Maternal Thyroid-Stimulating Hormone Level in the First Trimester and Sex Ratio at Birth

Objective: Few studies have explored the influence of thyroid status on sex ratio at birth, and conclusions are inconsistent. The aim of this study was to determine if there is an association between serum thyroid-stimulating hormone (TSH) level in first trimester and sex ratio at birth.Methods: The study was a retrospective cohort study performed at a tertiary care center. From March 2014 to February 2017, a total of 4,822 women who had thyroid function testing during the first trimester were included. Study population was divided into five groups according to quintile of TSH level (≤0.60 mIU/L; 0.61 to 1.02 mIU/L; 1.03 to 1.44 mIU/L; 1.45 to 2.13 mIU/L; and ≥2.14 mIU/L). Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of the percentage of male infants across the quintiles, with the lowest quintile as the reference category.Results: Median level of TSH was 1.27 mIU/L in women who delivered a boy, which was significantly higher than that in women who delivered a girl (1.15 mIU/L). After adjusting for age, gravidity, and parity, multivariate logistic analysis found that women in quintiles 3, 4, and 5 all showed significantly higher ORs for delivering a boy than those in quintile 1. In addition, after adjusting for age, gravidity, and parity, serum TSH was significantly associated with likelihood of having a boy (OR, 1.08; 95% CI, 1.03 to 1.13).Conclusion: Maternal TSH level in the first trimester is positively associated with the probability of delivering a male newborn.Abbreviations: CI = confidence interval; FT3 = free triiodothyronine; FT4 = free thyroxine; OR = odd ratio; SRB = sex ratio at birth; TBG = thyroxin-binding globulin; TSH = thyroid-stimulating hormone     

Case Finding for Hypothyroidism Should Include Type 2 Diabetes and Metabolic Syndrome Patients: A Latin American Thyroid Society (LATS) Position Statement

Objective: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients.Methods: A search was made in PubMed using the following terms: “hypothyroidism” AND “diabetes” OR “metabolic syndrome.” The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected.Results: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60).Conclusion: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients.Abbreviations: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

The Impact of Age in the Management of Hypothyroidism: Results of a Nationwide Survey

Objective: Evidence exists that thyroid-stimulating hormone (TSH) increases with age and lowering the TSH goal in older patients on thyroid hormone may cause over-treatment. Risks of overtreatment include cardiac and skeletal events. We assessed practice patterns regarding TSH goals and explored factors influencing physicians' decision making when managing hypothyroidism.Methods: Members of the American College of Physicians, the American Academy of Family Practice, and the Endocrine Society were surveyed to determine goal TSH when treating hypothyroidism.Results: Fifty-three percent of physicians reported factoring patient age into their decision making when managing hypothyroidism. Patient age was prioritized third (53%), following patient symptoms (69.2%) and cardiac arrhythmias (65.7%). In multivariable analysis, endocrinologists (P = .002), internists (P = .049), physicians in academic settings (P = .003), and high-volume physicians (P = .021) were more likely to consider patient age when determining goal TSH. When presented with scenarios differing in patient gender and age, 90% of physicians targeted a TSH ≤3.0 mIU/L in 30-year-old patients. Fifty-three percent of respondents targeted a TSH ≤3.0 mIU/L in octogenarians, but 90% targeted a TSH >1.5 mIU/L in this group. Regardless of gender, physician-reported TSH goal ranges (0.1 to 0.5, 0.6 to 1.5, 1.6 to 3.0, and 3.1 to 5.0 mIU/L) increased in a direct relationship to patient age (P<.001).Conclusion: Just over half of physicians consider patient age when determining TSH goal. When presented with scenarios differing in patient age and gender, physicians targeted a higher TSH goal in octogenarians. This may indicate an attempt to avoid overtreatment in this group. Consensus is needed among physicians regarding the role of patient age in hypothyroidism management.Abbreviations:TSH = thyroid-stimulating hormone     

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     

Baseline TSH Level is Associated with Risk of Anti–PD-1–Induced Thyroid Dysfunction

Objective: To characterize anti–programmed cell death 1 (PD-1)–induced thyroid immune-related adverse events (irAEs) in metastatic melanoma patients treated at our institution and to identify risk factors associated with their development.Methods: We reviewed the files of 154 patients with metastatic melanoma treated with PD-1 inhibitors at a single institution from November 1, 2011, to February 28, 2017. The association of thyroid irAEs within 120 days posttreatment initiation with age, gender, melanoma characteristics, treatment protocol, and baseline thyroid-stimulating hormone (TSH) was examined.Results: Overall, 42.4% developed thyroid dysfunction following treatment, including 20.2% (20/99) subclinical thyroid dysfunction, 13.1% (13/99) overt hypothyroidism, and 9.1% (9/99) overt hyperthyroidism. Of those that developed overt hyperthyroidism, 8 progressed to overt hypothyroidism, consistent with thyroiditis. Age, gender, melanoma characteristics, or treatment protocol did not modify the risk of developing thyroid irAEs. Higher baseline TSH was observed in patients who developed overt hypothyroidism versus hyperthyroidism versus those who remained euthyroid (P = .05). A pretreatment TSH >2.19 mIU/mL was associated with an increased risk of overt thyroid dysfunction (odds ratio, 3.46; 95% confidence interval, 1.2 to 9.8).Conclusion: Thyroid dysfunction following treatment with PD-1 inhibitors is common, and patients with a higher baseline TSH appear to be at increased risk. Such patients may benefit from closer monitoring of their thyroid function following initiation of anti PD-1 agents.Abbreviations: CTLA-4 = cytotoxic T-lymphocyte antigen 4; FT3 = free triiodothyronine; FT4 = free thyroxine; irAE = immune-related adverse event; PD-1 = programmed cell death 1; TFT = thyroid function test; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone     

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     

Neonatal thyroid-stimulating hormone screening as an indirect method for the assessment of iodine deficiency in Estonia

According to neonatal thyroid screening the incidence of congenital hypothyroidism in Estonia is 1:2,860. Transient hyperthyrotropinemia with a raised thyroid-stimulating hormone level of 5 microU/ml occurred in 17.7% of infants and was not associated with low birth weight, small birth length, low gestational age or congenital anomalies. Based on WHO criteria (WHO/UNICEF, 1994) it corresponds to mild iodine deficiency in Estonia (3% or less is in iodine-sufficient areas). This is in agreement with the previously reported median urinary iodine content of 65 microg/l in children. The frequency of infants with TSH >5 microU/ml was 16.4, 21 and 17. 2% in three regions (north, central and south) of Estonia, respectively, indicating mild to moderate iodine deficiency. These findings show the possibility of using the results of newborn screening for congenital hypothyroidism to assess the severity of iodine deficiency in Estonia. The introduction of universal iodine prophylaxis is recommended.     

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     

Lack of An Association between BMI and TSH in Treated Hypothyroid Patients and Euthyroid Controls

Objective: The standard treatment for primary hypothyroidism is replacement with levothyroxine to achieve a thyroid-stimulating hormone (TSH) level within the normal range, (0.45–4.5 mIU/L), which is known to prevent complications including weight gain. While the normal TSH range includes the 95% confidence intervals, it is not known if there is an association between weight and TSH within this interval in treated hypothyroid patients.Methods: We conducted a retrospective analysis of patients treated within the Cooper Health System from January 1 to August 31, 2014. A sample of 245 treated hypothyroid patients and 162 euthyroid controls were studied. Data collected included age, sex, race/ethnicity, height, weight, levothyroxine dose, and diabetes and smoking history.Results: Hypothyroid and control groups were similar in height, weight, body mass index (BMI), and the number of patients with diabetes. There were more females, Caucasians, and nonsmokers in the hypothyroid group. The average TSH was slightly higher in the treated hypothyroid patients versus nonhypothyroid controls (median 1.87 vs. 1.55, P<.01). There was no significant relationship between TSH and BMI in the treated hypothyroid patients or the euthyroid controls.Conclusion: Since no significant relationship was found between BMI and TSH in treated hypothyroidism, there may be no weight reduction benefit gained by adjusting TSH to the lower end of normal range. Patients should be counseled that properly treated hypothyroidism is unlikely to contribute to weight gain. Other treatments such as nutrition and exercise counseling should be offered instead.Abbreviations:BMI = body mass indexTSH = thyroid stimulating hormone     

Hyperthyroidism and Hyperprolactinemia: Is There any Association?

Objective: To compare the serum prolactin level in hyperthyroid and normal control females. Hyperthyroidism is a common disease. Although a direct association has been demonstrated between hypothyroidism and increased prolactin levels, this association has not been established for hyperthyroidism.Methods: Cross-sectional study in cases and control groups. Control subjects were chosen from those participating in the Kerman Coronary Artery Disease Risk Factors study. To select the cases, all women referred to the laboratories of Kerman with a thyroid-stimulating hormone (TSH) level ≤0.5 mIU/L who met the inclusion criteria were entered in the study. A total of 231 women aged 15 to 50 years were enrolled. The case group included 71 hyperthyroid women, and the control group included 160 women with normal thyroid function matched by age.Results: The mean (SD) serum level of prolactin was 16.56 (0.97) ng/mL (95% confidence interval [CI], 15.41 ng/mL to 15.71 ng/mL) in the controls and 23.07 (1.49) ng/mL (95% CI, 22.7 ng/mL to 23.4 ng/mL) in the case subjects. Hyperprolactinemia was more common in the hyperthyroid group (16.5 [0.97] ng/mL versus 23.07 [1.49] ng/mL; P<.001). The prolactin level decreased with age. Hyperthyroidism and estradiol increased the prolactin level. After adjusting for age and estradiol, hyperthyroidism increased the serum prolactin level (P<.001).Conclusion: The results of this study revealed that hyperprolactinemia is more frequent in hyperthyroid females. Serum prolactin level can be increased in hyperthyroidism.Abbreviations:PRL = prolactinT4 = thyroxineTRH = thyrotropin-releasing hormoneTSH = thyroid-stimulating hormone     

Congenital anomalies associated with congenital hypothyroidism

The French national neonatal screening program for congenital hypothyroidism (CH) was initiated in 1978. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with congenital hypothyroidism (CH) and to compare it with the Northeastern France Birth Defect Monitoring System data from 1979 to 1996. Among 129 CH infants on whom adequate data were available, 20 infants (15.5%) had associated congenital anomalies. Eight out of 76 infants with persistent CH had ETAs (10.5%) whereas 12 out of 53 children with transient hypothyroidism had ETAs (22.6%, p < 0.05). Some additional anomalies were considerably more common than in the general population. Nine infants had congenital cardiac anomalies (6.9%). This rises the question if teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETAs.     

Italian Association of Clinical Endocrinologists Statement–Replacement Therapy for Primary Hypothyroidism: A Brief Guide for Clinical Practice

Objective: Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled.Methods: The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed.Results: LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy.Conclusion: LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being.Abbreviations:AACE = American Association of Clinical EndocrinologistsFT3 = free triiodothyronineFT4 = free thyroxineLT3 = levotriiodothyronineLT4 = levothyroxineMeSH = medicine medical subject headingsQoL = quality of lifeTSH = thyroid-stimulating hormone     

No Longterm Severe Thyroid Dysfunction Seen In Patients With Preexisting Reduced Serum Tt3 Concentrations After A Single Large Dose Of Iodinated Contrast

Objective: After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease.Methods: This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention.Results: There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative (P<.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative (P>.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative (P<.001).Conclusion: The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery.Abbreviations: FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization     

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     

An Italian Survey of Compliance With Major Guidelines for L-Thyroxine of Primary Hypothyroidism

Objective: The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment.Methods: This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology.Results: The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers.Conclusion: Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography     

Risk factors for congenital hypothyroidism: an investigation of infant's birth weight, ethnicity, and gender in California, 1990-1998

BACKGROUND: Approximately 85% of primary congenital hypothyroidism (CH) is sporadic and due to malformations of the thyroid gland. Past studies have reported an increased birth weight among infants with CH. We have attempted to replicate and expand these observations, examining the association between different birth weight categories and CH stratified by infant's sex. We have also examined the prevalence of CH by mother's age and infant's ethnicity, gender, and year of birth. METHODS: A cross-sectional study was conducted on 5, 049,185 infants screened by the statewide California Newborn Screening Program between 1990 and 1998, an estimated 98.6% of all newborns in the state. Dried blood spots from a heel stick were assayed for thyroxine (T4), and presumptive positives had follow-up assays of thyroid-stimulating hormone (TSH) to determine definite positives. RESULTS: A total of 1,806 cases of CH were identified. The following findings are unlikely to be due to chance. Compared with infants with birth weights of 3,000-3,499 g, infants weighing <2,000 g and those weighing >/=4,500 g had a twofold or greater increase in the prevalence of CH. This was not explained as a result of confounding by the infant's ethnicity or gender. Compared with whites, elevated prevalence rates were found in most ethnic groups, which include the following: Hispanics, Chinese, Vietnamese, Asian Indians, Filipinos, Middle Easterners, and Hawaiians. As reported previously, black infants had about one-third the prevalence rate of whites. We also observed the frequently described female preponderance of CH. The female excess was maintained at all birth weights, however it varied by infant's ethnicity. Trends in the prevalence of CH were not associated with mother's age or with the time interval between 1990 and 1998. CONCLUSIONS: We observed an increased risk of CH in both low-birth-weight (<2,000-g) and macrosomic (>/=4,500-g) infants. This U-shaped association has not been described in past studies. We have also expanded the previously described ethnic differences in CH risk to include ethnic groups not previously studied. The unique pattern of CH occurrence suggests that further studies to define modifiable risk factors may be useful.     

The Association Between Body Mass Index and Subclinical Thyroid Dysfunction in Different Sexes of Chinese

Objective: To study subclinical thyroid dysfunction (SCTD)—subclinical hyperthyroidism and subclinical hypothyroidism—in Chinese patients in relation to body mass index (BMI) and to determine whether a difference between sexes exists.Methods: This cross-sectional study recruited 13,503 healthy participants (8,345 male, 5,158 female) who participated in a health examination. Clinical data, including anthropometric measurements and serum parameters, were collected. The association between SCTD and the BMI of each sex was analyzed separately by stratifying the data by SCTD type and regarding BMI as a categorical or as a continuous variable in different models. The odds ratio of SCTD was calculated from binary logistic regression models.Results: The prevalence of both subclinical hyperthyroidism and subclinical hypothyroidism was significantly lower in males compared to females. For subclinical hypothyroidism, we found no significant association with BMI in females. In males, there was a significant negative relationship between BMI and subclinical hypothyroidism. For subclinical hyperthyroidism, we did not find any significant relationship with BMI in either sex after stratifying the data and treating BMI as a categorical or as a continuous variable.Conclusion: For subclinical hyperthyroidism, no significant effect was found in either sex. For subclinical hypothyroidism, high BMI was associated with lower rates of subclinical hypothyroidism in males, and no significant correlation was found in females. The mechanism of this sex-specific association between BMI and SCTD needs more verification.Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; BUN = blood urea nitrogen; CI = confidence interval; Cr = creatinine; DBP = diastolic blood pressure; FG = fasting glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HDL = high-density lipoprotein; LDL = low-density lipoprotein; OR = odds ratio; SBP = systolic blood pressure; SCTD = subclinical thyroid dysfunction; TBIL = total bilirubin; TC = total cholesterol; TG = triglyceride; TSH = thyroid-stimulating hormone; UA = uric acid; WBC = white blood cell; WC = waist circumference     

Multivariate analysis on factors affecting suppression of thyroid-stimulating hormone in treated congenital hypothyroidism

AIMS: To determine the factors which influence the suppression of thyroid-stimulating hormone (TSH) in infants with congenital hypothyroidism (CH) following treatment. METHODS: We examined retrospectively the patterns of thyroid function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH from screening. Patients were classified into 3 groups: athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH suppression was defined as plasma TSH concentration <6 mU/l. The factors affecting the suppression of TSH at 6 months and 1 year of age which were evaluated were: initial confirmatory plasma TSH, initial plasma thyroxine (T4), mean age of starting treatment with L-T4, dose of L-T4 at diagnosis, 6 weeks, 3 months and 6 months, and aetiology of the congenital hypothyroidism. Variables were then entered in a stepwise logistic regression model for TSH suppression at 6 months and 1 year of age. RESULTS: All infants had radionuclide scans prior to treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23). 58% of patients had persistently raised TSH at 6 months of age while 31% of patients had a persistently raised TSH at 1 year of age. There was a significant delay in the normalisation of plasma TSH in athyreosis and ectopia groups compared with dyshormonogenesis. Multiple regression analysis for TSH suppression at 6 months of age found plasma T4 levels and aetiology of CH as independent factors affecting the timing of TSH suppression. Aetiology of CH was the only independent factor affecting TSH suppression at 1 year of age. CONCLUSION: At 6 months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were independent factors affecting timing of TSH suppression. However, by 1 year of age, the aetiology of CH was the only independent factor affecting suppression of TSH.     

Hyperkalemia Develops in Some Thyroidectomized Patients Undergoing Thyroid Hormone Withdrawal in Preparation for Radioactive Iodine Ablation for Thyroid Carcinoma

Objective: Hyponatremia is observed in hypothyroidism, but it is not known if hypo- or hyperkalemia is associated with hypothyroidism. To study these questions, we determined serum potassium (K⁺) levels in thyroidectomized patients undergoing levothyroxine withdrawal before radioactive iodine (RAI) therapy for thyroid carcinoma.Methods: We retrospectively studied the records of 108 patients who had undergone total thyroidectomy for thyroid carcinoma followed by levothyroxine withdrawal and then ablation with RAI at Nagasaki University Hospital from 2009–2013. Blood samples were analyzed for serum K⁺ concentrations when patients were euthyroid just before levothyroxine withdrawal and hypothyroid 21 days after levothyroxine withdrawal. We determined the proportion of patients who developed hyperkalemia (K⁺ ≥5 mEq/L) and hypokalemia (K⁺ ≤3.5 mEq/L).Results: Five (4.6%) patients developed hyperkalemia and 2 (1.9%) patients developed hypokalemia after levothyroxine withdrawal. The mean serum K⁺ level after levothyroxine withdrawal was significantly higher than before levothyroxine withdrawal (4.23 ± 0.50 mEq/L vs. 4.09 ± 0.34 mEq/L; P<.001). After levothyroxine withdrawal, serum K⁺ values were significantly correlated with age, serum sodium and creatinine levels, and the estimated glomerular filtration rate but not with serum free thyroxine or thyroid-stimulating hormone concentrations. The finding of an elevated serum K⁺ of >0.5 mEq/L after levothyroxine withdrawal was more prevalent with age >60 years (odds ratio [OR], 4.66; P = .026) and with the use of angiotensin-II receptor blockers or angiotensin-converting enzyme inhibitors (OR, 3.53; P = .033) in a multivariate analysis.Conclusion: Hyperkalemia develops in a small percentage of hypothyroid patients after thyroid hormone withdrawal, especially in patients over 60 years of age who are using antihypertensive agents that inhibit the reninangiotensin- aldosterone system.Abbreviations: ACE-I = angiotensin-converting enzyme inhibitor ARB = angiotensin-II receptor blocker Cr = creatinine eGFR = estimated glomerular filtration rate Eu-K⁺ = serum level of K⁺ in the euthyroid state Hypo-K⁺ = serum level of K⁺ in the hypothyroid state K⁺ = potassium Na⁺ = sodium ?K⁺ = Hypo-K⁺ value minus Eu-K⁺ value RAI = radioactive iodine TSH = thyroid-stimulating hormone