Assessment and outcome of the management of hyperthyroidism in Malaysian primary care clinics: A national multicentre study

Abstract

Purpose

This study assesses the management of hyperthyroidism in primary care clinics, focusing on adherence to clinical guidelines and resulting treatment outcomes.

Methods

This study retrospectively reviews medical records of patients with overt hyperthyroidism attending 11 primary care clinics between 1st January 2023 and 31st December 2023. Patients are identified through laboratory results, electronic medical records, or pharmacy records. Eligible cases include adults diagnosed with overt hyperthyroidism with at least 12 months of follow-up. Data were collected and analysed descriptively.

Results

A total of 143 patients were included, with a mean age of 49.0 ± 14.8 years, predominantly female (73.4%) and Malay (81.1%). While 96.5% of cases were correctly diagnosed, documentation of aetiology (52.4%) and treatment counselling (28.7%) was suboptimal. Thyroid function monitoring was inconsistent, with only 52.4% undergoing repeat testing within 2–6 weeks. ATD therapy was appropriately initiated in 65.0% of cases, but side effect counselling was documented in only 11.9%. Within 18 months, 59.4% achieved euthyroidism, and 62.2% avoided iatrogenic hypothyroidism.

Conclusion

Despite appropriate diagnosis and treatment initiation, gaps exist in monitoring, documentation, and referrals. Future efforts should focus on strengthening adherence to guidelines and improving patient tracking systems to enhance hyperthyroidism management in primary care.

Introduction

Hyperthyroidism is a relatively common condition worldwide. The prevalence of overt hyperthyroidism has been reported to range from 0.2 to 1.3% in iodine-sufficient parts of the world [1]. The prevalence of hyperthyroidism has increased over the years, according to a study conducted in Tayside, Scotland [2]. This rise can be attributed to a higher incidence of the disease, improved detection methods, and earlier diagnoses [2]. In Malaysia, a multicentre cross-sectional study has showed that the prevalence of overt hyperthyroidism is 0.6% and subclinical hyperthyroidism is 2.8% [3]. Hyperthyroidism develops due to inappropriately high thyroid hormone synthesis and secretion by the thyroid gland [4]. Hyperthyroidism is known to cause many complications to various systems in the body. Uncontrolled hyperthyroidism can increase heart rate, cardiac output, and blood pressure, leading to various cardiovascular problems such as atrial fibrillation, hypertension, and heart failure [5–7]. Hyperthyroidism can lead to unintentional weight loss despite an increased appetite. The excessive metabolic activity caused by high levels of thyroid hormones can result in the breakdown of muscle tissue and fat stores. Prolonged weight loss and inadequate nutrient intake can lead to malnutrition, weakness, and overall decline in health. Thyroid hormones play a crucial role in regulating mood and mental health. Uncontrolled hyperthyroidism can contribute to anxiety, irritability, restlessness, and sleep disturbances. In some cases, it may also be associated with emotional instability, depression, and cognitive impairment. Thyroid eye disease, also known as Graves’ ophthalmopathy, is a common complication specific to autoimmune hyperthyroidism (Graves’ disease) characterized by inflammation and swelling of the tissues around the eyes. In severe cases, it can cause vision loss or impairment. Untreated hyperthyroidism can also lead to accelerated bone loss by promoting bone resorption and impairing bone formation, increasing the risk of osteoporosis, particularly in the spine, hips, and wrists. In severe cases of uncontrolled hyperthyroidism, thyroid storm, a life-threatening condition, can also occur. Uncontrolled hyperthyroidism in pregnancy can increase the chances of miscarriage, preterm birth, preeclampsia, and foetal thyroid dysfunction [4, 8].

Proper management and close monitoring of thyroid function are essential in patients with hyperthyroidism, especially given the rising prevalence of its associated complications [9, 10]. This involves a well-organized clinic structure, that adheres to the correct management processes, aligning with the current local guidelines for hyperthyroidism management, all aimed at ensuring favourable clinical outcomes for patients [4]. Primary care holds a central role in the management of hyperthyroidism through early detection, diagnosis, and initial management of the condition. Various guidelines have been published, including a recent one in Malaysia, to assist clinicians in the management of thyroid disorders at various levels of care [4, 8]. However, among those with history of thyroid disorders, only 48.0% who were on anti-thyroid drugs (ATD) were found to be euthyroid [3]. This may be attributed to suboptimal management of hyperthyroidism, as evidenced by a global clinical audit which demonstrated that proper management of hyperthyroidism may reduce the risk of treatment failure and relapse [11]. Worldwide, studies on management and outcomes of hyperthyroidism including overt hyperthyroidism especially in primary care is very limited. Therefore, there is a need to evaluate the existing approach to hyperthyroidism management, particularly in community-based primary care clinics that handle the majority of these cases. Conducting a clinical audit is one method to assess the structure, processes, and outcomes of the care provided. For that reason, this UITM-GRAD study was set to be carried out among adult patients diagnosed with overt hyperthyroidism, attending 10 government and 1 university primary care clinics across Malaysia.

Methods

This UITM-GRAD study involved a retrospective review of medical records for patients attending 11 primary care clinics between 1 st January 2023 and 31 st December 2023. In clinical settings, hyperthyroidism is typically suspected in patients presenting with symptoms such as heat intolerance, tremors, palpitations, anxiety, weight loss despite normal or increased appetite, increased bowel movement frequency, and shortness of breath [4, 5]. On physical examination, goitre is commonly observed. Once hyperthyroidism is suspected, a thyroid function test (TFT), including serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4), should be performed during the initial evaluation. Reference ranges for TFT may vary depending on the measurement method and the local population. If TSH is below the lower limit of the reference range but fT4 remains normal, free triiodothyronine (fT3) should also be measured.

For this study, overt hyperthyroidism was defined as a TSH level below the lower limit of the reference range, along with either an elevated fT4 or, in cases where fT4 was normal, an elevated fT3. The management of confirmed overt hyperthyroidism depends on the underlying diagnosis, contraindications to specific treatments, severity of the disease, and patient preference. The three primary treatment modalities are radioactive iodine (RAI), surgery (thyroidectomy), and anti-thyroid drugs (ATD). In primary care, ATDs are the most commonly used treatment. Following ATD initiation, regular follow-up and dose adjustments are necessary to achieve treatment goals. Initially, therapy is guided by fT4 and fT3 levels, with dose titration as these levels normalize. Monitoring of fT4 and fT3 should be conducted every 2–6 weeks, ensuring that patients under proper follow-up undergo regular TFT assessments.

Since a dedicated hyperthyroidism registry was not available in health clinics, patients under follow-up were identified using laboratory results from TFT records. The patient list was obtained through different approaches. In clinics with electronic medical records, specific keywords or ICD-10 codes related to hyperthyroidism were used to extract relevant data. In clinics with manual records, data were traced from laboratory results or pharmacy records of patients prescribed ATDs within the study period. These methods ensured a comprehensive list of hyperthyroid patients, from which those meeting the inclusion and exclusion criteria were selected. The medical records of eligible patients were reviewed by family medicine specialists to assess the management of overt hyperthyroidism.

The inclusion criteria for this study included all adult patients (aged 18 years and above) diagnosed with overt hyperthyroidism, who had undergone thyroid function testing within the study period and had been under follow-up for at least 12 months. Patients were be excluded if they were pregnant or receiving palliative care.

To ensure consistency in data collection, a training session was conducted for the investigators, primarily family medicine specialists, to establish a shared understanding of the study proforma. Investigators adhered to ethical guidelines and maintained patient confidentiality throughout the study process. Ethical approval was obtained from the institutional ethics committee before the start of this study (NMRR ID-23-03008-EBJ and UiTM REC/03/2024 (ST/MR/61)).

Data were analysed using IBM^® SPSS^® Statistics software, v.27.0 for Windows (IBM, Somers, NY, USA). All patient data were de-identified and analysed as a cohort. Missing data were handled using listwise deletion. Numerical data were presented as means with standard deviations (SD) while categorical data were summarized using frequencies and percentages.

Results

A total of 143 patients with overt hyperthyroidism were included in the study. The mean age was 49.0 ± 14.8 years, with a majority being female (73.4%) and of Malay ethnicity (81.1%). Common comorbidities included hypertension (51.0%), dyslipidaemia (44.1%), and diabetes mellitus (21.0%). Graves’ disease was identified as the most common aetiology (23.8%), while 47.6% of cases had an undocumented aetiology. (Table 1)

Table 1.

Sociodemographic and clinical characteristics of patients

Characteristics	Results
Age (years), mean ± SD	49.0 ± 14.8
Sex, n (%)
Female	105 (73.4)
Male	38 (26.6)
Ethnicity, n (%)
Malay	116 (81.1)
Chinese	22 (15.4)
Others	5 (3.5)
Smoking status, n (%)
Never smoker	91 (63.6)
Current smoker	9 (6.3)
Ex-smoker	3 (2.1)
Marital Status, n (%)
Married	88 (61.5)
Unmarried	10 (7.0)
Widowed	4 (2.8)
Divorce	1 (0.7)
BMI (kg/m2), mean ± SD
Underweight (< 18.5)	35 (24.5)
Normal (18.5–22.9)	86 (60.1)
Overweight (23.0–27.4)	9 (6.3)
SBP (mmHg), mean ± SD	134.2 ± 27.4
DBP (mmHg), mean ± SD	76.1 ± 15.6
Pulse Rate (bpm), mean ± SD	96.5 ± 25.9
Comorbidities, n (%)
Diabetes	30 (21.0)
Hypertension	73 (51.0)
Dyslipidaemia	63 (44.1)
Atrial Fibrillation	10 (7.0)
Ischemic Heart Disease	4 (2.8)
Aetiology
Graves’ Disease	34 (23.8)
Multinodular Goitre	29 (20.3)
Toxic Adenoma	12 (8.3)
Unknown	68 (47.6)
TFT at diagnosis
TSH (multiples of lower normal limit)	0.053 ± 0.179
FT4 (multiples upper normal limit)	2.5 ± 1.4
Thyroid-related Medications, n (%)
Carbimazole	139 (97.2)
Propylthiouracil	4 (2.8)
Propranolol	76 (53.1)
Bisoprolol	7 (4.9)
Atenolol	2 (1.4)
Metoprolol	1 (0.7)

In terms of structural measures, only 27.3% of clinics maintained a hyperthyroidism registry. Most clinics had facilities or referral pathways for thyroid function tests (72.7%), ultrasound (72.7%), and thyroid antibodies (81.8%). Training in hyperthyroidism management was conducted annually in 72.7% of clinics, and clinical practice guidelines (CPG) were available in 81.8% of consultation rooms (Table 2).

Table 2.

Measures of structure for hyperthyroidism care in primary care clinics. (n = 11)

Criteria	n (%)
All patients with hyperthyroidism should be registered in a registry.	3 (27.3)
The clinic has facilities or referral pathways for performing thyroid function tests.	8 (72.7)
The clinic has facilities or referral pathways for performing ultrasound.	8(72.7)
The clinic has facilities or referral pathways for performing thyroid antibodies.	9 (81.8)
Training in the management of hyperthyroidism is done annually.	8 (72.7)
The Clinical Practice Guideline (CPG) on the management of thyroid disorders is available in the consultation room.	9 (81.8)

For process measures, 96.5% of patients were correctly diagnosed, though documentation of aetiology was only available in 52.4% of cases. Counselling on treatment options was documented in 28.7% of cases. Monitoring was suboptimal, with only 52.4% undergoing repeat TFT within 2–6 weeks of initial diagnosis. However, follow-up testing at 2–3 months post-normalization of fT4 was documented in 81.1% of cases. ATD therapy was appropriately guided by fT4 levels in 65.0% of patients, but side effect counselling was documented in only 11.9%. Regarding management, osteoporosis risk assessment was performed in only 0.8% of patients, and psychiatric assessments were documented in 7.0%. Among patients requiring referral for definitive therapy, adherence varied, with 65.9% of those with toxic multinodular goitre or toxic adenoma being referred, while only 58.7% of patients failing ATD therapy and 59.4% of those experiencing relapse were referred (Table 3).

Table 3.

Measures of processes for hyperthyroidism care

Criteria	Frequency	Result (%)
a. Diagnosis
Patient with hyperthyroidism is correctly diagnosed with hyperthyroidism.	138/143	96.5
Documentation of diagnosis based on aetiology.	75/143	52.4
Documentation of counselling on appropriate choice of treatments was offered.	41/143	28.7
b. Monitoring
TFT is repeated after 2–6 weeks of the initial diagnosis.	75/143	52.4
TFT is repeated 2–3 months after free T4 has normalized.	116/143	81.1
c. Pharmacotherapy
ATD is started based on the free T4 level	93/143	65.0
Documentation of side effects of ATD counselling.	17/143	11.9
ATD was tapered down when indicated.	121/143	84.6
FBC results are monitored when patients developed fever or sore throat.	33/33	100
LFT results are monitored when patients become jaundiced.	2/6	33.3
d. Management
An assessment for osteoporosis (using the Fracture Risk Assessment Tool) was done.	1/127	0.8
An assessment psychiatric disorders was done.	9/129	7.0
Patient with comorbidities or who develop comorbidities is referred to a tertiary centre.	8/26	30.8
Patient with toxic MNG or TA is referred for definitive therapy.	27/41	65.9
Patient who failed to achieve the euthyroid biochemical state despite adequate treatment with ATD is referred for definitive therapy.	37/63	58.7
Patient with relapsed hyperthyroidism after an initial course of ATD treatment is referred for definitive therapy.	19/32	59.4
After stopping ATD, follow ups were given to confirm remission.	39/41	95.1

For outcome measures, 59.4% of patients achieved euthyroid status within 18 months, while 62.2% did not develop iatrogenic hypothyroidism during ATD treatment (Table 4).

Table 4.

Measures of outcomes for hyperthyroidism care

Criteria	Frequency	Result (%)
Patient achieved normal TFT within 18 months after starting antithyroid	85/131	59.4
Patient did not developed hypothyroidism during treatment with ATD.	89/143	62.2

Discussion

This study highlights key gaps in the management of overt hyperthyroidism in primary care settings. While diagnostic accuracy was high (96.5%), documentation of aetiology was only 52.4%. There is a lack of data on the documentation of aetiology in the management of hyperthyroidism. A comparable study conducted in the United Kingdom (UK) examined the most common clinical causes of thyrotoxicosis, classifying them as autoimmune, nodular, or mixed, based on the presence of goitres, clinical features of Graves’ disease, and records of drug-induced hyperthyroidism, thyroiditis, or thyroid antibody results [12]. In our study, we found that almost half of the recorded aetiologies were due to Graves’ disease, which is slightly lower than the 85.9% reported in the previous study [12]. However, the number of autoimmune cases in our study could potentially be higher if those with unknown aetiologies were properly investigated. International surveys among endocrinologists, medical specialists, surgeons, and nuclear medicine specialists have shown increased use of thyrotropin receptor antibody for diagnosis and reciprocal decreases in nuclear medicine [13, 14]. Proper investigations and documentation of aetiology are crucial, as they helps guide long-term treatment decisions, including the need for definitive therapy in Graves’ disease or toxic nodular goitre [4, 15].

Monitoring of thyroid function was inconsistent, with only 52.4% of patients undergoing repeat TFT testing within 2 to 6 weeks of diagnosis. Although major guidelines recommend repeating TFTs 2 to 4 weeks after diagnosis, there have been discrepancies in the management of hyperthyroidism [4, 8]. Some centres immediately reduce ATD after 4 weeks without conducting follow-up TFTs [12]. Factors such as variations in healthcare access, physician workload, and patient adherence to follow-up appointments may contribute to this issue, as TFTs are often not performed in clinics. Patients may need to visit on specific days to have blood drawn and reviewed after 2 to 4 weeks. However, our study indicated that 81.1% of patients had repeat testing 2 to 3 months after free T4 normalization, suggesting better adherence to monitoring at later stages.

Pharmacological management generally aligned with clinical guidelines, with 97.2% of patients receiving carbimazole as first-line therapy. This is higher than a study conducted in a hospital in Thailand where only 78.0% of patients received ATD treatment [16]. This is in line with international surveys of clinical practice patterns which have shown that more than three-quarters of specialists preferred ATD followed by RAI and thyroidectomy for uncomplicated GD [13, 14]. However, documentation of counselling for ATD side effects was poor, at only 11.9%. This discrepancy may result from variations in healthcare documentation practices, where advice was given but not recorded, or from counselling provided by pharmacists during medication dispensing that was not documented in this study. Although serious ATD-related adverse effects were rare, complications such as agranulocytosis and hepatotoxicity are significant [12]. Therefore, systematic patient education and documentation should be emphasized [4, 8].

Referral rates for definitive therapy varied, with only 58.7% of patients who failed ATD therapy and 59.4% of those experiencing relapse being referred for definitive treatment. This is comparable to an audit conducted in the UK [11]. Referral rates observed in our study may be lower than expected due to a combination of factors, including patient reluctance to undergo definitive therapy, limited access to specialized care, or physician preference for prolonging ATD therapy based on patient profiles [4, 8, 15, 17]. A study in the UK showed that, in the long term, only about one-third of patients completed definitive therapy, one-third remained on long-term ATD, and one-third were off treatment altogether [12]. TFT control was broadly similar across all three long-term treatment options, although the highest percentage of normal TSH levels was seen in patients on long-term ATD [12, 18].

In terms of outcomes, 59.4% of patients achieved euthyroidism within 18 months, comparable to other international and local studies where euthyroid status was achieved in 37–68% of patients following ATD therapy [3, 12, 15, 16, 19]. However, our study found that 62.2% of patients avoided iatrogenic hypothyroidism. Most studies do not assess the frequency of hypothyroidism during treatment but only report outcomes after treatment completion, which has been noted to be less than 5% [12]. This suggests that dose titration strategies used in primary care effectively prevent overtreatment. From a structural perspective, only 27.3% of clinics maintained a hyperthyroidism registry, which limits the ability to systematically track and monitor patients. Maintaining a dedicated registry is cost-effective and has been shown to improve adherence to treatment guidelines and patient outcomes [20, 21]. Implementing a structured registry could therefore enhance the quality of care in our setting.

Overall, this study underscores key areas for improvement, including better documentation, improved adherence to monitoring guidelines, enhanced patient education on ATD side effects, and timely referrals for definitive therapy. While some findings align with international studies, variations in documentation, monitoring frequency, and referral rates highlight the need for a more structured approach to hyperthyroidism management in primary care. Future efforts should focus on strengthening adherence to clinical guidelines, integrating structured patient registries, and improving access to specialist care to optimize outcomes for patients with hyperthyroidism.

This study has several limitations. As a retrospective study, it relies on medical records, which may have missing or incomplete data, particularly in documenting aetiology and patient counselling. This could lead to an underestimate of actual clinical practices. Retrospective audits are inherently susceptible to bias, as they depend on the quality and completeness of existing records rather than real-time observation. The study was conducted in selected primary care clinics, which may not fully represent or be generalizable to all healthcare settings in Malaysia. Differences in resources, clinician practices, and patient demographics could affect the generalizability of the findings. While adherence to clinical guidelines was assessed, patient adherence to treatment and follow-up was not evaluated, which may have influenced outcomes. Additionally, patient-reported symptoms, quality of life, and long-term complications were not included, limiting a comprehensive assessment of disease impact. Referral practices for definitive therapy varied among clinicians and were not standardized, potentially affecting referral rates for RAI or surgery. The absence of a dedicated hyperthyroidism registry in most clinics also made long-term patient tracking challenging. Future studies should incorporate prospective designs, standardized data collection, and patient-reported outcomes to provide a more comprehensive evaluation of hyperthyroidism management in primary care.

Conclusion

This study identified both strengths and areas for improvement in the management of overt hyperthyroidism in primary care. While diagnostic accuracy and initial treatment selection were generally appropriate, gaps exist in the monitoring, patient education, referral practices, and comprehensive risk assessments. Structured documentation, adherence to monitoring protocols, and timely referrals for definitive therapy should be prioritized. Future efforts should focus on implementing a dedicated patient registry and strengthening clinician training to improve the quality of care.

Author contributions

JJ and MAMK conceptualized the study. JJ, ANIZA, MAMK, NANAK, MYMY, SNHAR, NAR, NSSD and NI collected the data. JJ and ANIZA analysed the data, wrote, and critically revised the manuscript. All authors approved the final version of the manuscript.

Funding

None.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Ethical approval

This study received ethics approval from the Medical Research Ethics Committee (MREC), Ministry of Health, Malaysia (NMRR ID-23-03008-EBJ) and University Teknologi MARA (REC/03/2024 (ST/MR/61)).

Consent to participate

Not applicable.

Competing interests

The authors declare no competing interests.

Clinical trial number

Not applicable.