A Rare Case of Cushing’s Syndrome caused by ‘cyclical’ Ectopic ACTH secretion

Behary P1, Kadiyala R1, Falinska A1, Beckwith H1, Jackson J1, Mitchell C 2, Todd JF1

1Imperial Centre for  Endocrinology, Imperial college Healthcare NHS Trust , Hammersmith Hospital, Du Cane road , London UK

2 Diabetes and Endocrinology, The Hillingdon Hospital NHS Trust

Abstract: A 61 year old lady presented with rapid onset of lethargy and reduced mobility with inability to use stairs over one month.  Prior to this, she was fit and well and had no significant medical history and was a lifelong non-smoker.  At presentation, it was noted that she was overweight with a BMI of 35 kg/m2 and had evidence of skin bruising, severe proximal myopathy of her legs and bilateral leg cellulitis. A midnight cortisol was >1710 nmol/l with a corresponding ACTH of 610 nmol/L confirming ACTH dependent Cushing’s syndrome. Serum potassium was 2.6 mmol/l and a new diagnosis of type 2 diabetes was made. Her inpatient stay was complicated by bilateral pneumonia requiring non-invasive ventilation. She was commenced on metyrapone 500mg tds for her significant disease burden. MRI of Pituitary revealed no lesion and CT scan of adrenals showed bilateral adrenal hyperplasia consistent with ACTH dependant Cushing’s syndrome.  In preparation for IPSS, metyrapone was stopped and cortisol levels were monitored. It was noted that her cortisol levels were consistently below 250 nmol/L with a corresponding ACTH of 34 ng/L.  A midnight cortisol after discontinuation of metyrapone for 2 weeks was low 41nmol/L consistent with spontaneous resolution of Cushing’s syndrome. An Insulin Tolerance Test showed sub-optimal cortisol response and she was commenced on hydrocortisone replacement therapy.  However, within 3 months since discharge, she represented to hospital with reduced mobility and hypokalaemia.  A LDDST after stopping hydrocortisone, confirmed relapse of Cushing’s syndrome with a cortisol of >1650 at 48 hours. IPSS excluded a central ACTH source and a gallium 68 DOTATATE PET CT identified a 1.6 cm gallium avid lung lesion consistent with possible ectopic source. She is awaiting resection of the Lung nodule. Learning points:

·         In patients with Cushing’s syndrome whose cortisol levels respond briskly to low dose metyrapone, spontaneous remission should be considered.

·         Careful monitoring of patients with Cushing’s, who appear to recover spontaneously is essential as relapses are frequent.

·         This is a very unusual case as Cyclical Cushing’s has only once been reported in patient with ectopic ACTH production.