Endocrine Abstracts

Background: Cyclical Cushing’s syndrome is a rare condition marked by fluctuating episodes of cortisol excess (peaks) followed by periods of normal or low cortisol levels (troughs). These intermittent features can make diagnosis challenging and can often overlap with evolving Cushing’s disease.

Clinical Case: A 30-year-old female self-reported features of hypercortisolaemia including intracapsular adiposity, a round facial appearance and abdominal hirsutism. She was recently also diagnosed with type 1 diabetes and commenced on insulin. Her biochemistry demonstrated elevated late-night salivary cortisol (6.0 nmol/l, RR<2.6) and cortisone (37.9 nmol/l, RR<18) levels, and a raised 24 hr-urinary free cortisol (UFC, 212 nmol/l, RR 0-164). Additionally, she failed to suppress cortisol (228 nmol/l, RR<50) after an overnight dexamethasone suppression test (ONDST). An MRI demonstrated a normal pituitary with a small area of non-enhancement on the left side suggestive of a microadenoma. However, at the time of performing these tests she was also diagnosed with Graves’ disease, and there were some concerns that her thyrotoxic state could impact her cortisol levels and her ability to process dexamethasone, causing misleading results. Given her mild clinical features, ambiguous biochemistry and inconclusive MRI findings, repeated testing was warranted. Over the next 9-months, her late-night salivary cortisol and cortisone levels fluctuated from raised (peak: cortisol 6.0 nmol/l, cortisone 37.9 nmol/l) to normal (nadir: cortisol 1.6 nmol/l, cortisone 12 nmol/l). Her ONDSTs continued to demonstrate failure of cortisol suppression. However, her paired dexamethasone levels were low at times (2.0 nmol/l and 1.7 nmol/l; RR<3), suggesting impaired absorption of or poor compliance with dexamethasone. Furthermore, during a time where she had positive salivary and ONDTs results, her 24 hr-UFC level remained normal (94 nmol/l), which resulted in diagnostic uncertainty. Despite her variable biochemistry, her appearance began to change, and she was now considered to be clinically Cushingoid. Furthermore, her DEXA scan revealed osteoporosis of the spine and osteopenia of the hips. As a result, she was commenced on rivaroxaban for VTE prevention and referred for inferior petrosal sinus catheter sampling (IPSS). Her IPSS excluded an ectopic source of ACTH production, and she is currently awaiting a repeat MRI +/- methionine PET/CT.

Questions for Discussion: How does thyrotoxicosis impact biochemical testing for hypercortisolaemia? Does she have cyclical Cushing’s or evolving Cushing’s disease? Are her fluctuating dexamethasone levels due to excess metabolism or poor absorption/ non-compliance of dexamethasone? How useful is a methionine PET/CT scan for diagnosing Cushing’s disease in a patient without a clear lesion on MRI?