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DOI: 10.1055/s-0034-1372154
Transient pregnancy-induced Cushing's Syndrome with Aberrant Adrenal hCG receptor
Introduction: ACTH-independent Cushing's syndrome (CS) can be associated to the expression of ectopic- or overexpression of eutopic adrenal receptors. These receptors activate adenylate cyclase and subsequently stimulate steroid synthesis, resulting in ACTH-independent CS and growth promotion with hyperplasia or macronodular adrenal changes. Excess cortisol (Co)-secretion better correlates with variations of ligands for the aberrant receptors than the suppressed circulating ACTH.
Results: We report a 22 y-old pat. with repeated, transient pregnancy-induced CS due to LH/hCG stimulated Co-secretion. The 1st pregnancy was characterized by biochemical hypercortisolism [urinary free cortisol 5fold ULN, non-suppressibility of Co by dexamethasone] and an enlarged left adrenal. After preterm parturition CS and adrenal hyperplasia resolved spontaneously. Testing for aberrant adrenal regulation of Co-secretion was neg. except for vasopressin-increased Co-secretion (1700%, yet at a low level, while ACTH still suppressed). Stimulation with hCG, [ßhCG = 890 IU/ml (ULN at 12th w of pregnancy ˜12000 IU/ml)] induced hypercortisolism. 1 y later, during an extra-uterine pregnancy, hypercortisolism recurred and normalized after termination of the pregnancy. 6 mo later, after bilateral adrenalectomy, adrenal histology was normal. In vitro adrenal LH-, vasopressin 1A- and 2 receptor mRNA expression was pos. while LHR-expression was neg. by IHC. rhCG stimulation of prim. cells increased 11-desoxy-Co, Co, corticosterone, androstenedione and cAMP.
Conclusion: We demonstrated the role of hCG as activating ligand for ACTH-independent Co-secretion. The need for long-term/high-dose stimulation by LH/hCG for the induction of Co-secretion explains transient pregnancy-induced CS while hypercortisolism is not observed during a normal menstrual cycle. The regression of adrenal hyperplasia after delivery suggests a primary role of chronic stimulation of aberrant receptors by hCG in adrenal hyperplasia.