae"
    explanation: "This confirms purple striae as a characteristic skin manifestation."
- name: Proximal Muscle Weakness
  description: >
    Progressive weakness and wasting of proximal muscles, particularly of the
    lower extremities and pelvic girdle, due to cortisol-induced protein
    catabolism and myopathy.
  phenotype_term:
    preferred_term: proximal muscle weakness
    term:
      id: HP:0003701
      label: Proximal muscle weakness
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders."
    explanation: "Protein catabolism from cortisol excess causes proximal muscle weakness and myopathy."
- name: Hypertension
  description: >
    Elevated blood pressure occurring in the majority of patients, resulting from
    cortisol's mineralocorticoid effects on sodium retention and vascular reactivity.
  phenotype_term:
    preferred_term: hypertension
    term:
      id: HP:0000822
      label: Hypertension
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition"
    explanation: "This confirms hypertension as a characteristic metabolic manifestation."
- name: Glucose Intolerance
  description: >
    Impaired glucose tolerance or overt diabetes mellitus due to cortisol-induced
    insulin resistance and increased hepatic gluconeogenesis.
  phenotype_term:
    preferred_term: glucose intolerance
    term:
      id: HP:0001952
      label: Glucose intolerance
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders."
    explanation: "Hyperglycemia from cortisol-induced insulin resistance is a key feature."
- name: Osteoporosis
  description: >
    Decreased bone mineral density and increased fracture risk due to cortisol's
    inhibitory effects on osteoblast function, calcium absorption, and increased
    bone resorption.
  phenotype_term:
    preferred_term: osteoporosis
    term:
      id: HP:0000939
      label: Osteoporosis
- name: Easy Bruising
  description: >
    Increased skin fragility and easy bruising resulting from cortisol-induced
    loss of subcutaneous connective tissue and capillary fragility.
  phenotype_term:
    preferred_term: bruising susceptibility
    term:
      id: HP:0000978
      label: Bruising susceptibility
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae"
    explanation: "Easy bruising is confirmed as a characteristic skin change."
treatments:
- name: Surgical Resection
  description: >
    First-line treatment for most endogenous Cushing's syndrome: transsphenoidal
    surgery for pituitary adenomas (Cushing's disease), adrenalectomy for adrenal
    tumors, or resection of ectopic ACTH-secreting tumors.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production"
    explanation: "Surgery is confirmed as the first-line treatment for endogenous Cushing's syndrome."
- name: Medical Therapy
  description: >
    Steroidogenesis inhibitors (ketoconazole, metyrapone, osilodrostat) or
    glucocorticoid receptor antagonists (mifepristone) to control hypercortisolism
    when surgery is not possible or has failed.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers"
    explanation: "Multiple medication classes are used for hypercortisolism management."
- name: Radiation Therapy
  description: >
    Pituitary radiation (conventional or stereotactic radiosurgery) for persistent
    or recurrent Cushing's disease after unsuccessful surgery.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate."
    explanation: "Radiation therapy is confirmed as an option for refractory cases."
- name: Bilateral Adrenalectomy
  description: >
    Definitive treatment option for patients with persistent hypercortisolism,
    resulting in permanent adrenal insufficiency requiring lifelong hormone
    replacement.
  treatment_term:
    preferred_term: adrenalectomy
    term:
      id: MAXO:0001030
      label: adrenalectomy
  evidence:
  - reference: PMID:37432427
    reference_title: "Cushing Syndrome: A Review."
    supports: SUPPORT
    snippet: "For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate."
    explanation: "Bilateral adrenalectomy is confirmed as a treatment for refractory cases."
datasets: