Endocrine Abstracts

Case history: A 43-year-old man was admitted to Intensive care with life-threatening pneumonia, along with acute hypertension and hypokalaemia. There were several Cushingoid clinical features, therefore ectopic ACTH syndrome was suspected.

Investigations: The diagnosis of severe ACTH-dependent Cushing’s syndrome was confirmed with unsuppressed cortisol after low dose dexamethasone (763 nmol/l with ACTH 131 ng/l, 24-h urinary cortisol levels (x2) of >6000 nmol/24 h, and no response to CRH. Axial imaging with CT and ¹⁸FDG-PET/CT failed to localise the source of ACTH, but there was marked adrenal hypertrophy. He was commenced on metyrapone.

Results and treatment: When reviewed in Sheffield bilateral adrenalectomy was discussed due to the extreme severity of his disease and lack of source for ACTH being identified (including urgent Gallium-68 DOTA-TATE PET/CT), but after careful counselling he continued on medical therapy: metyrapone (titrated to total 5500 mg per day) with additional ketoconazole, however the later was not tolerated. Long-acting octreotide (Sandostin LAR 30 mg I.M. every 28 days) was added with the aim to reduce ACTH (and cortisol) levels: these reduced to normal. Replacement doses of hydrocortisone were given throughout in a ‘block and replace’ regime with serum day curve monitoring using LC–MS/MS for serum cortisol. The patient’s clinical condition improved, greatly. After six months of medical treatment repeat CT revealed mediastinal and right hilar lymphadenopathy suspicious for malignancy. Biopsy, however, was consistent with sarcoidosis and serum ACE levels were elevated. The repeat CT also showed that the adrenal hypertrophy had now reduced. After a further six months of medically induced eucortisolaemia a repeat Gallium-68 DOTA-TATE PET/CT was performed which revealed uptake in a <1 cm nodule in right middle lobe (confirmed on dedicated CT) but with avid uptake in mediastinal lymph nodes. The patient underwent VATS right middle lobectomy and the histology confirmed a 14 mm ENETS grade 1 tumour (Ki67 <1%) and strong immune-staining for ACTH, and is currently in full remission. Lymph node histology was negative for tumour but positive for sarcoidosis, which is being monitored.

Conclusions and points for discussion: • The urgent need for treatment of severe Cushing’s, even if cause is unidentifiable, often in combination.

• SST2 receptor down-regulation due to severe Cushing’s, but reversal with eucortisolaemia – may explain why SST2R-directed imaging fails to demonstrate the source of ectopic Cushing’s.

• Although autoimmune conditions have been reported after Cushing’s remission, sarcoidosis due to steroid withdrawal has never been reported before.