| Domain | Test / intervention | What to do / when to use | Key details / outcome statistics | Suggested MAXO term(s) | Evidence |
|---|---|---|---|---|---|
| Diagnostics | Serum prolactin (PRL) assay | First-line biochemical test when prolactinoma is suspected; confirm hyperprolactinemia with careful sampling | Basal PRL should be measured with attention to assay conditions; prolactinomas account for ~50% of pituitary adenomas, with prevalence ~50/100,000 and incidence 3–5/100,000/year in the cited guideline context (pqac-00000022) | MAXO:0000001 clinical test; MAXO:0000408 hormone measurement | (pqac-00000022, pqac-00000024) |
| Diagnostics | Macroprolactin assessment | Check when PRL is only mildly elevated or incidentally high to avoid misclassification | Polyethylene glycol precipitation is recommended; recovery <40% suggests macroprolactin predominance, >60% suggests true monomeric hyperprolactinemia (pqac-00000021) | MAXO:0000001 clinical test; MAXO:0000408 hormone measurement | (pqac-00000021, pqac-00000019) |
| Diagnostics | Hook effect / assay dilution | Use serial dilutions for large pituitary lesions with only modest PRL elevation | The high-dose hook effect can mask severe hyperprolactinemia and is reported in ~5% of macroprolactinomas in the pediatric consensus excerpt (pqac-00000019) | MAXO:0000001 clinical test | (pqac-00000019, pqac-00000021) |
| Diagnostics | MRI of sellar region | Standard imaging to define pituitary lesion size, invasion, optic apparatus compression, and treatment planning | Macroadenoma versus microadenoma classification and invasive extension are central for management; CDH23-associated cases reported macroadenoma and giant invasive phenotypes (pqac-00000002, pqac-00000007) | MAXO:0000376 magnetic resonance imaging | (pqac-00000002, pqac-00000007, pqac-00000022) |
| Diagnostics | Hormone panel: GH/IGF-1 | Use when acromegaly or mixed somatotroph disease is suspected | CDH23-associated cases include GH excess/acromegaly and acromegaly–prolactinoma macroadenoma; elevated GH or IGF-1 was reported in affected carriers (pqac-00000000, pqac-00000002) | MAXO:0000408 hormone measurement | (pqac-00000000, pqac-00000002) |
| Diagnostics | Hormone panel: ACTH/cortisol | Use when Cushing disease/corticotroph PitNET is suspected | CDH23-associated disease spectrum includes ACTH-secreting adenoma/Cushing disease models; organoid data support corticotroph lineage skewing (pqac-00000001, pqac-00000003) | MAXO:0000408 hormone measurement | (pqac-00000001, pqac-00000003) |
| Diagnostics | Broader endocrine workup | Assess thyroid, gonadal, renal/hepatic confounders and pituitary function | Guideline excerpts recommend excluding severe hypothyroidism, renal/hepatic disease, medications, and assessing related pituitary axes; IGF-1 should be measured to exclude mixed GH secretion in prolactinoma workup (pqac-00000019, pqac-00000024) | MAXO:0000001 clinical test; MAXO:0000408 hormone measurement | (pqac-00000019, pqac-00000024) |
| Genetic evaluation | Germline testing trigger: young onset | Consider germline testing in young-onset pituitary adenoma/macroadenoma | Young age at diagnosis is repeatedly highlighted as a major determinant of germline variant detection; 7.1% of 225 young-onset sporadic macroadenoma patients carried pathogenic/likely pathogenic variants overall in one panel study, including one CDH23 case (~0.4%) (pqac-00000005, pqac-00000006) | MAXO:0000127 genetic testing | (pqac-00000005, pqac-00000006, pqac-00000013) |
| Genetic evaluation | Germline testing trigger: family history / FIPA | Strongly consider testing when pituitary adenoma clusters in a family or syndromic features are present | Familial pituitary tumors account for ~5% of all pituitary adenoma cases; CDH23 emerged as an FIPA/predisposition candidate from familial segregation and enrichment studies (pqac-00000013, pqac-00000026) | MAXO:0000127 genetic testing; MAXO:0000055 genetic counseling | (pqac-00000013, pqac-00000026, pqac-00000028) |
| Genetic evaluation | Testing approach | Prefer multigene panel or exome sequencing rather than single-gene testing in unclear hereditary cases | Studies identifying CDH23 in familial and sporadic PAs used WES or multigene panels; recent cohorts continue to recover rare CDH23 variants among broader PA predisposition genes (pqac-00000000, pqac-00000004, pqac-00000005) | MAXO:0000127 genetic testing | (pqac-00000000, pqac-00000004, pqac-00000005) |
| Treatment | Cabergoline | First-line dopamine agonist for prolactinomas and hyperprolactinemic tumors | 2023 Italian guideline recommends cabergoline over bromocriptine as first choice; adult/pediatric guideline data report median PRL normalization 68% (range 40–100%), tumor shrinkage 62% (20–100%), visual field improvement 67% (33–100%), menses normalization 78%, fertility improvement 53%, galactorrhea resolution 86% (pqac-00000018, pqac-00000019) | MAXO:0001298 dopamine agonist therapy; MAXO:0000745 cabergoline administration | (pqac-00000018, pqac-00000019, pqac-00000022) |
| Treatment | Bromocriptine | Alternative dopamine agonist when cabergoline is not tolerated or unsuitable | Less favored because of poorer tolerability and multiple daily dosing; guideline recommends bromocriptine mainly as an alternative for cabergoline-intolerant patients not eligible for surgery (pqac-00000021, pqac-00000022) | MAXO:0001298 dopamine agonist therapy; MAXO:0000746 bromocriptine administration | (pqac-00000021, pqac-00000022) |
| Treatment | Transsphenoidal pituitary surgery | Use for DA resistance/intolerance, lack of neuro-ophthalmologic improvement, recurrence/escape, patient preference, or non-prolactinoma subtypes where surgery is standard | Italian guideline recommends resection when no significant neuro-ophthalmologic improvement occurs within 2 weeks of cabergoline, with DA resistance/intolerance, treatment escape, or unwillingness for chronic DA therapy; pediatric consensus excerpt notes adult remission rates of ~30–50% in prolactinoma surgery (pqac-00000022, pqac-00000019) | MAXO:0000437 transsphenoidal surgery | (pqac-00000022, pqac-00000019, pqac-00000016) |
| Treatment | Radiotherapy | Consider for residual, recurrent, or progressive tumors, especially in multimodal management | Used after surgery/medical therapy failure or for progressive disease; contemporary reviews describe radiotherapy as an option for residual, recurrent, or progressive tumors (pqac-00000022) | MAXO:0000014 radiotherapy | (pqac-00000022) |
| Treatment | Temozolomide | Reserve for aggressive pituitary tumors/carcinomas or refractory disease in multidisciplinary care | In guideline synthesis, temozolomide produced tumor shrinkage in 73.5% and PRL reduction in 75%, but PRL normalization only in 8.3%; progression occurred in ~20.6% (pqac-00000020) | MAXO:0000063 chemotherapy; MAXO:0000754 temozolomide administration | (pqac-00000020, pqac-00000022) |
| Monitoring | Long-term follow-up | Continue endocrine, imaging, and genetic follow-up because penetrance may be incomplete/age-dependent | In the discovery family, two CDH23 variant carriers were unaffected but under age 30, suggesting possible age-dependent penetrance; long-term surveillance is therefore reasonable in predisposed families (pqac-00000000, pqac-00000026) | MAXO:0000011 follow-up evaluation; MAXO:0000055 genetic counseling | (pqac-00000000, pqac-00000026) |


*Table: This table summarizes clinically relevant diagnostic and treatment actions for suspected CDH23-associated pituitary adenoma predisposition, using disease-specific genetic evidence plus modern prolactinoma/pituitary adenoma guidelines. It is useful for translating the literature into structured knowledge-base actions, including testing triggers, assay pitfalls, therapies, and outcome benchmarks.*