Received Thyroid Hormone Replacement Research Articles

The clinicopathological features, treatment outcomes and follow-up results of 47 ectopic thyroid gland cases: a single-center retrospective study.

Ectopic thyroid gland (ETG) is an uncommon clinical condition, presenting various challenges and limitations in its regulate diagnosis and treatment currently. This study aims to enhance our understanding of ETG and improve the strategies for its diagnosis and treatment. The retrospective single-center study was conducted, encompassing clinical data from ETG patients screened at our institution between 2013 and 2022. Patients were categorized based on the location of the disease, and follow-ups were performed on each. This study included a total of 47 patients who were confirmed to hav confirmed to have ETG. Among them, we found 29 cases of accessory thyroid and 18 cases of aberrant thyroid. Furthermore, 42 cases exhibited the single ETG, while 5 cases displayed the double ETG. The distribution of the ETG was as follows: 20 were lingual, 10 were submandibular, 10 were lateral cervical, 4 were thoracic mediastinal, 1 was esophageal, and 7 were ovarian. Of these cases, 22 patients underwent surgery, 18 received thyroid hormone replacement therapy, and 7 were placed under observation. All patients were followed up for 59.4 (12-117) months. No significant abnormalities were detected at the conclusion of the follow-up period. ETG is frequently observed in the head and neck, particularly in lingual. Accessory thyroid glands are commonly reported, with most cases being single ETG. Notably, these glands usually do not manifest specific clinical symptoms. Therefore, the appropriate and comprehensive examinations during the initial diagnosis are crucial to avoid misdiagnosis. Treatment should be individualized, and long-term follow-up is essential for managing ETG effectively.

FRI565 Spontaneous Conversion Of Long-standing Hypothyroidism To Grave’s Disease: A Case Report

Abstract Disclosure: M. Dominic: None. M. Shakir: None. A. Kakkar: None. O.Z. Syed: None. A. Sood: None. D.A. Alvarez: None. Introduction: Autoimmune thyroid diseases associated with IgG4 include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT involves a combination of antibody-mediated thyroid gland destruction and inhibition of thyroid hormone production through a predominance of TSH receptor-blocking antibodies (TBAb). GD is due to increased thyroid hormone production in response to thyroid-stimulating antibodies (TSAb). Although transition to hypothyroidism in patients with GD is commonly encountered in clinical practice, conversion of primary hypothyroidism to GD is a rare event and is described here. Clinical Case: We describe the case of an 81-year-old female with primary hypothyroidism diagnosed more than 10 years ago. She was briefly treated with desiccated thyroid which was later changed to levothyroxine, and she remained euthyroid for several years on Levothyroxine 88 mcg daily. In 05/2021 her routine blood test showed suppressed TSH of less than 0.01uIU/mL for the first time, and it remained consistently low with elevated free T4 & T3 levels despite gradually reducing levothyroxine dose. Patient also started to have tremors, weight loss and anxiety during this period. She was found to have a hypermetabolic thyroid nodule during a PET-CT for evaluation of newly diagnosed Gastrointestinal Stromal Tumor in 09/2022. Levothyroxine was stopped shortly thereafter, but the hyperthyroid labs persisted, following which TSAb levels were obtained and found positive. She was started on methimazole 10 mg twice daily, which resulted in symptomatic improvement and marked reduction of T3 & T4 levels in one month. Clinical lessons: Over-replacement is the most common cause of hyperthyroid symptoms in patients receiving thyroid hormone replacement. Primary hypothyroidism is usually a permanent condition requiring lifelong therapy. Conversion of this condition to GD is a rare entity and can be missed in clinical practice by being mistaken for levothyroxine over-replacement. Proposed mechanisms for conversion of long-standing hypothyroidism to hyperthyroidism include fluctuating levels of TBAbs and TSAbs, spontaneous development of autoimmunity and rarely, production of TSAbs in patients with established Hashimoto’s thyroiditis. Another proposed theory is initial hypothyroidism due to extensive autoimmune gland damage in patients with GD who later develop hyperthyroidism after tissue recovery. It should be noted that this transition to GD has been reported to occur even 30 years after the diagnosis of hypothyroidism. Thus in patients with well-established hypothyroidism requiring lower thyroid replacement doses than before, and labs showing persistent hyperthyroid picture with no evident cause, a careful evaluation is required to check for conversion to GD in order to start appropriate treatment at the earliest. Presentation: Friday, June 16, 2023

Sensorineural hearing loss in a child with congenital hypothyroidism receiving thyroid hormone replacement therapy

ABSTRACTBackground: Congenital hypothyroidism remains as one of the most common causes of hearing loss in children, considering that thyroid hormone plays an essential role in the development and maturation of auditory organs. Purpose: To report a case of hearing loss in a child with congenital hypothyroidism who had received thyroid hormone replacement therapy. Case report: Presenting a 3-year-old boy with congenital hypothyroidism, growth and developmental delays, and a very severe bilateral sensorineural hearing loss. He was diagnosed at 6 months old, and even after subsequent therapies, the hearing impairment of the child remained profound. Clinical question: Could thyroid hormone replacement therapy improve the prognosis of hearing function in congenital hypothyroid patients accompanied by sensorineural hearing loss? Review method: Literature review through database PubMed, ProQuest, EBSCO, EBSCOhost and Embase, using keywords: “congenital hypothyroidism”, “hearing loss”, and “thyroid hormone replacement therapy”. Result: Screening on 1088 articles found no studies that were relevant with the clinical question and inclusion criteria. Conclusion: This report supported the evidence on the effects of congenital hypothyroidism on hearing loss, and the importance of early diagnosis and prompt treatment in congenital hypothyroid children. A missed diagnosis of congenital hypothyroidism in neonates may result in unfavorable effects on the child’s growth and development. Further studies are needed to assess the improvement of hearing function in congenital hypothyroid patients accompanied by sensorineural hearing loss that received thyroid hormone replacement therapy. ABSTRAKLatar belakang: Hipotiroidisme kongenital merupakan salah satu penyebab paling umum gangguan pendengaran pada anak-anak, terutama mengingat hormon tiroid berperan penting dalam perkembangan dan maturasi organ pendengaran. Tujuan: Melaporkan satu kasus gangguan pendengaran pada anak dengan hipotiroidisme kongenital yang menetap setelah terapi sulih hormon tiroid. Laporan kasus: Seorang anak laki-laki berusia 3 tahun dengan hipotiroidisme kongenital yang mengalami keterlambatan pertumbuhan dan perkembangan, dan gangguan pendengaran tipe sensorineural bilateral derajat sangat berat. Pasien didiagnosis pada usia 6 bulan, dan walaupun setelah terapi, gangguan pendengaran pada anak tersebut menetap. Pertanyaan klinis: Apakah terapi sulih hormon tiroid mempengaruhi prognosis perbaikan fungsi pendengaran pada pasien hipotiroid kongenital yang disertai gangguan pendengaran sensorineural? Tinjauan literatur: Melalui database PubMed, ProQuest, EBSCO, EBSCOhost dan Embase, menggunakan kata kunci: “hipotiroidisme kongenital”, “gangguan pendengaran”, “terapi sulih hormon tiroid”. Hasil: Setelah skrining 1088 artikel, tidak ada penelitian yang sesuai dengan pertanyaan klinis dan kriteria inklusi. Kesimpulan: Laporan ini menambah bukti tentang efek hipotiroidisme kongenital pada gangguan pendengaran, serta pentingnya diagnosis dini dan pengobatan segera pada anak hipotiroid kongenital. Diagnosis hipotiroidisme kongenital yang tidak terdeteksi pada neonatus, dapat mengakibatkan efek buruk pada pertumbuhan dan perkembangan anak. Diperlukan penelitian lebih lanjut untuk menilai prognosis peningkatan fungsi pendengaran pada pasien hipotiroid kongenital dengan gangguan pendengaran sensorineural, yang mendapatkan terapi sulih hormon tiroid.

Comparison of fetal cardiac structure in hypothyroid pregnant women receiving thyroid hormone replacement therapy and healthy controls

Objective: Thyroid hormone is required for normal fetal brain development, neuronal proliferation, migration and structural organization. We aimed to investigate fetal cardiac structure in fetuses of hypothyroid pregnant women receiving thyroid hormone replacement therapy and to compare it with normal pregnancies, including fetal outcome and delivery results. Methods: Singleton pregnant women whose ages were between 18–45 years and weeks of gestation were between 26–34 were included in the study. Their routine laboratory test reports, ultrasonographic measurements (fetal echo) and postnatal follow-up data were recorded. Patients were grouped according to the presence of diagnosis of hypothyroidism. The patients with hypothyroidism during pregnancy were included in Group 1 while healthy pregnancies with similar features were considered as controls and included in Group 2. All women with hypothyroidism were taking thyroid hormone replacement. All ultrasonographic and laboratory data measurements were collected from the system files and were compared between groups. Results: A total of 89 patients (41 hypothyroidism and 48 controls) were recruited to the study. Serum TSH levels of patients with hypothyroidism (Group 1) was significantly higher than the controls. In fetal cardiac examination, left ventricular (LV) and right ventricular (RV) wall thicknesses, and interventricular septum thicknesses at the end of systole and diastole were not statistically significant in both groups. Apgar scores, fetal gender and mean fetal birth weight were all similar between the groups. Conclusion: There is no myocardial structural difference in fetuses of pregnant women who were diagnosed with hypothyroidism and received thyroid hormone replacement therapy compared to healthy controls. Thyroid replacement therapy in hypothyroid mothers might affect and treat fetal cardiac abnormalities.

Risk factors for thyroid hormone replacement therapy after hemithyroidectomy and development of a predictive nomogram

PurposeHemithyroidectomy is a valid operation to retain functional contralateral thyroid lobe that is indicated for a variety of thyroid diseases. This study aimed at determination of the risk factors for thyroid hormone replacement following hemithyroidectomy and to develop a predictive nomogram.MethodsData of patients treated by hemithyroidectomy for benign thyroid disease between January 2015 and January 2020 were retrospectively analyzed. Baseline characteristics, surgery-related variables, and preoperative and postoperative thyroid function of patients were collected from the case records and compared between patients with postoperative euthyroidism and patients with postoperative hypothyroidism. Postoperative euthyroidism patients without thyroid hormone replacement were compared to those who developed postoperative hypothyroidism with thyroid hormone replacement. The factors associated with thyroid hormone replacement were used to construct a binomial logistic-regression model and visualized as a predictive nomogram to evaluate the risk of thyroid hormone replacement following hemithyroidectomy.ResultsOf the 378 patients (74% female) included in the study, 110 (29.1%) developed postoperative hypothyroidism. Preoperative serum thyroid-stimulating hormone (TSH) > 2.172 μIU/mL was identified as an independent risk factor for postoperative hypothyroidism (odds ratio [OR] = 8.02; 95% confidence interval [CI]: 4.87–13.20; P < 0.001). Of 110 patients with postoperative hypothyroidism, 56 (50.9%) received thyroid hormone replacement. Unilateral thyroid nodule and preoperative serum TSH > 2.172 μIU/mL were independent predictors of postoperative thyroid hormone replacement (P = 0.01, and P < 0.001, respectively). Temporary subclinical hypothyroidism occurred in 12 patients; all 12 reverted to euthyroid state without thyroid hormone replacement. The discriminative effect of the binomial regression model was proved reliable by the Hosmer–Lemeshow goodness-of-fit test (P = 0.503), and predictive ability of the nomogram was satisfactory with a C-index of 0.833.ConclusionsHypothyroidism is common after hemithyroidectomy, and almost half of the patients will need thyroid hormone replacement. Elevated preoperative serum TSH level and unilateral thyroid nodule were independent predictors of thyroid hormone replacement following hemithyroidectomy. The predictive nomogram could be a useful tool for clinical practice.

The effect of receiving thyroid hormone replacement on the dysphonia severity index for congenital hypothyroid children

ObjectivesDysphonia is a common compliant in hypothyroid patients. Subjective voice changes could be clearly found in congenital hypothyroid children (CHC); however, the early treated children with thyroid hormone replacement (THR) may not experience dysphonia. The objective of this study is to determine if the CHC who were receiving early THR would have objectively measurable changes on vocal function as assessed by the dysphonia severity index (DSI).MethodsParticipants were 29 children aged from 6 to 12 years. Fifteen children had congenital hypothyroidism on eltroxin therapy started before the age of 1 year and 14 were typically developing children (TDC). All children did not have voice compliant. DSI was calculated for all children through the measure of maximum phonation time (MPT), highest frequency (F0-high), lowest intensity (I-low), and jitter percent (j %).ResultsCHC receiving early THR were not significantly different from TDC on DSI value; however, both groups showed significant difference on MPT and F0-high. Degree of voice changes by DSI in males was significantly higher than females in CHC on eltroxin therapy while no significant difference regarding gender has been found on DSI in TDC.ConclusionsThe results suggested that there is no evidence of DSI objective voice changes in CHC receiving THR compared to TDC, yet separate objective voice measures alternations had been found in CHC. This highlights the importance of achieving efficient neonatal screening programs for CHC and providing strong support to initiate early THR to avoid any alternation of laryngeal function.

Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.

AimsAtrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.Methods and ResultsA retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e–02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e–04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).ConclusionHomozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.

A Clinical Audit on Diagnosis and Management of Hypopituitarism in Scarborough General Hospital

Objectives: The main objective was to evaluate the use and compliance to the guidelines issued by the Endocrine Society in diagnosis and management of hypopituitarism and their impact on the clinical practice in Scarborough General Hospital (SGH). Design: A retrospective review of secondary data of patients with a diagnosis of hypopituitarism in SGH. Methodology: The data was collected from both patients’ case notes and electronic medical records. Data analysis was performed using Microsoft excel. Results: 18 patients with the diagnosis of Hypopituitarism were identified. 5 patients were females and 13 were males. 11 patients aged between 60-80 years, 4 patients were between 51-60 years and 3 patients were between 31-50 years. All the patients had low cortisol levels; however, cortisol was checked at 9AM in only 4 patients. All the patients had their thyroid stimulating hormone levels checked, which were low in all of them. Free T4 levels were normal in 2 patients, and low in 16 patients. 17 patients had low follicular stimulating hormone levels, whereas 15 had low luteinising hormone levels. Testosterone levels were checked in 9 male patients out of which 7 had low levels. Insulin-like growth factor-1(IGF1) was done in all patients and levels were low in 10 patients. All those with low IGF1 had glucagon stimulation test. Serum sodium levels were low in 3 patients and high in 5 patients. Plasma osmolality was only checked in 8 patients (was high in 5 patients). Urine osmolality was checked in 10 patients, and it was low in 5 patients. Brain MRI was performed in 16 patients, and 2 patients had brain CT. The most common cause of hypopituitarism was non-functioning pituitary adenoma (44.4%), and the least common causes were empty Sella syndrome (5.6%) and craniopharyngioma (5.6%). All patients received glucocorticoid replacement therapy, 17 received thyroid hormone replacement therapy, 8 received testosterone replacement therapy, 3 received desmopressin (DDAVP) treatment, and one patient received growth hormone replacement therapy. Conclusion: This Audit shows that our practice in diagnosis and management of hypopituitarism is mostly in line with the recommendation of the Endocrine Society. However, cortisol levels were not always measured at 9:00 am and we are not compliant with performing Growth Hormone stimulation test in every patient.

Subclinical and Clinical Hypothyroidism in Proteinuric Nephropathies: Amelioration of Proteinuria and Preservation of Renal Function by Thyroid Hormone Replacement Therapy

Background: Emerging evidence shows a bi-directional talk between the kidney and thyroid; yet to date, sparse data exist as to the screening and treatment of hypothyroid states, whether Subclinical Hypothyroidism (SCH) or Clinical Hypothyroidism (CHT), in Chronic Kidney Disease (CKD) patients. Objectives: The aim of the current study was to examine the association between thyroid hypofunction (whether subclinical or clinical) and proteinuric CKD (low eGFR and/or proteinuria), and to assess the impact of treating thyroid hypofunction on the progression of CKD. Patients and methods: We conducted a prospective cohort study on 100 participants with baseline proteinuric CKD who were subcategorized according to their thyroid status into three groups: 20 euthyroid, 40 (SCH), 40 (CHT). All subjects were then followed up for 2 years after receiving Thyroid Hormone Replacement Therapy (THRT) according to their thyroid status. Results: At baseline, we found a highly statistically significant association between SCH/CHT and low eGFR and proteinuria (P-value 0.001 for both) in univariate and multivariate analyses. After THRT, we found a statistically significant reduction in CKD progression as evidenced by preservation of mean eGFR and decrease in proteinuria in both groups with SCH and CHT (P-value 0.001 and 0.016 respectively) after the first 6 months of treatment that persisted over the remainder of 2-year follow-up period at a P-value 0.001. Conclusion: The current study demonstrated a strong association between baseline proteinuric CKD and hypothyroid states and showed that THRT significantly halted CKD progression in hypothyroid patients who achieved euthyroid state.

Proteinuria in Severe Hypothyroidism: A Prospective Study.

Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most important markers for clinical assessment of kidney function. Though hypothyroidism is associated with proteinuria in cross-sectional data, the impact of treatment on proteinuria is unknown. This study explores the effect of thyroid hormone replacement therapy on eGFR and 24-hour urine protein excretion in patients with severe primary hypothyroidism. This study was a prospective, observational cohort study in adults with severe primary hypothyroidism (serum thyrotropin [TSH] > 50 µIU/mL). Individuals with preexisting or past kidney disease, kidney or urinary tract abnormalities, calculi or surgery, diabetes mellitus, or hypertension were excluded. The participants received thyroid hormone replacement therapy. Thyroid functions, eGFR, 24-hour urine protein excretion, and biochemical parameters were measured at baseline and 3 months. This study took place at a single center, a tertiary care referral and teaching hospital. Of 44 enrolled participants, 43 completed 3 months of follow-up. At 3 months, serum TSH levels decreased and thyroxine levels increased (P < .001 for both). Significant increases in eGFR (mean difference, 18.25 ± 19.49 mL/min/1.73 m2; 95% CI, 12.25 to 24.25, P < .001) and declines in 24-hour urine protein excretion (mean difference, -68.39 ± 125.89 mg/day; 95% CI, -107.14 to -29.65, P = .001) were observed. Serum cholesterol and low-density lipoprotein levels also significantly decreased (P < .001). Thyroid hormone replacement therapy in patients with severe primary hypothyroidism improves eGFR and decreases 24-hour urine protein excretion, thereby suggesting reversible alterations.

Over- and Under-Treatment of Hypothyroidism Is Associated with Excess Mortality: A Register-Based Cohort Study.

This study investigated the association between hypothyroidism and mortality in both treated and untreated hypothyroid patients, and the consequences of over- and under-treatment with respect to mortality. This was a register-based cohort study of 235,168 individuals who had at least one serum thyrotropin (TSH) during 1995-2011 (median follow-up 7.2 years). Hypothyroidism was defined as at least two measurements of TSH >4.0 mIU/L within a half year spaced by at least 14 days, or one measurement of TSH >4.0 mIU/L and two filled prescriptions of levothyroxine the following year. All-cause mortality rates were calculated using multivariable Cox regression analysis adjusted for age, sex, and comorbidities using the Charlson Comorbidity Index. Mortality was increased in untreated hypothyroid individuals (n = 673; hazard ratio [HR] = 1.46 [confidence interval (CI) 1.26-1.69]; p < 0.001) compared to euthyroid controls. Results remained significant even when subdividing according to mild (TSH >4.0 mIU/L and ≤10 mIU/L; p < 0.001) and marked hypothyroidism (TSH >10 mIU/L; p = 0.002). Mortality was increased in both treated and untreated hypothyroid individuals for each six months a patient had increased TSH (HR = 1.05 [CI 1.02-1.07], p < 0.0001, and HR = 1.05 [CI 1.02-1.07], p = 0.0009, respectively). In patients who received levothyroxine, the HR for mortality increased by a factor 1.18 ([CI 1.15-1.21]; p < 0.0001) for each six months a patient exhibited decreased TSH. This finding was essentially unchanged after stratification by disease severity (mild or marked hypothyroidism) and age (older and younger than 65 years). Mortality was increased in untreated but not in treated hypothyroid individuals, independently of age and severity of hypothyroidism. Duration of decreased TSH in treated individuals had a greater impact on mortality than did duration of elevated TSH. These results stress the need for close monitoring of treatment in individuals receiving thyroid hormone replacement therapy.

Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

In preparation for 131I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n=90) and healthy women similar in age and educational level (n=90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

Subclinical Hypothyroidism is a Useful Predictor of Adverse Events in Heart Failure Patients with Reduced Left Ventricular Ejection Fraction

Thyroid dysfunction has an adverse effect on cardiac function and relates to poor prognosis of patients with heart failure (HF), but data of hypothyroidism as a predictor of adverse events are scarce. In this study, we evaluated the predictive value of subclinical hypothyroidism for poor outcome in HF. Continuous 71 ambulatory patients with HF with reduced LVEF who had never received thyroid hormone replacement therapy were enrolled. We assessed their baseline thyroid-stimulating hormone (TSH) and classified them into euthyroid (TSH: 0.35 to 5.50 uU/ml), hypothyroid (>5.50 uU/ml), or hyperthyroid (<0.35 uU/ml). We defined cardiovascular death or hospitalization for HF as study endpoints and compared outcomes among 3 thyroid states. Furthermore, we evaluated the prognostic value of TSH for poor outcome, using multivariate Cox proportional-hazards model. Sixty-one patients (85.9%) had euthyroidism, 8 patients (11.3%) hypothyroidism, and 2 patients (2.8%) hyperthyroidism. Kaplan-Meier event-free survival analysis revealed that the patients with hypothyroidism showed worse event-free survival compared to those with euthyroidism (p=0.013). Multivariate analysis demonstrated that TSH was a significantly independent predictor of adverse events after adjustments for age, gender, LVEF, and BNP. (HR: 1.216; 95% CI: 1.029 to 1.438; p=0.022). More than 10% of HF patients with reduced LVEF had subclinical hypothyroidism which demonstrated poor prognosis. High TSH level was a useful predictor of adverse events.

The effects of screening and intervention of subclinical hypothyroidism on pregnancy outcomes: a prospective multicenter single-blind, randomized, controlled study of thyroid function screening test during pregnancy

Purpose: To evaluate the effect of subclinical hypothyroidism (SCH) screening and intervention on pregnancy outcomes and explore the significance of thyroid function during early pregnancy. Methods: Pregnant women were recruited from Peking Union Medical College Hospital (screening group for measuring thyroid function and thyroid antibody in early pregnancy) and Haidian Maternal & Child Health Hospital (control group whose serum was stored and measured shortly after delivery) from July 2011 to December 2012. Thyrotropin levels 2.5–10 mIU/L and free T4 levels in normal range were considered SCH. Some of the screening group were treated with levothyroxine and adjusted. The others did not take medicine but kept a regular follow-up visit to doctors after antenatal clinic. The pregnancy outcomes and complications were compared. Results: 1671 women (675 in screening group and 996 in control group) were recruited. 419 (167 from screening group) women was diagnosed as SCH. In screening group, 105 SCH and 4 hypothyroid women received thyroid hormone replacement therapy. The miscarriage and fetal macrosomia risks were lower, and cesarean was higher in screening group than control. Conclusion: Screening and intervention of SCH can significantly reduce the incidence rate of miscarriage.

Free thyroxine level as an independent predictor of infection-related mortality in patients on peritoneal dialysis: a prospective multicenter cohort study.

BackgroundPrevious studies have reported the relationship between thyroid hormone levels and mortality in dialysis patients. However, little is known about the association of free thyroxine (fT4) and mortality in patients on peritoneal dialysis (PD). This study investigated the association between basal and annual variation in fT4 level and mortality in PD patients.MethodsPatients on maintenance PD were enrolled from a prospective multicenter cohort study in Korea; their serum triiodothyronine, fT4, and thyroid-stimulating hormone levels were measured 12 months apart. Patients with overt thyroid disease and those receiving thyroid hormone replacement therapy were excluded from the analysis. Patients were divided into two groups based on the median levels of fT4. The differences of all-cause, infection-related, and cardiovascular mortalities were analyzed between the two groups. The association of basal levels and annual variation with mortality was investigated with Kaplan–Meier curves and Cox proportional hazard models.ResultsAmong 235 PD patients, 31 (13.2%) deaths occurred during the mean follow-up period of 24 months. Infection (38.7%) was the most common cause of death. Lower basal fT4 levels were an independent predictor of all-cause and infection-related death (hazard ratio [HR] = 2.74, 95% confidence interval [CI] 1.27–5.90, P = 0.01, and HR = 6.33, 95% CI 1.16–34.64, P = 0.03, respectively). Longitudinally, patients with persistently lower fT4 levels during the 12-month period had significantly higher all-cause mortality than those with persistently higher levels (HR = 3.30, 95% CI 1.15–9.41, P = 0.03). The area under the receiver operating characteristic curve of fT4 for predicting all-cause and infection-related mortality was 0.60 and 0.68, respectively.ConclusionsfT4 level is an independent predictor of mortality and is especially attributable to infection in PD patients. This predictor was consistent when considering both baseline measurements and annual variation patterns. Close attention to infection in PD patients with relatively lower fT4 levels should be considered.

Intracerebral Hemorrhage with Hypothyroidism

Hypothyroidism is associated with increased ischemic stroke risk but paradoxically results in more favorable outcomes once a stroke occurs. Whether a similar pattern emerges in patients with primary intracerebral hemorrhage (ICH) is unknown. A retrospective analysis of a prospective stroke center database was performed to analyze the clinical presentation and outcomes of hypothyroid patients with spontaneous ICH. Patients were classified into groups with no history of thyroid disease (n=491) versus those with hypothyroidism (n=72). Hypothyroid patients were further classified into patients receiving thyroid replacement on admission or those without replacement. The Glasgow Coma Scale, ICH score, and the National Institutes of Health Stroke Scale (NIHSS) were used to assess the initial severity. Outcome was assessed by admission to discharge change in the NIHSS and modified Barthel Index (mBI), in-hospital mortality, discharge disposition and mortality, and the mBI at 3 and 12 months. There were 563 patients in the analysis. Seventy-two patients had a history of hypothyroidism, and of these, 63% received thyroid hormone replacement. Patients receiving replacement had significantly lower NIHSS at presentation (median 4 [IQR 1, 11]) compared with either the control group (median 8 [IQR 3, 16]) or hypothyroid patients without replacement (median 9 [IQR 3.8, 15.5]; P=.004). There was no difference in in-hospital and 3-month mortality or functional outcomes at 3 and 12 months among the groups. This study suggests that the history of hypothyroidism does not affect clinical severity or outcome after ICH.

The Normal TSH Reference Range: What Has Changed in the Last Decade?

Serum TSH assessment is the most sensitive screening test for the diagnosis of thyroid dysfunction in the absence of pituitary or hypothalamic disease. This test has been used increasingly in the last decade to detect subclinical thyroid dysfunction (STD). Recent data suggest that STD is a common disorder that may be associated with important adverse events (1–5). The American Association of Clinical Endocrinologists (AACE) and American Thyroid Association (ATA) 2012 guidelines recommend treatment of subjects with persistent increased serum TSH levels 10 mIU/L and undetectable serum TSH ( 0.1 mIU/L) (6, 7). The treatment of mild thyroid hormone excess (TSH 0.1–0.4 mIU/L) ordeficiency (serumTSH 10mIU/L) is controversial (1,2). However, what is the normal TSH reference range? Obviously, this issue is critical in deciding whether or not to treat patients with mild STD and in identifying individuals with high-normal or low-normal serum TSH. It is also important in defining the TSH target level in patients receiving thyroid hormone replacement therapy. In 2002, the National Health and Nutrition Examination Survey (NHANES) III, a US population-based study, evaluated the normal TSH range in the “thyroid disease-free adult population” (8).Theauthors excludedsubjectswith risk factorsandafamilyhistoryofthyroiddysfunction,self-reported thyroid disease or goiter, and thyroid autoimmunity. The study suggested that 95% of the US disease-free population had a serum TSH concentration between 0.45 and 4.12 mIU/L (8). However, TSH values did not have a Gaussian distribution because the curve was skewed by individuals with occult autoimmune thyroid dysfunction despite negative thyroid peroxidase antibodies (9). In 2005, the National Academy of Clinical Biochemistry (NACB) recommended that thyroidultrasonographybeperformedineuthyroidsubjects to exclude the presence of occult thyroid autoimmunity in order to define the serum TSH reference interval more accurately (10). They suggested that the upper limit of the TSH reference range be lowered to 2.5 mIU/L (10). The upper and lower limits of the normal serum TSH concentration continue to be debated by expert clinical thyroidologists. In 2005, two back-to-back articles appeared in the JCEM: one article, by Wartofsky and Dickey (11), favored a narrower TSH reference range, but according to the other, by Surks et al (12), the TSH range should remain unchanged. It should be mentioned that the sensitivity and specificity of TSH assays can affect the evaluation of serum TSH because some assays may detect biologically inactive circulating TSH isoforms (1). The upper TSH reference limit has progressively declined over the last decade thanks to more sensitive TSH assays, more accurate thyroid antibody tests, and a more accurate selection of the reference population. Different TSH cut-off limits have been reported in population-based studies conducted in various countries (1). Subsequent findings confirmed that ethnicity, iodine intake, gender, age, and body mass index can influence the reference range of serum TSH. In fact, the normal TSH upper limit was lower in African Americans (3.6 mIU/L) than in Mexican Americans or Caucasians (4.2 mIU/L) (8). Reanalysis of these data 5 years later showed that the upper limit of normal serum TSH at the 97.5th percentile was 3.5 mIU/L in individuals 20–29 years old, 4.5 mIU/L in those 50–59 years old, and 7.5 mIU/L in those older than 80 years (13). Variations in thyroid function within the reference range have been associated with body weight in several cross-sectional and longitudinal studies (14). Moreover, serum TSH levels at the upper limit of the normal range have been found in obese adults and have been positively correlated with body mass index (14).

A Case of Neonatal Dual Ectopic Thyroid Glands with Congenital Hypothyroidism

An ectopic thyroid occurs when thyroid tissue has not properly migrated from the foramen cecum to the fourth tracheal ring along the midline of the ventral portion of the neck, but instead is located elsewhere. There are some cases of dual-site ectopic thyroid glands, usually involving adolescents or adults. Cases of neonatal dual ectopic thyroid glands are even rarer. We report a case of a dual ectopic thyroid with congenital hypothyroidism found during a neonatal screening of the lingual and upper cervical regions of a patient . The patient had no airway obstruction symptoms, such as dysphagia or grunting. The thyroxine (T4) level was 2.49 μg/dL (normal value: 6.2-22.0 μg/dL) and the thyroid-stimulating hormone (TSH) level was 217.85 μIU/mL (normal value: 1.7-9.1 μIU/ mL). A dual ectopic thyroid was diagnosed based on a Tc-99m thyroid scan. After receiving thyroid hormone replacement therapy, the child has developed normally.

Lower Free Thyroxin Associates with a Less Favorable Metabolic Phenotype in Healthy Pregnant Women

A lower free T(4) (fT4), within the euthyroid range, has been shown in adults to associate with an adverse metabolic phenotype. Thyroid physiology changes significantly during gestation and affects maternal and fetal well-being. The aim of the study was to test the hypothesis that a lower serum fT4 in healthy euthyroid pregnant women is related to a less favorable metabolic phenotype and to fetal or placental weight. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: We examined associations of thyroid function tests (TSH and fT4) and the free T(3) (fT3)-to-fT4 ratio (as a proxy of deiodinase activity) with a metabolic profile [preload and postload glucose, glycosylated hemoglobin (HbA1c), high molecular-weight (HMW)-adiponectin, homeostasis model of assessment for insulin resistance (HOMA-IR), and serum lipids] in 321 healthy pregnant women. All women were euthyroid and had negative anti-thyroid peroxidase antibodies. None received thyroid hormone replacement. Blood tests were performed in women between 24 and 28 wk gestation. Placentas and newborns were weighed at birth. Circulating TSH did not relate to metabolic parameters, but decreasing fT4 and increasing fT3-to-fT4 ratio associated with a less favorable metabolic phenotype, as judged by higher postload glucose, HbA1c, fasting insulin, HOMA-IR, and triglycerides, and by a lower HMW-adiponectinemia (all P ≤ 0.005). In multiple regression analyses, fT4 was independently associated with HbA1c (β = -0.135; P = 0.038), HMW-adiponectin (β = 0.218; P < 0.001), and placental weight (β = -0.185; P < 0.005), whereas the fT3-to-fT4 ratio was independently associated with maternal body mass index (β = 0.265; P < 0.001), HMW-adiponectinemia (β = -0.237; P < 0.002), HOMA-IR (β = 0.194; P = 0.014), and placental weight (β = 0.174; P = 0.020). In pregnant women without a history of thyroid dysfunction, lower concentrations of fT4 and a higher conversion of fT4 to fT3, as inferred by changes in the fT3-to-fT4 ratio, were found to be associated with a less favorable metabolic phenotype and with more placental growth.