Multiple Endocrine Neoplasia Type 2 (MEN2) Clinical Presentation

Updated: Jun 11, 2021
  • Author: Melanie L Richards, MD, MPHE; Chief Editor: George T Griffing, MD  more...
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Presentation

History

The presentation in patients with multiple endocrine neoplasia type 2 (MEN2) varies with the specific MEN2 syndrome (see Overview/Practice Essentials) and the presence and severity of associated conditions, as well as the patient's age. The most important questions to ask relate to a family history of multiple endocrine neoplasms.

Patients may present with symptoms related to medullary thyroid carcinoma (MTC), hyperparathyroidism, or pheochromocytoma. However, a young patient with an identified RET proto-oncogene mutation is likely to be asymptomatic. These patients generally have thyroid C-cell hyperplasia without progression to MTC.

Virtually all index patients have MTC at the time of diagnosis, although their clinical presentation may be consistent with pheochromocytoma or hyperparathyroidism.

Clinical manifestations of MEN2 can include hypertension, episodic sweating, diarrhea, pruritic skin lesions, or compressive symptoms from a neck mass. Patients with hypercalcemia may present with constipation, polyuria, polydipsia, memory problems, depression, nephrolithiasis, glucose intolerance, gastroesophageal reflux, and fatigue, or they may have no symptoms. They may also lose bone density.

If pheochromocytomas develop, an increase in blood pressure and heart rate may be the only signs. These increases can be chronic or episodic. Some patients have episodes of sweating and headaches.

Patients with extensive MTC may have a history of diarrhea as a result of elevated prostaglandin or calcitonin levels. Chronic constipation is a consistent finding in MEN2B patients and results from hyperplasia of the intrinsic autonomic ganglia in the intestinal wall. Infants may fail to thrive.

Cutaneous lichen amyloidosis in MEN2A patients manifests as multiple pruritic, hyperpigmented, lichenoid papules in the scapular area of the back. [15] These lesions are associated with the deposition of altered cytokeratins rather than of calcitoninlike peptides. Dermal hyperneury (the presence of increased, hypertrophic myelinated and nonmyelinated nerve fibers in the dermis) and multiple sclerotic fibromas have been reported in a family with familial medullary thyroid carcinoma (FMTC). [16]

 

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Physical Examination

The physical signs of MEN2 are extremely variable and often subtle. A neck mass or a dominant thyroid nodule may be palpable. Anterior neck lymph nodes are nontender; lymphadenopathy develops insidiously, and its presence may signify regional metastasis. Blood pressure and heart rate may be elevated if a pheochromocytoma is present.

Almost all MEN2B patients have the marfanoid habitus of high-arched palate, pectus excavatum, bilateral pes cavus, and scoliosis. Neuromas on the eyelids, conjunctiva, nasal and laryngeal mucosa, tongue, and lips are frequent findings. Patients also have prominent, hypertrophied lips, resulting in a characteristic facies. Localized pruritus appears over the upper back in MEN2B patients. These patients may have ectopic lenses in the eye or very flexible joints. [9]

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