The diurnal change of thyroid-stimulating hormone and the effect of this change on thyroid functions in patients with chronic kidney disease.

PURPOSE: Thyroid-stimulating hormone (TSH) has a pulsatile and circadian rhythm in healthy individuals. We aimed to evaluate the diurnal changes of free thyroid hormones and serum TSH levels in patients with end-stage renal failure (ESRF) whose thyroidal functions are at normal ranges. METHODS: Thirty hemodialysis patients with chronic renal failure and without a known thyroidal disease who are over 18 and 35 healthy individuals were included. The serum TSH, free T3, and free T4 levels were examined among the patient and control group which were taken at 8:00 a.m., 4:00 p.m., and 0:00 a.m. RESULTS: Twenty-two (73.3%) patients were male, and the mean age of the patient group was 64 (sd = 14.45 years). Seventeen (48.6%) of the control group were female, and the mean age was 31.9 (sd = 6.4 years). Serum free T3 levels, measured at three different time points (8:00 a.m., 4:00 p.m., and 0:00 a.m.), were significantly lower in the patient group than in the control group and serum free T4 levels were measured at three different time points (8:00 am, 4:00 p.m., and 0:00 a.m.) were significantly higher in the patient group than in the control group. Serum TSH levels were higher in the patient group than in the control group at 08:00, and were lower at 24:00 (p < 0.001). The nocturnal increase of serum TSH level under 0.525 suggested diurnal rhythm disruption with 83% sensitivity and 87% specificity. CONCLUSION: The nocturnal serum TSH increase is not seen in ESRF patients who did not have a thyroid disease. We think that not observing a nocturnal TSH increase could be an early indication of the sick euthyroid syndrome.

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Impact of Endothelial NOS VNTR Variant on Susceptibility to Diabetic Neuropathy and Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study was to evaluate whether the VNTR intron 4b/4a variant in the eNOS gene is associated with type 2 diabetes mellitus (T2DM) and DPN. METHODS: A total of 598 subjects were enrolled in the study. eNOS VNTR 4b/4a variant was genotyped by polymerase chain reaction (PCR) method. RESULTS: eNOS VNTR intron 4b/4b genotype and b allele increased in patients with both DPN and T2DM compared healthy controls (p=0.0005, OR:1.94, p= 0.000002, OR:4.10, respectively). 4a/4b genotype was more prevalent in controls than in DPN and T2DM patients (p=0.00008, OR:0.46; p=0.000004, OR:0.24, respectively). eNOS VNTR b allele was more common in DPN patients and T2DM patients compared with controls (p=0.007, p=0.00002, respectively). CONCLUSION: The eNOS VNTR "4b/4b" homozygous genotype and hence "4b"allele as a genetic risk factor for T2DM and DPN, which may serve as a useful marker of increased susceptibility to the risk of these disorders.