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endo.men2b.core.v1

Multiple endocrine neoplasia type 2B (MEN2B)

endocrinologychronicsyndromepediatricadultoutpatientinpatient
Start encounter →Print handoutPRODUCTION

MEN2B = RET M918T (codon 918, ~95%) — ATA HIGHEST risk; most aggressive, earliest-onset MTC of any MEN2 (metastatic in infancy/early childhood described). Cardinal sequence: recognize phenotype + RET test → EXCLUDE & treat pheochromocytoma (α before β) FIRST → PROPHYLACTIC TOTAL THYROIDECTOMY in the first year of life → metastatic MTC RET inhibitor → GI supportive → lifelong surveillance. Key distinction from MEN2A: NO primary hyperparathyroidism; instead mucosal neuromas + marfanoid habitus + intestinal ganglioneuromatosis + thickened corneal nerves + alacrima; ~50% de novo (paternal origin) so absent family history must not lower suspicion. Manifest path is a PLACEHOLDER (reuses endo.pheochromocytoma.v1 manifest) — no MEN2B-specific manifest or problem-package folder on disk yet. Open: MEN2B manifest, problem-package + atoms, RxNav RxCUI verification (no rxcui assigned by design), Bayesian LRs for phenotype features deferred.

Entry points (5)

  • symptom
    Mucosal neuromas ("bumpy lip"/tongue/eyelid) + marfanoid habitus in a child (2015 ATA Wells)
    mucosal_neuroma_marfanoid_phenotype
  • symptom
    Infantile chronic constipation / megacolon / feeding failure — intestinal ganglioneuromatosis (often earliest clue) (2015 ATA Wells)
    infantile_constipation_megacolon_feeding_failure
  • lab_abnormality
    Elevated calcitonin / CEA or thyroid nodule = medullary thyroid carcinoma (2015 ATA Wells)
    elevated_calcitonin_or_thyroid_mass
  • history
    RET M918T (codon 918) carrier or first-degree relative with MEN2B (2015 ATA Wells)
    ret_m918t_positive_or_men2b_family
  • symptom
    Paroxysmal/resistant HTN or pheochromocytoma triad (2015 ATA Wells)
    paroxysmal_or_resistant_htn_pheo

Required inputs (13)

  • agerequired
    demographic • used at CONTEXT
    Age dictates thyroidectomy timing — first year of life for ATA highest-risk M918T; infants present with GI/phenotype before MTC is clinically apparent
  • ret_genotyperequired
    history • used at CONTEXT
    RET M918T (codon 918, ~95% of MEN2B) defines ATA HIGHEST risk; genotype is the single most consequential input
  • family_history_men2brequired
    history • used at CONTEXT
    ~50% de novo (paternal origin) — ABSENT family history must NOT lower suspicion; positive history triggers cascade testing
  • mucosal_neuromas_phenotyperequired
    symptom • used at ENTRY
    Mucosal neuromas + marfanoid habitus + thickened corneal nerves + alacrima = the recognizable phenotype enabling EARLY diagnosis
  • gi_ganglioneuromatosis_symptomsrequired
    symptom • used at ENTRY
    Infantile constipation / megacolon / feeding failure is frequently the earliest presenting clue, often before MTC
  • calcitoninrequired
    lab • used at INITIAL_WORKUP
    Primary MTC tumor marker — basal (± stimulated) calcitonin drives surgical urgency and surveillance
  • cearequired
    lab • used at INITIAL_WORKUP
    Carcinoembryonic antigen — second MTC marker; doubling time prognosticates MTC progression
  • plasma_or_urine_metanephrinesrequired
    lab • used at INITIAL_WORKUP
    Pheochromocytoma (~50%, often bilateral) MUST be excluded and treated BEFORE any thyroid/adrenal surgery
  • calcium_pthrequired
    lab • used at INITIAL_WORKUP
    Confirm ABSENCE of primary hyperparathyroidism — its presence argues against MEN2B and toward MEN2A (key distinction)
  • sbprequired
    vital • used at RED_FLAGS
    Pheochromocytoma crisis recognition + pre-operative blockade target
  • hr
    vital • used at RED_FLAGS
    Tachycardia drives β-blocker timing (only AFTER adequate α-blockade) in pheo
  • neck_us_thyroid
    imaging • used at BRANCHING_WORKUP
    Thyroid US ± FNA for MTC staging; central/lateral nodal mapping pre-thyroidectomy
  • adrenal_ct_or_mri
    imaging • used at BRANCHING_WORKUP
    Adrenal cross-sectional imaging localizes pheochromocytoma before adrenalectomy

12-phase flow (12)

  1. 1FRAME
    Frame MEN2B as ATA HIGHEST-risk RET syndrome — most aggressive earliest-onset MTC + pheo (~50%) WITHOUT primary hyperparathyroidism; phenotype recognition in a child is the determinant of MTC outcome
    inputs: age, ret_genotype
    advance: MEN2B suspected on phenotype or RET M918T confirmed
  2. 2ENTRY
    Trigger captured — mucosal neuromas/marfanoid phenotype, infantile GI ganglioneuromatosis (earliest clue), elevated calcitonin/thyroid mass, RET carrier/MEN2B family, or pheo presentation
    inputs: mucosal_neuromas_phenotype, gi_ganglioneuromatosis_symptoms
    advance: Entry trigger captured
  3. 3CONTEXT
    Capture RET genotype (M918T ~95%), family history (note ~50% de novo / paternal origin — absent history does NOT lower suspicion), age (thyroidectomy timing), prior pheo screening
    inputs: ret_genotype, family_history_men2b, age
    advance: Genotype + family context classified
  4. 4RED_FLAGS
    Screen for unprepared pheochromocytoma crisis (paroxysmal/resistant HTN), metastatic MTC at presentation (esp. infancy), and infantile feeding failure / obstructive megacolon — any precludes elective surgery until stabilized
    inputs: sbp, hr
    actions: workup.secondary_htn
    advance: Red flags screened; pheo crisis and feeding failure addressed
  5. 5INITIAL_WORKUP
    Basal calcitonin + CEA, fractionated plasma/urine metanephrines (exclude pheo FIRST), calcium + PTH (confirm NO primary hyperparathyroidism), CMP, CBC; RET targeted/cascade testing if not done
    inputs: calcitonin, cea, plasma_or_urine_metanephrines, calcium_pth
    actions: workup.men_screening, panel.thyroid, panel.hormone, panel.tumor, panel.cmp, panel.cbc
    advance: MTC markers + pheo screen + Ca/PTH + RET status obtained
  6. 6BRANCHING_WORKUP
    Pheo positive → adrenal CT/MRI ± functional imaging, α-then-β blockade pathway; MTC markers elevated → neck US ± FNA, nodal mapping, cross-sectional staging for distant disease (esp. infant)
    inputs: neck_us_thyroid, adrenal_ct_or_mri
    actions: workup.thyroid_nodule, workup.adrenal_incidentaloma
    advance: Pheo localized/cleared and MTC staged
  7. 7DIFFERENTIAL
    MEN2B vs MEN2A (PHPT + cutaneous lichen amyloidosis / Hirschsprung-associated RET) vs isolated FMTC vs marfanoid connective-tissue mimic (Marfan/MEN1 habitus differential — Marfan has NO mucosal neuromas, normal calcitonin)
    advance: MEN2B confirmed and mimics excluded
  8. 8RISK_STRATIFICATION
    ATA risk category = HIGHEST (M918T); calcitonin/CEA level + doubling time stratify MTC burden; qSOFA/NEWS2 only if intercurrent decompensation (pheo crisis, post-op sepsis, infant feeding failure)
    inputs: calcitonin, cea
    actions: calc.qsofa, calc.news2
    advance: ATA risk = HIGHEST documented; MTC burden tier set
  9. 9TREATMENT
    Sequence: (1) recognize phenotype + RET test → (2) EXCLUDE & treat pheo FIRST (α-blockade then β, then adrenalectomy) → (3) PROPHYLACTIC TOTAL THYROIDECTOMY in the first year of life (ATA highest risk; ideally ≤6 mo, by 1 yr) → (4) selpercatinib/pralsetinib for advanced/metastatic MTC → (5) supportive GI management of ganglioneuromatosis → lifelong surveillance
    inputs: plasma_or_urine_metanephrines, calcitonin, age
    advance: Pheo cleared first, prophylactic thyroidectomy planned/done, RET-inhibitor + GI plan documented
  10. 10DISPOSITION
    Outpatient genetics + endocrine + pediatric endocrine surgery for elective prophylactic thyroidectomy planning; inpatient/peri-operative admission for pheo optimization, thyroidectomy, or metastatic MTC therapy initiation
    advance: Disposition + multidisciplinary referrals booked
  11. 11MONITORING
    Post-thyroidectomy: calcitonin/CEA + lifelong levothyroxine + calcium/PTH for surgical hypoparathyroidism; annual metanephrines for pheo; serial RET-inhibitor toxicity (QTc, LFTs, BP) if on selpercatinib/pralsetinib
    inputs: calcitonin, cea
    actions: panel.thyroid, panel.tumor, panel.metabolic
    advance: Surveillance schedule active
  12. 12FOLLOWUP
    Lifelong endocrine/oncology/genetics; cascade RET testing of at-risk relatives (counsel ~50% de novo); annual calcitonin/CEA/metanephrines; GI follow-up for ganglioneuromatosis; reproductive counseling (autosomal dominant, prenatal/PGT options)
    advance: Lifelong surveillance + cascade testing + counseling scheduled