ABSTRACT
CONTEXT: Cushing's disease (CD) is a life-threating disease, with increased mortality in comparison with the general population. OBJECTIVE: This study aimed to evaluate standardized mortality ratios (SMRs) in CD patients. We also analyzed independent risk factors related to increased mortality. DESIGN: We conducted a longitudinal cohort study in a 3rd level specialty center, from 1979 to 2018, in patients with CD. RESULTS: From 1375 cases with a pathology diagnosis of pituitary adenoma, 191 cases had the confirmed diagnosis of CD (14%). A total of 172 patients completed follow-up, with a mean age at diagnosis of 33â ±â 11 years, female predominance (nâ =â 154, 89.5%), majority of them with microadenoma (nâ =â 136, 79%), and a median follow-up of 7.5 years (2.4-15). Eighteen patients (10.5%) died, 8 of them (44%) were with active CD, 8 (44%) were under remission, and 2 (11%) were under disease control. Estimated all-cause SMRâ =â 3.1, 95% confidence interval (CI) 1.9-4.8, Pâ <â 0.001. Cardiovascular disease was the main cause of death (SMRâ =â 4.2, 1.5-9.3, Pâ =â 0.01). Multivariate Cox regression models adjusted for potential cofounders showed that diabetes (HRâ =â 5.2, IC 95% 1.8-15.4, Pâ =â 0.002), high cortisol levels after 1600 hours at diagnosis (3.4, 2.3-7.0, Pâ =â 0.02), and active CD (7.5, 3.8-17.3, Pâ =â 0.003) significantly increased the risk of mortality. CONCLUSIONS: Main cause of CD mortality was cardiovascular disease. Main risk factors for mortality were uncontrolled diabetes, persistently high cortisol levels after 1600 hours at diagnosis, and active disease at last follow-up.
Subject(s)
Hydrocortisone/blood , Pituitary ACTH Hypersecretion/diagnosis , Pituitary ACTH Hypersecretion/mortality , Adenoma/blood , Adenoma/complications , Adenoma/diagnosis , Adenoma/mortality , Adult , Circadian Rhythm , Cohort Studies , Disease Progression , Female , Follow-Up Studies , History, 20th Century , History, 21st Century , Humans , Longitudinal Studies , Male , Mexico/epidemiology , Middle Aged , Mortality , Pituitary ACTH Hypersecretion/blood , Pituitary ACTH Hypersecretion/etiology , Pituitary Neoplasms/blood , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/mortality , Prognosis , Young AdultABSTRACT
Ectopic ACTH-secretion causing Cushing's syndrome is unusual and its diagnosis is frequently challenging. The presence of high-molecular-weight precursors throughout pro-opiomelanocortin (POMC) translation by these tumors is often not reported. We present the case of a 49-year-old woman with a 3-month history of proximal muscular weakness, skin pigmentation, and weight loss. Upon initial evaluation, she had a full moon face, hirsutism, and a buffalo hump. Laboratory workup showed hyperglycemia, hypokalemia and metabolic alkalosis. ACTH, plasma cortisol, and urinary free cortisol levels were quite elevated. Serum cortisol levels were not suppressed on dexamethasone suppression testing. An octreo-SPECT scan showed enhanced nucleotide uptake in the liver and pancreas. Transendoscopic ultrasound-guided biopsy confirmed the diagnosis of a pancreatic ACTH-secreting neuroendocrine tumor (NET). Surgical excision of both pancreatic and liver lesions was carried out. Western blot analysis of the tumor and metastases revealed the presence of a high-molecular-weight precursor possibly POMC (at 30 kDa) but not ACTH (normally 4.5 kDa). ACTH-precursor secretion is more frequent in ectopic ACTH-secreting tumors compared with other causes of Cushing's syndrome. Hence, the measurement of such ACTH precursors warrants further evaluation, especially in the context of ACTH-dependent hypercortisolism.
