Endocrine Abstracts

We are reporting a rare case of ectopic ACTH secreting tumour causing cyclical Cushing’s syndrome. A 63-year-old lady presented in March 2013 with tiredness and bilateral leg swelling and weakness associated with easy bruising. She was admitted to local hospital in April 2013 with worsening proximal myopathy and peripheral oedema. Her midnight cortisol was elevated at 1710 nmol/l. ACTH 610 mU/l, prolactin 476 mU/l, GH 0.21 IU/l, TSH 0.73 mU/l, free T₄ of 11.0 pmol/l, LH 0.5 IU/l, and FSH 1.5 IU/l. A cortisol day curve on metyrapone 500 mg tds showed elevated cortisol of 507, 989, and 273 nmol/l at 0900, 1200, and 1800 h. MRI pituitary showed normal appearance of the pituitary gland. Abdominal CT scan revealed bilateral adrenal hyperplasia. Despite metyrapone 250 mg tds her cortisol levels remained elevated (200–400 nmol/l). Metyrapone was stopped a week before (30th May) bilateral inferior petrosal sinus sampling. Results were suggestive of central ACTH-dependent Cushing’s syndrome. However her cortisol levels normalised post IPSS, without reintroduction of metyrapone (between 125 and 250 nmol/l). Her midnight cortisol was low at 41 nmol/l and ACTH of 43 mU/l. She was discharged home as her symptoms resolved and biochemistry normalised post discharge insulin stress test in August showed suboptimal cortisol response of 409 nmol/l. She was started on hydrocortisone replacement. Her symptoms relapsed in September 2013 with midnight cortisol of 1400 nmol/l with ACTH of 431 nmol/l consistent with relapsed Cushing’s syndrome. She failed to suppress on a low dose dexamethasone test and she was restarted on metyraone to improve her symptoms. She underwent Gallium DOTATATE scan, which showed right lower lobe Gallium avid lesion. Repeat IPSS done in September did not show any central gradient confirming an ectopic source. She underwent surgical excision of lung lesion in December 2013. Histology was consistent with neuro endocrine tumour (Ki67 <3%). Her symptoms improved after surgery and her cortisol levels fell. She was started on hydrocortisone after she failed on short Synacthen test.

Conclusion: Cyclical Cushing’s syndrome is a rare cause of hypercortisolism. Corticotroph adenoma is the most common cause. Cyclical Cushing’s syndrome due to ectopic ACTH is extremely difficult to diagnose due to fluctuating clinical picture and biochemistry. In suspected cases specific biochemical and imaging investigation for neuroendocrine tumour is required.