Proof of Concept for Endogenous Testosterone As a Trophic Factor for Hepatic Adenoma in a Case of ACTH Dependent Cushing's Syndrome
Presentation Number: SUN-0778
Date of Presentation: June 22nd, 2014
Sadishkumar Kamalanathan*1, Jaya Prakash Sahoo2, Ashok Kumar Das2, Anurag Lila3, Tushar Ramkrishna Bandgar3 and Nalini Samir Shah3
1JIPMER, Puducherry, India, 2JIPMER, 3KEM Hospital, Mumbai, India
Background: Anabolic androgenic steroids have been documented to associated with growth and recurrence of hepatic adenomas. However, association between endogenously produced androgens and growth of hepatic adenoma has not been documented in literature. We produce evidence for concept that endogenously produced testosterone is a trophic factor for growth of hepatic adenomas using support of a clinical case of ACTH dependent Cushing’s syndrome.
Case report: A 25 year old lady presented to us with characteristic Cushingoid habitus, amenorrhoea , metabolic abnormalities and past history of hypokalemic paralysis .There was no history of intake of oral contraceptive use or of anabolic steroids in past. Biochemical evaluation revealed a ACTH dependent Cushing’s syndrome.[ basal cortisol- 963 nmol/L(normal range NR 138-618) , basal ACTH- 35.2 pmol/L(NR 2-11) ,midnight cortisol-869 nmol/L (NR< 50), 24 hour urine free cortisol -67,040 nmol/d(NR < 2759) , Low dose dexamethasone suppression test cortisol- 1129 nmol/L (NR< 50).Her baseline total testosterone was 3.75 nmol/L(NR 0.5-2.4).
MRI pituitary revealed a 4 x 4 mm microadenoma in left lobe of pituitary. An inferior petrosal sinus sampling (IPSS) and whole body positron emission tomography FDG-PET were done to rule an ectopic focus. FDG PET-CT and 99mTc-HYNIC-TOC scintigraphy were non-contributory towards localisation. IPSS was suggestive of central lesion (central: peripheral ACTH gradient of 20:1) lateralized to left pituitary(gradient of 3:1). Her ultrasound abdomen revealed an asymptomatic hepatic mass of size 2x2.5 cm in segment 7 of liver . CT guided FNAC of mass was suggestive of hepatic adenoma. Post central localization of etiological lesion, a transsphenoidal pituitary surgery was done ,following which, her Cushingoid features regressed along with her metabolic abnormalities . Her testosterone levels became undetectable (<0.3 nmol/L) postoperatively. Currently, she is in remission, being on replacement dose of corticosteroids. Nevertheless, she remained amenorrhoeic ever since .Her hepatic adenoma partially but significantly regressed (> 50%) in size 1 year postoperatively and is expected to regress further with time. The contribution of endogenously produced cortisol and estradiol towards the hepatic adenoma growth could not be assessed appropriately in this paradigm case.
Conclusion: We document significant regression of hepatic adenoma following induction of cure in Cushing’s disease and hence propose endogenously produced testosterone under ACTH control as a probable trophic factor for growth of hepatic adenomas. This hypothesis needs confirmation by future basic research studies.
Nothing to Disclose: SK, JPS, AKD, AL, TRB, NSS