Multi-step approach in a complex case of Cushing’s syndrome and medullary thyroid carcinoma

Abstract

The diagnosis of Cushing's syndrome (CS) may sometimes be cumbersome. In particular, in ACTH-dependent CS it may be difficult to distinguish between the presence of an ACTH-secreting pituitary adenoma and ectopic ACTH and/or CRH secretion. In such instances, the etiology of CS may remain unknown despite extensive diagnostic workout, and the best therapeutic option for each patient has to be determined. We report here the case of a 54-yr-old man affected by ACTH-dependent CS in association with a left adrenal adenoma and medullary thyroid carcinoma (MTC). He presented with clinical features and laboratory indexes of hypercortisolism associated with elevated levels of calcitonin. Ectopic CS due to MTC was reported previously. In our case hypercortisolism persisted after surgical treatment of MTC. Thorough diagnostic assessment was performed, in order to define the aetiology of CS. He was subjected to basal and dynamic hormonal evaluation, including bilateral inferior petrosal sinus sampling. Extensive imaging evaluation was also performed. Overall, the laboratory data together with the results of radiological procedures suggested that CS might be due to inappropriate CRH secretion. However, the source of CRH secretion in this patient remained unknown. It was then decided to remove the left adenomatous adrenal gland. Cortisol level fell and has remained within the normal range nine months after surgery. This case well depicts the complexity of the diagnostic workout, which is needed sometimes to correctly diagnose and treat CS, and suggests that monolateral adrenalectomy may represent, at least temporarily, a reasonable therapeutic option in occult ACTH-dependent hypercortisolism.

Phaeochromocytoma and ACTH‐dependent cushing's syndrome: tumour crf secretion can mimic pituitary cushing's disease

“…To distinguish between ectopic ACTH and CRF syndromes, plasma assay and immunostaining of tumour samples for both ACTH and CRF would ideally be available, but plasma CRF levels are rarely reported in the literature, because there is typically no clinical imperative to do so. We were able to identify only two cases of phaeochromocytoma-associated ACTH-driven Cushing's syndrome, in which plasma CRF was either frankly elevated, or 'inappropriately normal'; upper end of normal in one case 12 and well above the quoted reference range in the other. 25 Several reports of ectopic CRF secretion describe impaired cortisol-decrement following HDDST, but it is not commonly appreciated that this condition will necessarily result in false-positive localization of the primary tumour to the pituitary gland by IPSS.…”

“…There are reports of tumours co‐expressing ACTH and CRF, but ectopic CRF production alone is rarely reported (Table a). To our knowledge, there have been only 23 convincing reports of isolated ectopic CRF production, among which medullary thyroid cancer was the commonest cause, while phaeochromocytoma accounted for only five cases (Table b). The diagnostic evaluation of ACTH‐dependent Cushing's syndrome has been extensively reviewed, but it is worth restating that the key investigations in differentiating ectopic secretion from Cushing's disease are pituitary MRI, IPSS with CRF stimulation and high‐resolution cross‐sectional imaging of the chest and abdomen.…”