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     

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     

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     

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     

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)     

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     

Circulating Th17 cytokine levels are altered in Hashimoto’s thyroiditis

The disrupted autoimmune response in Hashimoto’s thyroiditis (HT) has long been considered to be dominantly T helper type 1 (Th1) mediated. Recent advances in the field of immunology have introduced a new class of effector T cells, named ‘Th17’, which plays important roles in autoimmune disorders once thought to be merely Th1 mediated. We aimed to examine the levels of major Th17 cytokines in patients with HT in this study. We studied serum interleukin 17 (IL-17) and interleukin 23 (IL-23) levels in 46 newly diagnosed, untreated patients with HT (40 women and 6 men, aged 40.0 ± 11.8 years) divided into euthyroid (n = 22) and hypothyroid (n = 24) groups and compared them with age and sex matched 26 healthy euthyroid controls without HT (21 women and 5 men; aged 36.0 ± 12.9 years). Serum IL-17 and IL-23 levels were significantly different among euthyroid and hypothyroid HT patients and controls, with highest levels obtained in the euthyroid HT group (p = 0.041 for IL-17 and p < 0.001 for IL-23). TSH was negatively and FT4 was positively correlated with IL-17 (p = 0.016 for TSH and p = 0.004 for FT4) and IL-23 (p < 0.001 for TSH and p = 0.003 for FT4) levels. There were no correlations between thyroid volumes calculated on thyroid ultrasonography and IL-17 (p = 0.630) or IL-23 (p = 0.321) levels. In conclusion, the levels of IL-17, one of the major effector cytokines of the Th17 system, and IL-23, which had been implicated in the generation, survival and expansion of Th17 cells, are altered in HT. How thyroid hormone status and the course of disease affect Th17 system in chronic autoimmune thyroiditis needs to be determined with further studies.     

Association Between Thyroid Function and Objective and Subjective Sleep Quality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study

ObjectiveTo determine the association between thyroid hormone levels and sleep quality in community-dwelling men.MethodsAmong 5,994 men aged ≥ 65 years in the Osteoporotic Fractures in Men (MrOS) study, 682 had baseline thyroid function data, normal free thyroxine (FT₄) (0.70 ≤ FT₄ ≤ 1.85 ng/dL), actigraphy measurements, and were not using thyroid-related medications. Three categories of thyroid function were defined: subclinical hyperthyroid (thyroid-stimulating hormone [TSH] < 0.55 mIU/L), euthyroid (TSH, 0.55 to 4.78 mIU/L), and subclinical hypothyroid (TSH > 4.78 mIU/L). Objective (total hours of nighttime sleep [TST], sleep efficiency [SE], wake after sleep onset [WASO], sleep latency [SL], number of long wake episodes [LWEP]) and subjective (TST, Pittsburgh Sleep Quality Index score, Epworth Sleepiness Scale score) sleep quality parameters were measured. The association between TSH and sleep quality was examined using linear regression (continuous sleep outcomes) and log-binomial regression (categorical sleep outcomes).ResultsAmong the 682 men examined, 15 had subclinical hyperthyroidism and 38 had subclinical hypothyroidism. There was no difference in sleep quality between subclinical hypothyroid and euthyroid men. Compared to euthyroid men, subclinical hyperthyroid men had lower mean actigraphy TST (adjusted mean difference [95% confidence interval (CI)], − 27.4 [− 63.7 to 8.9] minutes), lower mean SE (− 4.5% [− 10.3% to 1.3%]), and higher mean WASO (13.5 [− 8.0 to 35.0] minutes]), whereas 41% had increased risk of actigraphy-measured TST < 6 hours (relative risk [RR], 1.41; 95% CI, 0.83 to 2.39), and 83% had increased risk of SL ≥ 60 minutes (RR, 1.83; 95% CI, 0.65 to 5.14) (all P > .05).ConclusionNeither subclinical hypothyroidism nor hyperthyroidism is significantly associated with decreased sleep quality. (Endocr Pract. 2014;20:576-586)     

Thyroid-stimulating Hormone Levels Are Inversely Associated With Serum Total Bile Acid Levels: a Cross-Sectional Study

Objective: Bile acids (BAs) synthesized from cholesterol play a critical role in eliminating excess cholesterol to maintain cholesterol homeostasis. BAs are also signaling molecules that are involved in the regulation of lipid, glucose, and energy metabolism. Thyroid-stimulating hormone (TSH) has been found to decrease liver BA synthesis via a sterol regulatory element-binding protein 2/hepatocyte nuclear factor 4 alpha/cholesterol 7α-hydroxylase (SREBP-2/HNF-4α/CYP7A1) pathway in vivo and in vitro. However, the relationship between serum TSH and total BA levels in humans is still unclear.Methods: This was a single-center cross-sectional study of 339 subclinical hypothyroidism (SCH) patients and an equal number of controls matched by age and sex from 11,000 subjects.Results: Serum total BA levels significantly decreased (3.11 ± 2.05 vs. 5.87 ± 2.39, P<.01), while total cholesterol (TC) levels increased (5.02 ± 0.65 vs. 4.88 ± 0.63, P<.01) in subclinical hypothyroidism (SCH) patients compared to control subjects. Serum TSH and BA levels were significantly and negatively correlated in subclinical hypothyroid patients who were also hypercholesterolemic (r_s = -0.189, P = .004). Each 1 μIU/mL increase in TSH level was associated with a decrease in log-transformed values of total BAs (logTBAs) by 0.182 after controlling for confounding factors relevant to BA metabolism. The relationship between TSH and serum total BAs was more significant in subjects younger than 65 years.Conclusion: Our results suggested that TSH is correlated with the total BA level in SCH patients independent of thyroid hormone, which suggests a potential physiological role of TSH and the importance of maintaining normal range TSH in SCH patients.Abbreviations:BA = bile acidCYP7A1 = cholesterol 7α-hydroxylaseFBG = fasting blood glucoseHDL-C = highdensity lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterollogTBAs = log-transformed values of total BAsSCH = subclinical hypothyroidismTC = total cholesterolTG = triglycerideTH = thyroid hormoneTSH = thyroid-stimulating hormone     

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     

Vitamin D-Binding Protein in Healthy Pre- and Postmenopausal Women: Relationship with Estradiol Concentrations

Objective: To examine the relationship between endogenous serum estradiol and vitamin D–binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women.Methods: In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels.Results: Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in prethan postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05).Conclusion: Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration.Abbreviations: 25OHD = 25-hydroxyvitamin D BMI = body mass index CV = coefficient of variation DBP = vitamin D–binding protein PTH = parathyroid hormone SHBG = sex hormone–binding globulin     

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     

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     

Cardiac Structural and Functional Abnormalities in Females with Untreated Hypopituitarism due to Sheehan Syndrome: Response to Hormone Replacement Therapy

Objective: Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment.Methods: Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state.Results: Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state.Conclusion: Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism.Abbreviations:ACTH = adrenocorticotrophic hormoneBMI = body mass indexDT = deceleration timeEDV = end-diastolic volumeEF = ejection fractionFS = fractional shorteningGH = growth hormoneIGF-1 = insulin growth factor-1ITT = insulin tolerance testIVSd = interventricular septal diameterLH = luteinizing hormoneLV = left ventricularLVEDD = LV end diastolic dimensionLVEDV = LV end diastolic volumeLVM = LV massMRI = magnetic resonance imagingMVP = mitral value prolapsePPH = postpartum hemorrhagePWd = posterior wall diameterSS = Sheehan syndromeSV = stroke volumeT3 = triiodothyronineT4 = thyroxineTSH = thyroid-stimulating hormone     

The Association of Decreased Serum Gdnf Level with Hyperglycemia and Depression in Type 2 Diabetes Mellitus

Objective: Comorbidity of diabetes and depression is a critical problem. Decreased glial-derived neurotrophic factor (GDNF) has been demonstrated in depression, but no evidence of a relationship between GDNF and diabetes has been shown. The present studies were designed to investigate the relationship between GDNF and metabolism.Methods: In Study 1, we performed a case-control study in which subjects with type 2 diabetes mellitus (T2DM), prediabetes (p-DM), and normal glucose tolerance (NGT) were included. In Study 2, we performed a cross-sectional study in 296 patients having pre-existing diabetes in whom the levels of serum GDNF, blood glucose, blood lipids, blood pressure, body mass index, scores from the Patient Health Questionnaire (PHQ-9), the EuroQol-5 scale, and the diabetes distress scale were measured, as well as single-nucleotide polymorphisms of GDNF including rs884344, rs3812047, and rs2075680.Results: In Study 1, serum GDNF concentration was significantly lower in the T2DM group than in the NGT group (NGT: 11.706 ± 3.918 pg/mL; p-DM: 10.736 ± 3.722 pg/mL; type 2 diabetes mellitus &lsqb;T2DM group]: 9.884 ± 2.804 pg/mL, P = .008). In Study 2, significantly decreased serum GDNF levels were observed in subjects with poor glycemic control or depression (glycated hemoglobin &lsqb;HbA1c] <7.0% without depression: 11.524 ± 2.903 pg/mL; HbA1c ≥7.0% without depression: 10.625 ± 2.577 pg/mL; HbA1c <7.0% with depression: 10.355 ± 2.432 pg/mL; HbA1c ≥7.0% with depression: 8.824 ± 2.102 pg/mL, P = .008). Double-factor variance analysis showed that glycemic control and depression were independent factors for the GDNF level. Moreover, the serum GDNF level was significantly inversely associated with the fasting plasma glucose, 2 hours postprandial plasma glucose, HbA1c, and PHQ-9 score.Conclusion: Glycemic dysregulation was an independent factor for the GDNF level. These findings suggest that GDNF level might be involved in the pathophysiology of T2DM and depression through various pathways.Abbreviations: BP = blood pressure; CHO = cholesterol; DDS = diabetes distress scale; DM = diabetes mellitus; EQ-5D = the health-related dimensions of the EuroQol-5 scale; FPG = fasting plasma glucose; GDNF = glial-derived neurotrophic factor; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NGT = normal glucose tolerance; PHQ-9 = Patient Health Questionnaire; p-DM = prediabetes; PPG = postprandial plasma glucose; SNP = single-nucleotide polymorphism; T2DM = type 2 diabetes mellitus; TG = triglyceride     

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     

Serum Levels of Carcinoembryonic Antigen in Patients with Type 2 Diabetes

Objective: To investigate whether serum carcinoembryonic antigen (CEA) levels are associated with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c).Methods: A comparative, cross-sectional, observational study was conducted at Jordan University Hospital, Amman, Jordan, on 282 adult subjects from March 2012 to June 2015. Subjects were classified into 2 groups: T2DM subjects (n = 168) and a healthy comparison group (n = 114). Subjects with any condition known to be associated with elevated CEA levels were excluded. HbA1c and serum CEA levels were measured, and body mass index (BMI) was determined.Results: Subjects with T2DM had significantly higher mean serum CEA than controls (2.4 ± 1.5 vs. 1.5 ± 1.2 ng/mL, P<.0001). Sex did not correlate with CEA levels, while age (Spearman's rho [ρ] = 0.18, P =.002) and HbA1c (ρ = 0.56, P<.0001) did; however, age no longer correlated after correcting for diabetic status. HbA1c was the only variable shown to correlate with CEA in a stepwise linear regression (r = 0.37, P<.001).Conclusion: We observed a statistically significant association between elevated CEA and T2DM, despite average CEA values for both groups being within the reference range. In addition, serum CEA levels correlated positively with HbA1c values.Abbreviations:ADA = American Diabetes AssociationBMI = body mass indexCA 19-9 = carbohydrate antigen 19-9CEA = carcinoembryonic antigenCRP = C-reactive proteinDM = diabetes mellitusHbA1c = glycated hemoglobinJUH = Jordan University HospitalT2DM = type 2 diabetes mellitusρ = Spearman's correlation coefficient     

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     

Evaluation of Treatment of Central Hypothyroidism Versus Primary Hypothyroidism in Relation to Levothyroxine Replacement Dose

Objective: The aim of this study was to evaluate levothyroxine (LT4) replacement daily doses in patients with central hypothyroidism (CeH) and compare them with those adequate for patients with primary hypothyroidism (P-HYPO).Methods: We included 53 patients with CeH and 57 with P-HYPO, matched by sex, age, weight, and body mass index, in the period of 1 year. At the time of inclusion, all presented a stable and adequate dose of LT4 for at least 3 months, considering as adequate the dose associated with normal thyroid-stimulating hormone (TSH) levels and free thyroxine (T4) in P-HYPO patients, and free T4 levels in CeH patients.Results: The absolute daily dose of LT4 differed significantly between the two groups, 103.0 ± 27.1 μg (CeH) and 89.3 ± 32.0 μg (P-HYPO) (P = .017), even after adjustment for age, gender, and free T4 (P = .04). The LT4 dose adjusted to weight was also higher after adjustment for age, gender and free T4 (P = .04), with an average of 1.3 ± 0.4 μg/kg (CeH) and 1.2 ± 0.4 μg/kg (P-HYPO). Sheehan syndrome patients had a lower absolute daily dose of LT4 (P = .001), and patients who underwent pituitary radiotherapy required higher doses (P = .008). There was no difference in the daily dose of LT4 according to other pituitary hormone deficiencies.Conclusion: The results reinforce the relevance of a careful individualization of LT4 replacement in CeH management and the need for new markers for proper LT4 replacement therapy in such cases.Abbreviations: BMI = body mass index; CeH = central hypothyroidism; GH = growth hormone; LT4 = levothyroxine; P-HYPO = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Deterioraron of Ovarian Function After Total Abdominal Hysterectomy with Preservaron of Ovaries

Objective: To evaluate ovarian function after total abdominal hysterectomy in premenopausal women.Methods: In the present cross-sectional study, we enrolled 52 healthy female subjects having normal menstrual cycle as controls and 37 female patients (age <45 years) who had undergone total abdominal hysterectomy (TAH) with preservation of at least one ovary for the evaluation of ovarian function. Serum antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) were measured by enzyme-linked immunosorbent assay in both groups. Transvaginal Doppler ultrasonography was done to measure ovarian stromal blood flow indices (resistive index [RI] and pulsatility index [PI]). The means obtained from different sample groups were compared using the nonparametric Mann-Whitney U test, and correlations between two variables were evaluated using the Spearman nonparametric correlation test. A value of P<.05 was considered statistically significant.Results: Mean postoperative duration of patients who had undergone hysterectomy was 2.5 years. Mean serum AMH level was 7.68 ± 6.70 ng/mL in the cases, significantly lower than the level in controls (10.98 ± 7.83 ng/mL) (P = .016). Serum FSH level in controls was 12.01 ± 6.27 μIU/mL, which was significantly higher in the cases (20.27 ± 12.91 μIU/mL) (P = .001). An inverse correlation between serum AMH and FSH was observed (P = .0006; r = -0.4583). However, the ovary RI and PI values in both groups were similar.Conclusion: TAH affects ovarian function, despite normal ovarian blood supply.Abbreviations:AMH = antimüllerian hormoneFSH = follicle-stimulating hormoneRI = resistive indexPI = pulsatility indexTAH = total abdominal hysterectomy