An unusual case of severe ACTH-dependent Cushing’s syndrome with prolonged spontaneous resolution

Allum M; Falinska A; Todd  JF

Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust , Hammersmith Hospital, Du Cane  Road , London UK


A 62 year old man presented to a local hospital with hypokalaemia (potassium 1.7mmol/L) and severe proximal myopathy. On examination, he was cushingoid and hypertensive. His past medical history included rapid onset diabetes requiring insulin within one month, asthma, hypertension, dyslipidaemia and renal calculi. Initial investigations showed a grossly elevated cortisol and ACTH (3325 nmol/L and 517 ng/L respectively).  On low dose dexamethasone suppression test 48 hours cortisol level was 2499 nmol/L consistent with Cushing’s syndrome.  He was commenced on Ketoconazole and Metyrapone therapy. Within one week of transfer to our hospital he developed severe pneumonia requiring ITU support.  While on ITU, hydrocortisone was initiated as a ‘block and replace’ regime. On discharge from ITU his cortisol levels started to fall requiring withdrawal of metyrapone and ketoconazole therapy. At four weeks post admission his morning ACTH was 19ng/L with cortisol of < 50nmol/L.  Insulin tolerance test confirmed cortisol deficiency with peak Cortisol of 280nmol/l from a baseline of 23nmol/l and he was commenced on hydrocortisone replacement therapy.  The patient made a steady recovery from his myopathy and his insulin was stopped.

In order to identify the source of ACTH a number of radiological investigations were performed.  MRI pituitary was normal.  FDG PET CT and Octreotide scan at the referring hospital did not show any abnormality.  Subsequent Ga68 DOTATATE PET CT scan did not show any abnormal uptake.

Although inferior petrosal sinus sampling (IPSS) had been planned to identify the source of ACTH, this was postponed due to spontaneous resolution of Cushing’s syndrome.  He remains well on hydrocortisone replacement and his proximal myopathy has completely resolved.

This is an unusual case of rapid onset severe ACTH dependent Cushing’s Syndrome that resolved spontaneously.  Whether the excess ACTH was due to ectopic secretion or from a pituitary source has not been established.  The initial degree of cortisol excess and severity of symptoms made an ectopic source appear most likely but spontaneous remission is more in keeping with a pituitary source. There is also possibility that this may have been the first stage of a cyclical Cushing’s phenomenon.