Hyperparathyroidism in multiple endocrine neoplasia type II A

Primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia (MEN) 2A occurs in only 15-30% of patients. It is rarely the first feature recognized in the syndrome, is generally mild and is sometimes expressed only as parathyroid tumors discovered during surgery for medullary thyroid carcinoma. A predisposition to MEN 2 is caused by germline mutations of the RET proto-oncogene on chromosome 10q11.2. Genetic studies have demonstrated the association of PHPT with a specific mutation at codon 634 (C634R). Therefore, all codon 634 mutation carriers are at some risk for hyperparathyroidism and should be submitted to an early screening of the disease. The rarity of MEN 2A-related PHPT has prevented the establishment of a well-defined therapeutic strategy for treating this condition, so that recommendations about the surgical approach have been controversial. Patients with MEN 2A should have annual screenings for hyperparathyroidism by serum calcium and intact parathyroid hormone level measurements. Parathyroidectomy should be considered in all patients who have some evidence of symptomatic disease. The objectives of parathyroid surgery are to a) obtain and maintain normocalcemia for the longest time possible, b) avoid iatrogenic hypoparathyroidism, and c) facilitate future surgery for recurrent disease. Finally, most of the patients with MEN 2A-related PHPT have mild disease and they could be classified as asymptomatic based on the NIH consensus conference regarding the diagnosis and management of asymptomatic PHPT. Therefore, these patients can be followed up safely without parathyroid surger

Cardiopulmonary Bypass in the Setting of Waldenström’s Macroglobulinemia

Waldenström’s Macroglobulinemia (WM) is a rare lymphoma caused by the overproduction of immunoglobulin M (IgM). The elevated level of IgM causes serum hyperviscosity, cold agglutinins, and cryoglobulinemia. Anemia is also present because of impaired production of erythrocytes. For these reasons, placing a patient with WM on cardiopulmonary bypass (CPB) requires careful preparation. In this case, the patient was a 73-year-old male with known Waldenström’s disease who required coronary artery bypass graft surgery. This report details the perioperative considerations used for successful CPB on a Waldenström’s patient. Critical to this case was the use of plasmapheresis before surgery. Temperature management and acid/base status were carefully controlled. A successful coronary revascularization surgery was performed. Many of the Wadenstrom’s disease complications expected on CPB failed to materialize

RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors

The RET gene encodes a receptor tyrosine kinase that is expressed in neural crest-derived cell lineages. The RET receptor plays a crucial role in regulating cell proliferation, migration, differentiation, and survival through embryogenesis. Activating mutations in RET lead to the development of several inherited and noninherited diseases. Germline point mutations are found in the cancer syndromes multiple endocrine neoplasia (MEN) type 2, including MEN 2A and 2B, and familial medullary thyroid carcinoma. These syndromes are autosomal dominantly inherited. The identification of mutations associated with these syndromes has led to genetic testing to identify patients at risk for MEN 2 and familial medullary thyroid carcinoma and subsequent implementation of prophylactic thyroidectomy in mutation carriers. In addition, more than 10 somatic rearrangements of RET have been identified from papillary thyroid carcinomas. These mutations, as those found in MEN2, induce oncogenic activation of the RET tyrosine kinase domain via different mechanisms, making RET an excellent candidate for the design of molecular targeted therapy. Recently, various kinds of therapeutic approaches, such as tyrosine kinase inhibition, gene therapy with dominant negative RET mutants, monoclonal antibodies against oncogene products, and nuclease-resistant aptamers that recognize and inhibit RET have been developed. The use of these strategies in preclinical models has provided evidence that RET is indeed a potential target for selective cancer therapy. However, a clinically useful therapeutic option for treating patients with RET-associated cancer is still not available