BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) levels can increase the cardiometabolic risk factors in patients with hypothyroidism, but the findings across studies have not been consistently conclusive. The aim of this study was to find the association between non-HDL-C and cardiometabolic risk factors in patients with hypothyroidism.
METHODS: In this case-control study, a total of 120 subjects among which 60 diagnosed hypothyroidism patients and 60 age-matched healthy controls were enrolled, aged 30-65 years. Body mass index (BMI), waist circumference (WC), and systolic and diastolic blood pressures (SBP and DBP) were measured. Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), fasting blood sugar (FBS), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were estimated. Low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and non-HDL-C were calculated. A p-value of <0.05 was considered statistically significant.
RESULTS: Mean of BMI, WC, FBS, TSH, TC, TG, non-HDL-C, LDL-C, VLDL-C, SBP, and DBP were significantly elevated in cases compared to controls (p<0.001). However, the mean of T3, T4, and HDL-C were significantly reduced in cases compared to controls (p<0.001). Non-HDL-C has shown a significant positive correlation with age (r=0.345, p<0.01), TC (r=0.451, p<0.01), TG (r=0.269, p<0.05), LDL-C (r=0.402, p<0.01), and VLDL-C (r=0.269, p<0.05) among cases. However, non-HDL-C has shown a significant negative correlation with HDL-C (r=-0.330, p<0.05) among cases. Non-HDL-C significantly predicted cardiometabolic risk in patients with hypothyroidism (F(13,46)=3.500, p<0.001).
CONCLUSIONS: Non-HDL-C has shown a significant association with age and lipid abnormalities in patients with hypothyroidism. Non-HDL-C significantly predicts cardiometabolic risk factors in patients with hypothyroidism.

BACKGROUND: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of acute and chronic thyroid eye disease (TED) related to hyperthyroidism. Given the lower incidence of TED associated with hypothyroidism / euthyroidism, there is a paucity of data regarding the efficacy of teprotumumab in this group.
METHODS: In this multicenter study, consecutive patients who had been diagnosed with TED, presenting with either hypothyroidism or euthyroidism as their baseline thyroid dysfunction and treated with teprotumumab were included. All patients had measurements of proptosis, clinical activity scores (CAS), diplopia scores and four-point strabismus scores before and after therapy.
RESULTS: Twenty-six patients met the inclusion criteria. Mean age was 48 ± 14 years old and mean duration of TED prior to treatment was 31 ± 43 months. All patients received 8 infusions. Mean (SD) reduction in proptosis for study orbits was 2.7 mm (1.8) (p < 0.05) and 1.8 mm (2.0) for the fellow orbit (p < 0.05). In the study orbit, mean (SD) CAS was 2.3 (1.3) before therapy and 1.0 (1.0) following therapy (p < 0.05). At baseline, mean (SD) diplopia score was 1.2 (1.1) and 0.9 (1.1) following therapy (p < 0.05).
CONCLUSIONS: Teprotumumab reduces proptosis and inflammation in patients presenting with TED associated with hypothyroidism and euthyroidism. The results of this study highlight the potential for teprotumumab therapy in this subgroup and also provide a unique insight into the potential role of the IGF-1R in these patients.

BACKGROUND: Subclinical hypothyroidism (SCH) in pregnancy is associated with adverse foetomaternal outcomes. The literature is scarce with respect to maternal and perinatal outcomes in women with mild SCH (TSH levels between 2.5-4 mIU/L).
OBJECTIVE: The primary objective of the study was to compare the pregnancy outcome between SCH and euthyroid women. The secondary objectives were to find out the proportion of women with SCH having thyroid peroxidase antibodies (TPOAb) and to see the effect of TPOAb positivity on foetomaternal outcomes.
METHODS: A total of 178 pregnant women were recruited in the first trimester, and those with TSH between 0.1 and 2.4 mIU/L were considered as euthyroid and 2.5-4mIU/L were labelled as SCH. Women with SCH underwent testing for TPOAb. All women were followed until delivery, and foetomaternal outcomes were assessed.
RESULTS: Amongst SCH group, there was a significantly higher proportion of overweight and obese women (76/91 (83.51%) vs 59/87 (68%), p = 0.031). The neonatal intensive care unit (NICU) admission was higher with adjusted odds ratio of 3.24 (1.41-7.43) in women with SCH as compared to euthyroid women. Otherwise, there was no difference in foetomaternal outcomes between the two groups. The proportion of gestational diabetes mellitus, intrauterine growth retardation and still birth were higher in SCH women with TPOAb as compared to euthyroid. Amongst SCH women, the proportion of induced labour was lower (aOR:0.27 (0.08-0.93) whereas the proportion of stillbirth and low APGAR scores were higher in TPOAb-positive women with a statistically significant difference and adjusted odds ratio (aOR:20.18 (1.84-220.83)) and (aOR:4.77 (1.06-21.3)), respectively, when compared to TPOAb-negative women.
CONCLUSIONS: There appears to be no difference in pregnancy outcomes between women with SCH and euthyroid women except higher NICU admission in SCH group. Future multi-centre large prospective studies are required to understand better about the pregnancy outcomes in these women.

Hypothyroidism is an endocrine disorder with a high worldwide prevalence and diverse clinical presentation and can affect multiple organ systems. It can be asymptomatic and subclinical or overtly symptomatic and can prove to be fatal if left untreated. It is an established cause of pericardial effusion, which can rarely lead to cardiac tamponade and severe haemodynamic instability. Herein, we present a few unusual case reports of patients presenting with hypothyroidism with varied causes who presented with tamponade.

BACKGROUND: The incidence of hypothyroidism following hemithyroidectomy and risk factors associated with its occurrence are not completely understood. This systematic review investigated the incidence and risk factors for hypothyroidism, thyroxine supplementation following hemithyroidectomy as well as the course of post-operative hypothyroidism, including the time to hypothyroidism and incidence of transient hypothyroidism.
METHODS: Searches were conducted in MEDLINE, EMBASE, Scopus, and Cochrane library for studies reporting the incidence of hypothyroidism or thyroxine supplementation following hemithyroidectomy.
RESULTS: Sixty-six studies were eligible for inclusion: 36 reported risk factors, and 27 reported post-operative course of hypothyroidism. Median follow-up was 25.2 months. The pooled incidence of hypothyroidism was 29% (95% CI, 25-34%; P<0.001). Transient hypothyroidism occurred in 34% of patients (95% CI, 21-47%; P<0.001). The pooled incidence of thyroxine supplementation was 23% (95% CI, 19-27%; P<0.001), overt hypothyroidism 4% (95% CI, 2-6%, P<0.001). Risk factors for development of hypothyroidism included pre-operative thyroid stimulating hormone (TSH) (WMD, 0.87; 95% CI, 0.75-0.98; P<0.001), TSH ≥ 2 mIU/L (RR, 2.87; 95% CI, 2.43-3.40; P<0.001), female sex (RR, 1.19; 95% CI, 1.08-1.32; P=0.007), age (WMD, 2.29; 95% CI, 1.20-3.38; P<0.001), right sided hemithyroidectomy (RR, 1.35; 95% CI, 1.10-1.65, P=0.003), the presence of autoantibodies anti-TPO (RR, 1.92; 95% CI, 1.49-2.48; P<0.001), anti-Tg (RR, 1.53; 95% CI, 1.40-1.88; P<0.001), and Hashimoto\'s thyroiditis (RR, 2.05; 95% CI, 1.57-2.68; P=0.001).
CONCLUSIONS: A significant number of patients will develop hypothyroidism or require thyroxine following hemithyroidectomy. An awareness of patient risk factors and postoperative thyroid function course will assist in counselling patients on their risk profile and guiding management.

BACKGROUND: Thyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid-treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known.
OBJECTIVE: To determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes.
METHODS: Prospective cohort study involving 46 euthyroid (anti-thyroid peroxidase antibody negative) and 16 levothyroxine-replaced women with baseline thyroid-stimulating hormone (TSH) <2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick-up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared.
RESULTS: Median serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine-replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine-replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ.
CONCLUSIONS: Adequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.

Thyroid hormone (TH) system disrupting compounds can impair brain development by perturbing TH action during critical life stages. Human exposure to TH system disrupting chemicals is therefore of great concern. To better protect humans against such chemicals, sensitive test methods that can detect effects on the developing brain are critical. Worryingly, however, current test methods are not sensitive and specific towards TH-mediated effects. To address this shortcoming, we performed RNA-sequencing of rat brains developmentally exposed to two different thyroperoxidase (TPO) inhibiting compounds, the medical drug methimazole (MMI) or the pesticide amitrole. Pregnant and lactating rats were exposed to 8 and 16 mg/kg/day(d) MMI or 25 and 50 mg/kg/d amitrole from gestational day 7 until postnatal day 16. Bulk-RNA-seq was performed on hippocampus from the 16-day old male pups. MMI and amitrole caused pronounced changes to the transcriptomes; 816 genes were differentially expressed, and 425 gene transcripts were similarly affected by both chemicals. Functional terms indicate effects from key cellular functions to changes in cell development, migration and differentiation of several cell populations. Of the total number of DEGs, 106 appeared to form a consistent transcriptional fingerprint of developmental hypothyroidism as they were similarly and dose-dependently expressed across all treatment groups. Using a filtering system, we identified 20 genes that appeared to represent the most sensitive, robust and dose-dependent markers of altered TH-mediated brain development. These markers provide inputs to the adverse outcome pathway (AOP) framework where they, in the context of linking TPO inhibiting compounds to adverse cognitive function, can be used to assess altered gene expression in the hippocampus in rat toxicity studies.

Myxedema is a medical emergency with high mortality rates if not treated aggressively. Here, we present a middle-aged female with complaints of generalized body swelling for one year, shortness of breath, hoarseness of voice, neck swelling, and cough for 20 days. The patient was diagnosed to be having severe hypothyroidism with polyserositis. Contrast-enhanced computed tomography (CECT) of the neck and thorax revealed extensive soft tissue edema causing airway narrowing, bilateral pleural effusion, moderate pericardial effusion, and features of atypical pneumonia. The patient was started on levothyroxine and antibiotics as per cultures to which she had initially improved; however, she developed ventilator-associated pneumonia leading to sepsis, acute respiratory distress syndrome followed by refractory type 1 respiratory failure and succumbed.

BACKGROUND: Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism; however, 10-15% of patients have persistent hypothyroid symptoms despite normalizing thyroid hormone levels with LT4. This study aims to summarize the best available evidence on interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms.
METHODS: A systematic search was conducted in March 2022 for randomized controlled trials and observational studies on interventions for adult patients with persistent hypothyroid symptoms despite biochemical euthyroidism on thyroid hormone replacement.
RESULTS: A total of 277 articles were reviewed and seven fulfilled the inclusion criteria. 455 participants were included. Most intervention participants were female (78.6%) with a mean age of 47.5 (±2.8) years. Five clinical trials evaluating ginger (vs. starch), L-carnitine (vs. placebo), combination LT4 and liothyronine (LT3) (vs. LT4 or placebo), and surgery for patients with serum antithyroid peroxidase (TPO Ab) titers greater than 1000 IU/ml (vs. LT4) found inconsistent improvement in hypothyroidism related symptoms and general health. The two clinical trials with the largest improvement in fatigue scores were the use of ginger and surgery. One observational study comparing thyroidectomy vs observation found no significant difference on general health. Lastly, another observational study evaluating combination LT4/LT3 (vs. LT4 monotherapy) found improvement in fatigue and quality of life. There were 31 (12%) adverse events in the intervention group and 18 (10.8%) in the comparator group.
CONCLUSIONS: There is no high-quality evidence supporting any intervention for persistent symptoms in hypothyroidism. Available evidence, limited by the risk of bias, inconsistency, and heterogeneity, suggests that some persistent symptoms, particularly fatigue, could improve with ginger and thyroidectomy.

OBJECTIVE: Hypothyroidism is a known possibility after hemithyroidectomy, with a highly variable incidence in the literature ranging from 8 to 60 %. Incidence of hypothyroidism after hemithyroidectomy was evaluated with a secondary aim to assess incidence in patients with Hashimoto\'s disease.
METHODS: A retrospective study using the TriNetX global federated research network was performed. We included patients within the last 15 years that were ≥18 years of age and had Current Procedural Terminology codes for hemithyroidectomy. Patients were excluded if they had a total or completion thyroidectomy at any time, a history of thyroid cancer, were preoperatively either on levothyroxine, diagnosed with hypothyroidism, or had a Thyroid Stimulating Hormone ≥ 4 m[IU]/L. We assessed the 3 month incidence of hypothyroidism postoperatively based on the International Classification of Diseases code, TSH ≥ 4 m[IU]/L, or taking levothyroxine after surgery.
RESULTS: 6845 patients met the inclusion criteria. Most of the cohort was female (67 %) and white (63 %). The mean age at surgery for this population was 54 ± 14.8 years. During the 15 years of data, we found the 3-month incidence of hypothyroidism following hemithyroidectomy to be 23.58 %. The median time to develop the disease was 41.8 months. A subgroup analysis of those with Hashimoto\'s revealed a 3-month incidence of 31.1 % of patients developing hypothyroidism after surgery.
CONCLUSIONS: This population-based study gives additional insight into the incidence of hypothyroidism after hemithyroidectomy. This will help improve perioperative patient counseling and management.