Review Question - QID 106767

This patient's presentation of pheochromocytoma (palpitations and anxiety attacks in the setting of bilateral adrenal lesions), parathyroid adenoma (elevated PTH), and medullary thyroid carcinoma (increased calcitonin level and a neck mass) is consistent with a diagnosis of multiple endocrine neoplasia (MEN) type IIa.

MEN II (encompasing IIa, IIb, and familial medullary thyroid cancer or FMTC) is a hereditary cancer syndrome caused by mutations in the RET proto-oncogene. All 3 forms have medullary thyroid cancer as a component. Pheochromocytoma is seen only in MEN IIa and IIb. MEN IIb lacks the parathyroid hyperplasia/adenomas seen in MEN IIa, while MEN IIa does not exhibit the mucosal neuromas and marfanoid habitus seen in MEN IIb patients.

Carroll et al. discuss the diagnosis and treatment of hypercalcemia. After hypercalcemia is detected on initial lab work, PTH levels should be measured. If PTH is suppressed, a malignancy work-up should be pursued; however, if PTH is normal or high, a 24-hour urinary calcium level can be checked. If urinary calcium is normal or high, the most likely diagnosis is primary (parathyroid adenoma) or tertiary hyperparathyroidism.

Raue et al. discuss the genotype-phenotype relationships in the management of MEN II syndromes. MEN IIa, MEN IIb, and FMTC are each associated with different RET gene mutations. Genetic testing has become invaluable for predicting the time of onset of thyroid cancer, the aggressiveness of the tumor, and the presence of other endocrine tumors.

Illustration A is a chart summarizing the characteristic pathologies seen in MEN I, MEN IIa, and MEN IIb.

Incorrect Answers:
Answer 1: FMTC is a form of MEN II; however, these patients present only with medullary thyroid cancer and not the other conditions associated with MEN IIa or IIb.
Answer 2: Li-Fraumeni syndrome is an autosomal dominant hereditary cancer disorder due to germline mutations in the p53 tumor suppressor gene; the disease is characterized by multiple different types of cancers developing throughout life and starting at an early age. The most common cancers associated with this condition include sarcomas, breast cancer, adrenocortical carcinoma, brain cancers, and leukemia.
Answer 3: MEN I consists of parathyroid tumors, pituitary tumors, and pancreatic islet cell tumors.
Answer 5: MEN IIb is characterized by medullary thyroid carcinoma, pheochromocytoma, and oral or intestinal ganglioneuromatosis that is often associated with a marfanoid habitus.