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Thyroid hormones play an important role in brain development, and thyroid hormone insufficiency during the perinatal period results in severe developmental delays. Perinatal thyroid hormone deficiency is clinically known as congenital hypothyroidism, which is caused by dysgenesis of the thyroid gland or low iodine intake. If the disorder is not diagnosed or not treated early, the neuronal architecture is perturbed by thyroid hormone insufficiency, and neuropathological findings, such as abnormal synapse formation, defects in neuronal migration, and impairment of myelination, are observed in the brains of such patients. Furthermore, the expression of psychiatric disorder-related molecules, especially parvalbumin, is significantly decreased by thyroid hormone insufficiency during the perinatal period. Animal experiments using hypothyroidism models display decreased parvalbumin expression and abnormal brain architecture, and these experimental results show reproducibility and stability. These basic studies reinforce the results of epidemiological studies, suggesting the relevance of thyroid dysfunction in psychiatric disorders. In this review, we discuss the disruption of brain function associated with congenital hypothyroidism from the perspective of basic and clinical research.

Thyroid hormone exerts effects across all organ systems. Hence, patients with thyroid dysfunction are at a risk of numerous complications. The stresses encountered during the perioperative period may exacerbate underlying thyroid disorders, potentially precipitating decompensation, and even death. Thus, it is of the utmost importance for the clinician to comprehend the mechanisms by which thyroid disease may complicate surgery and postoperative recovery and to optimize the status of thyrotoxic and hypothyroid patients. This article describes the adverse effects of thyroid dysfunction in patients undergoing nonthyroid surgery and recommends treatment approaches aimed at appropriate build-up to decrease perioperative risk.

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). Conclusion 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.

ObjectiveTo compare the demographic and clinical phenotypes of thyroid-associated ophthalmopathy (TAO) with euthyroidism (Eu-TAO), hyperthyroidism (Hr-TAO), and hypothyroidism (Ho-TAO).MethodsWe enrolled 2158 TAO patients in this retrospective study and assessed their demographics, clinical manifestations, activity, and severity.ResultsAmong the enrolled patients, 526 (24.37%) had Eu-TAO, 1544 (71.55%) had Hr-TAO, and 88 (4.08%) had Ho-TAO. Compared to Hr-TAO (2.02) and Ho-TAO (2.52) patients, Eu-TAO (1.57) patients had the lowest female-to-male ratio (p = 0.026). The mean ages of Eu-TAO, Hr-TAO, and Ho-TAO patients were 43.11 ± 12.05, 42.23 ± 13.63, and 47.39 ± 13.28 years, respectively (p = 0.001). Patients with Eu-TAO had more unilateral involvement (50% vs. 14.38% vs. 21.59%, p < 0.001) than Hr-TAO or Ho-TAO patients. Clinically active TAO patients presented 8.56% in euthyroid vs. 13.86% in hyperthyroid vs. 11.36% in hypothyroid (p = 0.006). Regarding the severity of the European Group on Graves’ Orbitopathy (EUGOGO) classification among euthyroid, hyperthyroid, and hypothyroid patients, mild TAO was present in 67.68, 54.27, and 72.72% of participants, moderate-to-severe TAO in 31.18, 42.49, and 26.14%, and sight-threatening TAO in 1.14, 3.24, and 1.14%, respectively. Eu-TAO was positively correlated with unilateral involvement (OR = 5.671, p < 0.001) and age (OR = 1.013, p = 0.003) and negatively correlated with the female-to-male ratio (OR = 0.656, p < 0.001) and TAO severity (OR = 0.742, p < 0.01).ConclusionsEu-TAO patients are older and less likely to be female, and show more unilateral and milder clinical phenotypes than hyper/hypothyroid TAO patients.

Context: The association between depression and thyroid function is well known. Both conditions express many similar symptoms, thus making the diagnosis and treatment difficult. Aims: To find the prevalence of anxiety and depressive symptoms among patients with hypothyroid. Settings and Design: Cross-sectional study. Materials and Methodology: A total of 100 patients diagnosed as hypothyroidism were evaluated using Hamilton depression rating scale (HDRS) and Hamilton scale for anxiety (HAM-A). Statistical Analysis Used: The data were analyzed using the SPSS for Windows version 17.0 software. The quantitative data were expressed in number and percentage. The results obtained were compared using the Chi-square test. Results: Females constituted 70% of the sample. A total of 60% reported some degree of depression based on HDRS (males - 56.63% and females - 64.29%) whereas about 63% out of the total patients screened showed some degree of anxiety (males -56.66% and females - 65.72%) based on HAM-A. The most common depressive symptom among the males was depressed mood (73.33%) and among females was gastrointestinal somatic symptoms (68.54%). The most common anxiety symptom among the males was depressed mood (70.0%) and among females was anxious mood (92.85%). Conclusions: Psychiatric symptoms/disorders are common in patients with thyroid dysfunction.

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.

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). Conclusion 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. Key messages What is known Teprotumumab’s established efficacy in treating Thyroid Eye Disease (TED) associated with Grave’s disease is grounded in its ability to target and modulate the insulin-like growth factor 1 receptor (IGF-1R) pathway. What is new This series highlights teprotumumab’s efficacy in treating TED in patients suffering from autoimmune thyroid disease with hypothyroid or euthyroid state. The results suggest that teprotumumab effectiveness in this group is not inferior to what is currently known, suggesting dysfunction of the IGF-1R pathway is common to all patients with TED irrespective of the accompanying thyroid dysfunction.

Hypothyroidism is associated with metabolic, neurobehavioral, and reproductive alterations that may involve neuroendocrine regulatory peptides. Spexin, a neuropeptide implicated in energy homeostasis, has recently attracted attention for its possible role in thyroid and reproductive axis regulation. Therefore, this study aimed to investigate the effects of spexin on neurobehavioral responses and the tissue-specific expression of irisin and KISS-1 in the cerebral cortex and testis under hypothyroid conditions. Thirty-two male rats were randomly divided into four groups: Control, Hypothyroid (methimazole, 0.03% in drinking water for 35 days), Hypothyroid + Spexin (methimazole plus spexin, 25 µg/kg, intraperitoneally), and Spexin (25 µg/kg, intraperitoneally). Behavioral assessments were performed using the Open Field Test and Forced Swim Test. Serum thyroid hormone levels were analyzed, and brain and testis tissues were evaluated immunohistochemically for irisin and KISS-1 expression. Hypothyroid rats showed increased thyroid-stimulating hormone levels, decreased thyroxine concentrations. Spexin administration significantly reduced TSH levels and increased T4 concentrations. Spexin treatment reduced thigmotaxis compared to controls. No significant differences were found among groups in overall locomotor activity, time spent in the central zone, or FST parameters. Immunohistochemical analyses demonstrated reduced irisin and KISS-1 expression in hypothyroid rats, which was restored following spexin treatment. In conclusion, spexin exerted TSH-suppressive and T4-enhancing effects in experimental hypothyroidism. Its effects on irisin and KISS-1 expression suggest potential involvement in neuroendocrine and reproductive axis regulation.

Decompensated hypothyroidism, formerly known as myxedema coma, is an endocrine emergency that commonly presents with altered mental status, as well as hypothermia and depressed vital signs. The condition is often caused by an inciting event, which may lead to significant delays in the diagnosis and management of this disease. Although the incidence is low, this disease is associated with significant morbidity and mortality. Therefore, it is important for emergency clinicians to be aware of this condition. This narrative review evaluates the emergency medicine diagnosis and management of adult patients with decompensated hypothyroidism. Decompensated hypothyroidism is a severe hypothyroid state associated with multiple organ failure. The diagnosis can be challenging due to similarities with more common diseases and lack of consideration of the diagnosis. Many patients may present with altered sensorium or depressed vital signs. Clinicians should obtain a thyroid stimulating hormone and free thyroxine level when considering the diagnosis. Management involves resuscitation, early steroid supplementation, thyroid hormone replacement, and treatment of the inciting event. Decompensated hypothyroidism should be considered in the evaluation of patients with altered sensorium and depressed vital signs so as to not miss this critical diagnosis.

Hypothyroid myopathy is a muscle disease with endocrine disease related abnormal hormone levels and Hoffman’s syndrome is a rare form of hypothyroid myopathy. The disease commonly involves muscle weakness, muscle pain, and cramps. In this case, we talked about the clinical and laboratory findings and his good response to hormone replacement therapy of a patient with Hoffmann syndrome who developed due to hypothyroidism myopathy. A 22-year-old male patient, diagnosed with graves 2 years ago, after that he had a bilateral thyroidectomy surgery 1.5 years ago, has been still using L-thyroxine 150 mcg/day. In the patient’s history, it was learned that intramuscular hormone therapy was administered to his 2 months ago for bodybuilding purposes without the doctor’s advice. When he applied to us, he was suffering from widespread muscle cramps, muscle pain, and weakness for 1 month. It is learned that he had methyltestosterone injection 2 months ago and after 3 weeks of injections, symptoms had been showed up. In laboratory findings, while sT3, sT4 levels were low, TSH and CK levels were high. On examinations, muscle hypertrophy was more specifically seen on proximal muscles. He is diagnosed with Hoffmann’s Syndrome and L thyroxine treatment has rearranged from 150 mcg/day to 250 mcg/day. During the follow-up of the patient, complete improvement was observed in the clinical and laboratory findings and the follow-up, and treatment continues.