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endo.men2a.core.v1PRODUCTION
endo.men2a.core.v1

Multiple endocrine neoplasia type 2A (MEN2A)

endocrinologychronicsyndromeadultpediatric
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Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Establish MEN2A: germline RET activating mutation + ≥1 component (MTC ~100%, pheo ~50%, PHPT ~20–30%); classify proband vs at-risk carrier; distinguish 2A from 2B and MEN1 (ATA 2015)

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Advance rule
Set
Advance when

RET status + syndrome scope established

Patient inputs (14)

ATA risk category × age drives prophylactic thyroidectomy timing (highest <5y / by-calcitonin; high by age 5; moderate individualized)

Specific RET codon (e.g., C634, M918T excludes 2A) sets ATA risk tier (highest/high/moderate) and component penetrance

Cascade testing of first-degree relatives; index vs at-risk carrier; de novo vs inherited

Pheochromocytoma crisis recognition + preop α/β blockade target

Tachycardia drives β-blocker timing (only AFTER adequate α-blockade)

Pheo in pregnancy is life-threatening; alters blockade drug choice and delivery planning

MTC tumour marker — basal ± stimulated; drives surgical timing and post-op cure/recurrence surveillance + doubling time

Second MTC marker; rising CEA with stable/falling calcitonin suggests dedifferentiation/progression

Pheochromocytoma must be EXCLUDED before any thyroid/parathyroid surgery, pregnancy or delivery

Primary hyperparathyroidism component (~20–30%); albumin-corrected calcium screen

PTH-dependent hypercalcaemia confirms MEN2A primary hyperparathyroidism (multiglandular)

Thyroid + central/lateral nodal mapping for MTC extent before thyroidectomy

Pheochromocytoma localisation (often bilateral) once metanephrines positive

MEN2A variant flags — cutaneous lichen amyloidosis (codon 634) / Hirschsprung disease (exon 10, codons 609/611/618/620)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (5)

5 need judgement
  • informationallife_threateningunprepared_pheo_before_surgery_or_delivery
    Thyroid/parathyroid surgery, delivery, or anaesthesia planned in a MEN2A patient with unexcluded or unblocked pheochromocytoma (ATA 2015)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpheo_hypertensive_crisis
    BP ≥180/120 with end-organ damage or catecholamine cardiomyopathy in a MEN2A carrier (ATA 2015)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateninghypercalcaemic_crisis
    Corrected calcium >14 mg/dL or symptomatic hypercalcaemia (AMS, AKI, arrhythmia) from MEN2A primary hyperparathyroidism (ATA 2015)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpregnancy_with_pheo_in_men2a
    Pregnant MEN2A carrier with confirmed/suspected pheochromocytoma (ATA 2015)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererapidly_rising_calcitonin_or_metastatic_mtc
    Short calcitonin/CEA doubling time (<6–24 mo) or radiographically metastatic MTC (ATA 2015)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

MEN2A sequenced management — pheo FIRST (α→β) → thyroidectomy by ATA risk + calcitonin → parathyroidectomy → advanced-MTC RET inhibitor → surveillance (ATA 2015)
axis: men2a_sequenced_managementstep 1 - Step 1 — EXCLUDE & treat pheochromocytoma FIRST (α-blockade THEN β-blockade)
Selected step "Step 1 — EXCLUDE & treat pheochromocytoma FIRST (α-blockade THEN β-blockade)" — Any MEN2A carrier before thyroid/parathyroid surgery, pregnancy or delivery; positive plasma free metanephrines
  • phenoxybenzamine
    first line
    alpha_blocker_non_selective
    10 mg BID, titrate q2–3 d to BP <130/80 + mild postural drop • PO • BID for 10–14 d preop
    triggers: pheo_confirmed, preop_blockade
    ATA 2015 / Endocrine Society 2014 — irreversible α-blockade must precede β; pheo excluded & treated before any MTC/parathyroid surgery
    rxcui 8149
  • doxazosin
    second line
    alpha_1_blocker_selective
    1 mg daily → titrate to 8–16 mg/day • PO • daily
    triggers: phenoxybenzamine_unavailable, pregnancy
    Selective α1 reversible alternative; preferred in pregnancy (ATA 2015)
    rxcui 49276
  • propranolol
    add on
    beta_blocker_non_selective
    20 mg TID • PO • TID
    triggers: adequate_alpha_blockade, persistent_tachycardia
    β ONLY after adequate α-blockade — never before (unopposed α → crisis) (ATA 2015)
    rxcui 8787
  • phentolamine
    rescue
    alpha_blocker_non_selective_IV
    5 mg IV bolus, repeat q5–10 min • IV • PRN
    triggers: pheo_hypertensive_crisis
    Rapid IV α-blockade for intra/perioperative catecholamine crisis (ATA 2015)
    rxcui 8153

outpatient playbook — drug actions (3)

  1. 1. phenoxybenzamine (if pheo confirmed) before any surgery
    10 mg BID titrate • PO • BID 10–14 d preop
    trigger: Positive metanephrines (ATA 2015)
    α before β; pheo cleared first (ATA 2015)
  2. 2. levothyroxine after total thyroidectomy
    1.6 mcg/kg/day • PO • once daily
    trigger: Post-thyroidectomy (ATA 2015)
    Lifelong replacement (ATA 2015)
  3. 3. selpercatinib if advanced metastatic MTC
    160 mg BID • PO • BID
    trigger: Advanced RET-mutant MTC (NCCN 2025)
    Selective RET inhibitor (NCCN 2025)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Positive germline RET mutation (proband or cascade-tested relative) (ATA 2015); Family history of MEN2 / MTC / pheochromocytoma (ATA 2015); Elevated basal/stimulated calcitonin or CEA (ATA 2015).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Multiple endocrine neoplasia type 2A (MEN2A)** (endo.men2a.core.v1).
Phenotype framing: MEN2A vs MEN2B (2B: marfanoid habitus + mucosal neuromas + earliest/most-aggressive MTC, NO PHPT) vs MEN1 (3Ps: parathyroid/pituitary/pancreatic — NO MTC or pheo) vs sporadic MTC/pheo/PHPT vs familial MTC (ATA 2015)
Scope: Establish MEN2A: germline RET activating mutation + ≥1 component (MTC ~100%, pheo ~50%, PHPT ~20–30%); classify proband vs at-risk carrier; distinguish 2A from 2B and MEN1 (ATA 2015)

No severity triggers fired against current inputs.

Plan

Regimen axis: **MEN2A sequenced management — pheo FIRST (α→β) → thyroidectomy by ATA risk + calcitonin → parathyroidectomy → advanced-MTC RET inhibitor → surveillance (ATA 2015)** — step "Step 1 — EXCLUDE & treat pheochromocytoma FIRST (α-blockade THEN β-blockade)".
1. phenoxybenzamine 10 mg BID, titrate q2–3 d to BP <130/80 + mild postural drop PO BID for 10–14 d preop (alpha_blocker_non_selective, first line) — ATA 2015 / Endocrine Society 2014 — irreversible α-blockade must precede β; pheo excluded & treated before any MTC/parathyroid surgery
2. doxazosin 1 mg daily → titrate to 8–16 mg/day PO daily (alpha_1_blocker_selective, second line) — Selective α1 reversible alternative; preferred in pregnancy (ATA 2015)
3. propranolol 20 mg TID PO TID (beta_blocker_non_selective, add on) — β ONLY after adequate α-blockade — never before (unopposed α → crisis) (ATA 2015)
4. phentolamine 5 mg IV bolus, repeat q5–10 min IV PRN (alpha_blocker_non_selective_IV, rescue) — Rapid IV α-blockade for intra/perioperative catecholamine crisis (ATA 2015)

Setting playbook (outpatient) — Confirm RET status, run three-component screen, plan prophylactic thyroidectomy by ATA risk + calcitonin, cascade-test relatives (ATA 2015)
5. phenoxybenzamine (if pheo confirmed) before any surgery 10 mg BID titrate PO BID 10–14 d preop — Positive metanephrines (ATA 2015) (α before β; pheo cleared first (ATA 2015))
6. levothyroxine after total thyroidectomy 1.6 mcg/kg/day PO once daily — Post-thyroidectomy (ATA 2015) (Lifelong replacement (ATA 2015))
7. selpercatinib if advanced metastatic MTC 160 mg BID PO BID — Advanced RET-mutant MTC (NCCN 2025) (Selective RET inhibitor (NCCN 2025))

Non-pharmacologic actions:
- Prophylactic total thyroidectomy timing by ATA risk tier + calcitonin (ATA 2015)
- Cascade RET testing of all first-degree relatives (ATA 2015)
- Pre-conception counselling — exclude pheo before pregnancy (ATA 2015)
- Multidisciplinary endocrine surgery + genetics referral (ATA 2015)

AVOID / contraindication checks:
- Beta blocker NEVER before alpha in pheo (ATA 2015; Endocrine Society 2014)
- No thyroid or parathyroid surgery or delivery until pheo excluded and blocked (ATA 2015)
- Unprepared pheo anaesthesia causes lethal catecholamine crisis (ATA 2015)
- Phenoxybenzamine postural hypotension counsel and volume expand (Endocrine Society 2014)
- Selective RET inhibitor QTc and hypertension monitoring (NCCN 2025)
- Post thyroidectomy hypocalcaemia monitor calcium PTH (ATA 2015)

Monitoring

Regimen monitoring:
- plasma free metanephrines before every surgery and pregnancy (ATA 2015)
- calcitonin CEA at 3mo then 6-12 monthly with doubling time (ATA 2015)
- annual plasma free metanephrines lifelong (ATA 2015)
- annual corrected calcium PTH lifelong (ATA 2015)
- preop BP HR postural during alpha then beta blockade (Endocrine Society 2014)
- RET inhibitor BP QTc LFTs on selpercatinib pralsetinib (NCCN 2025)
- post thyroidectomy calcium PTH TSH (ATA 2015)

Setting (outpatient) monitoring:
- Calcitonin + CEA periodic with doubling time (ATA 2015)
- Annual plasma free metanephrines (ATA 2015)
- Annual corrected calcium ± PTH (ATA 2015)

Follow-up plan: Genetic counselling + cascade RET testing of first-degree relatives; lifelong endo/surgery/genetics follow-up; pre-conception counselling (pheo exclusion before pregnancy); patient education on component surveillance and return precautions (ATA 2015)
- Close-out criterion: Cascade testing + lifelong follow-up + counselling arranged

Monitoring phase: Lifelong biochemical surveillance — calcitonin + CEA (with doubling-time post-thyroidectomy), annual plasma free metanephrines, annual corrected calcium ± PTH; RET-inhibitor toxicity monitoring (BP, QTc, LFTs) when on selpercatinib/pralsetinib (ATA 2015)

Disposition

Current setting: outpatient — Confirm RET status, run three-component screen, plan prophylactic thyroidectomy by ATA risk + calcitonin, cascade-test relatives (ATA 2015)

Disposition criteria:
- Continue outpatient surveillance once components stable and surgery planned/done (ATA 2015)

Escalation triggers (move to higher acuity):
- Pheo crisis / hypertensive emergency → ED/inpatient (ATA 2015)
- Hypercalcaemic crisis → inpatient (ATA 2015)
- Rapidly rising calcitonin / metastatic MTC → oncology + inpatient staging (ATA 2015)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Thyroid/parathyroid surgery, delivery, or anaesthesia planned in a MEN2A patient with unexcluded or unblocked pheochromocytoma (ATA 2015)
- [LIFE_THREATENING] BP ≥180/120 with end-organ damage or catecholamine cardiomyopathy in a MEN2A carrier (ATA 2015)
- [LIFE_THREATENING] Corrected calcium >14 mg/dL or symptomatic hypercalcaemia (AMS, AKI, arrhythmia) from MEN2A primary hyperparathyroidism (ATA 2015)

Citations

- 2015 revised ATA Medullary Thyroid Carcinoma Guidelines (Wells); 2021-2025 MEN2/RET updates (selpercatinib LIBRETTO-001, pralsetinib ARROW; NCCN Neuroendocrine 2025) [PMID:25810047](https://pubmed.ncbi.nlm.nih.gov/25810047/)
- Cited evidence (PMID 32846061) [PMID:32846061](https://pubmed.ncbi.nlm.nih.gov/32846061/)
- Cited evidence (PMID 34118198) [PMID:34118198](https://pubmed.ncbi.nlm.nih.gov/34118198/)
- Cited evidence (PMID 24893135) [PMID:24893135](https://pubmed.ncbi.nlm.nih.gov/24893135/)
- Cited evidence (PMID 22025146) [PMID:22025146](https://pubmed.ncbi.nlm.nih.gov/22025146/)

Last reconciled with current guidelines: 2026-05-22.
References
  • 2015 revised ATA Medullary Thyroid Carcinoma Guidelines (Wells); 2021-2025 MEN2/RET updates (selpercatinib LIBRETTO-001, pralsetinib ARROW; NCCN Neuroendocrine 2025) — PMID:25810047
  • Cited evidence (PMID 32846061) — PMID:32846061
  • Cited evidence (PMID 34118198) — PMID:34118198
  • Cited evidence (PMID 24893135) — PMID:24893135
  • Cited evidence (PMID 22025146) — PMID:22025146