Median TSH Research Articles

ENDOCRINE TUMOURS: Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases.

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20-7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure.

Predictors of Improvement in Quality of Life When Treating Hypothyroidism.

Background Primary hypothyroidism is characterized by reduced quality of life (QoL). Although thyrotropin (TSH) is utilized as the primary indicator of thyroid disease and treatment adequacy, no simple correlation between QoL and TSH has been shown. This study aimed to investigate changes in clinically relevant predictors during initiation of levothyroxine (L-T4) therapy and their ability to predict improvement in QoL. Method Quality of life was measured in patients with newly diagnosed hypothyroidism, during the initial 12 months of L-T4 therapy, by the thyroid-related patient-reported outcome questionnaire, ThyPRO-39. The main outcome measures were the Composite QoL scale and the Tiredness and Emotional Susceptibility subscales (0–100, higher scores worse). Clinical variables (resting energy expenditure (REE), body composition, thyroid function, L-T4 dose, and cognitive function tests) were evaluated as predictors of improvement in QoL by univariate and multiple regression analysis. Results Thirty-seven hypothyroid patients with a baseline median TSH of 30 mU/l and a median QoL score of 29 were included. After twelve months of L-T4 treatment, the ThyPRO-39 QoL score had significantly improved to a median score of 14, while REE per kg fat-free mass (FFM) increased significantly from a mean of 26.5 to 28.7 kcal/day/kg (p < 0.001). Change in ThyPRO-39 was not associated with a change in REE/FFM (unstandardized coefficient (USC): 0.09 with confidence interval (CI): −1.93 to 2.11, p=0.93) but was positively predicted by baseline body mass index (BMI) (USC: 1.54 with CI: 0.59 to 2.49, (p=0.002), without association with weight loss (USC: 0.33 with CI: −1.21 to 1.27, p=0.96). Conclusion Improvement in QoL as measured by ThyPRO-39 after initiation of L-T4 therapy for hypothyroidism was not associated with changes in REE. High baseline BMI, but not weight loss during therapy, was associated with improvement in QoL. This trail is registered with www.Clinicaltrials.gov (registration no. https://clinicaltrials.gov/ct2/show/NCT02891668).

Endocrine and metabolic aspects of narcolepsy type 1 in children.

To study whether the onset of narcolepsy type 1 (NT1) in children and adolescents affects BMI, specific metabolic risk factors, the onset of puberty, longitudinal growth or other endocrine functions. A population-based study, comprising 34 patients, was performed with a clinical evaluation, an assessment of puberty and growth, actigraphy and blood samples at fasting, from patients and controls, to evaluate pituitary function, growth factors, thyroid gland, gonads, insulin sensitivity, appetite regulation and blood lipids. In the post-H1N1 vaccination (PHV) narcolepsy group, the median BMI SDS was higher 6-12 months after the onset of narcolepsy (p<0.01), but it was no different 10 years after the onset of narcolepsy (p=0.91), compared with 12-24 months before the onset of narcolepsy. There was a correlation between an increase in BMI and a decrease in total energy expenditure (R=-0.74). In the nPHV group, weight and BMI changes were smaller and no significant changes were recorded. Early puberty was more common in patients with puberty onset after narcolepsy onset (n=16/19) compared with patients with puberty onset before narcolepsy onset (n=3/11, p=0.02). There was no significant change in height SDS during the studied period. Although they were within normal ranges, both median HDL and median TSH levels were significantly lower in NT1 patients, compared with controls. We found a high prevalence of large BMI gain in the period immediately after the onset of narcolepsy, which had almost normalized at the long-term follow-up. The onset of narcolepsy led to early puberty in both sexes. Linear growth was not affected. We did not find any strong indicators of metabolic disturbances.

Intravenous Thyroxine Administration in Hospitalized Patients, a Common but Unreported Practice: a Single Institution Recent Experience

Background: Intravenous levothyroxine (IVT4) is FDA-approved for the treatment of myxedema coma (ME). ATA guidelines also acknowledge other rare situations, mostly such where oral/enteral access is compromised for prolonged periods, in which IVT4 may be appropriate. We noticed that at our hospital, IVT4 is administered more frequently than expected. Aim of study: To assess the extent of IVT4 administration, the indications for such a treatment, and its outcome at a tertiary facility. Study design and Methods: A retrospective study of IVT4 administered to adult inpatients at Tel Aviv-Sourasky Medical Center between January 2017 and July 2020. A list of dispensed T4 vials during the period of interest was generated from the hospital pharmacy computerized database. Patients’ charts were searched for relevant clinical and laboratory data. Results: 107 patients (62 W/45 M), age 62.5±17.3 y (range 20-97) received IV T4, in the course of 113 hospitalizations. 94 subjects had primary hypothyroidism (PH), 10 had central hypothyroidism, while 3 subjects had no documented evidence of hypothyroidism. ME was likely in only 4 cases (3.5%). The leading stated indication for IVT4 was profound hypothyroidism in 57 instances (50.4%), jeopardized enteral route in 11 (9.7%), while no clear or justifiable indication was found in 39 cases (34.5%). An official endocrine consult backed treatment 74 times (65.5%). In subjects with PH, median serum TSH prior to treatment was 36.4 mIU/L (IQR 8-42), while free T4 was 0.4 ng/dl (IRQ 0.22-0.61, normal 0.8-1.7). In subjects with no ME, altered consciousness was present in 19%, bradycardia in 6.3% and 4.5% were hypothermic. The median initial dose of IV-T4 was 150 μg (range 20-500). Repeated administrations ranged from 1 to 29 times, with a median cumulative dose of 250 μg (IQR 150-400, range 20-3300). We could not identify adverse events directly attributable to IV-T4. Of the 113 admissions, 61 ended in patient’s recovery and discharge (54%), 22 (19.5%) in transfer to a rehab or nursing facility, while there were 30 cases of death (26.5%). Only one of the 4 patients with presumed ME died. In a logistic regression model, that also included age, gender, and ICU admission, the only variable that significantly predicted death was a need for artificial ventilation (OR:27.8, CI 3.5-189). In contrast, free T4, TSH, hospitalization length, altered consciousness, and other potential variables, were excluded from the equation. Conclusions: IVT4 administration is a common practice at our hospital. In a small minority of cases (13.2%), it is given for approved clinical conditions, while in all the others it appears to be unjustified. Reports on this practice are all but absent from the literature. Studies from other institutions are needed to determine its global extent, safety, and efficacy. Until it is proven safe and cost-effective, greater caution should be exercised before allowing it.

Early Follow-up of Atypical Thyroiditis Induced by SARS-CoV-2

Background: In Spring 2020 the severe acute respiratory syndrome coronavirus 2 pandemic disease (Covid-19) badly affected Northern Italy. We have described for the first time the occurrence of thyrotoxicosis due to atypical subacute thyroiditis in 15% of patients hospitalised for Covid-19 pneumonia, compared with only 1% among patients hospitalised in the same wards during Spring 2019, thus before the Covid-19 pandemic. The whole group of Covid-19 patients also had median serum TSH concentrations significantly lower compared with the control group. The atypical thyroiditis induced by Covid-19 is not associated with neck pain, affects more men than women and especially those severely ill, thus coexists with non-thyroidal illness syndrome. Subacute thyroiditis is classically followed by subsequent occurrence of permanent thyroid dysfunction and autoimmunity, thus we have started a systematic follow-up program of these patients. Methods: Longitudinal follow-up study of survived Covid-19 patients without previous known history of thyroid disorders and/or medications, assessing serum thyroid function and autoantibodies, C reactive protein (CRP), full blood count (FBC) and thyroid ultrasound (US) every 3 months. Patients showing baseline (at hospitalisation for Covid-19) thyroid dysfunction and/or focal hypoechoic areas suggestive for subacute thyroiditis at US performed 3 months post-infection, also underwent thyroid 99mTc or I123uptake. Results: To date, 53 patients have been included in the follow-up study. At 3 months post-infection, all of them presented with increased median (IQR) serum TSH concentrations compared with baseline: 1.3 (0.9–2.0) mIU/L versus 0.9 (0.5–1.8) mIU/L (p=0.0001). Similarly, serum concentrations of free-thyroxine, free-triiodothyronine, CRP and FBC had normalised compared with baseline. All patients had negative autoantibodies to TSH receptor; autoantibodies to thyroglobulin and to thyroid peroxidase were positive in 6/53 (11%) and 5/53 (9%) of patients, respectively. The thyroid US showed the presence of focal hypoechoic areas of thyroiditis in 16/51 (32%) patients, with thyroid uptake normal in 6/16 (37%), focally reduced in 8/16 (50%) and diffusely reduced in 2/16 (12%). Conclusions: At 3 months after Covid-19 disease all patients had a normalised thyroid function, however imaging findings suggestive for subacute thyroiditis were still present in about one third of cases. The thyroid dysfunction induced by Covid-19 seems not mediated by autoimmunity. It is important to continue to follow these patients since they might develop thyroid dysfunction during the following months.

Thyroid Gland and Male Reproductive Anomalies Among Fuel Handlers in Gampaha District, Sri Lanka

Abstract Introduction:Fuel handlers at petrol stations are continuously exposed to organic solvents from fuel and vehicle emissions. Endocrine disrupting chemicals (EDC) are present in fuel, which are harmful to endocrine organs. Thyroiditis and hypogonadism are reported among fuel handlers. Thyroid gland and male reproductive function anomalies were investigated among fuel handlers in the Gampaha district of Sri Lanka. Method: 43 were recruited from 6 fuel stations in the Gampaha district for the study and 28 age matched male workers who were not exposed to fuel in an occupational setting were recruited as controls. Thyroid gland was examined clinically and TSH, free T4, FSH, LH and Testosterone were done on all the participants. TPO antibody and a thyroid scan was done on the fuel handlers. Results: Median (IQR) age was 38 years (27-46 years). The mean TSH value was 1.62 IU/mL (1.15-2.35) vs 1.33 IU/mL (0.83-1.79) respectively in study and control populations with significantly higher levels in the study population (p=0.023). The median (IQR) TSH value above the reference range was identified in 7% of fuel handlers and all controls were within the normal range, while 16.9% of fuel handlers had a derangement in the TPO levels. On examination, only one control had a small goiter but his T4 and TSH levels were normal. On ultrasound thyroid scans, benign nodules were seen in 2 fuel handlers. TPO levels did not correlate with the TSH levels among the fuel handlers (r=-0.078, p=0.652). Inability to sustain an erection was reported by 35.5% fuel handlers which was significantly higher than controls who reported 5.6% (p=0.019). Premature ejaculation was reported by 27.9% of fuel handlers which was significantly higher than controls (p=0.023). The testosterone levels were significantly higher among fuel handlers compared to controls (p=0.048). The FSH and LH levels positively correlated with each other as expected in each subgroup and the total population (p&amp;lt;0.005). The TSH levels significantly negatively correlated with the testosterone levels among the fuel handlers. (r=- 0.338, p=.0.023). When the fuel handlers with premature ejaculation was considered the FSH, LH, Testosterone levels were not significantly different between the two groups, however the duration of employment was significantly longer among those reporting premature ejaculation. (p=0.024). Conclusion: There are thyroid and reproductive abnormalities among those exposed to fuel in an occupational setting. Disturbances to sexual functions may also be related to alteration of autonomic functions. Limiting exposure to fuel vapor will eliminate these detrimental effects and we propose self-service fuel pumps to be the best alternative to avoid occupational health hazards among fuel handlers.

Thyroid Immune-Related Adverse Events Are Associated With Improved Survival in Cancer Patients

Abstract Introduction: Thyroid immune-related adverse events (irAEs) occur frequently after immune checkpoint inhibitor (ICI) cancer therapy, but their risk factors and potential influence on survival need further investigation. Methods: We performed a retrospective single-center cohort study of adult cancer patients who received ICIs including CTLA-4, PD-1, PD-L1 inhibitors from 12/1/2012- 12/31/2019. Patients who developed thyroid irAEs after excluding surgical or ablative hypothyroidism were included. Survival analysis was performed by Kaplan-Meier curves and Cox-proportional hazards model. Results: Thyroid irAEs occurred in 145 (17.4%) of 834 ICI-treated patients (median age 64.9 y, 43.4% females) during a median follow-up of 11.6 mo. New-onset thyroid dysfunction occurred in 118 (14.2%), of which 55 presented with thyrotoxicosis (32 progressed to hypothyroidism, 22 returned to euthyroid state, 1 had Graves’ disease). Worsening of pre-existing autoimmune hypothyroidism (≥50% increase in levothyroxine dose) occurred in 27 (3.2%). Of those with new-onset thyroid dysfunction, 79 (67%) required levothyroxine eventually. Patients with thyroid irAE had similar age, sex and cancer type as compared to those without but had higher median pre-treatment TSH [2.4 vs. 1.7 mIU/L (p&amp;lt;0.0001); multivariable OR for TSH ≥2.4 mIU/L of 2 (95% CI 1.3, 3.2; p=0.004)] and higher frequency of autoimmune disease history [26.9% vs. 14.8% (p=0.0009); multivariable OR of 2 (95% CI 1.2, 3.5; p=0.013)]. Thyroid irAEs occurred after a median of 2.4 mo from ICI, most frequently with PD-1/PD-L1 inhibitor. Thyroid irAEs were associated with better median overall survival [38.8 mo (95% CI 26.6, not reached) vs. 18.9 (95% CI 14.2, 24.8); p&amp;lt;0.0001] which persisted on restricting to patients with new-onset thyroid dysfunction [40.1 mo (95% CI 26.6, not reached) vs. 18.8 (95% CI 13.6, 24.8); p&amp;lt;0.0001]. On multivariable analysis, thyroid irAEs had HR for mortality of 0.51 (95% CI 0.37, 0.71; p&amp;lt;0.0001), which persisted on restricting to new-onset thyroid dysfunction [HR 0.48 (95% CI 0.34, 0.69; p&amp;lt;0.0001)]. Conclusions: Thyroid irAEs frequently occur after PD-1/PD-L1 inhibitor therapy, presenting as hypothyroidism or thyrotoxicosis usually progressing to hypothyroidism. Higher TSH even within normal range and autoimmune disease history may be risk factors for thyroid irAE. Improved survival with thyroid irAEs suggests these could be a marker for anti-tumor activity.

Multi-center clinical characterization of patients with pediatric vitiligo: a retrospective study in Colombia

Introduction. Pediatric vitiligo is a chronic acquired condition of the skin that differs from adult vitiligo in many clinical parameters. Few descriptive studies have been carried out to determine the clinical characteristics in Latin-American patients.Aim. To describe the clinical features of pediatric patients with vitiligo who consulted dermatology referral centers in Bogota D.C., Colombia.Methods. We carried out a descriptive study of all pediatric patients with a diagnosis of vitiligo treated at three referral centers in Bogota, Colombia between 2012-2018. Site distribution of the lesions and treatment features are presented using UpSet plots.Results. Of 377 patients with a diagnosis of vitiligo and age <18, 355 remained after applying our exclusion criteria. Median age at diagnosis was slightly over 9 years, and frequency was not higher in females (49.01%). Non-segmental vitiligo was the most frequent type (n=213). Lesions were predominantly found in the face and neck (62%) and pelvis (31%). In a subset group (n=98), median TSH level was 2.58 mIU/L. A family history of the disease and atopic dermatitis were found in 10.4% and 11.8%, respectively. Tacrolimus was the most commonly used medication (83.4%). In turn, the most common treatment regimen consisted of tacrolimus and topical corticosteroids (32.15%). However, treatment regimens were mostly heterogeneous. On follow-up, 106/160 subjects reported a clinically significant improvement.Conclusion. Findings such as the age of onset, lesion location distribution and first line treatments were consistent with previous reports. Some features, like family history of atopy, differed from North American, Asian, and European populations reports.

Relationship of TSH Levels with Cardiometabolic Risk Factors in US Youth and Reference Percentiles for Thyroid Function.

Thyroid hormones play an important role in metabolic homeostasis, and higher levels have been associated with cardiometabolic risk. To examine the association of cardiometabolic risk factors with TSH levels in US youth. Cross-sectional study of youth aged 12 to 18 years without known thyroid abnormalities from 5 National Health and Nutrition Examination Survey cycles (n = 2818) representing 15.4 million US children. Subclinical hypothyroidism (SH) was defined as thyrotropin (TSH) levels of 4.5 to 10 mIU/L. Assessed cardiometabolic risk factors include abdominal obesity (waist circumference >90th percentile), hypertriglyceridemia (triglyceride ≥130 mg/dL), low high-density lipoprotein cholesterol (<40 mg/dL), elevated blood pressure (systolic and diastolic blood pressure ≥90th percentile), hyperglycemia (fasting blood glucose ≥100 mg/dL, or known diabetes), insulin resistance (homeostatic model for insulin resistance > 3.16), and elevated alanine transferase (≥ 50 for boys and ≥44 U/L for girls). Age and sex- specific percentiles for thyroid parameters were calculated. In this cohort of youth (51.3% male), 31.2% had overweight/obesity. The prevalence of SH was 2.0% (95% CI 1.2-3.1). The median TSH levels were higher in youth with overweight/obesity (P < 0.001). Adjusting for age, sex, race/ethnicity, and obesity, youth with TSH in the fourth quantile had higher odds of abdominal obesity (OR 2.53 [1.43-4.46], P = .002), insulin resistance (OR 2.82 [1.42-5.57], P = .003), and ≥2 cardiometabolic risk factors (CMRF) (OR 2.20 [1.23-3.95], P = .009). The prevalence of SH is low in US youth. The higher odds of insulin resistance and cardiometabolic risk factors in youth with TSH levels >75th percentile requires further study.

Elevated TPOAb is a Strong Predictor of Autoimmune Development in Patients of Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Case-Control Study.

ObjectiveThe aim of this study was to assess the prevalence of thyroid autoimmunity in T2DM with NAFLD, furthermore explore the relationship between elevated TPOAb titer and the severity of NAFLD.MethodsA total of 400 patients with T2DM were divided into two groups according to NAFLD. Thyroid function and other metabolic indicators were measured.ResultsThere were more TPOAb-positive patients in both groups, and the prevalence of TPOAb positive was significantly different in two groups (17% vs 6.9%, p< 0.01). FT4 was significantly lower in patients with T2DM with NAFLD (median FT4 0.89 vs 1.08, p < 0.001), while TSH was increased (median TSH 2.85 vs 2.28, p < 0.05). In patients with T2DM with NAFLD, the proportion of women in the thyroid autoimmune-positive group was significantly higher than the negative (71.1% vs 46%, p < 0.01). Similarly, thyroid autoimmune-positive T2DM and NAFLD patients had lower FT4 levels (median FT4 0.59 vs 0.92, p < 0.001), higher TSH levels (median TSH 3.65 vs 2.67, p < 0.001), and much higher TPOAb/TGAb (median TPOAb/TGAb 6.8 vs 1.46, p < 0.001). The increase of TPOAb was significantly correlated with the severity of fatty liver. HbA1c, TC, TG, TSH, TPOAb/TGAb and severity of fatty liver were risk factors of thyroid autoimmunity.ConclusionAutoimmune thyroid disease is more common in patients with T2DM complicated with NAFLD. Elevated TPOAb titer is closely related to fatty liver, suggesting that elevated TPOAb titer is a predictor of autoimmune development in T2DM with NAFLD.

Iodine Status and Thyroid Functions of Turkish and Syrian Mother-Newborn Dyads in a County of Istanbul

Background: Inappropriate iodine intake can result in thyroid disorders in mothers and newborns in addition to their adverse effects on prenatal and postnatal developmental processes. Determination of median urinary iodine concentration (MUIC) is an established tool for monitoring of iodine nutrition. Aim: The aim of this cross-sectional study was to investigate iodine status by measuring the MUIC and serum TSH and free T4 levels of Turkish and Syrian mother-newborn dyads in a county of Istanbul. Methods: In a tertiary care center, in the Turkish and Syrian, low-risk, term-pregnant mothers and their newborns, urine samples were collected from mothers and newborns within first 24 hours after birth. For the measurements of TSH and free T4, blood samples were obtained from mothers at admission to labor and delivery unit and from newborns on day 5 of neonatal life. Results: In the study population of mothers, mild iodine deficiency was more prominent with an incidence of about 18%, followed by moderate and severe forms with an incidence of about 5% and 0.5%, respectively. Turkish and Syrian mothers had similar incidence of mild, moderate, and severe iodine deficiencies. The incidence of iodine deficiency of newborns were 41%. Overall, in the Turkish and Syrian participants, there were no prominent correlations between the MUICs of mothers and newborns. Regarding serum TSH and free T4 levels, the median TSH concentration of Turkish mothers was significantly lower (p 0.05). Considering TSH values of newborns, in 40 of them, there was higher TSH values requiring attention during neonatal follow-up. They had mild and moderate but not severe form of TSH elevation. Conclusion: Despite the mandatory salt iodization and official health care support for all mothers and newborns, daily iodine supplementation during pregnancy and breastfeeding seems to be a helpful measure to prevent the adverse effects of iodine deficiency to newborns and children. Funding Statement: This study was supported by a grant of Turk Pediatri Kurumu Dernegi (the Association of Turkish Pediatrics Institution). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Association of Turkish Pediatrics Institution. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The study was approved by the Human Research Ethics Committee (Registry No. 464). All participants provided written informed consent.

Effect of Ramadan Fasting on Thyroid Hormone Levels in Patients on Levothyroxine Treatment.

To evaluate the changes in thyroid functions in Ramadan, and compare late evening and pre-seheri use of levothyroxine in patients with hypothyroidism. Cross-sectional study. Department of Endocrinology, Ankara Ataturk Education and Research Hospital and Ankara Yildirim Beyazit University, Turkey, from May to June 2018. Patients who were on levothyroxine treatment and having normal thyroid functions were recruited for the study in the last one week before Ramadan. Patients were offered to take levothyroxine at 22.30-23.00 pm before sleep or between 01:30-03:00 am at least 30 min pre-seheri. There were 53 (85.5%) female and 9 (14.5%) male patients. Basal thyrotrophin (TSH) was 2.02 μIU/mL (0.27-4.14) and insignificantly increased at the end of Ramadan [2.18 μIU/mL (0.04-19.69), p=0.167]. Free-triiodothyronine (fT3) decreased while free-thyroxine (fT4) increased (p<0.001 for both). Eighteen patients preferred to take levothyroxine in late evening and 44 preferred to take at pre-seheri. There were insignificant increases in TSH in both groups (p=0.401 and p=0.276, respectively). At the end of Ramadan, TSH increased in 39 (63.9%), decreased in 22 (36.1%), and did not change in one patient. Increase in TSH was not significant after Ramadan. While there was an insignificant increase in median TSH, about one-third of patients had lower TSH, indicating for the need to evaluate every patient individually and follow closely during Ramadan. Clinical studies with larger sample sizes will be helpful to determine the optimal time for levothyroxine use during Ramadan. Key Words: Thyroid functions, Ramadan fasting, Hypothyroidism, Levotyhroxine.

Serum thyroid stimulating hormone level for predicting utility of thyroid uptake and scan

ABSTRACT Background Thyroid uptake and scan (TUS) is a clinical tool used for differentiation of thyrotoxicosis etiologies. Although guidelines recommend ordering a TUS for evaluation of low TSH levels, no specific value is defined. This study aimed to determine a TSH cutoff at which TUSs yield a greater likelihood of successful determination of etiology to avoid unnecessary testing. Methods This was a retrospective study on 137 patients seen by an endocrinologist who underwent TUS for evaluation of low TSH (<0.4 μU/mL). A receiver operating curve analysis was performed to determine the TSH cutoff with maximal sensitivity and specificity for prediction of diagnostic utility. Results Ninety percent of TUSs (n = 123) led to a diagnosis, while 10% (n = 14) were inconclusive or normal. Diagnoses included Graves’ diseases (52%), toxic multinodular goiter (19%), thyroiditis (12%), and solitary toxic adenoma (7%). The median TSH value was 0.008 μU/mL (IQR 0.005, 0.011), and the median free T4 value was 1.7 μU/mL (IQR 1.3, 2.8). The ROC analysis produced an area under the curve of 0.86. The optimal TSH cutoff value was 0.02 μU/mL (sensitivity 80%, specificity 93%) for prediction of diagnostic yield. Conclusion This study demonstrates that TSH is a useful predictor of the utility of TUS in yielding an etiology of thyrotoxicosis. Our analysis showed that TUS had a greater likelihood of determining an etiology when TSH was ≤0.02 μU/mL. This information can help clinicians avoid unnecessary cost and patient time burden when TUS is unlikely to aid in determining the etiology of thyrotoxicosis.

Associations Between Maternal Thyroid Function in Pregnancy and Obstetric and Perinatal Outcomes

Context The effects of maternal subclinical hypothyroidism on pregnancy outcomes are not clear. Objective We aimed to assess potential associations between maternal thyrotropin (thyroid-stimulating hormone [TSH]) levels in pregnancy and obstetric and perinatal outcomes. Design Retrospective cohort study. Setting Tertiary academic medical center. Patients Women aged ≥18 years with a singleton gestation and no known thyroid disease seen for prenatal care at Boston Medical Center from January 1, 2003 through May 22, 2014, and their fetuses and infants were included. Main outcome measures Risk ratios of adverse obstetric and perinatal outcomes. Results A total of 8,413 pregnant women (mean age 29.1 years, 15% white, 60% black, 13% Hispanic) and their fetuses and infants (mean gestational age at birth 38.5 weeks, 52% male, mean birth weight 3.2 kg) were included in the analyses. The median (interquartile range) TSH level was 1.06(0.62-1.60) mIU/L, and 130 women (1.6%) had TSH > 4 mIU/L. Maternal TSH levels > 4 mIU/L were associated with increased risks of prematurity (risk ratio [RR] 2.17 [95% confidence interval 1.15-4.07] P = .016) and neonatal respiratory distress syndrome (RDS) (RR 2.83 [95% confidence interval 1.02-7.86] P = .046) compared to TSH levels ≤ 4 mIU/L. Although not statistically significant, TSH levels > 4 mIU/L were also associated with increased RRs for fetal loss, preeclampsia/eclampsia, and low birth weight. TSH levels > 4 mIU/L were not associated with preterm labor, placental abruption, cesarean section, gestational hypertension or diabetes, or neonatal intensive care unit admission. Conclusion Maternal serum TSH concentration > 4 mIU/L in pregnancy was associated with approximately 2-fold increased risks of prematurity and RDS in offspring. Elevated TSH was also associated with statistically non-significant increases in the risk of fetal loss, preeclampsia/eclampsia, and low birth weight.

HDL Cholesterol Efflux Capacity is Impaired in Severe Short-Term Hypothyroidism Despite Increased HDL Cholesterol.

Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown. To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity. Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228). University hospital setting in The Netherlands. Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma. HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation). During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P ≤ 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P < 0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P < 0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change. During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.

Levothyroxine dose adjustment in hypothyroid patients following gastric sleeve surgery

IntroductionEuthyroid patients show decreased TSH level following sleeve gastrectomy. However, studies of levothyroxine absorption after bariatric surgery reported contradictory results and data on levothyroxine dose adjustment according to weight are sparse. The aim of this study was to evaluate levothyroxine dose adjustment during weight loss following sleeve surgery. MethodThis retrospective study assessed change in levothyroxine dose in patients undergoing sleeve gastrectomy at the university hospital center of Nîmes (France) between January 2010 and March 2016. Patients were receiving standard bariatric surgery follow-up with levothyroxine therapy for hypothyroidism. ResultsFifty-two of the 271 patients who underwent sleeve gastrectomy (19.2%) were being treated with levothyroxine. Among these patients, 31 were followed up for 12 months, including 12 who were followed up for 24 months. Mean weight loss was 35±11kg at 12 months and 41.8±10.2 kg at 24 months. Daily levothyroxine dose decreased from 108 [88–144] μg/day to 94 [63–125] μg/day at 12 months and 69 [44–134] μg/day at 24 months, with positive correlation between dose and weight loss at 12 months (P=0.03). Weight-adjusted dose was 1.04 [0.81–1.24] μg/kg/day at baseline, 1.14 [0.85–1.66] μg/kg/day at 12 months, and 0.85 [0.53–2.10] μg/kg/day at 24 months, showing no correlation with weight loss. Median TSH level dropped to 1.30 [0.63–2.27] mIU/l at 12 months and 1.48 [1.08–2.42] mIU/l at 24 months. ConclusionDespite a decrease in daily levothyroxine dose correlating with weight loss at 12 months, the absence of correlation with weight-adjusted dose suggests the involvement of confounding factors such as poor levothyroxine absorption or altered thyroid function. Further studies are required to elucidate the absorption of levothyroxine.

SAT-414 A Single Center Retrospective Analysis and Review of Endocrinopathies from Immune Checkpoint Inhibitors Between 2007 and 2017

Immune checkpoint inhibitors (ICI) specifically target and dysregulate immune tolerance. As a result of this immune activation, immune related adverse events (irAEs) are common. These can include endocrinopathies like immune hypophysitis (IH), primary adrenal insufficiency (PAI), autoimmune thyroid disease, Graves disease and type 1 Diabetes Mellitus (T1DM)[1]. The aim of this retrospective review was to describe the prevalence, timing, and clinical characteristics of ICI-related endocrinopathies at our institution. Methods: A retrospective chart review was conducted for all patients between January 01, 2007 and February 01, 2017 who met predefined clinical, biochemical and imaging criteria for endocrinopathies including IH, T1DM, autoimmune thyroid disease, Graves disease and PAI. Results: Among 690 patients who received ICPI during the study period, 91 unique patients with complete data developed endocrinopathies, for an overall prevalence of 13%. The study included 50 (55%) men and 41 (45%) women with a median age of 64 years (range 20-96 years). Grade 2 endocrinopathies were reported more commonly (n=49, 54%); grade 3/4 events were rare (15%). Among the ICIs, Nivolumab was the most common ICI noted for study patients (n=51, 56%). Autoimmune thyroid disease was the most common irAE in our study (n= 63, 9.1% overall prevalence). We also report 25 cases of IH (3.6%), 2 cases of PAI (0.3%) and 1 case of Graves disease (0.1%). Most patients with autoimmune thyroid disease developed subclinical hypothyroidism (n=26, 3.8%) and overt hyperthyroidism (n=21, 3.0%). We note a high median TSH of 67.3 µIU/mL; range- 20.6-111.0 in overt hypothyroidism compared to subclinical hypothyroidism (14.0 µIU/mL; range- 5.6-100 µIU/mL). Overall, median time to developing any endocrinopathy after initiating ICI was 13.7 weeks; range- 0.7-351.5 weeks. Among the subjects who developed IH, the median TSH was 0.37 µIU/mL (0.01 - 62.39 µIU/mL) with a free T4 of 0.74 ng/dL (0.25-1.86 ng/dL) and the median cortisol was 0.80 µg/dL (0.25-24.5 µg/dL). Amongst the IH group, 17 patients developed isolated secondary adrenal insufficiency and 8 patients developed combination of other hormone deficiencies with secondary AI including 6 with secondary hypothyroidism, 1 patient with hypogonadotropic hypogonadism and 1 with hypothyroidism and hypogonadism in addition to secondary AI. Despite development of irAEs, ICI therapy was continued in 59 pts (65%) who developed an endocrine irAE. Conclusions: In summary, this is one of the largest single institution retrospective studies on ICI related endocrinopathies. The majority of endocrinopathies were low grade, and most patients continued ICI treatment. Reference: Barroso-Sousa, Romualdo. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA, Sept 2017

SAT-437 Influence of Smoking on Thyroid Function in Japanese Subjects: Longitudinal Study for One Year of On-Off Smoking

Recent studies showed that various factors, including age, gender, race, iodine intake, obesity, the thyroid peroxidase antibody (TPO-Ab), and/or smoking, influence the thyroid status. In the present study, we analyzed and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab) in Japanese euthyroxinemia individuals with serum free T4 level within normal range. A total of 12,289 subjects who underwent health check-ups were analyzed in a cross-sectional and longitudinal study. The mean age of subjects was 50 ± 10 years (age range: 21–88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese euthyroxinemia subjects. Mean and median serum TSH levels increased with age in smokers and non-smokers, but were significantly lower in smokers than in non-smokers among men and women in most age groups; the median 97.5th percentiles of TSH levels were 1.2 mU/liter and 2.9 mU/liter in smokers, and 1.4 mU/liter and 3.9 mU/liter in non-smokers in 31- to 40-year-old men, p<0.01, and 1.4mU/liter and 4.3 mU/liter, and 1.8mU/liter and 6.2 mU/liter in 61- to 70-year-old men, p<0.01. However, smoking had a negligible effect on serum TSH levels in women older than 50 years; 1.3 mU/liter in smokers and 1.6 mU/liter in non-smokers in 31- to 40-year-old women, p<0.01, and 1.5 mU/liter and 1.8 mU/liter in 51- to 60-year-old women, p=0.3. Furthermore, the present study confirmed that serum free T4 levels in men progressively decreased with age, whereas no significant change was observed in women. Smoking did not affect the relationship between age and serum free T4 levels in men or women, except for men in their 20s. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both genders; however, smoking did not affect free T4 levels or the positivity for TPO-Ab. The rate of smokers in men was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%, p<0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels one year after the start of smoking in men (p<0.05). Since smoking appears to lower serum TSH levels in Japanese euthyroxinemia subjects careful consideration of the smoking status is needed when evaluating subclinical thyroid function.

High prevalence of TPO-Abs and subclinical hypothyroidism in iodine-sufficient pregnant women in Northern Algeria

BackgroundIodine is a trace element whose adequate intakes are essential during gestation to promote the correct growth and development of the fetus. Historically, endemic goiter and cretinism affected northern regions of Algeria, and iodized salt was introduced in 1990. However, there has been no national study of iodine nutrition in Algeria since 1994. The aim of this study was to assess the iodine status and thyroid function of women of reproductive age (WRA) and pregnant women (PW) in northern Algeria. MethodsHealthy WRA and PW were recruited from an urban area (Algiers) and healthy WRA from a rural area (Tizi-Ouzou). Spot urine and venous blood samples were collected to assess iodine status (urinary iodine concentration, UIC) and serum thyroid hormones (TSH, FT4), thyroglobulin (Tg), and anti-thyroid peroxidase antibodies (TPO-Ab) concentrations. ResultsThe median UIC in WRA was 256 μg/L (IQR: 166−354 μg/L; n = 151) in Algiers and 253 μg/L (167−341 μg/L; n = 150) in Tizi-Ouzou. The median UIC for the PW in Algiers was 233 μg/L (IQR: 157−326 μg/L; n = 173).Thirty-five percent of WRA and 30% of PW had an UIC > 300 μg/L. Median TSH, FT4 and Tg concentrations were within reference ranges in all groups of women. Among PW, 72.7%, 75.4% and 75.5% in the first, second and third trimester were TPO-Ab+. Among TPO-Ab + PW in the first, second and third trimesters, 18.7%, 13% and 10.3% had subclinical hypothyroidism. ConclusionIn northern Algeria, median UICs in PW indicate iodine sufficiency, and in WRA indicate more than adequate intakes. About 75% of PW are TPO-Ab + and the prevalence of subclinical hypothyroidism is high. Monitoring and surveillance of iodine fortification programs is vital to avoid both iodine deficiency and excess. There is an urgent need for a comprehensive national iodine status survey including school-age children and other vulnerable population groups in Algeria.

Management of Hypothyroidism in Patients with Acute Myocardial Infarction.

Background and Objectives: Thyroid hormones (TH) affect cardiac function through effects on cardiac contractility and systemic vascular resistance. While TH replacement for patients with hypothyroidism might be necessary for restoration of cardiac output after an acute myocardial infarction (AMI), it could theoretically lead to excessively rapid restoration of the metabolic rate. The appropriate management of hypothyroidism in patients with AMI is unknown. We describe the practice patterns in the management of hypothyroidism in the setting of AMI as well as patients’ clinical outcomes. Material and Methods: Retrospective study of patients that were admitted to a tertiary care hospital with AMI and newly diagnosed or uncontrolled hypothyroidism (TSH ≥ 10 mIU/L) between 2011–2018. Eligible patients were identified using diagnosis codes for AMI and laboratory values, followed by medical record review. We categorized patients according to treatment status with TH and by degree of hypothyroidism. Clinical outcomes included: 30-day mortality/readmission, bleeding, stroke, arrhythmia, sudden cardiac death, and new or worsening heart failure. Summary statistics and group comparisons are presented. Results: Sixty-four patients were included, their median age was 64 years and 61% (n = 39) were women. Most of the patients (59%) had a documented history of hypothyroidism. Of these, all were restarted on levothyroxine (LT4) during the index admission when compared to patients without a history of hypothyroidism, of which 54% received LT4 treatment (p = 0.001). The median TSH in those treated with LT4 was higher (25 mIU/L) when compared to those who were not (12 mIU/L), (p = 0.007). Patients who received intravenous LT4 had higher TSH levels and other variables suggesting worse clinical presentation, but these differences were not statistically significant. No statistically significant differences were noted on clinical outcomes according to LT4 treatment status. Conclusion: A history of hypothyroidism and the degree of TSH elevation seem to guide the management of hypothyroidism in patients with AMI. The clinical effect of correcting hypothyroidism in this setting requires further evaluation.