R015

Successful control of Cushing’s disease in pregnancy with unilateral adrenalectomy following failed transsphenoidal hypophysectomy.

Azraai Nasruddin, Derek Sandeman

Department of Endocrinology, Southampton General Hospital

Abstract:

We report a 27 year old lady, initially seen in the infertility clinic with a diagnosis of PCOS (hyperandrogenism and oligomenorrhoea). Investigations were consistent with ACTH dependent Cushing’s (24hr urinary cortisol (UFC) – 3170nmol , serum cortisol 271nmol/L and 76nmol/L after 1mg and 8mg overnight dexamethasone suppresion respectively, 9am serum ACTH 45ng/L). Pituitary MRI was normal. Petrosal sampling lateralised source of ACTH excess to the left side of the pituitary (Central/peripheral ACTH ratio and Left/Right IPS ACTH ratio were both >40)

She underwent transsphenoidal surgery (TSS) – abnormal tissue was removed inferior to the normal gland. No adenoma was seen on histology and post-op day 2 serum cortisol was high (1277nmol/L) therefore she underwent further TSS on day 4.  During her admission, she developed persistent vomiting and unexpectedly was found to be 6 weeks pregnant. She developed multiple complications (CSF leak, pleural effusion, sepsis, diabetes insipidus). Serum cortisol (605nmol/L) and ACTH (54ngl/L) levels remained high but was difficult to interpret in view of her pregnancy and pathologies.

Repeat  UFC done 4 and 6 weeks later remained high (3201 and 4954 nmol) indicating failed TSS. CT abdomen showed bilateral adrenal hyperplasia. In view of the risk of complications of Cushing’s in pregnancy, she was referred for urgent bilateral adrenalectomy. She was reluctant but agreed to a unilateral right laparoscopic adrenalectomy with the option of having the remaining adrenal resected subsequently. (Surgical view was that there was no excess morbidity from two-stage vs one stage bilateral adrenalectomy).

She developed hypoadrenalism post-adrenalectomy (hyponatraemia (131mmol/L), nausea, postural syncope, random cortisol 77nmol/L). Despite normal ACTH levels (24-33ng/L), she required steroid replacement throughout pregnancy. Synacthen test 2 months post-partum showed reasonable response (cortisol 508nmol/L) and steroid therapy was stopped. There was concern of possible Cushing’s recurrence in future but she declined cranial radiotherapy. Pituitary MRI showed no residual tissue. A year later, she has again become hypoadrenal although asymptomatic, (24hr UFC <50nmol, cortisol 174nmol/L post-synacthen, Adrenal Ab negative, ACTH 14ng/L).  She is currently on hydrocortisone, thyroxine and desmopressin and is undergoing ovulation induction with HMG.

This case illustrates the importance of considering the possibility of pregnancy in Cushing’s. Unilateral adrenalectomy followed by pituitary radiotherapy have been previously advocated for pituitary Cushing’s before TSS became routine. We conclude that unilateral adrenalectomy may be a viable option in the management of Cushing’s disease in pregnancy following failed TSS, with the advantage of preserving the renin/aldosterone axis. The role of pituitary radiotherapy in this case is unclear and merits discussion.