Unusual causes of Cushing's syndrome

Abstract

Although in the majority of the patients with Cushing's syndrome (CS), hypercortisolism is due to ACTH hypersecretion by a pituitary tumour or to ectopic ACTH secretion from an extrapituitary neoplastic lesion or to autonomous cortisol secretion by an adrenal tumour, in occasional patients a much rarer entity may be the cause of the syndrome. Herein, we attempted to summarise and categorise these unusual causes according to their presumed aetiology. To this end, we performed a comprehensive computer-based search for unusual or rare causes of CS. The following unusual forms of CS were identified: (i) ACTH hyperesecretion due to ectopic corticotroph adenomas in the parasellar region or the neurohypophysis, or as part of double adenomas, or gangliocytomas; (ii) ACTH hypersecretion due to ectopic CRH or CRH-like peptide secretion by various neoplasms; (iii) ACTH-independent cortisol hypersecretion from ectopic or bilateral adrenal adenomas; (iv) glucocorticoid hypersensitivity; (v) iatrogenic, due to megestrol administration or to ritonavir and fluticasone co-administration. Such unusual presentations of CS illustrate why Cushing's syndrome represents one of the most puzzling endocrine syndromes. RESUMOCausas Incomuns da Síndrome de Cushing. Embora na maioria dos pacientes com síndrome de Cushing (SC), o hipercortisolismo se deva à hipersecreção de ACTH resultante de um tumor hipofisário ou de uma fonte ectópica de ACTH por uma lesão neoplásica extra-hipofisária, ou ainda pela secreção autônoma de cortisol por um tumor adrenal, ocasionalmente uma entidade muito mais rara pode ser a causa da síndrome. Nesta revisão, tentaremos sumarizar e categorizar essas causas incomuns de acordo com sua pressuposta etiologia. Para isso, fizemos uma ampla pesquisa por computador em busca dessas causas raras ou não usuais de SC. As seguintes formas não usuais de SC foram identificadas: (i) hipersecreção de ACTH devida a adenomas corticotróficos ectópicos na região parasselar ou na neurohipófise, ou como parte de adenomas duplos, ou gangliocitomas; (ii) hipersecreção de ACTH devida à secreção ectópica de CRH ou peptídeo CRH-símile por várias neoplasias; (iii) hipersecreção de cortisol ACTHindependente por adenomas adrenais ectópicos ou bilaterais; (iv) hipersensibilidade aos glicocorticóides; (v) iatrogênica, devida à administração de megestrol ou à co-administração de ritonavir e fluticasona. Essas apresentações incomuns da SC ilustram por que essa síndrome é considerada uma das mais desafiadoras da endocrinologia.

Ectopic corticotropin-releasing hormone (CRH) syndrome from metastatic small cell carcinoma: a case report and review of the literature

“…However, in the case presented here as well as that of seven other ectopic CRH cases, the lack of suppression of ACTH and cortisol are consistent ectopic ACTH production, avoiding the superfluous performance of other, sometimes invasive, pituitary-centered procedures (e.g. IPSS) [3]. Similarly, a single dose of 8 mg dexamethasone (overnight) has not suppressed cortisol in cases of isolated ectopic CRH [12,17].…”

“…Although autonomous cortical adrenal adenomas or carcinomas are a cause of elevated cortisol, most cases (85 to 90%) are adrenocorticotropic hormone (ACTH) dependent and are caused by corticotroph pituitary adenomas (Cushing's Disease or CD) [1]. The remaining ACTH-dependent cases mostly involve non-pituitary malignancies (Ectopic ACTH) which often are tumors of neuroendocrine origin such as small cell lung carcinoma or bronchial carcinoid [3,4]. Here, we describe a case of Cushing's syndrome which initially appeared to be caused by ectopic ACTH secretion from metastatic small cell carcinoma.…”

Ectopic Cushing’s syndrome in a patient with inferior petrosal sinus sampling indicating pituitary‐dependent ACTH secretion

“…Ectopic corticotroph adenomas located in the parasellar or cavernous sinuses behave similarly to anterior pituitary corticotroph adenomas during both stimulatory and suppression tests performed for the differential diagnosis of Cushing's disease . Moreover, inferior petrosal sinuses drain the whole cavernous sinus into the respective internal jugular veins, so IPSS results confirm the central origin of ACTH secretion.…”

Cushing’s Syndrome Due to CRH and ACTH Co-secreting Pancreatic Tumor—Presentation of a New Case Focusing on Diagnostic Pitfalls

“…On the other hand, in patients with isolated ectopic CRH syndrome (ECS), baseline ACTH and cortisol levels are in the range usually found in patients with Boccult^ectopic ACTH syndrome or CD [1]. In those cases with ectopic secretion of both CRH and ACTH, the levels of ACTH and cortisol are variable.…”

“…Pituitary hyperfunction syndromes caused by ectopic hypersecretion of the corresponding hypothalamic hypophysiotropic hormones are extremely rare [1]. The most frequent cases are those of ectopic growth hormone releasing hormone production, causing GH hypersecretion [2].…”