The diagnosis and prevalence of hypoprolactinemia in patients with panhypopituitarism and the effects on depression and sexual functions.

PURPOSE: We aimed to investigate the prevalence and the diagnostic criteria of hypoprolactinemia in patients with panhypopituitarism and the effects of hypoprolactinemia on depression and sexual functions. MATERIALS AND METHODS: Forty-eight patients with panhypopituitarism and 20 healthy volunteers were included. Basal hormone levels were measured and a TRH stimulation test was performed. For the evaluation of sexual functions, questionnaries of Female Sexual Functional Index (FSFI) for females and International Erectile Functional Index for males were performed to the subjects. Depressive symptoms were evaluated by Beck Depression Envontory score (BDI-II). RESULTS: The peak PRL response to TRH stimulation test at 5th percentile in the control group was 18.6 ng/ml in males and 41.6 ng/ml in females and accepted as the cut-offs for sufficient response of PRL. Prolactin was insufficient in 42(87.5%) patients. A basal PRL level of ≤ 5.7 ng/ml in males and 7.11 ng/ml in females was 100% specific in predicting an inadequate response to TRH stimulation test with 80% and 70% sensitivity respectively. A basal PRL level of ≥ 8.5 ng/dl in males was 100% specific and 76% sensitive, and in females a level of ≥ 15.2 ng/dl was 96% specific and 66% sensitive in predicting an adequate response to TRH. PRL deficient patients with panhypopituitarism had higher depression scores compared to the controls, lower sexual function scores in males. CONCLUSION: PRL deficiency is prevalent among individuals with panhypopituitarism, with the potential to result in elevated depression scores in both sexes and impaired sexual functions in males. A basal PRL level seems to be sufficient for the diagnosis of hypoprolactinemia in routine clinical practice.

Association of OSR-1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is associated with oxidative stress and hypertension development before renal function decline and cardiovascular disease development. Oxidative stress-responsive kinase-1 (OSR-1) participates in the signaling regulating Na+ transport during oxidative stress and also plays a role in the regulation of cell volume and blood pressure. Therefore, we aimed to investigate the potential role of OSR-1 in ADPKD patients. Eighty ADPKD patients, 80 healthy controls, and 80 non-ADPKD patients with hypertension were enrolled in this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood samples were taken after 12-h fasting for the measurement of biochemical parameters and OSR-1 gene expression. Vascular dysfunction was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Briefly, of the 80 ADPKD patients, 41(51%) were male, and 53(66%) of them were hypertensive. The mean age of the 80 controls was 35.3 ± 12.6 years, and 37(46%) of them were male. The mean age of the 80 non-ADPKD patients with hypertension was 44.6 ± 11.9 years, and 38(47.5) of them were male. There were significant differences in serum OSR-1 gene expression between the ADPKD patients and the control subjects. Serum OSR-1 gene expression was also significantly increased in hypertensive ADPKD patients in comparison with both normotensive ADPKD counterparts and non-ADPKD hypertensive subjects. Serum OSR-1 gene expression was increased in patients with ADPKD than healthy subjects. Low estimated glomerular filtration rate (eGFR), OSR-1 gene expression, total kidney volume (TKV), and high-density lipoprotein (HDL) were also independently associated with hypertension in ADPKD patients.

Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1ß Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension.

BACKGROUND AND OBJECTIVES: Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1ß activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1α gene expression from whole blood and urine samples and IL-1ßgene expression from whole blood were measured. METHODS: One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for HIF-1α and IL-1ß geneexpression by using quantitative real-time PCR. RESULTS: There were significant differences in whole blood HIF-1α, IL-1ß geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1αgene expression, IL-1ß geneexpression, and serumsuccinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (p < 0.05). Serum succinate levels and blood IL-1ß geneexpression were increased in ADPKD patients with high levels of HIF-1α geneexpression (p = 0.018 and p = 0.029, respectively). CONCLUSIONS: Increased age,low eGFR, and HIF-1α and IL-1ß geneexpressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.

Toll-Like Receptors in the Progression of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of chronic kidney disease. The intriguing role of innate immune system and inflammation become a target for potential therapeutic approach to slow progression. When toll-like receptors (TLRs) signaling and their receptors activate, they start a cascade of intracellular signaling that induces the production of the inflammatory cytokines and chemokines. Thus, we aim to investigate the association of TLRs between progression of ADPKD. Ninety ADPKD patients and ninety matched controls were enrolled this prospective study and were followed during 3 years. TLR-2 and TLR-4 gene polymorphisms and expressions were measured. Hypertension was diagnosed with ambulatory blood pressure monitoring. Rapid progression was defined as sustained decline in estimated glomerular filtration rate (eGFR) of more than 5 mL/min per 1.73 m2 per year. TLR-4Asp299Gly polymorphisms were significantly different between patient and control group (P < 0.05). Also, TLR-2 and TLR-4 gene expressions were significantly different between the ADPKD patients and the control subjects (P < 0.05). The expression levels of both TLR-2 and TLR-4 were found to be higher in the rapid progression groups comparing the slow progression group (P < 0.05). TLR-2 gene expression, hypertension and uric acid were found to be independent risk factors in identifying rapid progression in ADPKD patients. TLR-2 and TLR-4 gene expressions are associated with rapid progression in ADPKD patients. TLRs may play a role in the progression of ADPKD.