Endocrine neoplasms in familial syndromes of hyperparathyroidism

Abstract

Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential.

Keywords: hyperparathyroidism-jaw tumor (HPT-JT); malignant tumor; multiple endocrine neoplasia type 1 (MEN1); multiple endocrine neoplasia type 2A (MEN2A); neuroendocrine tumor.

Figure 1

Pre-operative images of a parathyroid carcinoma located in the inferior anterior left neck of a HPT-JT patient. A: Ultrasonographic left longitudinal view showed a large 3.5 × 2 cm, hypoechoic, and heterogeneous lesion with irregular border suspicious for parathyroid carcinoma (arrow). B: Doppler image showed that the lesion is hypervascular. C: Neck CT image showed a heterogeneous mass lesion, marked by the arrow, with internal cystic/necrotic changes located inferiorly to the left lower pole of the thyroid gland. D: Technetium-99m pertechnetate scan of the neck showed normal appearing thyroid glands. E: Sestamibi scan of the neck showed an area of excess increased uptake seen just below the left lobe of the thyroid (arrow). F: Sestamibi-technetium subtraction image showed an increased uptake in a parathyroid lesion that was later proven to be a parathyroid carcinoma by surgical pathology (arrow).

Figure 2

CT of the chest showed a lung nodule of 1.1 cm diameter located in the left upper lobe (marked by arrow) in an MEN1 patient. It was surgically resected and proven to be a well-differentiated pulmonary neuroendocrine tumor (“bronchial carcinoid”).

Figure 3

CT of the chest of an MEN1 patient with a history of thymic neuroendocrine tumor and prior surgical resection, showed a 2.5 × 1.2 cm suspicious mediastinal lesion (marked by arrow). It was resected and proven to be a thymic neuroendocrine tumor by surgical pathology.