Endocrine Abstracts

Cushing’s syndrome and obesity share clinical similarities. Here we present a 31-year-old lady with type 2 diabetes, renal failure, polycystic ovarian syndrome, depression, hirsutism and morbid obesity, whose abnormal phenotype and biochemistry normalised with weight loss.

She was admitted with a history of recent onset recurrent hypoglycaemia and poor mobility. A detailed history revealed increase in weight over a 10 year period associated with irregular periods and hirsutism. She was commenced on norethisterone following which there was further weight gain. She developed type 2 diabetes and was commenced on metformin and rosiglitazone with good glycaemic control. She weighed 239 kg on admission and was not in heart failure. She had proximal muscle weakness but there was no obvious bruising or abnormal striae. Investigations revealed creatinine 156 μmol/l, Bilirubin 265 mmol/l, rest of liver function test was normal. Prolactin 1917 IU/l, LH<0.1 IU/l and FSH<0.1 IU/l. Midnight cortisol was 495 nmol/l and cortisol was not suppressed with overnight dexamethasone. Abdominal ultrasound was normal.

She was commenced on very low calorie diet along with Orlistat, frusemide, calcium and vitamin supplements. Oral hypoglycaemic agents were discontinued as she was euglycaemic. Hypoglycaemia was due to renal failure. She could not have MRI pituitary because of her weight. After more than three months following her admission she weighed 137 kg. Isolated hyperbilirubinaemia, hyperprolactinaemia, diabetes, renal failure and hypercortisolaemia resolved with weight loss. There was no significant regain in her weight or abnormal biochemistry, nine months following discharge.

The elevated midnight cortisol and non suppression of cortisol with overnight dexamethasone may be due to either dysregulation of the hypothalamus pituitary adrenal axis, upregulation of 11 beta-hydroxy steroid dehyorgenase 1 or alternatively increased expression of glucocorticoid receptors, which is encountered in obesity. Weight loss may have normalised the above presumed abnormalities.