Diabetes, Active Disease, and Afternoon Serum Cortisol Levels Predict Cushing's Disease Mortality: A Cohort Study.

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 33 ±â€…11 years, female predominance (n = 154, 89.5%), majority of them with microadenoma (n = 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 SMR = 3.1, 95% confidence interval (CI) 1.9-4.8, P < 0.001. Cardiovascular disease was the main cause of death (SMR = 4.2, 1.5-9.3, P = 0.01). Multivariate Cox regression models adjusted for potential cofounders showed that diabetes (HR = 5.2, IC 95% 1.8-15.4, P = 0.002), high cortisol levels after 1600 hours at diagnosis (3.4, 2.3-7.0, P = 0.02), and active CD (7.5, 3.8-17.3, P = 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.

High Molecular Weight ACTH-Precursor Presence in a Metastatic Pancreatic Neuroendocrine Tumor Causing Severe Ectopic Cushing's Syndrome: A Case Report.

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.

Quality of life is significantly impaired in both secretory and non-functioning pituitary adenomas.

OBJECTIVE: To evaluate the quality of life (QoL) in patients with pituitary adenomas in comparison with healthy Mexican population QoL scores. DESIGN & MEASUREMENTS: Cross-sectional study using the short form 36 questionnaire (SF-36) in 175 patients with pituitary adenomas grouped by adenoma subtype and disease activity, and compared them with the healthy Mexican population normative QoL scores. PATIENTS: A total of 44 patients with non-functioning pituitary adenomas (NFPA), 48 with acromegaly, 53 with prolactinomas and 30 with Cushing disease (CD) were enrolled in this study. RESULTS: Mental and physical components scores (MCS & PCS) of SF-36 questionnaire were lower in patients with active disease in all adenoma subtypes (P < 0.03). A significant negative relationship between prolactin levels and MCS (r = -0.30, P < 0.01) and PCS (r = -0.41, P < 0.01) were found in prolactinomas. Patients with CD showed 24 hours urine-free cortisol levels negatively correlated with MCS (r = -0.43, P < 0.01) but not with PCS. No significant correlation was found between IGF-1 ULN and QoL scores in acromegaly. NFPA patients had lower QoL scores than patients with controlled CD, acromegaly or prolactinoma (P < 0.02). Active CD and prolactinoma have lower QoL scores in comparison of NFPA (P < 0.05). Having an adenoma, secretory or non-functioning, decrease QoL scores in comparison of results in the healthy Mexican population register. Using an adjusted-multivariate model, we confirmed that disease activity in all secretory adenomas is an independent risk factor, reducing SF-36 scores significantly. CONCLUSION: Activity in all secretory pituitary adenomas' patients decrease mental and physical QoL. However, independently of disease activity, secretory and NFPA significantly decrease QoL in comparison with healthy Mexican population QoL register.