Evaluation of Neuro-Hormonal Dynamics after the Administration of Probiotic Microbial Strains in a Murine Model of Hyperthyroidism.

The microbiota-gut-brain axis has received increasing attention in recent years through its bidirectional communication system, governed by the ability of gut microorganisms to generate and regulate a wide range of neurotransmitters in the host body. In this research, we delve into the intricate area of microbial endocrinology by exploring the dynamic oscillations in neurotransmitter levels within plasma and brain samples. Our experimental model involved inducing hyperthyroidism in mice after a "probiotic load" timeframe using two strains of probiotics (Lactobacillus acidophilus, Saccharomyces boulardii, and their combination). These probiotic interventions continued throughout the experiment and were intended to uncover potential modulatory effects on neurotransmitter levels and discern if certain probiotic strains exhibit any protection from hyperthyroidism. Moreover, we aimed to outline the eventual connections between the gut microbiota and the hypothalamus-pituitary-thyroid axis. As our study reveals, there are significant fluctuations in crucial neurotransmitters within the hyperthyroidism model, related to the specific probiotic strain or combination. These findings could support future therapeutic approaches, help healthcare professionals choose between different probiotic therapies, and also allow us proceed with caution when administering such treatments, depending on the health status of hyperthyroid patients.

GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context.

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Hyperthyroidism: A Review.

Importance: Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. Observations: The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Conclusions and Relevance: Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study.

BACKGRUOUND: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service. METHODS: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months. RESULTS: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. CONCLUSION: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

Evaluation of the diagnostic performance of thyroid-stimulating immunoglobulin and thyrotropin receptor antibodies for Graves' disease.

OBJECTIVE: To evaluate thyroid-stimulating immunoglobulin (TSI) and thyrotropin receptor antibodies (TRAb) diagnostic performance for Graves' disease (GD) and determine clinical cut-off value for diagnosing GD. METHODS: Of 1369 retrospectively enrolled subjects, 1364 had a definitive diagnosis of untreated GD (GD-UT, n = 87); treated GD (GD-T, n = 206); autoimmune thyroid disease (AIT, n = 241); thyroid nodules (TN, n = 677); subacute thyroiditis (ST, n = 28); healthy subjects (HS, n = 125); other diseases with serological hyperthyroidism (n = 5) and were grouped into the following: UT-GD and control groups (AIT, TN, ST, and HS); and UT-GD and non-GD hyperthyroidism groups. Diagnostic performance of TSI and TRAb was evaluated using area under the curve (AUC) of receiver-operating characteristic (ROC) curve, and optimal clinical cut-off value was determined using maximization of Youden index. RESULTS: TRAb AUC and clinical cut-off value for diagnosing GD were 0.981 and 1.245 IU/L (sensitivity, 96.6%; specificity, 97.1%; positive predictive value [PPV], 71.8%; negative predictive value [NPV], 99.9%; positive likelihood ratio [PLR], 33.31; negative likelihood ratio [NLR, 0.035), respectively, for the GD-UT and control groups. Those for TSI were 0.992 and 0.467 IU/L (sensitivity 98.8%; specificity, 96.4%; PPV, 68.8%; NPV, 99.9%; PLR, 27.472; NLR, 0.011). Those for TRAb in GD-UT and non-GD hyperthyroidism groups were 0.923 and 1.78 IU/L (sensitivity, 92.0%; specificity, 89.1%; PPV, 93%; NPV, 87.5%; PLR, 8.44; NLR, 0.089), respectively. For TSI, these were 0.92 and 0.545 IU/L (sensitivity, 97.7%; specificity, 83.6%; PPV, 90.4%; NPV, 95.8%; PLR27.472, NLR, 0.011), respectively. CONCLUSION: TSI diagnostic performance for GD was excellent and had better sensitivity than TRAb.

Identification and Management of Thyroid Dysfunction Using At-Home Sample Collection and Telehealth Services: Retrospective Analysis of Real-World Data.

BACKGROUND: Programs aimed at modernizing thyroid care by pairing at-home sample collection methods with telehealth options may serve an important and emerging role in thyroid care. OBJECTIVE: The primary objective of this analysis was to evaluate telehealth use, demographics, and clinical characteristics of a cohort of consumer-initiated at-home laboratory thyroid test users who were also offered the option of follow-up telehealth consultations. METHODS: This was a retrospective analysis of real-world data from a deidentified consumer database of home-collected, mail-in thyroid tests used from March to May 2021 (N=8152). The mean age was 38.6 (range 18-85) years, and 86.6% (n=7061) of individuals identified as female. RESULTS: In total, 7% (n=587) of test takers fell into a thyroid dysfunction category (overt hypothyroidism: n=75, 0.9%; subclinical hypothyroidism: n=236, 2.9%; overt hyperthyroidism: n=5, 0.1%; and subclinical hyperthyroidism: n=271, 3.3%). Overall, 12% (n=984) of the overall sample opted into a telehealth consultation, with 91.8% (n=903) receiving a nontreatment telehealth consultation and 8.2% (n=81) receiving a treatment telemedicine consultation. Furthermore, 16% (n=96) of individuals with overt or subclinical thyroid dysfunction engaged in telehealth consultations. The majority of treatment consultations (59.3%, n=48) were conducted with people reporting a history of thyroid issues, with 55.6% (n=45) of people indicating wanting to discuss their current thyroid medication and 48% (n=39) receiving a prescription medication. CONCLUSIONS: The combination of at-home sample collection and telehealth is an innovative model for screening thyroid disorders, monitoring thyroid function, and increasing access to care, which can be implemented at a large scale and across a wide range of age groups.

Thyroid disease in pregnancy.

Pregnancy is accompanied by metabolic changes associated with the thyroid gland. It is therefore important to understand the underlying physiological alterations and the management of patients with thyroid disorders in pregnancy. This review focuses on the physiology and the management of hyperthyroidism, hypothyroidism and thyroid nodules in the context of pregnancy.

Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis.

Hyperthyroidism is a common condition with a global prevalence of 0·2-1·3%. When clinical suspicion of hyperthyroidism arises, it should be confirmed by biochemical tests (eg, low TSH, high free thyroxine [FT4], or high free tri-iodothyonine [FT3]). If hyperthyroidism is confirmed by biochemical tests, a nosological diagnosis should be done to find out which disease is causing the hyperthyroidism. Helpful tools are TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy. Hyperthyroidism is mostly caused by Graves' hyperthyroidism (70%) or toxic nodular goitre (16%). Hyperthyroidism can also be caused by subacute granulomatous thyroiditis (3%) and drugs (9%) such as amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors. Disease-specific recommendations are given. Currently, Graves' hyperthyroidism is preferably treated with antithyroid drugs. However, recurrence of hyperthyroidism after a 12-18 month course of antithyroid drugs occurs in approximately 50% of patients. Being younger than 40 years, having FT4 concentrations that are 40 pmol/L or higher, having TSH-binding inhibitory immunoglobulins that are higher than 6 U/L, and having a goitre size that is equivalent to or larger than WHO grade 2 before the start of treatment with antithyroid drugs increase risk of recurrence. Long-term treatment with antithyroid drugs (ie, 5-10 years of treatment) is feasible and associated with fewer recurrences (15%) than short-term treatment (ie, 12-18 months of treatment). Toxic nodular goitre is mostly treated with radioiodine (131I) or thyroidectomy and is rarely treated with radiofrequency ablation. Destructive thyrotoxicosis is usually mild and transient, requiring steroids only in severe cases. Specific attention is given to patients with hyperthyroidism who are pregnant, have COVID-19, or have other complications (eg, atrial fibrillation, thyrotoxic periodic paralysis, and thyroid storm). Hyperthyroidism is associated with increased mortality. Prognosis might be improved by rapid and sustained control of hyperthyroidism. Innovative new treatments are expected for Graves' disease, by targeting B cells or TSH receptors.

Therapeutic plasma exchange in hyperthyroidism prior to surgery.

PURPOSE: Therapeutic plasma exchange (TPE) is a treatment option to reduce thyroid hormones in the event of contraindication or unresponsiveness to antithyroid drugs (ATDs). METHODS: We analyzed 11 patients with hyperthyroidism who received TPE prior to surgery between January 2008 and December 2016 at our center. RESULTS: In total, 41 processes were applied to 11 patients with hyperthyroidism. The median age was 40 years, and 90.9% of the patients were female. Seven patients had Graves' disease, while four had a toxic multinodular goiter. The distribution of TPE indications comprised contraindication to ATDs (64%) and insufficient response to ATDs (36%). An adequate response was not obtained with TPE in two patients, and cholestyramine plus methimazole and Lugol solution were applied. The median number of TPE sessions was 3. During the TPE period, a ß-blocker was applied concurrently except in one patient who was contraindicated for the drug. The reduction in FT3 and FT4 hormones and the increase in TSH levels were statistically significant after TPE application (p values of 0.003, 0.033 and 0.008, respectively). Regarding adverse events of TPE application, an allergic reaction was seen in one patient, while prolongation of prothrombin time without any clinical findings was seen in another patient. Ten patients underwent total thyroidectomy, and one patient underwent a gynecological surgery procedure without any major complications. CONCLUSION: The American Society for Apheresis guideline, which is the most referenced guideline, mentions the utilization of TPE before thyroid surgery, only in patients with thyrotoxicosis despite the wider necessity of this treatment choice under the condition of uncontrolled hyperthyroidism prior to any kind of surgery. We concluded that TPE is a reliable and effective application in patients with hyperthyroidism before any surgical procedure, according to our study results.

The management and metabolic characterization: hyperthyroidism and hypothyroidism.

Hyperthyroidism and hypothyroidism are common diseases resulting from thyroid dysfunction, and are simple to diagnose and treat. The traditional treatment for hypothyroidism is thyroid hormone replacement therapy. The traditional treatments for hyperthyroidism include antithyroid drug, iodine radiotherapy, and surgery. Thyroid disease can be fatal in severe cases if untreated. Current statistical reference ranges used for diagnosis based on relevant biochemical parameters have been debated, and insufficient treatment can result in long-term thyroid hormone deficiency, which is associated with increased risk of cardiovascular disease and persistent symptoms. In contrast, overtreatment can result in heart disease and osteoporosis, particularly in older people and pregnant women. Therefore, under- or over-treatment should be avoided and treatment regimens should be monitored closely. A significant proportion of patients who achieve biochemical treatment goals still complain of significant symptoms. Systematic literature review was performed through the Embase (Elsevier), PubMed and Web of Science databases, and studies summarized evidence regarding treatment and management of hypothyroidism and hyperthyroidism, and reviewed clinical practice guidelines. We also reviewed the latest research on the metabolic mechanisms of hyperthyroidism and hypothyroidism, which contributed to understanding of thyroid diseases in the clinic. A reliable algorithm is needed to management, assessment, and treatment patients with hyperthyroidism and hypothyroidism, which can not only improve management efficiency, but also providing a broad application. In addition, the thyroid disorder showed a lipid metabolism tissue specificity in the Ventromedial Hypothalamus, and effect oxidative stress and energy metabolism of whole body. This review summarizes an algorithm for thyroid disease and the latest pathogenesis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition.

Subclinical hyperthyroidism in children.

Subclinical hyperthyroidism (SH) is defined as serum thyroid-stimulating hormone (TSH) below the lower limit of the reference range in the presence of normal free T4 and free T3 levels. Depending on the degree of TSH suppression, SH could be defined as mild (TSH, 0.1-0.45 mU/L) or severe (TSH<0.1 mU/L). Patients with SH are often asymptomatic when symptoms are present, they are similar to the symptoms in patients with overt hyperthyroidism, although they are usually milder. The management of the SH is uncertain and should be individualized. We present this review after an extensive literature search and long-standing clinical experience. This review provides the prevalence, causes, clinical presentation, investigation, and therapeutic approach of SH in children.

Approach to the Patient With a Suppressed TSH.

Subclinical hyperthyroidism (SCH) is a laboratory diagnosis defined by a serum thyrotropin (TSH) concentration below the reference range (< 0.4 mU/L in most assays), and a free thyroxine (FT4) and 3,5,3'-triiodothyronine levels (FT3) in the reference range. Many patients diagnosed with SCH will be clinically euthyroid while others may present with manifestations characteristic of thyroid hormone excess, such as tachycardia, tremor, intolerance to heat, bone density loss, or weight loss. In addition to the laboratory abnormalities, patient factors such as age, symptoms, and underlying heart and bone disease are used to stratify patients for the risk of adverse outcomes and determine the appropriate treatment. Evaluation should include repeat thyroid function tests to document persistent TSH suppression, investigation of the underlying cause, as well as evaluation of the patient's risk of adverse outcomes in the setting of a subnormal TSH. Persistent SCH has been associated with an increased risk of a range of adverse events, including cardiovascular events such as atrial fibrillation and heart failure, bone loss and fracture, and in some studies, cognitive decline. Despite the consistent association of these adverse events with SCH, prospective studies showing improved outcomes with treatment remain limited. Management options include observation without active therapy, radioactive iodine ablation of the thyroid, antithyroid medication, thyroid surgery, or radiofrequency ablation, as appropriate for the patient and clinical setting. The choice of therapy should be guided by the underlying etiology of disease, patient factors, and the risks and benefits of each treatment option.

Management of Thyroid Eye Disease: A Consensus Statement by the American Thyroid Association and the European Thyroid Association.

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this consensus statement.