An unusual case of Cushing’s Syndrome: Ectopic ACTH associated with Metastatic Ovarian Teratoma
Dr Sarah Ali, Dr Anjali Amin, Professor Karim Meeran
Department of Endocrinology, Charing Cross and Hammersmith Hospitals, Imperial College Healthcare NHS Trust, London, W6 8RF
We present a challenging case of a 40 year old Caucasian lady, who initially presented in 1989 with abdominal pain and swelling. Investigations revealed an ovarian tumour and she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histology from the tumour revealed a teratoma with mature neuro-ectodermal and cartilagenous elements. The teratoma recurred early and she underwent partial hepatectomy and splenectomy, followed by chemotherapy and alpha-interferon. Treatment was discontinued when residual disease appeared calcified.
She remained well for approximately 10 years, when she re-presented with a 9 month history of weight gain, weakness and lethargy. Examination revealed features of Cushing’s syndrome. Cortisol levels failed to suppress with a low dose dexamethasone suppression test (levels falling from 1065 to 829nmol/l) and ACTH was raised at 124.9 ng/l. Cortisol levels fell minimally from 829 to 819 nmol/l with a subsequent high dose dexamethasone suppression test, with ACTH reducing from 124.9 to 80.4 ng/l. Inferior petrosal sinus sampling showed little response to CRF in the peripheral samples and no central to peripheral gradient. An MRI pituitary scan was normal. These results were consistent with a diagnosis of non-pituitary driven ACTH-dependent Cushing’s Syndrome.
Whole body venous sampling for ACTH and cortisol showed relatively high levels of ACTH in the right hepatic vein, the low IVC below the renal veins and the right common iliac vein. These suggested ACTH production from residual teratoma tissue in the liver and pelvis. Repeat imaging of chest, abdomen and pelvis showed no evidence of disease progression from a previous scan. An Octreotide scan showed two areas of increased uptake, one in the proximity of the liver consistent with an area of stable metastatic disease and the second at the site of the splenic bed, where a small area of tissue, suggestive of a splenunculus was identified on CT scanning.
Metyrapone was initiated to control hypercortisolaemia. There was great difficulty in determining which of the calcified metastases were responsible for the ectopic ACTH production. Due to uncontrollable disease, she underwent bilateral adrenalectomy in 2001. Post-operatively she commenced on hydrocortisone and fludrocortisone replacement, and metyrapone was stopped. There was a dramatic improvement in her appearance and symptoms. She has remained well with stable ACTH levels.
This case highlights the difficulties of treating Cushing’s syndrome secondary to ectopic ACTH production. Ovarian tumours remain very rare causes of Cushing’s syndrome and generally have a poor prognosis. In a situation, where the source of ectopic ACTH is difficult to localise, this case shows the benefit of performing bilateral adrenalectomy, in order to treat the Cushing’s syndrome. In addition, although not a tumour marker per se, a general rise in ACTH may have a role as a potential tumour marker for recurrence in this case.