Endocrine Abstracts

Case History: A 53-year-old female with MEN2A (C634P mutation) and localised medullary thyroid cancer (MTC) was noted to have an adrenal nodule that was presumed by referring centre to be a phaeochromocytoma, given symptoms of anxiety and palpitations. There were also concerns about possible Cushing’s syndrome, as she reported fatigued, weight gain and a recent diagnosis of type 2 diabetes mellitus. Furthermore, she suffered a tibial plateau fracture which had been managed conservatively given concerns about her endocrine issues. The initial plan was for an adrenalectomy prior to thyroidectomy for her MTC.

Investigations: CT scan showed a 5 cm heterogeneous nodule in the left lobe of the thyroid, and a right adrenal 8 mm nodule that remained indeterminate on MRI evaluation. On ultrasound, the thyroid nodule was graded as U4. Plasma metanephrines were within normal range (metadrenaline 303 pmol/l, normetadrenaline 480 pmol/l, 3-methoxytyramine <85 pmol/l). Cortisol level failed to suppress following an overnight dexamethasone suppression test (177 nmol/l) with ACTH level of 29.1 ng/l. Random serum cortisol was 364 nmol/l and 24-hour urinary cortisol was within normal limits (152 nmol/day). Raised level of CEA (620 mg/l) and calcitonin (6240 ng/l) were in keeping with MTC. Her HbA1c was 53 mmol/mol.

Results and treatment: Functioning phaeochromocytoma was extremely unlikely given normal plasma metanephrines; hence treatment of malignant MTC was prioritised before reassessing cortisol secretion. Her overall cortisol levels were deemed satisfactory for her to proceed with total thyroidectomy for her MTC without cortisol lowering therapy. Reduced CEA (4 mg/l) and calcitonin (90.7 ng/l) levels following the operation demonstrated successful treatment of her MTC. Repeat overnight dexamethasone suppression test post-operatively showed suppression of cortisol to <28 nmol/l and reduced ACTH level (7.9 ng/l). Her HbA1c also improved to 47 mmol/mol. This confirmed that her Cushing’s syndrome was secondary to ectopic ACTH secretion from her localised MTC.

Conclusion and points for discussion:: Differentials considered for Cushing’s syndrome included ectopic ACTH from a phaeochromocytoma or the MTC, a cortisol-secreting adrenal adenoma or pituitary dependent Cushing’s incidental to her MEN2A. Although ectopic ACTH is usually seen in advanced MTC, it can be seen in localised disease. Importantly, although phaeochromocytomas are associated with MEN2A, this cannot be assumed for all adrenal nodules identified. Therefore, adrenal nodules in patients with MEN2A still warrant full clinical and biochemical evaluation to determine underlying aetiology, ensure correct sequencing of treatment and avoid unnecessary delays to treating the malignant pathology.