Low Serum Thyrotropin Research Articles

Effects of levothyroxine treatment on serum thyroid hormone levels in euthyroid patients with papillary thyroid microcarcinoma

We recently reported that lowering serum thyroid stimulating hormone (TSH) levels with levothyroxine (LT4) may be associated with decreased tumor growth during active surveillance (AS) of papillary thyroid microcarcinoma (PTMC). Most clinicians might believe that low serum TSH levels following LT4 therapy indicate subclinical thyrotoxicosis. This study aimed to evaluate the effects of TSH-lowering therapy using small doses of LT4 on serum thyroid hormone levels in euthyroid patients with PTMC. We retrospectively analyzed data from 28 patients with low-risk PTMC who had undergone measurement of both FT4 and FT3 consecutively and received LT4 to achieve serum TSH levels of < 0.5 μIU/mL and > 0.05 μIU/mL between January 2012 and May 2018 at Kuma Hospital. There were 24 females and 4 males (aged 55 ± 12 years [mean ± standard deviation {SD}]). We compared their serum FT4 and FT3 levels at diagnosis with those following TSH-lowering therapy with LT4. Following LT4 therapy, the patients’ serum FT4 levels were significantly increased (P < 0.001). Serum FT3 levels, however, remained unchanged (P = 0.10). The proportions of patients whose FT3 levels increased by more than 1 SD, remained unchanged, and decreased by more than 1 SD were 11 %, 57 %, and 32 %, respectively. Our study indicated that mild TSH-lowering doses of LT4 for euthyroid patients with PTMC increased serum FT4 levels but did not increase serum FT3 levels in most cases, suggesting that a mild TSH-lowering therapy for euthyroid patients may not necessarily cause thyrotoxicosis.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.

Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Sustained Euthyroidism during Thionamide Antithyroid Drug Treatment: Comparison of Short- and Long-term Methimazole Therapy

Background: Extended low serum thyrotropin (TSH) levels may increase the risk of cardiovascular events in patients with hyperthyroidism. Objectives: This study aimed to compare the time spent with sustained normal TSH concentration following short- and long-term methimazole treatment. Methods: A total of 258 patients with Graves’ hyperthyroidism completed 18 - 24 months of methimazole therapy and were randomized to discontinue treatment (n = 128, short-term group) or continue an additional 36 - 102 months of methimazole therapy (n = 130, long-term group). Clinical and laboratory evaluations were performed every 6 months for 132 months after randomization. Results: There was no difference in serum-free thyroxine, triiodothyronine, and TSH concentrations between the 2 groups at the time of randomization. Of 128 patients in the short-term group, 5 left in follow-up, 2 became hypothyroid, 67 (54%) had a relapse of hyperthyroidism, and only 54 (44%) were euthyroid at the end of the study. Among 130 patients on the long-term methimazole therapy, 4 were left in follow-up, 24 developed hyperthyroidism, 4 developed hypothyroidism, and 98 (78%) were euthyroid 132 months post-randomization. Total time spent on euthyroidism was 90.4% ± 8.1% of the study period in the short-term and 95.8% ± 7.0% in the long-term treatment groups (P &lt; 0.001). The lowest time spent in euthyroidism (74.6% ± 6.4% of the study period) belonged to 29 (24%) patients in the short-term group under levothyroxine therapy because of fluctuation in serum TSH. Patients in both groups with hyperthyroidism relapse who chose methimazole therapy spent &gt;90% of the study time in euthyroidism. Conclusions: In patients with Graves' hyperthyroidism, sustained normal serum TSH levels were more common in the long term as compared to the short-term methimazole treatment.

Association between thyroid hormone levels in the acute stage of stroke and risk of poststroke depression: A meta-analysis.

Thyroid hormones have been indicated to be associated with depression, but their relationship with poststroke depression (PSD) remains controversial. Therefore, we performed a meta-analysis to explore the correlation between thyroid hormone levels in acute stroke and PSD. We searched databases for eligible studies. Standard mean differences (SMD) and 95% confidence intervals (CI) were applied to evaluate the association among levels of thyroid hormones, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), in acute stroke patients and the risk of PSD. A total of 13 studies were included in the analysis. Compared to non-PSD patients, PSD patients had remarkably lower serum TSH and FT3 levels (TSH: SMD=-0.59, 95%CI=-1.04 to -.15, p=.009; FT3: SMD=-0.40, 95%CI=-.51 to -.30, p=.000) and higher serum FT4 levels (SMD=0.33, 95%CI=.07-.59, p=.013). Subgroup analysis showed that there may be a more statistically significant association between FT3 and the risk of PSD compared to TSH and FT4. Our results suggested that patients with lower serum TSH and FT3 levels as well as higher serum FT4 levels in the acute stage of stroke may be more susceptible to PSD.

SAT538 Thyrotoxicosis in the Setting of Metastatic Poorly Differentiated Thyroid Carcinoma, a Marker of Disease Progression?

Abstract Disclosure: B.L. Chang: None. M.A. Fernandez: None. K.M. Shikuma Lee: None. Background: Thyrotoxicosis is a rare manifestation of thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) causing thyrotoxicosis has even more rarely been reported. Here, we report a case of PDTC with thyrotoxicosis developing in a previously euthyroid individual with longstanding untreated follicular neoplasm. Clinical Case: A 79-year-old veteran presented to routine endocrine follow up with new symptoms of thyrotoxicosis. Although previously euthyroid, the evaluation revealed new findings of low serum thyrotropin (TSH) (&amp;lt;0.01 uIU/mL, n=0.34 – 5.60 uIU/mL), elevated free thyroxine (FT4) (2.6 ng/dL, n=0.58 – 1.64 ng/dL), and high total T3 (TT3) levels (223 ng/dL, n=76 – 181 ng/dL). Thyroid stimulating immunoglobulin antibodies (TSI) were positive (214, n&amp;lt;140). Patient has a nine-year history of a fine needle aspiration (FNA) of a large right-sided thyroid nodule with cytology suspicious for follicular neoplasm but declined surgical removal. Thyroid uptake and scan showed heterogeneous uptake throughout the right lobe with a relative photopenic region centrally and spots of more increased activity in areas within the right lobe. The left thyroid lobe showed uniformly low uptake. PET-CT evaluation confirmed spotty FDG-avid areas within the right thyroid mass but did not show other areas of hyperactivity. Methimazole was started with clinical and biochemical improvement. Patient underwent total thyroidectomy, and histopathologic examination showed PDTC with extensive angioinvasion involving the majority of the right thyroid lobe with the left lobe containing a mix of benign thyroid tissue and PDTC fragments. Areas of hyperintensity on the uptake scan correlated to pathological PDTC locations within the right lobe. Within three weeks of thyroidectomy, patient developed recurrent hyperthyroidism. Laboratory studies showed low TSH (0.04 uIU/mL) and elevated FT4 (2 ng/dL). In contrast to pre-operative studies, repeat TSI was below the reference range. Levothyroxine (LT4) was held in anticipation of radioactive iodine therapy, but four weeks later the TSH remained suppressed. 131I was administered which showed accumulation within small thyroid remnants and a single left level three 131I-avid lymph node without other metastases. Following 131I treatment, patient returned to a euthyroid state on standard LT4. Conclusion: Hyperthyroidism has rarely been associated with PDTC, although previous reports have linked more aggressive, multifocal, and locally invasive thyroid cancers to concurrent Graves’ disease or productive bulky metastatic disease. Even without bulky metastatic disease, clinicians should be aware that hyperproductivity may indicate development of autoimmune thyrotoxicosis within PDTC. Presentation Date: Saturday, June 17, 2023

Prediction of the recurrence risk of Graves' disease after antithyroid drug therapy

Objective: This study aimed at observing the prognostic factors for Graves' disease (GD) recurrence after treatment with antithyroid drugs. Patients and Methods: Clinical data for 247 patients with primary GD hyperthyroidism diagnosed in the endocrinology department of our hospital between March 2014 and February 2017 were collected. Age, sex, thyroid size, thyroid hormone levels, thyrotropin receptor antibody (TRAb), thyroglobulin antibody, thyroid peroxidase antibody, urinary iodine, and other prognostic factors before and after treatment were analyzed and compared. Results: After ATD treatment, 151 cases were in remission and 96 cases were not. The mean age at diagnosis was 37.3 ± 14.0 years in the remission group and 31.2 ± 12.2 years in the nonremission group (P = 0.032). The levels of free triiodothyronine (FT3) in the nonremission group and remission group were 25.7 ± 8.4 and 18.3 ± 9.1 pmol/L, respectively. The proportion of patients with goiter and thyroid-associated orbitopathy was higher in the nonremission group than the remission group. Similarly, both the FT3/FT4 ratio (4.63 ± 1.08 and 3.72 ± 0.69, P= 0.020) and TRAb level (27.4 ± 10.7% and 18.1 ± 9.8%, P= 0.001) significantly increased. Logistic regression analysis indicated that high thyroid volume (odds ratio [OR] =9.647, P= 0.003), high free T3/free T4 ratio (OR = 1.541, P= 0.019), and TRAb level (OR = 1.317, P= 0.002) were independent factors influencing drug treatment failure and were associated with poor prognosis. After drug withdrawal, patients with distinctly enlarged thyroid glands, thyroid-associated eye disease, and low serum thyroid-stimulating hormone (sTSH) levels were higher in the nonremission group than in the remission group. Conclusion: GD patients with goiter, high TRAb level and high FT3/FT4 ratio had poor poor response to drugs. The recurrence rate was high in patients with thyroid-related eye disease, and sTSH delayed recovery.

Association between Thyroid Function and Respiratory Distress Syndrome in Preterm Infants.

Thyroid hormones are known to influence the production and secretion of pulmonary surfactant. The objective of this study was to explore the relationship between respiratory distress syndrome (RDS) and thyroid hormones. This was a retrospective study of preterm infants at 24-33 weeks gestational age from April 2017 to February 2019. T3, free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured 1, 3, and 6 weeks after birth. Multivariate logistic regression analyses were performed to determine the relationship between RDS and TSH. A total of 146 infants were enrolled. Of these, 60 had RDS, 72 had no RDS, and 14 were excluded. T3 and TSH were lower in the RDS groups (p &lt; 0.05) on the day of birth. Multivariate logistic regression analysis indicated that lower serum TSH levels immediately after birth were associated with a higher incidence of RDS (OR, 0.89; 95% CI, 0.81-0.97). The TSH level was associated with the incidence of RDS. This suggests that suppression of the hypothalamus-pituitary axis function contributes to RDS, which is the result of surfactant deficiency.

Prevalence of Hyperthyroidism in Patients with Atrial Fibrillation

Background: Hyperthyroidism causes a rise in cardiovascular disease and dysrhythmias, leading to increased mortality. Low serum thyrotropin levels are a known independent risk factor for atrial fibrillation (AF). The frequency of hyperthyroidism in patients with AF is still unknown. Objectives: To determine the prevalence of hyperthyroidism in patients with AF admitted to a tertiary care hospital in Peshawar. Methodology: This was a cross sectional observational study that included 155 patients with AF. The study was conducted in the cardiology department of a tertiary care hospital in Peshawar, Pakistan, from December 2019 to May 2020. Results: Hyperthyroidism was found in 13(8.39%) patients with atrial fibrillation, while 142(91.61%) patients were without hyperthyroidism. There were 94 (60.65%) males and 61(39.35%) females. The ratio of male to female was 1.6: 1. The mean age of the patients enrolled was 50.35 years+14.95SD, with a range of 18-75 years. Patients were divided into three age groups, and atrial fibrillation was common in the 41-60 (years) age group. Conclusion: Hyperthyroidism is a recognized cause of atrial fibrillation. Every new-onset atrial fibrillation should be investigated with serum TSH levels. It can result in cerebral embolic episodes, particularly in the elderly and people with other risk factors. Keywords: Atrial fibrillation, Hyperthyroidism, Arrhythmia

TSH Receptor Antibody Testing in Early Pregnancy.

Graves disease (GD) is the leading cause of hyperthyroidism in women of childbearing age, and thus, low serum thyrotropin (TSH) during pregnancy might be expected to be largely secondary to GD. This is not the case for 2 reasons. First, autoimmunity frequently abates during pregnancy, including thyroid-specific autoimmunity (1), so that even those with previously diagnosed GD may go into remission during pregnancy. Second, the physiology of thyroid hormone regulation is altered as a result of the agonist activity of β-human chorionic gonadotropin (βhCG) at the TSH receptor (2). Under normal conditions this leads to a slight increase in thyroid hormone production, which is independent of pituitary TSH secretion. Serum TSH levels fall, resulting in a left shift of the TSH reference range in pregnancy, and a lower limit of 0.1 mU/L in most assays (3). In early pregnancy especially, elevations of serum βhCG above those typically seen can cause a further rise in serum free thyroxine and more dramatic suppression of the serum TSH, resulting in “gestational transient thyrotoxicosis” (GTT) (3). This is typically mild and resolves after the first trimester, and is not associated with adverse pregnancy outcomes (4). The very high levels of βhCG found in hyperemesis gravidarum are associated with more severe biochemical thyrotoxicosis, and extremely high levels seen with molar pregnancy and choriocarcinoma can require antithyroid drug therapy and other measures to mitigate thyrotoxicosis. Indeed, persistent thyrotoxicosis during pregnancy from any cause, especially GD, has been associated with poor outcomes including fetal loss, maternal heart failure, and preeclampsia (5).

Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia.

SummaryBiallelic pathological variants in the thyroid stimulating hormone (TSH) subunit β gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism.Learning pointsPathogenic variants in the TSH subunit β gene (TSHB) are rare causes of central congenital hypothyroidism (CCH).c.217A>C, p.(Thr73Pro), is a novel TSHB variant, presented in association with CCH in this case report.Thyroxine replacement is critical to prevent clinical hypothyroidism and pituitary hyperplasia.Pituitary hyperplasia can recur post-surgery if adherence to thyroxine replacement is not maintained.Pituitary hyperplasia can dramatically reverse if compliance with thyroxine replacement is improved to maintain free thyroxine (FT4) levels in the middle-to-upper normal range, without the need for additional medications or surgeries.

Sudden weakness due to thyrotoxic periodic paralysis: a case report

Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism. Lead to sudden hypokalemia and muscle weakness. In most cases, it is found mainly in young adult males of the Asian race. The paralysis is temporary and will return with potassium correction. There are very few cases reported in Indonesia regarding these cases of TPP. In our case, a 44-year old man complained of weakness that started later in the limbs but quickly improved. This case was diagnosed late at first, and uncorrected potassium levels led to recurrent paralysis. Laboratory test results showed severe hypokalemia (potassium level 1.81 mmol/L). The thyroxine level (T4) was 44.12 pmol/L and low serum thyroid-stimulating hormone (TSH) &lt;0.0025 IU/mL.

Comorbidities of patients with chronic obstructive pulmonary disease (COPD): thyroid abnormalities in stable COPD

Objective: The aim of the study is to evaluate the prevalence of thyroid abnormalities in patients with stable chronic obstructive pulmonary disease (COPD) and the relationship between thyroid disorder and ventilatory function tests and arterial blood gas analyses. Material and methods: This cross-sectional study was conducted with 60 patients with stable COPD without diagnosed thyroid disorder before the study (37 males and 23 females aged 40–75) as the Investigated Group (IG) and 30 subjects from the general population without COPD as the Control Group (CG). They were matched by age, gender and body mass index with the IG. All patients underwent laboratory tests, thyroid hormones –free thyroxin (fT4), thyroid-stimulating hormone (TSH), and free triiodothyronine (fT3), pulmonary function tests (FEV1, FVC%, FEV1/FVC, FEF25–75%), and ABG parameters (PH, PaCO2, PaO2, HCO3, O2 saturation). The severity level in patients with COPD was determined according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria and classified into four stages GOLD I, II, III, and IV. Results: Our results presented a statistically significant difference between prevalence of thyroid hormones abnormalities in stable COPD compared to controls 18 (30.0%) vs 3 (10.0%), p = 0.0355; p &lt; 0.05). Thyroid dysfunction among COPD patients was more common in females than males. Serum level of TSH was lower than the normal range in 18 patients (30.0%) from the IG and in 3 (10.0%) from the CG, with a statistically significant difference, p = 0.0355; p &lt; 0.05. Thyrotoxicosis with low serum TSH and a higher serum level of fT3, according to the referent range, was present in 8 patients (13.3%), and in no patients from the CG 0 (0.0%), p = 0.0375; p &lt; 0.05. The prevalence of subclinical hyperthyroidism with low serum TSH and normal serum level of fT3 was higher in the IG –10 patients (16.7%) compared with 3 (10.0%) of the CG, but the difference was not statistically significant p = 0.3970. Acute exacerbation frequency of IG was significantly higher than in the CG (1.6 ± 0.42 and 0.82 ± 0.79 respectively; p &lt; 0.0001). A positive significant relationship between acute exacerbation frequency and TSH values was found (p &lt; 0.0001; r = 0.82). The mean values of fT3 in the IG were significantly increasing with the increased severity of COPD. The degree of airflow limitation in COPD (FEV1 as a percentage of the predicted value, FEV1%pred) was significantly negatively correlated to fT3, Pearson correlation, (R = -0.525; p = 0.000; p &lt; 0.01). FEV1%pred was positively correlated with TSH (R = 0.358; p = 0.005; p &lt; 0.01). Significant negative correlations were present between fT3 levels and both PaO2 and SO2 in the IG, and elevation of fT3 was associated with higher PaCO2. Conclusion: The present study confirms that both clinical and subclinical hyperthyroidism was higher in patients with COPD compared to the non-COPD group. TSH and fT3 are related to lung function. A better understanding of the correlation between thyroid gland disorders and COPD may contribute to better care of patients.

Does serum TSH level act as a surrogate marker for psychological stress and cardio-metabolic risk among adolescent and young people?

The incidence of metabolic syndrome is increasing even at younger ages. Metabolic syndrome constitutes a group of cardiovascular risk factors that include high cholesterol, triacylglycerol, hyperglycemia, central obesity, etc., which increases the risk of cardiovascular disease, diabetes mellitus, may be even cancer. Indian students enter colleges just after crossing their adolescent age and will be exposed to greater academic stress. Psychological stress or depression is associated with transient change in thyroid hormones level or dysfunction. To explore an association among serum Thyroid Stimulating Hormone (TSH) levels, fT3:fT4 ratio, psychological stress scores, and selected known cardio-metabolic risk markers. Forty first year MBBS students were included. Their demographic, anthropometric variables, and the blood pressure were documented. Serum TSH, fT3, fT4, and salivary cortisol level was quantified. The stress level was assessed using Cohen Perceived Stress Scale Scoring. Data were expressed in mean±standard deviation. Data (parametric/non-parametric) were compared by Independent unpaired ANOVA or Kruskal Wallis test whichever is appropriate. Spearmen correlation analysis was performed. Serum TSH and Cohen stress score are negatively correlated (r=-0.152), but serum cortisol showed (r=0.763) a positive correlation. TSH levels and the marks obtained in the summative assessments were negatively correlated and the correlation was not statistically significant. The psychological stress is associated with low serum TSH, high cortisol, and poor academic performance in first year MBBS students. Blood pressure, plasma glucose, and anthropometric measures were not associated with the psychological stress.

Serial measurement of thyroid hormones in hospitalised dogs with canine parvoviral enteritis: Incidence of non-thyroidal illness syndrome and its association with outcome and systemic inflammatory response syndrome

The aim of this study was to serially evaluate the serum concentrations of total thyroxine (tT4), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) in dogs with canine parvoviral enteritis (CPVE) during a 5-day hospitalisation period and assess the association of these hormone concentrations with the outcome and the development of systemic inflammatory response syndrome (SIRS). Dogs with confirmed CPVE that were hospitalised for at least 5 days were included. The thyroid hormones concentrations were measured on days 1, 3 and 5 of hospitalisation.Twenty-eight dogs were included. All (28/28, 100%), 19/28 (69.7%) and 23/28 (82.1%) dogs had a low serum tT4, fT4 and TSH concentration, respectively, on at least 1 day during the hospitalisation period. Overall, 11/28 (39.3%) dogs were diagnosed with SIRS on at least 1 day. In survivors, serum tT4 concentration was significantly higher on day 5 (median, range: 11.8 nmol/L, <6.4–32.2 nmol/L) compared to those on days 1 (<6.4 nmol/L, <6.4–20.1 nmol/L; P = 0.010) or 3 (7.6 nmol/L, <6.4−25.2 nmol/L; P = 0.019). Survivors had a significantly higher tT4 concentration (median, range: 11.8 nmol/L, <6.4–32.2 nmol/L) on day 5 compared to non-survivors (<6.4 nmol/L, <6.4–7.2 nmol/L; P = 0.002). Regardless of the day of hospitalisation, dogs with SIRS had significantly lower tT4 (<6.4 nmol/L, <6.4–16.3 nmol/L) compared to dogs without SIRS (8.6 nmol/L, <6.4–32.2 nmol/L; P = 0.006). A significant difference was also found in fT4 between dogs with SIRS (<3.9 pmol/L, <3.9–16.2 pmol/L) and dogs without SIRS (15.1 pmol/L, <3.9−59.2; pmol/L; P < 0.001). Non-thyroidal illness syndrome was frequently observed in dogs with CPVE, and a negative association between tT4 and fT4 concentrations and SIRS was noted. Serial measurements of tT4 concentrations appeared to have prognostic value.

Changes in Serum Thyroid Function Predict Cognitive Decline in the Very Old: Longitudinal Findings from the Newcastle 85+ Study.

Background: Low serum thyrotropin (TSH) has been associated with an increased risk of cognitive impairment in observational studies of older individuals, but the mechanism underlying this is unclear. We investigated the association between changes in thyroid status and cognitive impairment in very old adults, using prospective data from the Newcastle 85+ study. Method: A cohort of 85-year-old individuals was assessed for health status and thyroid function. Complete data from a comprehensive multidimensional measure of health and repeat thyroid function were available for 642 participants with normal free thyroid hormones and TSH levels ranging between 0.1 and 10 mU/L. Cognitive performance, assessed using Mini-Mental State Examination (MMSE) and Cognitive Drug Research battery was examined by using linear mixed, logistic regression, and Cox proportional hazard models in relation to baseline and 3-year changes in serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3). Results: Over 3 years, declining serum TSH was associated with reductions in fT4 and fT3, and an increased risk of incident cognitive impairment by 5 years (odds ratio1.77 [95% confidence interval: 1.19-2.61]; p = 0.004). A greater reduction in MMSE score was associated with larger TSH decline, at 3 (p = 0.001) and 5 years (p < 0.001), respectively. Steady fT4 concentrations were found in participants with rising TSH. Conclusions: In contrast to physiological expectation, in this group of 85-year-olds, a declining serum TSH was associated with reductions in free thyroid hormones over time. A decreasing serum TSH trajectory over time anticipated cognitive decline in later life. Declining TSH concentrations are a biomarker for cognitive impairment in later life.

Low serum TSH levels are associated with low values of fat-free mass and body cell mass in the elderly

Previous studies on the association between thyroid function and body composition are conflicting and showed strong differences across age groups. Our aim was to clarify age-specific associations of serum thyroid-stimulating hormone (TSH) levels with markers of body composition including body mass index (BMI), waist circumference, fat mass (FM), fat-free mass (FFM) and body cell mass (BCM). We used data from two independent population-based cohorts within the framework of the Study of Health in Pomerania. The study population included 5656 individuals aged 20 to 90 years. Markers of body composition were measured by bioelectrical impedance analysis. Serum TSH levels were significantly positively associated with BMI (β = 0.16; 95% confidence interval [CI]: 0.06 to 0.27), waist circumference (β = 0.35; 95% CI: 0.08 to 0.62) and FM (β = 0.32; 95% CI: 0.12 to 0.52), but not with FFM and BCM. Interaction analysis revealed positive associations of serum TSH levels with BMI, waist circumference, FM, FFM and BCM in individuals older than 60 years, while no such associations were observed in younger individuals. We demonstrated that lower serum TSH levels were accompanied with lower values of BMI, waist circumference, FM, FFM, and BCM in the elderly, while no such associations were observed in younger individuals.

Thyrotoxicosis: A Primary Cause of Arrhythmias and Acute Heart Failure

Thyrotoxicosis results from excessive thyroid hormone and may occur in Graves’ disease, multinodular goiter, and thyroiditis. The association of hyperthyroidism with the worsening of pre-existing heart disease is very well recognized. Additionally, hyperthyroidism can also cause primary cardiac disease including arrhythmias and congestive heart failure. We present a 65-year-old female with a past medical history of intermittent palpitations who came to the emergency department with shortness of breath and bilateral lower extremity swelling. Physical exam revealed an anxious woman with bilateral proptosis, jugular venous distention, bibasilar crackles, and bilateral lower extremity edema. Laboratory data was significant for a brain natriuretic peptide level of 1,930. Chest x-ray revealed vascular congestion. Transthoracic echocardiogram showed an ejection fraction of 63% and diastolic dysfunction. She was admitted and received diuretics for acute heart failure. She developed atrial fibrillation with a rapid ventricular response, managed with a diltiazem infusion and anticoagulation. This event prompted thyroid evaluation which showed a thyroid-stimulating hormone (TSH) of 0.01mU/L, elevated free T4 at 3.37ng/dl, free T3 at 5.8pg/ml, positive Thyroid-stimulating immunoglobulins (TSI) 473%, and thyroid peroxidase (TPO) antibodies 158U/ml. Her symptoms improved after treatment with methimazole. The heart is susceptible to hyperthyroidism due to multiple thyroid hormone receptors on cardiac myocytes causing high sympathetic stimulation from an increased number of myocardial beta-cell receptors. Atrial fibrillation occurs in 10 to 20% of patients with hyperthyroidism and is prevalent among the elderly population. People 60 years and above with a low serum thyrotropin concentration are at a threefold higher risk of developing atrial fibrillation in the subsequent decade. Complications such as cerebrovascular accidents occur in about 14% of cases. About 6% of thyrotoxic individuals develop heart failure secondary to a tachycardia mediated mechanism, leading to an increased level of cytosolic calcium during diastole. This causes reduced ventricular contractility and diastolic dysfunction, often associated with tricuspid regurgitation. Graves’ disease is an autoimmune process characterized by hyperthyroidism due to circulating autoantibodies. TSI binds to and activates thyrotropin receptors, causing the increased synthesis of thyroid hormones. If left untreated, Graves’ disease can lead to severe thyrotoxicosis. Clinicians should be aware of this disease association and ensure thorough clinical investigation, prompt diagnosis, and treatment of thyrotoxicosis to avert these life-threatening events.

Painful Subacute Thyroiditis is Commonly Misdiagnosed as Suspicious Thyroid Nodular Disease.

ObjectiveTo investigate and characterize the clinical and radiologic features of 10 patients with painful subacute thyroiditis with ultrasound findings considered suspicious for malignancy or for whom biopsy of a suspicious area was recommended by an attending radiologist.Patients and MethodsTen patients with painful subacute thyroiditis were seen from June 1, 2016, through January 1, 2019. All 10 patients presented to an endocrine or thyroid clinic with a neck ultrasound report stating findings suspicious for malignancy or nodular disease. Clinical, laboratory, radiographic, and pathologic data were (retrospectively collected and) reviewed.ResultsThe mean ± SD patient age was 49.0±15.0 years at diagnosis; 8 patients were female. All the patients presented with a low or undetectable serum thyrotropin level. Six of 7 patients with available inflammatory markers had elevated levels. Thyrotropin receptor antibodies were absent in all 6 patients tested. On follow-up imaging, 8 patients had complete resolution or improvement of described findings, 1 was lost to follow-up, and 1 had an incidental nodule that was biopsied after the episode of thyroiditis and found to be papillary thyroid carcinoma.ConclusionPainful subacute thyroiditis demonstrates specific sonographic patterns that may be misdiagnosed as suspicious thyroid nodular disease. Recognition of the innocent and transient nature of these findings is important for the proper management and monitoring of these patients.

Association between Thyroid Hormones, Apolipoprotein E, and Cognitive Function among Cognitively-Normal Elderly Dwellers.

ObjectiveThe correlation among the thyroid-related hormones, Apolipoprotein E ε4 (APOE ε4) and cognitive function has been reported despite controversial results. This study was designed to investigate this correlation among cognitively-normal elderly dwellers. MethodsThis study assessed 507 cognitively normal individuals aged over 60 who underwent comprehensive hematological and neuropsychological assessments including the quantification of serum free thyroxine and thyroid stimulating hormone (TSH) as well as the Korean version of the Consortium Establish a Registry for Alzheimer’s disease. The Korean version of Geriatric Depression Scale was also employed to evaluate the severity of depression. Age, gender, education, and the presence of APOE ε4 were taken into account as covariates. ResultsThere was a significant positive association between verbal fluency test (VFT), Word List Memory Test (WLMT), and Word List Recall Test (WLRT) score and serum TSH levels (p=0.007, 0.031, and 0.023 respectively). The further analysis adding the interaction between APOE ε4 and TSH level, however, revealed only VFT score was significantly influenced by this interaction (p=0.026). ConclusionLower serum TSH levels had impacts on both semantic memory (VFT) and episodic memory (WLMT, WLRT) among cognitively-normal elderly, whereas the interaction of TSH and APOE ε4 influenced only the task of semantic memory (VFT) in this group.

Reirradiation for recurrent craniopharyngioma

PurposeReirradiation is rarely administered to patients with recurrent craniopharyngioma owing to concerns regarding visual and endocrine side effects. The purpose of this case series was to evaluate our institutional experience of patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy. Methods and MaterialsA retrospective study was performed of all patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy at a single institution. Electronic medical records and radiation therapy records were reviewed. ResultsWe identified 4 eligible patients with recurrent craniopharyngioma. With a median follow-up of 33 months after reirradiation, 3 patients attained disease control; 1 patient developed progressive disease, 27 months after reirradiation. In 3 evaluable patients, vision remained stable or improved after reirradiation; one patient had no light perception before reirradiation. None of the patients experienced additional endocrine toxicities after reirradiation, apart from one patient who had low serum thyroid stimulating hormone before reirradiation and later developed hypothyroidism after treatment. ConclusionsReirradiation may represent a safe and effective therapeutic option for selected patients with recurrent, refractory craniopharyngioma and without other salvage treatment options. Larger studies with longer-term follow up are warranted to better understand outcomes in these patients.