Hyperthyroidism is a common endocrine disorder characterized by excessive thyroid hormone production, leading to a range of systemic effects that significantly impact patients’ health and quality of life. The management of hyperthyroidism requires a comprehensive approach, incorporating accurate diagnosis, risk stratification, and individualized treatment plans. In Saudi Arabia, the burden of hyperthyroidism is influenced by genetic, environmental, and healthcare system factors, necessitating a tailored approach to management [1] [2] .

Despite established guidelines for hyperthyroidism treatment, variations in clinical practice exist, highlighting the need for a region-specific consensus. This expert meeting aims to assess the current management landscape of hyperthyroidism in Saudi Arabia, identify key challenges, and address unmet needs in medical therapy. Through a multidisciplinary discussion, this meeting will provide evidence-based recommendations to optimize patient outcomes, improve adherence to best practices, and enhance healthcare resource utilization. The task force, including endocrinologists and internal medicine experts, gathered to develop an explicit, evidence-based consensus on hyperthyroidism management in the Kingdom of Saudi Arabia (KSA). This article presents the recommendations of this expert panel.

Consensus Development Process ( Figure 1 ): This consensus report is based on a structured, multi-phase process, including a literature review, a pre-meeting survey, and an expert panel discussion. This approach ensures a comprehensive assessment of current clinical practices, challenges, and opportunities for improving hyperthyroidism management in Saudi Arabia.

Systematic Literature Review: A systematic literature review was conducted to evaluate the current evidence on hyperthyroidism diagnosis, management, and treatment strategies, with a specific focus on Saudi Arabia and the Middle East. Databases searched included PubMed, Scopus, and the Saudi Digital Library, covering publications from January 2010 to March 2024. The following search terms were applied using Boolean operators: (“hyperthyroidism” OR “thyrotoxicosis” OR “Graves’ disease”) AND (“Saudi Arabia” OR “Middle East”) AND (“management” OR “treatment” OR “guidelines”).

Inclusion criteria were: 1) peer-reviewed studies or national guidelines published in English or Arabic; 2) studies reporting on epidemiology, diagnosis, or management of hyperthyroidism; 3) human studies conducted in Saudi Arabia or Middle Eastern populations. Exclusion criteria were: 1) case reports with <5 patients; 2) animal or in vitro studies; 3) non-original articles such as commentaries or editorials unless they contained national recommendations; 4) duplicate publications.

From an initial 356 records identified across databases, 284 remained after duplicates were removed. Following title and abstract screening, 97 full-text articles were assessed for eligibility. Of these, 46 met the inclusion criteria and were included in the final synthesis ( Figure 2 ). Local reports, national guidelines, and epidemiological studies were additionally reviewed to ensure a comprehensive overview of disease burden and clinical practices in the region.

Pre-meeting Survey: Before the expert panel meeting, a structured electronic survey was distributed to endocrinologists, internists, and general practitioners across Saudi Arabia through the Saudi Endocrine Society membership list and professional mailing groups (sampling frame ≈ 420 clinicians). A total of 168 responses were received (response rate 40%). Respondents represented all five major regions of Saudi Arabia (Central 34%, Western 28%, Eastern 20%, Northern 10%, Southern 8%). Clinician demographics included 67% endocrinologists, 22% internists, and 11% general practitioners, with a mean clinical experience of 14 ± 6 years ( Table 1 ).

The survey assessed diagnostic and treatment strategies, barriers to optimal care, challenges in guideline implementation, unmet needs, and areas for improvement. Table 1 presents the core survey findings, including the most frequently cited diagnostic challenges (limited access to TSH-receptor antibody testing, regional referral delays) and treatment barriers (radioiodine availability, follow-up adherence).

Delphi Consensus Process: A multidisciplinary expert panel convened to review the survey and literature findings. The Delphi method was used, consisting of three iterative rounds of anonymous voting and feedback. A ≥ 75% agreement threshold was required for consensus on each recommendation. Evidence was graded using a modified GRADE approach (high, moderate, low, very low). Items without consensus were revised and re-voted in subsequent rounds until alignment was achieved.

Adaptation to Local Context: International guidelines (e.g., American Thyroid Association, European Thyroid Association) were systematically reviewed and adapted to Saudi Arabia’s specific context. Adjustments considered: A) Iodine status—accounting for historically borderline iodine sufficiency in certain regions. B) Healthcare access—variation in diagnostic resource availability (e.g., TRAb assays, nuclear medicine). C) Genetic/epidemiological factors—including higher prevalence of consanguinity-associated thyroid autoimmunity. This ensured recommendations were evidence-based yet clinically feasible in the Saudi healthcare system.

Expert Panel Meeting: The structured discussion focused on epidemiological trends, diagnosis and treatment, gaps in care, and practical recommendations. Panelists represented academic hospitals, Ministry of Health institutions, and private centers. Consensus statements were formulated, refined, and validated for clinical relevance and feasibility.

Dissemination Plan: The finalized recommendations will be disseminated through national conferences, workshops, webinars, and peer-reviewed publications. Targeted educational initiatives will support guideline adoption, with mechanisms for periodic updates based on new evidence.

Limitations: This consensus is limited by potential selection bias in the literature search and survey sampling, the relative scarcity of regional primary data, and the absence of formal cost-effectiveness analyses. Recommendations may evolve as new therapies and evidence emerge. A structured process for biennial updates has been planned to ensure continued relevance.

The global prevalence of hyperthyroidism is estimated at 0.2% - 2.5%. Overt hyperthyroidism, defined as suppressed thyrotropin (formerly thyroid-stimulating hormone) and elevated levels of triiodothyronine (T3) and/or free thyroxine (FT4), affects 0.2% to 1.4% of the global population. Graves’ disease is the leading cause of hyperthyroidism, with a global prevalence of 2% in women and 0.5% in males. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Subclinical hyperthyroidism, characterized as low thyrotropin and normal T3 and FT4 levels, affects 0.7% to 1.4% of the global population [3] [4] .

Large-scale epidemiological studies are lacking in Saudi Arabia. However, the meta-analysis by Kargar et al. (2024) examined the prevalence of thyroid dysfunction disorders among adult populations in the Middle East, including Iran, Saudi Arabia, Egypt, Iraq, Turkey, and Jordan. The study found an overall pooled prevalence of thyroid disorders of 19.2%, with Saudi Arabia having the highest prevalence at 31.3%. Specifically, the prevalence of overt hyperthyroidism was 2.4%, and subclinical hyperthyroidism was 3.2%. The analysis revealed an increasing trend in thyroid disorders from 2000 to 2022, attributed to factors such as changing lifestyles, unhealthy diets, obesity, alcohol use, and smoking. The findings highlight the underappreciation of subclinical thyroid diseases, which can significantly impact patient management and treatment, suggesting a need for increased thyroid function screening and awareness among adults [5] - [7] .

The high prevalence of thyroid disorders in Saudi Arabia may be linked to iodine deficiency and improper nutrition, as noted in previous studies. Variations in prevalence across Middle Eastern countries could be due to differences in study methodologies, environmental factors, iodination status, and diagnostic cut-off values. The study underscores the importance of addressing these disorders through improved screening, public health interventions, and awareness campaigns to mitigate the growing burden of thyroid dysfunction in the region [5] - [7] .

The meta-analysis by Kargar et al. (2024), in Saudi Arabia, used data from 14 studies encompassing a total population of 18,520 individuals and indicates a high prevalence of thyroid dysfunction, affecting 31.3% (range: 17.9% - 54.9%). Among these, hypothyroidism was observed in 17.9% (10.5% - 30.3%), with subclinical hypothyroidism accounting for 18.9% (9.6% - 37.1%). Hyperthyroidism was less common, with overt hyperthyroidism affecting 4.0% (2.1% - 7.6%) and subclinical hyperthyroidism reported in 4.6% (1.7% - 11.8%) ( Figure 3 ). These findings highlight a substantial burden of thyroid disorders in the region, emphasizing the need for effective screening and management strategies [5] .

The prevalence of thyroid-related disorders varies by gender, age, geographical region, and dietary iodine consumption. Regional variations are obvious, with some regions having a higher frequency, most likely due to disparities in healthcare availability, dietary habits, and iodine intake. Rural locations encounter difficulties in early detection and screening [8] - [10] .

Elmisbah et al. (2024), conducted a cross-sectional study between October 2023 and January 2024, enrolling 501 adults with diabetes in Arar, northern Saudi Arabia. The study found that 42.8% of participants had diabetes (mostly type 2), and 51.3% reported thyroid disorders. Vitamin D and B12 deficiencies were common

comorbidities, along with hypertension and dyslipidemia. The authors concluded that thyroid disorders are highly prevalent among diabetics in the region, emphasizing the need for better awareness and early detection [11] .

During the SARS-CoV2 (COVID) pandemic, there were reports of Graves’ disease and subacute thyroiditis linked to COVID infection or vaccination, most likely due to COVID’s immunogenic characteristics [12] - [14] . A retrospective analysis found that the prevalence of Graves’ illness in a Spanish hospital increased twofold between 2020 and 2021 compared to the pre-COVID period of 2017 to 2019 [15] .

In the current study, common diagnostic tests for hyperthyroidism reveal varying practices among clinicians surveyed. All clinicians (100%) use free T3, free T4, and TSH as standard tests. A significant portion (75%) also test for thyroid receptor antibodies (TRAbs) and conduct full blood counts, while half (50%) perform technetium thyroid scans. These tests are essential for accurate diagnosis, but their utilization varies depending on clinical settings and resources.

Low serum TSH is the best test for detecting thyroid dysfunction, with a sensitivity of 92% - 95% and a specificity of 89% - 85%. Thyroid hormone can circulate as T3 or T4, which is a prohormone that is converted to T3 in peripheral tissues. T3 is a biologically active type of thyroid hormone. Free T4 levels can be used to determine the level of hyperthyroidism. T3 levels can also aid in determining the source and severity of thyrotoxicosis. Graves’ disease or toxic nodules typically have a total T3:T4 ratio greater than 20:1, while thyroiditis has a ratio of less than 20:1 [16] [17] .

Once thyrotoxicosis has been confirmed, the etiology should be determined. TSH-receptor antibodies (TRAbs) are pathognomonic for Graves’ disease. Current guidelines advocate measuring TRAb as the first step in distinguishing Graves’ illness from other types of thyrotoxicosis. There are two types of assays available for measuring TRAb [18] - [20] .

The current study showed that barriers to diagnosis present significant challenges, particularly in rural and remote areas. Delayed referrals are a major issue, cited by 75% of respondents, often due to limited access to specialized diagnostic facilities. Geographical accessibility exacerbates the problem, as patients in remote regions struggle to reach centers offering advanced tests like TRAbs and nuclear scans. Additionally, over-testing in the private sector contrasts with underdiagnosis in rural areas, highlighting disparities in healthcare access. A lack of awareness about hyperthyroidism symptoms among both patients and primary care physicians further contributes to delayed diagnosis, underscoring the need for improved education and resource allocation.

One study aimed to assess knowledge about hypothyroidism and hyperthyroidism among Saudi adults through a cross-sectional survey conducted from December 2022 to January 2023, involving 996 participants (66.2% women) across five regions. Results showed that 70.1% knew the thyroid gland’s function, 66.4% recognized women’s higher susceptibility, and 49.5% understood the link between thyroid dysfunction and heart disease. Knowledge was higher among older, educated women, but overall awareness was inadequate, with significant gaps in certain populations. The study highlights the need for larger future studies and public health strategies to improve thyroid disease awareness and diagnosis in Saudi Arabia [1] .

Another study assessed awareness of thyroid diseases and their risk factors among residents of Jeddah, Saudi Arabia, through a cross-sectional survey conducted from January to December 2023. A self-administered online questionnaire, translated into Arabic, was completed by 393 participants (72.5% female, 27.5% male), most of whom held a bachelor’s degree or higher (78.1%). Results revealed that only 20% of participants had good knowledge about thyroid diseases, with hypothyroidism being the most prevalent diagnosed condition (14%). Awareness was particularly low regarding risks during pregnancy and postpartum (35%), medications like amiodarone (26%), soy consumption (22%), and gastrointestinal symptoms of thyroid diseases (36%). Attitudes toward thyroid health were largely negative (85.5%), though a history of thyroid disease was associated with more positive attitudes (p = 0.002). Educational level and employment status significantly influenced knowledge (p = 0.036 and 0.005, respectively), and a positive correlation was found between knowledge and attitudes (r = 0.321, p < 0.001). The study concluded that awareness was low, especially among the unemployed and less educated, highlighting the need for public health campaigns to address gaps in knowledge [2] .

Subclinical hyperthyroidism may resolve on its own but progresses to overt hyperthyroidism in about 8% of patients at 1 year and 26% by 5 years, particularly in those with undetectable baseline TSH or toxic multinodular goiter [21] [22] . Subclinical hyperthyroidism is associated with increased risks of atrial fibrillation, heart failure, cardiovascular mortality, and fractures, especially when TSH levels are <0.1 mIU/L [23] [24] .

Excess thyroid hormone accelerates bone resorption, leading to a 3 - 4-fold increase in hip and spinal fracture risks in postmenopausal women and a 36% higher hip fracture risk overall. A trial comparing RAI and ATD in older adults with subclinical hyperthyroidism found no significant differences in bone density or echocardiography results, with most RAI-treated patients becoming hypothyroid and most ATD-treated patients remaining euthyroid [25] .

The US Preventive Services Task Force does not recommend routine testing or treatment for subclinical hyperthyroidism, but other US and European guidelines suggest treatment for patients over 65 (or younger patients with symptoms, osteoporosis, or heart disease) when TSH is consistently < 0.1 mIU/L. Treatment may also be considered for TSH levels between 0.1 - 0.4 mIU/L in these groups, but it is generally avoided in asymptomatic patients under 65 without osteoporosis or heart disease. Additionally, clinicians should rule out exogenous subclinical hyperthyroidism caused by excessive thyroid hormone replacement or factitious thyrotoxicosis before initiating treatment [16] [26] .

Untreated overt thyrotoxicosis, particularly in older individuals, can lead to serious complications such as osteoporosis, atrial fibrillation, and, rarely, high-output heart failure because of the effects of excess thyroid hormone on thyroid hormone receptors in bone and heart tissues. Atrial fibrillation occurs in 10% - 25% of patients with thyrotoxicosis, with higher risks in men and those aged over 65 years [27] .

Treatment should be patient-centered and individualized, considering factors such as age, comorbidities, severity of hyperthyroidism, likelihood of remission, pregnancy plans, surgical expertise, and patient preferences [28] .

The underlying etiology of hyperthyroidism should guide treatment decisions; for Graves’ disease, the focus is on controlling hyperthyroidism with the expectation of eventual remission, whereas toxic nodular disease requires indefinite treatment if ATDs are used, as it does not remit. Symptomatic patients with thyrotoxicosis may benefit from beta blockers to reduce heart rate and alleviate hyperadrenergic symptoms, though these are relatively contraindicated in patients with bronchospastic disease [29] . Beta blockade alone is often sufficient for thyroiditis-induced thyrotoxicosis, as it is self-limiting and does not require ATDs unless thyroid hormone synthesis is increased [16] .

Most patients with overt hyperthyroidism caused by autonomous thyroid nodules or Graves’ disease require treatment with ATDs, radioactive iodine ablation, or surgery [3] . In the US, practice patterns have shifted toward prioritizing ATDs over radioactive iodine as the initial treatment, aligning more closely with practices in other regions [30] .

According to the surveyed doctors in the current study, antithyroid drugs (ATDs) are universally used by clinicians (100%) for managing uncomplicated hyperthyroidism, with 75% preferring carbimazole and 25% opting for methimazole, primarily due to availability and clinical experience. ATDs are consistently prescribed before radioiodine therapy in all cases.

Thionamides, including methimazole (MMI), carbimazole (CBZ), and propylthiouracil (PTU), reduce thyroid hormone synthesis and secretion, restoring euthyroidism in hyperthyroid patients. MMI or CBZ is the first-line agent, except in the first trimester of pregnancy . MMI dosing is based on free T4 (FT4) levels: 5 - 10 mg/day for FT4 1.0 - 1.5 times the upper limit of normal (ULN), 10 - 20 mg/day for FT4 1.5 - 2.0 times ULN, and 30 - 40 mg/day for FT4 2 - 3 times ULN . CBZ is converted to MMI in the body, but at a lower concentration (10 mg CBZ is equivalent to 6 - 7 mg MMI) [31] . Thyroid function tests (TFTs) should be monitored every 4 - 8 weeks initially, with MMI often tapered to 5 - 10 mg/day as hyperthyroidism improves. High-dose ATDs with levothyroxine (“block and replace”) are not routinely recommended due to increased toxicity risks without clear benefits [32] .

For autonomous thyroid nodules, MMI doses are typically ≤ 10 mg/day, with TFTs monitored every 3 months initially . In Graves’ disease, ATDs can be discontinued after 12 - 18 months if TSH normalizes and TRAbs are negative, with remission rates of 30% - 50% after initial treatment [16] [33] [34] .

Mahzari et al. (2024), conducted a retrospective chart review of 189 Graves’ disease patients treated with anti-thyroid drugs (ATD) between 2015-2022 at King Abdulaziz Medical City, Riyadh. The study found that 54.5% achieved remission, but about one-third later relapsed. Lower free T4 and TRAb levels at diagnosis were linked to remission, while longer ATD use and higher thyroid uptake were predictors of relapse. The authors concluded that although ATD achieved remission in about half of patients, relapse remained common, highlighting the need for further research to clarify predictors of long-term treatment success [35] .

Remission likelihood increases with longer ATD use (up to 80% - 85% after >5 years), but is lower in younger patients, those with higher baseline thyroid hormone levels, elevated TRAb titers, or larger goiters [36] - [39] . Hyperthyroidism recurrence is most likely within 6 months of ATD discontinuation, especially if TRAb remains elevated. Definitive therapy (radioactive iodine or thyroidectomy) is recommended for non-remission or recurrence after 12 - 18 months, though long-term MMI use (up to 24 years) is safe and effective [16] [36] [37] . TRAb titers and TFTs should be monitored every 1 - 2 years and 4 - 6 months, respectively, during long-term ATD therapy .

Adverse effects occur in ~13% of patients, with pruritus/rash being most common (6% on MMI and CBZ, 3% on PTU), often managed with antihistamines [16] [40] . Rare side effects include agranulocytosis (0.2% - 0.5%), typically within 90 days of initiation, and hepatitis (2.7% on PTU, 0.4% on MMI and CBZ), with liver injury risk highest in the first 90 days [40] - [42] . PTU carries a risk of fulminant hepatic failure, while both ATDs can cause antineutrophil cytoplasmic antibody-associated vasculitis (3% risk, higher with PTU) [43] . Pancreatitis, a newly recognized MMI/CBZ risk in Europe, has an absolute risk of <0.4% over 18 months [44] [45] . Baseline CBC and LFTs are recommended before ATD initiation, though the benefit of ongoing monitoring is unclear . Uncontrolled hyperthyroidism often causes abnormal LFTs (55% at baseline), which typically normalize after ATD treatment [46] . Patients should be counseled on potential adverse effects before starting ATDs [16] [37] .

Radioactive iodine (RAI) treatment effectively cures hyperthyroidism in over 90% of patients with Graves’ disease or autonomous thyroid nodules [30] [47] . Persistent hyperthyroidism after RAI in Graves’ disease is associated with male sex, prior antithyroid ATD therapy, delayed treatment (>6 months post-diagnosis), elevated FT4 levels, larger thyroid volume, and higher RAI uptake [48] . Beta blockers and pre-treatment ATDs are recommended for older patients or those at high cardiovascular risk to manage transient hyperthyroidism post-RAI. MMI/CBZ should be stopped 2 - 7 days before RAI and restarted 3 - 7 days post-treatment [16] [49] . The goal of RAI in Graves’ disease is to induce hypothyroidism, while in toxic nodular goiter, it is to alleviate hyperthyroidism. Hypothyroidism risk after RAI for autonomous nodules depends on the administered dose, reaching up to 60% [50] [51] . Post-RAI, thyroid function tests should be monitored every 4 - 6 weeks for 6 months or until stable hypothyroidism is achieved. Persistent hyperthyroidism after 6 months may require repeat RAI .

RAI can exacerbate Graves’ eye disease, especially in smokers or those with high TRAb levels. Pretreatment with prednisone (0.3 - 0.5 mg/kg/day, tapered over 3 months) is recommended for these patients [52] . The long-term cancer risk associated with RAI remains unclear, with a meta-analysis of 479,452 patients showing no significant overall cancer risk increase. However, a dose-response association was noted between RAI therapy and mortality from breast and other solid tumors [53] .

Thyroidectomy is recommended for hyperthyroidism patients with large goiters causing compressive symptoms, suspicious or malignant thyroid nodules, or moderate to severe Graves ophthalmopathy. It is the first-line treatment if thyroid malignancy is suspected or confirmed. For Graves’ disease, total thyroidectomy is preferred over subtotal thyroidectomy due to a lower risk of recurrent hyperthyroidism, while thyroid lobectomy may be chosen for toxic adenoma when rapid resolution, cosmesis, or compressive symptoms are concerns. Although total thyroidectomy effectively cures hyperthyroidism, it necessitates lifelong thyroid hormone replacement and carries risks such as recurrent laryngeal nerve damage, hematoma, and hypoparathyroidism, with higher complication rates among less experienced surgeons. Preoperative ATDs reduce the risk of thyroid storm, and high-dose iodine can decrease thyroid vascularity and operative blood loss in Graves’ disease patients, though it may not affect postoperative complication risks. Additionally, preoperative calcium and/or vitamin D supplementation may help reduce the risk of postoperative hypocalcemia [16] [17] .

Radiofrequency ablation (RFA) is a minimally invasive alternative to surgery or radioactive iodine for treating toxic thyroid nodules, particularly in selected centers. This technique uses heat energy to induce tissue necrosis, reducing nodule volume by 52% - 86% and normalizing thyroid function in 61.7% of cases (95% CI: 48.7% - 74.7%). Guidelines recommend RFA primarily for younger patients with small nodules, though it may also be considered for those with larger toxic multinodular goiters who are unsuitable for surgery or radioactive iodine. Additionally, novel therapies for Graves’ disease, such as small molecules, biologics, and immunomodulatory peptides targeting the TSH receptor, are currently under investigation, offering potential future advancements in treatment [16] [17] .

However, according to the current expert panel, treatment challenges persist, including limited access to medications, especially in rural areas, non-adherence to treatment and follow-up, and the absence of clear national guidelines for managing hyperthyroidism in special populations such as pregnant women and elderly patients. These barriers highlight the need for improved resource allocation, patient education, and standardized guidelines to enhance care for hyperthyroidism patients.

According to experts in our current study, current referral practices for hyperthyroidism in Saudi Arabia reveal significant inefficiencies, particularly in rural areas where delays in accessing specialist care are common due to geographical barriers and limited healthcare infrastructure. In contrast, urban areas experience over-referral and over-testing, with primary care physicians (PCPs) often referring mild or borderline cases to specialists unnecessarily. Additionally, other health care specialists frequently request thyroid tests without clear indications, contributing to overdiagnosis and straining healthcare resources. These disparities highlight the need for a more balanced and efficient referral system.

To address these challenges, several solutions have been proposed. Standardized referral algorithms could guide PCPs in determining when specialist consultations are truly necessary, reducing both delays in rural areas and over-referral in urban centers. Virtual consultations could further streamline access to specialist advice, minimizing unnecessary in-person visits and improving efficiency. Enhancing PCP education on recognizing and managing hyperthyroidism is also critical, as it would empower primary care providers to handle milder cases independently and refer only when appropriate. These measures could help bridge regional disparities and optimize the management of hyperthyroidism across Saudi Arabia.

Managing hyperthyroidism in Saudi Arabia presents several challenges, particularly in ensuring timely diagnosis and access to specialized care. One significant issue is the delayed diagnosis due to limited awareness among patients and PCPs about hyperthyroidism symptoms. This delay is exacerbated in rural areas, where access to diagnostic facilities and specialized tests, such as TRAb testing and nuclear scans, is limited. Over-reliance on private healthcare in urban areas can lead to over-testing, while rural regions face underdiagnosis due to resource constraints. These disparities highlight the need for improved public health campaigns and better distribution of diagnostic resources across the country [54] .

Another challenge is the limited availability of ATDs and other treatment options, particularly in remote areas. While ATDs like CBZ, MMI, and PTU are commonly used, their accessibility is inconsistent, leading to non-adherence and interrupted treatment. Additionally, there is a lack of clear national guidelines for managing hyperthyroidism in special populations, such as pregnant women and the elderly. This gap in standardized care can result in suboptimal treatment outcomes and increased risks of complications, such as congenital anomalies in pregnant women or cardiovascular issues in older patients [54] .

Finally, patient education and follow-up remain critical challenges. Many patients lack awareness of the importance of medication adherence and the potential side effects of hyperthyroidism treatments, such as agranulocytosis or liver injury. Regular monitoring of thyroid function tests and patient adherence to treatment plans are often inadequate, particularly in underserved areas. Addressing these challenges requires a multifaceted approach, including public health initiatives to raise awareness, improved access to medications and diagnostic tools, and the development of clear, standardized guidelines for managing hyperthyroidism across diverse patient populations [54] .

The current study showed that treatment preferences for hyperthyroidism during pregnancy vary. About 50% of clinicians use CBZ, 25% use MMI, and 25% prefer PTU, with PTU being favored in early pregnancy due to the higher risk of congenital anomalies associated with CBZ and MMI.

Gestational transient thyrotoxicosis (GTT), caused by elevated hCG levels stimulating the thyroid gland, affects 2% - 11% of pregnancies and is often linked to hyperemesis gravidarum [55] . Unlike other forms of hyperthyroidism, GTT does not require ATD treatment and is not associated with adverse obstetric outcomes [56] . It can be managed with serial thyroid function tests and typically resolves spontaneously as hCG levels decline [57] [58] .

However, all other forms of overt hyperthyroidism in pregnancy require treatment to mitigate risks such as preeclampsia, low birth weight, miscarriage, and preterm delivery [59] . ATDs, including PTU, CBZ, and MMI, are teratogenic, but PTU is associated with milder congenital anomalies (e.g., facial or neck cysts, urinary tract abnormalities) compared to MMI/CBZ, which are linked to more severe defects like aplasia cutis and esophageal atresia [60] . PTU is therefore preferred in the first trimester, with the lowest effective dose used to maintain maternal FT4 levels at or just above the upper reference limit, as ATDs can significantly affect fetal thyroid function [57] [58] . Moreover, ATDs are secreted in breast milk at low levels, but doses up to 20 mg/day of MMI (around 30 mg of CBZ) and 450 mg/day of PTU are considered safe during lactation and do not require thyroid function monitoring in breastfed infants .

Radioactive iodine (RAI) treatment is contraindicated during pregnancy and lactation and should be deferred until at least 3 months after breastfeeding ends to avoid radiation exposure to breast tissue [57] [61] . If necessary, thyroidectomy is safest during the second trimester of pregnancy [62] . These notions emphasize the importance of balancing maternal and fetal safety while managing hyperthyroidism in pregnancy and lactation.

Studies have shown that thyroid function, including levels of TSH, FT4, and FT3, changes with aging, though interpretations of these changes remain controversial [63] - [65] . Hyperthyroidism in the elderly presents diagnostic challenges due to atypical symptoms, often leading to delayed diagnosis and worse outcomes [66] [67] . Unlike younger patients, elderly individuals may not exhibit classic hyperthyroidism symptoms like tachycardia or heat intolerance but instead present with atrial fibrillation, heart failure, weight loss, osteoporosis, or depression [68] . Clinicians must differentiate true hyperthyroidism from non-thyroidal illness, which can also suppress TSH levels in acutely ill elderly patients [69] .

The American Thyroid Association (ATA) recommends a two-step approach to treating hyperthyroidism: rapid symptom control and reducing thyroid hormone synthesis [16] . Beta-blockers are first-line for symptom management, particularly in elderly patients with a resting heart rate over 90 bpm or cardiovascular disease, as they improve heart rate, blood pressure, and symptoms such as tremors and irritability [70] .

Glucocorticoids may also help by inhibiting T4-to-T3 conversion. Treatment options for Graves’ disease include ATDs, radioactive iodine ablation, and thyroidectomy, with methimazole being the preferred ATD for elderly patients due to its efficacy [71] . However, older adults are at higher risk of side effects such as agranulocytosis (0.5% risk), rash, and liver injury, necessitating baseline blood tests and regular monitoring of FT4 and T3 levels. Also, serum TSH is not reliable for early monitoring, as it may remain suppressed for months after treatment initiation. Personalized treatment is essential to balance efficacy and safety in this population [16] .

Most important recommendations are mentioned in Table 2 .

The entire developed recommendations are shown in Table 3 .