Cushing's Syndrome Exacerbation During Pregnancy: Stimulation of Cortisol-secreting Adenoma by Placental ACTH

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 29-49-Congenital Adrenal Hyperplasia & Ectopic Cushing's
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-36
Jessica M. MacKenzie-Feder*1, Sylvie Oble2, Robert A Benoit3 and André Lacroix4
1Centre hospitalier de l'Université de Montreal (CHUM), Montreal, QC, Canada, 2Centre hospitalier de l'Université de Montréal (CHUM), 3Montreal Gen Hosp, Montreal, QC, Canada, 4Centre hospitalier de l'Universite de Montreal, Montreal, QC, Canada
Background:  Cushing’s syndrome (CS) diagnosis during pregnancy is complicated by the physiological hypercortisolism mediated by placental-derived CRH and ACTH and by increased CBG levels. During pregnancy, adrenal CS is more frequent than pituitary corticotroph adenoma-driven hypercortisolism. Rare cases of CS that remit post-partum were found to result from aberrant adrenal expression of LHCG receptors. We now report exacerbation of CS during pregnancy probably secondary to adrenal adenoma stimulation by placental-derived ACTH.

Clinical case: A 29-yo G4A3 woman was found at 25 weeks of pregnancy to have a 3.4 X 3.1 cm right adrenal lesion during evaluation of nephrolithiasis.  She had signs of CS, mild hypertension and gestational diabetes requiring 100 U of insulin/d by 34 weeks of gestation. Investigation revealed loss of diurnal plasma cortisol levels and elevated urinary free cortisol (UFC) of 787 nmol/d at 25 weeks and 4338 nmol/d at 31 weeks of gestation (N: 98-500). Corresponding plasma ACTH levels were not suppressed at 4 and 6 pmol/L (N: 2-11).

One month post-partum her 24 h UFC had normalized (107 nmol/d, N <220) with corresponding suppressed ACTH of 1.1 pmol/L. Plasma cortisol did not suppress during a 4 mg IV dexamethasone test (basal: 304 nmol/L; next morning cortisol: 365 nmol/L).  CT scan re-demonstrated a 2.9X3.7 cm adrenal lesion with density of 20 HU. Right adrenalectomy was performed 7 months post-partum; pathology demonstrated an adrenocortical adenoma (Weiss score: 0) and atrophy of adjacent normal cortex. She remains glucocorticoid-dependent six months post-operatively. 

Results: In vivo screening tests performed 6 weeks post-partum to identify possible aberrant adrenal receptors (1,2) showed no cortisol response (including iv LHRH 100 µg and hLH 300 U) except following administration of 250 ug cosyntropin iv (basal: 399 to 30 min peak of 848 nmol/L). Quantitative RT-PCR analysis of the adenoma revealed levels of MC2 receptor mRNA levels similar to normal control adrenals, while LHCG receptor mRNA was almost undetectable.                                                                                                                                                                            

Conclusions: This study suggests that cortisol production by some adrenal adenomas can be enhanced during pregnancy by placental derived ACTH which is not completely suppressed by the cortisol overproduction.

(1) Lacroix, A.,Ndiaye, N.,Tremblay, J.,Hamet, P. Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome. Endocr. Rev.;22;75‐110, 2001 (2) Lacroix A., Bourdeau I, Lampron A, Mazzuco TL, Tremblay J, Hamet P.. Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction. Clin Endocrinol (Oxf).73(1):1-15, 2010

Disclosure: JMM: , Serono, , Novartis Pharmaceuticals. AL: Investigator, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Editor, Up To Date. Nothing to Disclose: SO, RAB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm