Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic association studies hinge on definite clinical case definitions of the disease of interest. This is why more penetrant mutations were overrepresented in early multiple endocrine neoplasia type 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2. The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2: from the removal of target organs at the expense of greater operative morbidity to close biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands. The lead time provided by early identification of asymptomatic MEN2 carriers under biochemical surveillance delimits a 'window of opportunity', within which (i) pre-emptive total thyroidectomy alone is adequate, circumventing morbidity attendant to central node dissection; (ii) subtotal 'tissue-sparing' adrenalectomy is sufficient, trading the risk of steroid dependency for the risk of a second pheochromocytoma in the adrenal remnant and (iii) parathyroidectomy is limited to enlarged glands, trading the risk of postoperative hypoparathyroidism for the risk of leaving behind hyperactive parathyroid glands. Future research should delineate further the mutation-specific, age-dependent penetrance of pheochromocytoma and primary hyperparathyroidism to refine the risk-oriented approach to MEN2. The sweeping changes in the management of MEN2 since the new millenium hold the hope that death and major morbidity from this uncommon disease can be eliminated in our lifetime.
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PMID:Advances in risk-oriented surgery for multiple endocrine neoplasia type 2. 2888 84