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MKSAP: 38-year-old man with a mass in his right neck

mksap
Conditions
December 6, 2014
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Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 38-year-old man is evaluated for a mass in his right neck that he first noticed 2 weeks ago while shaving. The patient also reports experiencing a pressure sensation when swallowing solid foods for the past year and daily diarrhea for the past 2 months. His personal medical history is unremarkable. His younger brother has nephrolithiasis, and his father died of a hypertensive crisis and cardiac arrest at age 62 years while undergoing anesthesia induction to repair a hip fracture.

On physical examination, vital signs are normal. A mass is palpated in the right lobe of the thyroid gland. No cervical lymphadenopathy is palpable.

Results of laboratory studies show a serum calcium level of 10.6 mg/dL (2.7 mmol/L) and a thyroid-stimulating hormone level of 1.9 µU/mL (1.9 mU/L).

A chest radiograph is normal. A thyroid ultrasound confirms a 1.4-cm mass in the right lobe of the thyroid gland.

Which of the following is the most likely diagnosis?

A: Benign familial hypocalciuric hypercalcemia
B: Multiple endocrine neoplasia type 2
C: Parathyroid cancer
D: Sarcoidosis

MKSAP Answer and Critique

The correct answer is B: Multiple endocrine neoplasia type 2.

The most likely diagnosis is multiple endocrine neoplasia type 2 (MEN2). The finding of mild hypercalcemia in a young man whose family history includes a brother with kidney stones and a father with an anesthesia-induced hypertensive crisis raises concern for MEN2. The patient likely has hyperparathyroidism, and his neck mass is most likely a medullary thyroid cancer. His history of diarrhea suggests a high serum calcitonin level caused by the medullary thyroid cancer. Undiagnosed pheochromocytoma may have been the cause of his father’s death, and the brother may have hyperparathyroidism. Together, these personal and family findings suggest that this patient may belong to a MEN2 kindred. MEN2 is caused by germline transmission of a mutantRET proto-oncogene. The MEN2 phenotype can include primary hyperparathyroidism, pheochromocytoma, and medullary thyroid cancer. The hyperparathyroidism of MEN2 is due to benign hyperplasia involving all parathyroid glands.

Benign familial hypocalciuric hypercalcemia is a rare familial condition caused by inactivating mutations of the calcium-sensing receptor, which has a major function in regulating calcium metabolism through parathyroid tissue and renal calcium. The disorder is autosomal dominant with high penetrance. Decreased sensitivity of the calcium-sensing receptor to calcium is typical of this disorder and thus higher calcium levels are required to suppress parathyroid hormone secretion. Fractional excretion of calcium is less than 1%, despite the hypercalcemia, and the PTH level is normal or slightly elevated. The clinical significance of this disease lies mostly in its mistaken diagnosis as hyperparathyroidism. Benign hypocalciuric hypercalcemia does not explain the patient’s thyroid mass or the father’s probable pheochromocytoma.

Parathyroid cancer may be palpable on physical examination, but hyperplastic parathyroid glands with benign enlargement would not. Additionally, parathyroid cancer would cause more severe hypercalcemia and does not explain the patient’s personal history of diarrhea or his family history.

Sarcoidosis causes hypercalcemia by production of 1,25-dihydroxyvitamin D by granulomas. This patient’s neck mass and normal chest radiograph are not typical of sarcoidosis.

Key Point

  • The finding of mild hypercalcemia in a young patient with a family history of related endocrinopathies raises concern for multiple endocrine neoplasia type 2.

This content is excerpted from MKSAP 16 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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