title: Hyperplasia in glands with hormone excess.
abstract: Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR, begins severely in utero; congenital non-autoimmune thyrotoxicosis, from mutated TSHR, varies from severe with fetal onset to mild with adult onset; familial male-limited precocious puberty, from mutated LHR, expresses testosterone oversecretion in young boys; hereditary ovarian hyperstimulation syndrome, from mutated FSHR, expresses symptomatic systemic vascular permeabilities during pregnancy; and familial hyperaldosteronism type IIIA, from mutated KCNJ5, presents in young children with hypertension and hypokalemia. The grouping of these five syndromes highlights predominant hyperplasia as a stable tissue endpoint and as their tissue stage for all of the hormone excess. Comparisons were made among this and two other groups of syndromes, forming a continuum of gland staging: predominant oversecretions express little or no hyperplasia; predominant hyperplasias express little or no neoplasia; and predominant neoplasias express nodules, adenomas, or cancers. Hyperplasias may progress (5 of 5) to neoplastic stages while predominant oversecretions rarely do (1 of 6; frequencies differ P<0.02). Hyperplasias do not show tumor multiplicity (0 of 5) unlike neoplasias that do (13 of 19; P<0.02). Hyperplasias express mutation of a plasma membrane-bound sensor (5 of 5), while neoplasias rarely do (3 of 14; P<0.002). In conclusion, the multiple distinguishing themes within the hyperplasias establish a robust pathophysiology. It has the shared and novel feature of mutant sensors in the plasma membrane, suggesting that these are major contributors to hyperplasia.
authors.affiliation: Genetics and Endocrinology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9C-103, Bethesda, Maryland 20892, USA marxs@mail.nih.gov.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Marx
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D002648:Child; D004702:Endocrine Glands / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006729:Hormones, Ectopic / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D006980:Hyperthyroidism / Q000151:congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011629:Puberty, Precocious / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D006729:Hormones, Ectopic
keywords: GPCR; adrenal cortex; cyclic AMP; gonad; neonate; parathyroid; proliferation; signal transduction; thyroid