Regulation of steroidogenesis in a primary pigmented nodular adrenocortical disease-associated adenoma leading to virilization and subclinical Cushing's syndrome

Hans Hofland, W.W. de Herder, L Derks, Leo Hofland, Peter van Koetsveld, Ronald de Krijger, Francien Nederveen, A Horvath, CA Stratakis, Frank Jong, R.A. Feelders

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Abstract

Context: Primary pigmented nodular adrenocortical disease (PPNAD) can lead to steroid hormone overproduction. Mutations in the cAMP protein kinase A regulatory subunit type 1A (PRKAR1A) are causative of PPNAD. Steroidogenesis in PPNAD can be modified through a local glucocorticoid feed-forward loop. Objective: Investigation of regulation of steroidogenesis in a case of PPNAD with virilization. Materials and methods: A 33-year-old woman presented with primary infertility due to hyperandrogenism. Elevated levels of testosterone and subclinical ACTH-independent Cushing's syndrome led to the discovery of an adrenal tumor, which was diagnosed as PPNAD. In vivo evaluation of aberrantly expressed hormone receptors showed no steroid response to known stimuli. Genetic analysis revealed a PRKAR1A protein-truncating Q28X mutation. After adrenalectomy, steroid levels normalized. Tumor cells were Results: Isolated PPNAD cells, analogous to normal adrenal cells, showed both increased steroidogenic enzyme expression and steroid secretion in response to ACTH. Dexamethasone did not affect steroid production in the investigated types of adrenal cells. 17 beta-HSD type 5 was expressed at a higher level in the PPNAD-associated adenoma compared with control adrenal tissue. Conclusion: PPNAD-associated adenomas can cause virilization and infertility by adrenal androgen overproduction. This may be due to steroidogenic control mechanisms that differ from those described for PPNAD without large adenomas. European Journal of Endocrinology 168 67-74
Original languageUndefined/Unknown
Pages (from-to)67-74
Number of pages8
JournalEuropean Journal of Endocrinology
Volume168
Issue number1
DOIs
Publication statusPublished - 2013

Research programs

  • EMC MM-01-39-01
  • EMC MM-01-39-04
  • EMC MM-03-24-01

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