Thyroid Hormone Replacement Reduces The Risk of Cardiovascular Diseases in Diabetic Nephropathy Patients With Subclinical Hypothyroidism

Objective: Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN.Methods: This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases.Results: Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk.Conclusion: THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding.Abbreviations:CV = cardiovascularDMN = diabetic nephropathyeGFR = estimated glomerular filtration ratefT4 = free thyroxineHbA1c = glycosylated hemoglobinHR = hazard ratiohs-CRP = high-sensitivity C-reactive proteinLDL-C = low-density lipoprotein cholesterolSCH = subclinical hypothyroidismT2DM = type 2 diabetesTHRT = thyroid hormone replacement therapyTSH = thyroid-stimulating hormone     

Arterial Wall Stiffness and the Risk of Atherosclerosis in Egyptian Patients with Overt and Subclinical Hypothyroidism

Objective: Hypothyroidism is associated with an increased risk of atherosclerosis. Pulse wave velocity (PWV) is an index of arterial wall stiffness widely used for noninvasive assessment of early atherosclerosis. We assessed PWV in Egyptian patients with hypothyroidism.Methods: The study included 100 Egyptian females aged 18 to 55 years. They were classified into three groups: group I, 40 women with overt hypothyroidism; group II, 40 women with subclinical hypothyroidism; and group III, 20 euthyroid women as a control group. The three groups were age matched. Doppler ultrasonography was used to calculate the heart-femoral PWV.Results: PWV was significantly higher in women with overt and subclinical hypothyroidism as compared with the control group (9.55 ± 1.81 m/s and 9.30 ± 1.28 m/s, respectively vs. 7.82 ± 2.14 m/s; P<.001 and <.01, respectively). There was a positive correlation between thyroid-stimulating hormone (TSH) and PWV in women with overt hypothyroidism and in those with subclinical hypothyroidism (P<.05 for both). Multivariate regression analysis showed that age and diastolic blood pressure were independent determinants of PWV in women with overt and subclinical hypothyroidism (P<.01 for all). TSH was also an independent determinant of PWV in both groups (P<.05 for both).Conclusion: PWV is significantly higher in Egyptian women with overt and subclinical hypothyroidism as compared with normal control subjects. This denotes early increase in arterial wall stiffness in patients with hypothyroidism, even in the subclinical phase. The positive correlation between PWV and TSH in both groups of patients suggests that the risk of atherosclerosis is proportionate to the severity of hypothyroidism.Abbreviations: ABI = ankle/brachial index; baPWV = brachial-ankle pulse wave velocity; BP = blood pressure; CIMT = carotid intima-media thickness; ECG = electrocardiogram; FT4 = free thyroxine; HDL = high-density lipoprotein; hfPWV = heart-femoral pulse wave velocity; LDL = low-density lipoprotein; PTT = pulse transit time; PWV = pulse wave velocity; SCH = subclinical hypothyroidism; TSH = thyroid-stimulating hormone     

Increased Atherogenic Low-Density Lipoprotein Cholesterol in Untreated Subclinical Hypothyroidism

ObjectiveTo evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).MethodsIn a prospective, double-blind, placebo- controlled study, we enrolled 120 patients—mostly, but not exclusively, premenopausal women—with SCH. Patients were randomly assigned to either a levothyroxine- treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.ResultsIn the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 ± 0.98 mmol/L versus 4.74 ± 0.87 mmol/L (P < .0001); LDL-C, 3.30 ± 0.90 mmol/L versus 2.89 ± 0.59 mmol/L (P < .01); TG, 1.18 ± 0.71 mmol/L versus 0.95 ± 0.53 mmol/L (P < .002); and HDL-C, 1.20 ± 0.33 mmol/L versus 1.19 ± 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 ± 0.60 mmol/L to 3.11 ± 0.77 mmol/L, a change that was statistically significant (P < .001). At the end of the study, the lipid profile changes between levothyroxine- treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P < .029 and P < .0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.ConclusionIn premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated. (Endocr Pract. 2008;14:570-575)     

ACTN3 Gene R577X Polymorphism Associated with High-Density Lipoprotein Cholesterol and Adiponectin in Rugby Players

Objective: To determine the relationship between the R577X polymorphism of the α-actinin-3 (ACTN3), which may play a role in the individual differences observed in the effects of exercise on health benefits and antiatherogenic markers (i.e., high-density lipoprotein cholesterol [HDL-C] and adiponectin) in athletes.Methods: Seventy-six male rugby players (mean age 19.8 years) were enrolled in this study. Genomic DNA was extracted from peripheral blood samples, and restriction fragment length polymorphism-polymerase chain reactions were conducted to assess ACTN3 genotypes. Body mass index (BMI), waist circumference, serum lipids including HDL-C, and adiponectin levels were measured. Current smoking and alcohol intake habits were evaluated with a questionnaire. All of the parameters were compared between 2 groups displaying frequently observed genotypes: one group consisting of patients having either the R/R or R/X genotype and a second group with the X/X genotype.Results: The frequency of the X allele was 0.55 and the distribution of the genotypes was 35.5% (n = 27) for X/X, 39.5% (n = 30) for R/X, and 25.0% (n = 19) for R/R. Serum HDL-C and adiponectin levels were significantly higher in X/X genotype compared to the R/R or R/X genotype (HDL-C 1.6 ± 0.3 [SD] vs. 1.4 ± 0.2 mmol/L; P<.01, adiponectin 8.8 ± 2.6 vs. 6.9 ± 2.3 μg/mL; P<.01), even after adjustments for confounders (P<.01).Conclusion: There may be a relationship between the ACTN3 genotype and HDL-C and adiponectin levels in rugby players. This may be useful information when determining the individual responses of antiatherogenic markers to exercise.Abbreviations:ACTN3 = α-actinin-3BMI = body mass indexCVD = cardiovascular diseaseHDL-C = high-density lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterolR = arginine (R) at amino acid position 577 of the ACTN3 proteinTC = total cholesterolTG = triglycerideX = truncation at amino acid position 577 of the ACTN3 protein     

Gender Determines Serum Free Cortisol: Higher Levels in Men

Objective: Because only the free fraction of serum cortisol can readily access glucocorticoid receptors, we investigated whether or not a gender-related difference in serum free cortisol (FC) exists in the basal and adrenocorticotropic hormone (ACTH)-stimulated state.Methods: Serum total cortisol (TC) and FC were measured in 323 subjects (175 men; 148 women). Additionally, the low-dose 1-μg ACTH test was performed in 56 subjects (30 women, 26 men). Subjects were healthy volunteers, recruited in a preventive medicine screening program and an outpatient clinic.Results: Overall, basal serum TC and FC level were ~18 and ~33%, respectively, higher in men than in women (TC, 14.5 ± 0.33 μg/dL vs. 12.3 ± 0.33 μg/dL; P<.0001; FC, 0.68 ± 0.02 μg/dL vs. 0.51 ± 0.02 μg/dL; P<.0001). The higher FC in men relative to women was apparent across a wide age range (17 to 86 years) and persisted after adjustment for age and body mass index. The FC fraction (%FC, out of TC) was concordantly higher in men (5.4 ± 0.09% vs. 4.8 ± 0.3%; P = .046). FC was not related to the estimated menopausal status (women age below and above 47, 50, or 53 years). ACTH-stimulated FC levels were significantly higher in men compared to women, as reflected by the area under the response curve (49.4 ± 3.4 μg × min vs. 39.6 ± 2.2 μg × min; P = .0014).Conclusion: Gender is an unrecognized determinant of serum FC in humans. The possibility of lifelong exposure to the higher bioactive fraction of cortisol under basal conditions or daily stress involving ACTH stimulation should be further investigated in the context of gender-related phenotypic features such as “android” (visceral) fat deposition and longevity.Abbreviations:ACTH = adrenocorticotropic hormoneBMI = body mass indexCBG = cortisol-binding globulinFC = free cortisolHPA = hypothalamic-pituitary-adrenalTC = total cortisol     

Higher Growth Hormone Levels are Associated with Erectile Dysfunction in Male Patients With Acromegaly

Objective: To investigate in vivo correlates of erectile dysfunction (ED) in male patients with acromegaly.Methods: Fifty-one male patients with acromegaly were assessed by the International Index of Erectile Function-5 and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched nonacromegalic controls.Results: Among 51 patients analyzed, 32 (62.7%) had ED. Patients with ED showed lower Acro-QoL scores regarding global (69.8 ± 17.7 versus 79.4 ± 11.2; P = .035) and personal relationship dimensions (59.6 ± 22.1 versus 76.8 ± 17.6; P = .012) than non-ED patients. ED patients were older (44.5 ± 11.2 years versus 33.2 ± 8.5 years; P = .04) and showed higher growth hormone (GH) levels (15.5 μg/L &lsqb;interquartile range of 9.5 to 34.5 μg/L] versus 5.9 μg/L &lsqb;interquartile range of 3.4 to 13.9 μg/L]; P = .001) compared to non-ED patients. The cutoff values for identifying ED were 7.9 μg/L for random GH and 5.3 μg/L for GH nadir after oral administration of 75 g of glucose. There was no significant difference in total testosterone levels between the two groups (6.36 ± 4.24 nmol/L versus 9.54 ± 5.50 nmol/L; P = .299). The NO levels in patients with acromegaly were significantly lower than those in nonacromegalic controls (8.77 ± 1.78 μmol/L versus 19.19 ± 5.02 μmol/L, respectively; P = .049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14 ± 0.98 μmol/L versus 12.09 ± 3.44 μmol/L; P = .027).Conclusion: Our study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required.Abbreviations: Acro-QoL = Acromegaly Quality of Life; ED = erectile dysfunction; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; IIEF-5 = international index of erection function-5; LH = luteinizing hormone; MRI = magnetic resonance imaging; NO = nitric oxide; OGTT = oral glucose tolerance test; QoL = quality of life; ROC = receiver operating characteristic     

Levothyroxine Replacement In Obese Hypothyroid Females After Total Thyroidectomy

Objective: Levothyroxine (LT4) replacement in hypothyroid obese patients is poorly understood. We assessed whether the LT4 regimen required to achieve euthyroidism differs between nonobese and obese hypothyroid females.Methods: We retrospectively identified nonobese and obese females who received LT4 starting with a standard dose of 1.6 μg/kg after total thyroidectomy for preoperative diagnosis of benign goiter. We examined the association between LT4 dosage required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4–2.5 mIU/L) and patient characteristics using linear regression models with and without adjustment for age, ethnicity, medication use, and postoperative hypoparathyroidism.Results: We identified 32 females (15 nonobese/17 obese) who achieved euthyroid state. Obese patients weighed more (104.1 ± 22.5 vs. 64.9 ± 10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 ± 38 vs. 102 ± 12 μg, P = .0002) but LT4 requirements per kg total body weight (TBW) were similar (1.60 ± 0.29 vs. 1.42 ± 0.38 μg/kg, P = .15). LT4 dose per kg ideal body weight (IBW) was higher in obese than in nonobese females (2.62 ± 0.67 vs. 1.88 ± 0.28 μg/kg, P = .0004) and this difference persisted after adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese patients had subnormal TSH episodes, respectively (P = .11). After taking LT4 compliance, malabsorption, and competing medication use into consideration, we found marked LT4 dose variability in obese patients. Patients who needed a mean daily LT4 dose ≤150 mg (124 ± 16 μg/day) compared with >150 μg (198 ± 4 μg/day) demonstrated lower LT4 per TBW (1.25 ± 0.18 vs. 1.84 ± 0.43 μg/kg, P = .03) and IBW (2.28 ± 0.47 vs. 3.44 ± 0.18 μg/kg, P<.0001), respectively.Conclusion: The standard approach to LT4 replacement in obese and nonobese females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and nonobese patients were similar if expressed per kg TBW, though there was variability in the final LT4 among obese patients. We suggest initiating LT4 at a dose lower than that routinely recommended in obese females.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationBMI = body mass indexIBW = ideal body weightLT4 = levothyroxineTBW = total body weightTSH = thyroid-stimulating hormone     

Seasonal Variation Of Vitamin D And Serum Thyrotropin Levels And Its Relationship In A Euthyroid Caucasian Population

Objective: It is unclear whether seasonal variations in vitamin D concentrations affect the hypothalamo-pituitary-thyroid axis. We investigated the seasonal variability of vitamin D and serum thyrotropin (TSH) levels and their interrelationship.Methods: Analysis of 401 patients referred with nonspecific symptoms of tiredness who had simultaneous measurements of 25-hydroxyvitamin D3 (25&lsqb;OH]D3) and thyroid function. Patients were categorized according to the season of blood sampling and their vitamin D status.Results: 25(OH)D3 levels were higher in spring-summer season compared to autumn-winter (47.9 ± 22.2 nmol/L vs. 42.8 ± 21.8 nmol/L; P = .02). Higher median (interquartile range) TSH levels were found in autumn-winter (1.9 &lsqb;1.2] mU/L vs. 1.8 &lsqb;1.1] mU/L; P = .10). Across different seasons, 25(OH)D3 levels were observed to be higher in lower quartiles of TSH, and the inverse relationship was maintained uniformly in the higher quartiles of TSH. An independent inverse relationship could be established between 25(OH)D3 levels and TSH by regression analysis across both season groups (autumn-winter: r = -0.0248; P<.00001 and spring-summer: r = -0.0209; P<.00001). We also observed that TSH varied according to 25(OH)D3 status, with higher TSH found in patients with vitamin D insufficiency or deficiency in comparison to patients who had sufficient or optimal levels across different seasons.Conclusion: Our study shows seasonal variability in 25(OH)D3 production and TSH secretion in euthyroid subjects and that an inverse relationship exists between them. Further studies are needed to see if vitamin D replacement would be beneficial in patients with borderline thyroid function abnormalities.Abbreviations: 25(OH)D2 = 25-hydroxyvitamin D2; 25(OH)D3 = 25-hydroxyvitamin D3; AITD = autoimmune thyroid disease; FT4 = free thyroxine; TFT = thyroid function test; TSH = thyrotropin; UVB = ultraviolet B     

Impact of Ramadan Fasting on Thyroid Status and Quality of Life in Patients with Primary Hypothyroidism: a Prospective Cohort Study from karachi,pakistan

Objective: Ramadan is the ninth month in the lunar calendar, during which Muslims fast from predawn to sunset and major changes occur in their dietary, sleep, and physical activity patterns. Most patients with hypothyroidism are unable to comply with the proper timings of levothyroxine (LT4) administration. The objective of the study was to determine the change in thyroid-stimulating hormone (TSH) level and quality of life (QOL) before and after Ramadan in patients with primary hypothyroidism.Methods: This prospective cohort study included adult patients on stable doses of LT4 who fasted for at least 20 days during the month of Ramadan in the Islamic year 1437 Hijri (June/July 2016). Baseline characteristics and TSH levels were recorded on all consenting patients within 6 weeks prior to Ramadan. Post-Ramadan TSH was tested within 1 to 2 weeks after Eid-ul-Fitr.Results: During the study period, 64 patients with hypothyroidism were enrolled, of which 58 were female. The mean age of participants was 44.2 ± 13.2 years. Average daily dose of LT4 was 95.3 ± 35.4 μg. On average, patients fasted for 26.5 days and missed a dose of LT4 on 1.27 days. Mean TSH pre-Ramadan was 2.37 ± 1.35 mIU/L, and post-Ramadan, it was 4.69 ± 3.87 mIU/L. Mean difference between TSH pre- and post-Ramadan was 2.32 ± 3.80 mIU/L (P<.001). However, the difference in TSH was not significantly different between those who were compliant with meals and LT4 interval versus those who were not (compliant, 2.04 mIU/L; noncompliant, 3.15 mIU/L; P = .30). Overall, an increase in QOL scores in the domains of physical health, psychological health, and social relationships was observed after Ramadan.Conclusion: We observed statistically significant changes in TSH concentrations after the month of Ramadan in hypothyroid patients who fasted. The change in TSH was not affected by timing of LT4 intake and interval from meal.Abbreviations: AKUH = Aga Khan University Hospital; LT4 = levothyroxine; QOL = quality of life; TSH = thyroid-stimulating hormone     

Effect Of Levothyroxine Treatment On Qt Dispersion In Patients With Subclinical Hypothyroidism

ObjectiveTo examine the effect of levothyroxine treatment in patients with subclinical hypothyroidism on electrocardiographic variables, especially on ventricular repolarization-related factors.Methods:Sixteen women (mean age, 48.2 years) with subclinical hypothyroidism were treated with levothyroxine for 16 weeks. All standard 12-lead electrocardiograph-ic recordings were scanned and transferred to a computer, and the QT intervals were measured on 300 times magnified recordings. QT dispersion, which reflects the heterogeneity of the ventricular repolarization, was calculated by the difference between the QT maximum and the QT minimum.ResultsWe found that, after 16 weeks of levothyroxine treatment, the QT interval decreased from 387.2 ± 10.8 ms to 345.6 ± 13.0 ms (P < 40.0001). The study patients exhibited a significant reduction of QT dispersion from 46.5 ± 5.3 ms to 30.7 ± 5.8 ms (P < 0.0001). On linear regression analysis, a positive relationship was found between QT dispersion and logarithmic serum TSH levels (r = 0.492; P < 0.0001).ConclusionWe conclude that serum TSH concentration has a role in ventricular inhomogeneity and, therefore, that subclinical hypothyroidism may predispose to ventricular arrhythmias. A large-scale, multicenter, randomized trial should be undertaken to address the benefit-to-risk ratio of levothyroxine treatment on cardiac inhomogeneity in patients with subclinical hypothyroidism. (Endocr Pract. 2007;13:711-715)     

The Association of Thyroid Hormones and Tsh with the Metabolic Syndrome in Euthyroid Taiwanese Individuals

Objective: There are conflicting studies in euthyroid males and females regarding associations between thyroidrelated hormones and parameters of the metabolic syndrome (MetS). We investigated the association between serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations and MetS in euthyroid men and women.Methods: Taiwanese subjects aged 20 to 65 years who had undergone a voluntary health examination at a preventive examination agency in Taipei were enrolled in this cross-sectional study. The definition of MetS was suggested by the Bureau of Health Promotion, Department of Health, Taiwan. Euthyroidism was defined as TSH and free thyroxine (FT4) levels within the normal reference ranges while not taking any thyroid medication. We conducted multiple logistic regression to identify the ability of serum triiodothyronine (T3), FT4, and TSH concentrations to identify the relative risk for the presence of MetS and components of the MetS in euthyroid Taiwanese individuals.Results: A total of 8,207 Taiwanese subjects (mean age: men, 45.3 ± 9.9 years; women, 43.5 ± 9.3 years) were enrolled in this study. A total of 1,672 subjects (20.4%) were defined as having MetS; these subjects had significantly higher (P<.0001) mean age (48.4 ± 9.1 years vs. 43.6 ± 10.7 years), prevalence of men (78.7% vs. 53.4%), and smoking (16.8% vs. 11.6%) than those without MetS. The median TSH, FT4, and T3 levels in all subjects were 1.70 mIU/L, 1.41 ng/dL, and 1.20 ng/mL, respectively. Higher T3 and lower FT4 values rather than TSH increased the odds ratio for MetS in men and women after adjusting for smoking and age, particularly for the association of T3 and MetS in women (uppermost quartile versus lowermost quartile: odds ratio, 2.4; 95% confidence interval, 1.6 to 3.5; P for trend <.0001).Conclusion: In euthyroid Taiwanese men and women, relatively high serum T3 concentrations was most strongly associated with the presence of the MetS; relatively low serum T4 was less strongly related, and serum TSH levels were not associated with the MetS. It is not known if the relationship of serum T3 and T4 to the MetS is causal.Abbreviations:BMI = body mass indexFT4 = free thyroxineMetS = metabolic syndromeOR = odds ratioT3 = triiodothyronineTSH = thyroid-stimulating hormoneWC = waist circumference     

Low Free (But Not Total) 25-Hydroxyvitamin D Levels in Subjects with Normocalcemic Hyperparathyroidism

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated PTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25&lsqb;OH]D) in NPHPT subjects and healthy controls.Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL, total 25(OH)D 30 to 40 ng/mL, and intact PTH (iPTH) ≥66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay.Results: Mean age of NPHPT subjects was 59.9 ± 5.4 years, and mean BMI was 28.4 ± 2.3 kg/m², which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 ± 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 ± 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 ± 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 ± 1.3 pg/mL; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P<.05) but did not correlate with levels of total 25(OH)D (r = -0.14; P>.10).Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CV = coefficient of variation; DBP = vitamin D–binding protein; iPTH = intact parathyroid hormone; NPHPT = normocalcemic primary hyperparathyroidism     

Impact of Lifestyle Changes During Ramadan on Thyroid Function Tests in Hypothyroid Patients Taking Levothyroxine

Objective: The holy month of Ramadan poses a challenge for levothyroxine-treated patients due to altered eating habits and time restrictions. The aim of this study was to examine the impact of lifestyle changes during Ramadan on thyroid function tests in hypothyroid patients taking levothyroxine in the United Arab Emirates.Methods: Retrospective design whereby levothyroxine-treated hypothyroid patients who had thyroid function tests within 3 months pre-Ramadan and within 2 months post-Ramadan were included. We looked at adherence to levothyroxine, eating pattern, and levothyroxine administration in relation to meal times during Ramadan. Pre- and post-Ramadan thyroid function tests and the potential impact of independent variables using a random-intercept mixed effects linear model were examined.Results: A total of 112 patients (89 females) were recruited in the study, with a mean age ± standard error (SE) of 44.70 ± 1.36 years (range, 19.0 to 79.0 years). The mean thyroid-stimulating hormone (TSH) within 3 months before Ramadan was 1.809 ± 0.094 mIU/L (median, 41.5 days; interquartile range &lsqb;IQR], 25.0 to 73.0 days), while the mean TSH within 2 months post-Ramadan was higher at 3.072 ± 0.312 mIU/L (median, 27.5 days; IQR, 14.0 to 42.0 days). Post-Ramadan, 36 out of 112 patients had a plasma TSH outside of the normal reference range. The independent variable outcomes model showed that older patients and males were more likely to have an increased plasma TSH post-Ramadan. There was no relationship between the time of levothyroxine administration and change in TSH level.Conclusion: Levothyroxine-treated hypothyroid patients showed a significant increase in plasma TSH post-Ramadan, amounting to 2.525 standard deviations, with older patients and males more likely to be affected.Abbreviations: IQR = interquartile range; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

Objective: Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid-stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS.Methods: This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight-management clinic between February 1, 2013 and February 1, 2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A_1c, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed.Results: A total of 3,447 patients, 75.6% female and 38% African American, without known thyroid dysfunction, were included. Mean ± SD age was 46.74 ± 15.11 years, and mean ± SD body mass index was 36.06 ± 9.89 kg/m². Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41 μIU/mL, compared with 1.36 μIU/mL in patients without MetS (P = .45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS.Conclusion: Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.Abbreviations: BMI = body mass index FT₄ = free thyroxine HDL-C = high-density-lipoprotein cholesterol HbA_1c = hemoglobin A_1c MetS = metabolic syndrome SE = standard error TSH = thyroid-stimulating hormone     

Concentraciones séricas de colesterol y triglicéridos en pacientes diabéticos con hipotiroidismo subclínico

ObjectiveTo assess whether subclinical hypothyroidism is associated to elevations in serum cholesterol and triglyceride levels in patients with type 2 diabetes.Patients and methodsFrom a total population of 1,112 patients with type 2 diabetes screened for thyroid dysfunction (thyrotropin measurement), a group of 325 patients with normal thyroid function and another group of 29 patients with subclinical hypothyroidism were selected. No patient had known dyslipidemia or was taking lipid lowering medication.ResultsPatients with subclinical hypothyroidism had serum levels of total cholesterol (4.88 ± 0.74 mmol/L), HDL cholesterol (1.37 ± 0.34 mmol/L), LDL cholesterol (2.94 ± 0.58 mmol/L), and triglycerides (1.05 [0.88-1.41] mmol/L) that did not significantly differ from those found in euthyroid patients (4.79 ± 0.83, 1.33 ± 0.36, 2.87 ± 0.76, and 1.11 [0.81-1.43] mmol/L, respectively). Multiple regression analysis showed no association between TSH and serum lipid levels.ConclusionThese results suggest that, in our population, there are no significant differences in serum cholesterol and triglyceride levels between diabetic patients with normal and reduced thyroid function.     

The Long-Term Impact Of Controlled Ovarian Hyperstimulation On Thyroid Function

Objective: Evidence on the long-term impact of controlled ovarian hyperstimulation (COH) on thyroid function is scarce. To investigate this, we report on serum thyroid-stimulating hormone (TSH) modifications in euthyroid and hypothyroid women during COH and 3 months after the end of the stimulation cycle.Methods: Women who underwent in vitro fertilization (IVF) and who did not become pregnant were eligible. Cases were women with treated hypothyroidism and basal serum TSH <2.5 mIU/L. Controls were euthyroid women matched to cases by age and basal serum TSH. Women could be included if serum TSH was available at 4 time points: prior to initiating COH (time 1); at the time of human chorionic gonadotropin (hCG) administration (time 2); 16 days after hCG administration (time 3); and 3 months after the end of the IVF cycle (time 4).Results: Thirty-seven case-control pairs were included. Serum TSH at times 1, 2, 3, and 4 was 1.7 ± 0.6, 3.1 ± 1.4, 3.1 ± 1.3, and 2.7 ± 1.7 mIU/L, and 1.7 ± 0.6, 2.9 ± 1.0, 2.7 ± 1.0, and 1.9 ± 0.7 mIU/L among cases and controls, respectively. A statistically significant difference emerged at time 4 (P<.001). In both groups, serum TSH was higher at time 4 compared to time 1. Serum TSH exceeded the recommended threshold of 2.5 mIU/L at time 4 in 51% of cases (95% confidence interval &lsqb;CI], 35 to 68%) and in 16% of controls (95% CI, 4 to 28%) (P = .003).Conclusion: COH seems to have a long-term impact on TSH levels. The magnitude of this effect is particularly pronounced in hypothyroid women.Abbreviations:CI = confidence intervalCOH = controlled ovarian hyperstimulationFT4 = free thyroxinehCG = human chorionic gonadotropinIVF = in vitro fertilizationT4 = thyroxineTBG = thyroxine-binding globulinTGAb = anti-thyroglobulin antibodiesTPOAb = anti-thyroperoxidase antibodiesTSH = thyroid-stimulating hormone     

Relationship Between the Environmental Endocrine Disruptor Bisphenol a and Dyslipidemia: A Five-Year Prospective Study

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia.Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively.Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (β= 0.13, P = .002) and negatively associated with HDL cholesterol (β= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29).Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia.Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A     

Vascularity-Targeted Percutaneous Ethanol Injection of Toxic Thyroid Adenomas: Outcomes of A Feasibility Study Performed in the USA

Objective: The recommended treatment options for toxic adenoma (TA) in the USA are radioactive iodine ablation and surgical resection, with continued observation for pre-toxic adenoma (PTA). Percutaneous ethanol ablation (PEI) has proven efficacy in the treatment of TA and is widely available in Europe but not in the USA.Methods: Retrospective analysis was performed of all patients who underwent PEI for TA/PTA at the University of Utah, from January 2010 to 2018. Ultrasound-guided PEI, with injections targeting power Doppler–mapped blood vessels within the adenomas, was conducted. Functionality was confirmed using thyroid scintigraphy prior to PEI.Results: Eighteen adults (15 female) underwent PEI. Mean age was 41 ± 13.7 years. Baseline thyroid-stimulating hormone (TSH) was suppressed (0.06 ± 0.09 mU/L), with normal free thyroxine (FT4) 1.43 ± 0.39 ng/dL. Median nodule volume was 5.7 cm³ (interquartile range &lsqb;IQR], 4.8 to 7.7 cm³). Seventy-eight percent (n = 14) underwent two or less PEI sessions. Median volume of ethanol used was 0.46 mL/mL nodule volume (IQR, 0.3 to 0.6 mL). There was a significant increase in TSH concentrations within the first 3 months after PEI (0.06 ± 0.09 mU/L vs. 1.22 ± 1.88 mU/L; P = .02), with a concomitant significant decrease in FT4 concentrations (1.43 ± 0.39 ng/day vs. 1.13 ± 0.25 ng/day; P<.01). Significant nodular volume reduction was observed following PEI (median 5.7 cm³ &lsqb;IQR 4.8–7.7 cm³] vs. 2.5 cm³ &lsqb;IQR 2.0–7.8 cm³]; P<.01).Conclusion: Vascularity-targeted PEI is safe and effective for treating PTA and TA. This unique approach required lower injected alcohol volume and fewer injections for therapeutic success.Abbreviations: ATA = American Thyroid Association; FT4 = free thyroxine; IQR = interquartile range; PD = power Doppler; PEI = percutaneous ethanol injection; PTA = pre-toxic adenoma; RAI = radioactive iodine ablation; RFA = radiofrequency ablation; TA = toxic adenoma; TT3 = total triiodothyronine; US = ultrasound     

Optimal Free Thyroxine Levels for Thyroid Hormone Replacement in Hypothyroidism

ObjectiveTo determine whether a difference exists in the free thyroxine level required to achieve a normal thyrotropin (thyroid-stimulating hormone or TSH) level between patients with primary hypothyroidism and euthyroid control subjects and compare the free thyroxine levels in patients with primary and secondary hypothyroidism receiving thyroid hormone replacement.MethodsWe retrospectively assessed TSH and free thyroxine values in 58 patients with primary hypothyroidism and 78 euthyroid control subjects for whom screening thyroid function tests had been performed. From the medical records, we also obtained free thyroxine values for 23 patients with central hypothyroidism receiving stable levothyroxine replacement therapy.ResultsThe mean free thyroxine level was significantly higher in patients with primary hypothyroidism than in euthyroid control subjects (1.36 ± 0.201 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), whereas the corresponding mean TSH concentrations did not differ significantly (1.60 ± 1.183 mlU/L versus 1.73 ± 0.792 mlU/L, P = .46). The mean free thyroxine value was also significantly higher in the patients with central hypothyroidism in comparison with that in the euthyroid control subjects (1.31 ± 0.278 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), and no significant difference was noted between the patients with primary and central hypothyroidism (1.36 ng/dL versus 1.31 ng/dL, P = .60).ConclusionPatients with hypothyroidism require a higher level of serum free thyroxine to achieve a normal TSH value in comparison with euthyroid control subjects. This finding suggests that patients with central hypothy-roidism should be treated to achieve free thyroxine levels in the upper part of the reference range. (Endocr Pract. 2008;14:550-555)     

Higher Serum Osteoprotegerin Levels In Subjects With Thyroid Nodules

Objective: A recent study demonstrated that osteoprotegerin (OPG) could be expressed both in benign and malignant thyroid tissue. However, epidemiologic studies investigating the association between serum OPG and thyroid nodules are not available. The objective of this study was to determine whether serum OPG is associated with thyroid nodules.Methods: We measured serum OPG, total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine, thyrotropin, antithyroid peroxidase antibodies, thyrotropin-receptor antibodies, antithyroglobulin antibodies, and thyroglobulin in 1,120 Chinese participants in a cross-sectional community-based study performed in downtown Shanghai. Thyroid nodule was diagnosed by thyroid ultrasonographic examination.Results: The serum OPG levels were significantly increased in nodule-positive subjects compared to nodule-negative subjects (2.8 ± 1.2 ng/mL versus 2.1 ± 1.0 ng/mL; P<.001). After multiple adjustments, the odds ratios were substantially higher for thyroid nodule (odds ratio, 3.09; 95% confidence interval, 1.60 to 5.97) in the highest OPG quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for potential confounders. Multivariate linear regression analysis demonstrated that age (P = .015) and OPG (P = .003) were independently associated with thyroid nodule.Conclusion: Serum OPG is elevated significantly in subjects with thyroid nodules among middle-aged and elderly individuals.Abbreviations:BMI = body mass indexCI = confidence intervalDBP = diastolic blood pressureFT3 = free triiodothyronineFT4 = free thyroxineOPG = osteoprotegerinOR = odds ratioRANKL = receptor activator of nuclear factor kappa ligandSBP = systolic blood pressureTg = thyroglobulinTGAb = antithyroglobulin antibodyTPOAb = antithyroid peroxidase antibodyTRAb = thyrotropin-receptor antibodyTRAIL = Tumor necrosis factor–related apoptosis-inducing ligandTSH = thyrotropinTT3 = total triiodothyronineTT4 = total thyroxine