Endocrine · Year 2 · from Endocrine

Case 2: Medullary Thyroid Carcinoma with MEN2A

Patient Demographics

  • Age: 28 years
  • Sex: Male
  • Occupation: Electrician

Chief Complaint

"I had genetic testing because my mother was diagnosed with thyroid cancer, and they found I have a mutation."

History of Present Illness

A 28-year-old man presents after genetic testing revealed he carries a RET proto-oncogene mutation (codon 634). His mother was recently diagnosed with medullary thyroid carcinoma at age 52 and subsequently found to have this mutation. Cascade genetic testing was recommended for all first-degree relatives. The patient is asymptomatic with no palpable thyroid nodules and no symptoms of hyperthyroidism, hypercalcemia, or pheochromocytoma. He has had episodes of headache with sweating over the past year that he attributed to work stress.

Physical Examination

  • Vital Signs: BP 148/92 mmHg (elevated), HR 88 bpm
  • General: Well-appearing young man
  • Neck: Thyroid gland normal size, no palpable nodules, no lymphadenopathy
  • Cardiovascular: Regular rhythm, no murmurs
  • Abdomen: No masses palpable
  • Skin: No café-au-lait spots, no neuromas

Workup

  • Laboratory Studies:
  • TSH: 2.2 mIU/L (normal)
  • Calcitonin: 86 pg/mL (elevated, normal <10)
  • CEA: 4.2 ng/mL (mildly elevated)
  • Plasma metanephrines: Elevated (normetanephrine 2.4 nmol/L)
  • Calcium: 10.8 mg/dL (high-normal)
  • PTH: 78 pg/mL (elevated)
  • 24-hour urine catecholamines: Elevated
  • Genetic testing: RET mutation codon 634 (MEN2A - high risk)
  • Ultrasound Thyroid: Two small hypoechoic nodules in right lobe (4mm and 6mm)
  • CT/MRI Abdomen: 2.5 cm right adrenal mass, hyperintense on T2
  • MIBG Scan: Uptake in right adrenal mass consistent with pheochromocytoma

Diagnosis

Multiple Endocrine Neoplasia Type 2A (MEN2A) with:

  1. Medullary thyroid carcinoma (early/microscopic)
  2. Pheochromocytoma (right adrenal)
  3. Primary hyperparathyroidism (developing)

Treatment

ORDER OF SURGERY IS CRITICAL:

  1. First: Adrenalectomy for pheochromocytoma
  • Alpha-blockade (phenoxybenzamine) for 10-14 days pre-operatively
  • Then add beta-blockade (never beta before alpha)
  • Adequate volume expansion
  • Laparoscopic right adrenalectomy
  1. Second: Total thyroidectomy with central lymph node dissection
  • After recovery from adrenalectomy
  • Prophylactic surgery indicated even without palpable tumor given RET mutation
  1. Parathyroid management:
  • Inspect parathyroids at surgery
  • Remove only grossly enlarged glands
  • Consider autotransplantation if all glands enlarged
  1. Post-operative:
  • Levothyroxine replacement
  • Monitor calcitonin and CEA
  • Screen for contralateral pheochromocytoma
  • Genetic counseling for family members

Clinical Pearl

MEN2A is an autosomal dominant syndrome caused by RET proto-oncogene mutations, characterized by medullary thyroid carcinoma (>95% penetrance), pheochromocytoma (50%), and primary hyperparathyroidism (20-30%). Medullary thyroid carcinoma arises from parafollicular C cells that produce calcitonin. In MEN2 patients, pheochromocytoma MUST be diagnosed and treated before thyroidectomy, as anesthetic induction in an undiagnosed pheochromocytoma can trigger life-threatening hypertensive crisis. Prophylactic thyroidectomy is recommended for RET mutation carriers, with timing based on the specific mutation's risk level.

Clinical Image

Histopathology of medullary thyroid carcinoma showing nests of tumor cells with amyloid stroma (Congo red positive) and immunohistochemistry positive for calcitonin.

Image Source: Wikimedia Commons - "Medullary thyroid carcinoma" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg

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