Clinical inertia in thyrotropin suppressive therapy for low-risk differentiated thyroid cancer: A real-world experience at an endocrine center in Bangkok.

The management of low-risk differentiated thyroid cancer (DTC) has evolved over time toward treatment de-escalation. However, overtreatment with supraphysiological dose of levothyroxine (LT4) continues to be observed despite current clinical guideline. This study aimed to assess the actual thyrotropin suppressive therapy for low-risk DTC patients at an endocrine center in Bangkok. This retrospective study included patients with low-risk DTC who were regularly follow-up for at least 18 months at Theptarin Hospital between 2016 and 2022. The serum thyroid stimulating hormone (TSH) levels were stratified as TSH < 0.1 mIU/L; TSH 0.1 to 0.5 mIU/L; TSH 0.5 to 2.0 mIU/L; and TSH > 2.0 mIU/L. The initial risk stratification (IRS) and dynamic risk stratification were determined at 12 months of follow-up after completing the initial treatment and at the last visit. The clinical factors associated with overtreatment with LT4 were analyzed. A total of 102 patients (83.3% female, age at diagnosis 41.8 ±â€…13.6 years, mean tumor size 1.6 ±â€…1.0 cm) were evaluated with a mean follow-up of 5.9 years. The IRS classified 92.2% of patients after the initial treatment and 93.1% of patients at the last follow-up visit into the excellent response category. The mean LT4 daily dosage at the last follow-up was 121.3 ±â€…44.8 µg/day. Serum TSH levels were in an appropriate target range according to IRS in only 8.8% (9/102) of the patients and then improved to 19.6% (20/102) at the last follow-up visit. Further analysis showed that treating physicians with ≥10 years of practice was associated with severe TSH suppression therapy (TSH < 0.1 mIU/L). Despite the current clinical guideline recommendations and scientific evidences, less than one-fifth of low-risk DTC patients achieved the appropriate serum TSH target. While the proportion of an optimum LT4 suppressive had improved during the study period, further efforts are needed to overcome this clinical inertia.

Real-World Use of Once-Weekly Semaglutide in Thai Patients With Type 2 Diabetes Mellitus in a Private Hospital Setting.

Objective: To evaluate the real-world use of once-weekly semaglutide among Thai patients with type 2 diabetes (T2DM) in a private hospital setting. Methodology: A retrospective review of Thai patients with T2DM who have initiated semaglutide for at least 1 month between June 2020 and March 2022 at Theptarin Hospital, Bangkok, Thailand. Results: A total of 58 patients (50% female, mean age 55.6 ± 15.9 years, with duration of diabetes 12.6 ± 10.3 years, BMI 31.5 ± 4.4 kg/m2, baseline HbA1c 7.9 ± 1.9%, with prior GLP-1 RA use 24.1%, and concomitant SGLT2i intake (41.4%) were included. During a median follow-up of 6 months, the mean serum HbA1c level reduction was 1.3 ± 1.7% with weight loss of 4.7 ± 4.1 kg. The proportion of patients who achieved optimal and sustainable glycemic control (HbA1c < 7.0%) increased from 43.1% to 55.8% at the last follow-up. The proportion of patients reaching both HbA1c targets of <7.0% and 5% weight loss was 27.8%. No cases of pancreatitis, cancer, or progressive retinopathy were observed. Conclusions: In this single center undertaking, it was shown that in among persons with T2DM and obesity in Thailand, semaglutide was associated with short-term glycemic control and weight loss comparable with what has been observed in randomized clinical trials and other RWE.

Hypertriglyceridemia as a main feature associated with 17q12 deletion syndrome-related hepatocyte nuclear factor 1ß-maturity-onset diabetes of the young.

Summary: Hepatocyte nuclear factor 1ß (HNF1B) gene is located on chromosome 17q12. It is a transcription factor implicated in the early embryonic development of multiple organs. HNF1B-associated disease is a multi-system disorder with variable clinical phenotypes. There are increasing reports suggesting that the 17q12 deletion syndrome should be suspected in patients with maturity-onset diabetes of the young type 5 (MODY5) due to the deletion of HNF1B gene. In contrast to classical 17q12 syndrome in childhood with neurological disorders and autism, patients with HNF1B-MODY deletion rarely had neuropsychological disorders or learning disabilities. The diagnosis of 17q12 deletion syndrome highlighted the phenotypic heterogeneity of HNF1B-MODY patients. In this study, we report the clinical course of a Thai woman with young-onset diabetes mellitus and hypertriglyceridemia as a predominant feature due to HNF1B deletion as part of the 17q12 deletion syndrome. Our findings and others suggest that hypertriglyceridemia should be considered a syndromic feature of HNF1B-MODY. Our case also highlights the need to use sequencing with dosage analyses to detect point mutations and copy number variations to avoid missing a whole deletion of HNF1B. Learning points: Maturity-onset diabetes of the young type 5 (MODY5) may be caused by heterozygous point mutations or whole gene deletion of HNF1B. Recent studies revealed that complete deletion of the HNF1B gene may be part of the 17q12 deletion syndrome with multi-system involvement. The length of the deletion can contribute to the phenotypic variability in patients with HNF1B-MODY due to whole gene deletion. Using next-generation sequencing alone to diagnose MODY could miss a whole gene deletion or copy number variations. Specialized detection methods such as microarray analysis or low-pass whole genome sequencing are required to accurately diagnose HNF1B-MODY as a component of the 17q12 deletion syndrome. Molecular diagnosis is necessary to distinguish other acquired cystic kidney diseases in patients with type 2 diabetes which could phenocopy HNF1B-MODY. Hypertriglyceridemia is a possible metabolic feature in patients with HNF1B-MODY due to 17q12 deletion syndrome.

Profile of Levothyroxine Replacement Therapy in Graves' Disease Patients with Hypothyroidism Post-Radioactive Iodine Ablation: Focus on Different Weight-Based Regimens.

Objective: To evaluate the status of euthyroidism achieved among Thai patients with post-ablative hypothyroidism and to examine the difference between various weight-based daily levothyroxine (LT4) replacement regimens in these patients. Methodology: We conducted a retrospective review of Thai patients with Graves' disease (GD) who developed hypothyroidism following radioactive iodine treatment from 2016 to 2020 at Theptarin hospital. Daily LT4 dose was calculated based on actual body weight (ABW), ideal body weight (IBW), and estimated lean body mass (LBM). Results: We reviewed a total of 271 patient records. Of these, 81.2% were females with a mean age of 40.8±11.7 years, LT4 intake duration of 27.1±14.6 months, and LT4 dose/kg ABW of 1.4±0.5 µg/kg/day. At the final follow-up, 62.4% of patients achieved thyroid-stimulating hormone (TSH) levels within the reference interval, 15.5% had TSH levels over, and 22.1% had TSH levels under the reference range. Obese patients required a lower daily LT4 dose relative to ABW and higher daily LT4 dose relative to IBW to attain euthyroidism (ABW 1.1±0.4 µg/kg/day and IBW 2.0±0.8 µg/kg/day). Estimated daily LT4 dose based on LBM showed a constant dosage of 2.0 µg/kg/day in all BMI categories. Conclusions: Suboptimum LT4 replacement therapy was found in almost half of hypothyroid patients with GD treated with radioactive iodine. Estimated LBM was a better indicator for dosing calculation in these patients compared with ABW and IBW.

Unilateral gynecomastia as an initial presentation of hyperthyroid Graves' disease.

SUMMARY: Graves' disease is an autoimmune condition leading to the activation of and an increase in thyroid hormone secretion. Manifestations of hyperthyroidism in Graves' disease can vary among people. In this case, we report a 24-year-old Thai man with a rare presentation of unilateral gynecomastia along with symptoms of thyrotoxicosis. Physical examination revealed a 3 cm non-tender palpable glandular tissue beneath and around the left areola without nipple discharge and moderately diffuse thyroid enlargement with thyroid bruit. Thyroid function test showed a typical thyrotoxicosis state with elevated serum-free T4 and decreased serum TSH. His diagnosis of Graves' disease was confirmed biochemically with a highly elevated anti-TSH receptor antibody. Early treatment with anti-thyroid medication was given first, followed by Radioiodine treatment (RAI) for definitive treatment due to high level of anti-TSH receptor antibody, enlarged thyroid and severe thyrotoxicosis presentation at a young age, which might not resolve by anti-thyroid medication alone. The patient responded well to treatment and achieved complete resolution of unilateral gynecomastia with clinically and biochemically euthyroid within 3 months after treatment. No recurrent gynecomastia was found during the 2-year follow-up. LEARNING POINTS: Characteristic of gynecomastia in hyperthyroidism is usually presented with bilateral progressive gynecomastia; however, unilateral gynecomastia is occasionally found as a presentation of hyperthyroidism. Complete resolution of gynecomastia without recurrence can be achieved within a few months of treatment after thyrotoxicosis is resolved in patients with hyperthyroidism with the recent development of gynecomastia. RAI for definitive treatment is recommended in young adult patients expressing very high anti-TSH antibody level with severe thyrotoxicosis.

Impacts of the American Joint Committee on Cancer (AJCC) 8th edition tumor, node, metastasis (TNM) staging system on outcomes of differentiated thyroid cancer in Thai patients.

BACKGROUND: In 2018, the American Joint Committee on Cancer (AJCC) 8th edition (AJCC8) was introduced to replace the previous version (AJCC7) due to superiority of AJCC8 over AJCC7 for better prediction of survival from thyroid cancer. AIM: To compare AJCC staging systems with the American Thyroid Association (ATA) risk classification for the prediction of 5-year disease-free survival (DFS), and 5-year disease-specific survival (DSS) in Thai patients. METHODS: We retrospectively reviewed all patients with histopathologic diagnosis of DTC who were treated at Theptarin Hospital, Bangkok, Thailand from 1987 to 2019. RESULTS: The study cohort included 262 differentiated thyroid cancer (DTC) patients (papillary thyroid cancer 89.7% with a median time of follow-up 7.8 years). The number (%) of patients within each stage group by AJCC7 and AJCC8 respectively are as follows: Stage I: 173 (66.0%) vs. 232 (88.5%), Stage II: 33 (12.6%) vs. 24 (9.2%), Stage III: 36 (13.7%) vs. 2 (0.8%), Stage IV: 20 (7.7%) vs. 4 (1.5%). The ATA high risk group was found in 24.3% of AJCC7 Stage I compared with 23.7% of AJCC8 Stage I. The 5-year DFS rates in patients classified as stages I, II, III, and IV by AJCC8 were 87.9%, 45.8%, 0% and 25%, respectively. The 5-year DSS rates in patients classified as stages I, II, III and IV by AJCC8 were 98.7%, 100%, 100% and 0%, respectively. AJCC8 was more predictive of DFS rate than AJCC7. CONCLUSIONS: Our study is in accord with previous studies that AJCC8 downstage a significant percentage of patients with DTC and correlated with better prognostic validity. However, even a person at low risk for mortality can be at high risk for recurrence.

Practice patterns and outcomes in the management of Thai patients with Graves' disease.

BACKGROUND: The treatment of hyperthyroid Graves' disease (GD) varies considerably among geographic areas. In this study, we aimed to evaluate practice patterns and treatment outcomes in Thai patients with hyperthyroid GD. METHODS: A retrospective cohort study over 35 years (1985-2019) in patients with hyperthyroid GD was conducted. The trends of treatment options were compared periodically during the study period and the overall remission rate from each option was determined. RESULTS: A total of 2736 hyperthyroid GD patients were treated and followed-up for at least 3 months over the study period (female 82.0%, mean age at diagnosis 36.3 ± 12.0 years, median duration of follow-up 74.5 months). Anti-thyroid drug (ATD) was the most commonly used treatment (78.0%), followed by RAI (21.0%), and surgery (1.0%). There was a significant downward trend for surgery, from 12.3% in the 1980s to only 0.2% in last phase of the study period. The preference for RAI therapy has also decreased in the last 5 years. Among ATD-treated patients, the remission rate was achieved only in 30.7 and 16.0% of all ATD-treated patients were eventually treated with RAI. Spontaneous hypothyroidism developed in 2.7% of the ATD-treated patients during a follow-up period. Almost all RAI-treated patients (97.1%) developed hypothyroidism. CONCLUSIONS: Our present study highlighted the changing landscape of primary treatments for hyperthyroid GD toward ATD and the sharp downward trend in the surgical option. Even though ATD was associated with a low remission rate, it was preferred by many patients and physicians. The use of RAI as the primary treatment decreased in the last decade. However, RAI was a very effective treatment for Graves' hyperthyroidism but will inevitably induce hypothyroidism and a requirement for life-long replacement therapy.

Clinical Features and Outcomes of Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid (DPP4i-Associated BP) in Thai Patients.

The use of dipeptidyl peptidase-4 inhibitors (DPP4i) appears to be associated with a small but significantly elevated risk of bullous pemphigoid (BP). Although the pathogenic mechanism of DPP4i-associated BP remains unclear, this adverse event is reported with multiple gliptins, suggesting a class effect. However, previous studies from various countries showed that vildagliptin had been implicated in most cases. The aim of this study was to illustrate a case series of DPP4i-associated BP in Thai patients. We conducted a retrospective study from consecutive cases of BP in people with type 2 diabetes mellitus (T2DM) from January 2008, the year in which the first DPP4i was introduced in Thailand, until December 2019. During the study period, 10 BP patients with T2DM were identified. A total of 5 DPP4i-associated BP (3 on vildagliptin, 1 on linagliptin, and 1 on sitagliptin) were found. All patients were male with a mean age at BP development of 80.4 years (73-86 years). All patients had a long-standing duration of diabetes (median duration 34 years), and mean A1C was 7.5 ± 1.4%. The median time to BP development after the introduction of DPP4i was 64 months (range 20-128 months). The severity of BP was classified as mild in 2 cases. In all cases, the association between the drug intake and BP onset was classified as "possible" according to the Naranjo causality scale. All of the patients continued taking DPP4i after BP diagnosis, and one patient died of lung cancer 18 months after BP diagnosis. Only 2 patients could achieve complete remission at least 2 months after stopping DPP4i. Our case series demonstrated a potential link between DPP4i and the development of BP, which mainly occurred in very elderly male patients. The latency period from an introduction of DPP-4i could be several years, and the clinical course after DPP4i discontinuation varied. Clinicians prescribing DPP4i should be aware of this association and consider stopping this medication before a refractory disease course ensues.

Impact of first-line treatment choice on long-term outcomes of hyperthyroid Graves' disease patients with thyrotoxic periodic paralysis.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a unique manifestation of Graves' disease. While it is uncommon in Asian, it is extremely rare in Caucasian patients (0.1-0.2%). Previous studies suggested that TPP indicate more severity of Graves' disease and definitive treatments should be used to prevent relapses. AIM: To describe clinical features and impact of first-line treatment on long-term outcomes of TPP patients. METHOD: A retrospective cohort study over 35 years (1985-2019) of TPP from Graves' disease patients was conducted. All cases were analyzed and their clinical courses were compared between those who received anti-thyroid drugs (ATD) versus radioactive iodine (RAI) as a primary treatment. None of them underwent surgery. RESULTS: A total of 2964 hyperthyroid Graves' disease patients were treated and followed-up at least 3 months over the study period. TPP was identified in 63 cases (2.1%) of all patients. There were 60 males and only 3 females with age at presentation of 35.0 ± 8.2 years. TPP was the first presentation of hyperthyroid Graves' disease in 82.5% of them. During the acute attack of TPP, all patients presented with bilateral lower limb flaccid weaknesses with median serum potassium of 2.1 mmol/L. No fatal TPP cases were found. RAI was selected as primary treatment in 27 patients (42.9%). Nearly all RAI-treated patients rendered hypothyroidism with the median RAI dose at 15 mCi. No patients who were in remission after RAI treatment developed recurrent attack of TPP. In the remaining 36 ATD-treated patients with mean follow-up time at 9.1 years, relapse was found in 10 patients (27.8%) after the drug discontinuation and 6 patients suffered recurrent TPP. Only 8 ATD-treated TPP patients (22.2%) went into remission. CONCLUSIONS: TPP is a rare complication of hyperthyroid Graves' disease. Definitive treatment with RAI or thyroidectomy should be employed to prevent relapse and further attacks of TPP.

Epidermoid cyst abscess of the neck masquerading as a thyroid abscess.

SUMMARY: In this case report, we describe a 37-year-old male who presented with fever and tender neck mass. Neck ultrasonography revealed a mixed echogenic multiloculated solid-cystic lesion containing turbid fluid and occupying the right thyroid region. Thyroid function tests showed subclinical hyperthyroidism. The patient was initially diagnosed with thyroid abscess and he was subsequently treated with percutaneous aspiration and i.v. antibiotics; however, his clinical symptoms did not improve. Surgical treatment was then performed and a pathological examination revealed a ruptured epidermoid cyst with abscess formation. No thyroid tissue was identified in the specimen. The patient was discharged uneventfully. However, at the 3-month and 1-year follow-ups, the patient was discovered to have developed subclinical hypothyroidism. Neck ultrasonography revealed a normal thyroid gland. This report demonstrates a rare case of epidermoid cyst abscess in the cervical region, of which initial imaging and abnormal thyroid function tests led to the erroneous diagnosis of thyroid abscess. LEARNING POINTS: Epidermoid cyst abscess at the cervical region can mimic thyroid abscess. Neck ultrasonography cannot distinguish thyroid abscess from epidermoid cyst abscess. Thyroid function may be altered due to the adjacent soft tissue inflammation.

De-differentiation of papillary thyroid carcinoma into squamous cell carcinoma in an elderly patient: A case report.

RATIONALE: The unpredictability of thyroid cancer can be striking, as the disease may rapidly progress to death in some individuals. Herein, we reported a rare case of aggressive papillary thyroid cell carcinoma (PTC) in an elderly patient de-differentiated into squamous cell carcinoma (SCC). PATIENT CONCERNS: We describe a case of a 79-year-old Thai woman presented with hoarseness and neck mass for 2 months and she had been diagnosed with a 3-cm papillary thyroid carcinoma (PTC) in the right side of the thyroid gland. Later on PTC de-differentiated into SCC within 3 years after initial presentation. DIAGNOSIS: De-differentiation from papillary thyroid carcinoma to squamous cell carcinoma. INTERVENTIONS: The patient underwent a total thyroidectomy at the initial hospital and received high dose radioactive iodine (RAI) treatment at our hospital 1 month following the surgery and then was lost to follow-up. Two years later she came back with new development of right solid-cystic neck mass which was found to be recurrent PTC. A radical neck dissection was done and another high dose RAI treatment was given. However, she developed recurrent mass with tenderness at the site above previous solid cystic mass 6 months later. Re-exploration of the neck mass revealed an inflamed midline mass 2 cm with enlarged right lateral cervical lymph nodes. OUTCOMES: A histopathological examination of the midline neck mass showed poorly differentiated SCC with lymphatic invasion. The intermingling of two morphologically distinct tumors, a typical PTC and a poorly differentiated SCC, had been identified in 1 out of 14 excised cervical lymph nodes. The patient underwent external beam radiation without chemotherapy. She is still in stable condition at 18 months post-treatment. LESSONS: This case clearly demonstrated that SCC transformed from a pre-existing PTC. The clinician should consider a possible transformation of papillary thyroid cancer into more aggressive histological types in elderly patients who present with rapidly progressive clinical behavior. However, some patients could have long-term survival if the tumor did not transform into anaplastic thyroid cancer.

Incidence and malignancy rates classified by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) - An 8-year tertiary center experience in Thailand.

Incidence and Malignancy Rates Classified by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) - An 8-year Tertiary Center experience in Thailand. BACKGROUND: Fine-needle aspiration (FNA) of the thyroid is considered the best diagnostic tool for preoperative evaluation of thyroid nodules. The introduction of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in 2010 provided the opportunity to establish worldwide standard for reporting and terminology guidelines for diagnostic categories. It is recommended that every institution evaluates the risk of malignancy (ROM) in each category for quality improvement process. AIM: To assess the effectiveness of TBSRTC method at our institution using cyto-histological correlation. METHOD: A retrospective 8-year (2010-2017) audit of thyroid FNA done by thyroid specialists at Theptarin hospital. The FNA results were classified according to TBSRTC. Histopathology reports for operated cases were used to correlate cytology and final histopathology. RESULTS: A total of 2735 thyroid FNA from 2115 patients (mean age 45.7 ±â€¯13.1 years, female 89.8%) were examined. The rates of non-diagnostic, benign, atypia of undetermined significance (AUS), follicular neoplasm, suspected for malignancy, and malignant cases were 21.1%, 66.6%, 4.7%, 2.4%, 1.8%, and 3.3% respectively. There were 188 patients (9%) who underwent surgical resection with available histopathology. Malignancy rates in operated thyroid nodules were 20.0%, 4.2%, 9.4%, 23.5%, 57.1%, and 90.3% for categories 1 to 6, respectively. The sensitivity, specificity, negative predictive value, and positive predictive value were 96.6%, 88.5%, 95.8%, and 90.3, respectively. CONCLUSIONS: Preoperative diagnosis of thyroid nodules using TBSRTC in our hospital was comparable with other studies. The uniform diagnostic criteria of the Bethesda System help avoid misinterpretation while sharing local experience with international benchmarks.

Performance of HbA1c versus oral glucose tolerance test (OGTT) as a screening tool to diagnose dysglycemic status in high-risk Thai patients.

BACKGROUND: Dysglycemic status defined by prediabetes and diabetes is known to be related with future risk of diabetic complications and cardiovascular diseases. Herein, we aimed to determine the diagnostic accuracy of glycated hemoglobin (HbA1c) when compared with oral glucose tolerance test (OGTT) as a reference test in identifying dysglycemic status among high-risk Thai patients receiving care in an out-patient setting. METHODS: An 11-year retrospective cross-sectional study of high-risk Thai patients who underwent OGTT during 2007-2017 was analysed. The OGTT was used as a reference test to identify subjects of dysglycemic status. The diagnostic accuracy of HbA1c and the agreement between HbA1c and OGTT were examined. Validated Thai diabetes risk score, Thai cardiovascular risk score (Thai CV risk score), and visceral fat area (VFA) were also compared in each glycemic status from OGTT as surrogate markers for future diabetes and cardiovascular diseases. RESULTS: A total of 512 subjects (females 60.5%, mean age of 50.3 ± 12.7 years, BMI of 26.5 ± 4.6 kg/m2) were reviewed. Normal glucose tolerance (NGT) was found in 220 patients (43.0%), impaired glucose tolerance (IGT) in 191 patients (37.3%), and diabetes in 101 patients (19.7%). The prevalence of diabetes using OGTT was approximately two times higher than those defined by HbA1c (19.7% versus 11.1%). There were poor agreements between the classifications of prediabetes and diabetes defined by OGTT and HbA1c (Cohen's Kappa 0.154 and 0.306, respectively). Using a cut-off value for HbA1c ≥6.5% as a threshold for HbA1c-defined criteria of diabetes, sensitivity was 32% (95% CI 23-41%) and specificity was 94% (95% CI 92-96%). The optimal cut-off HbA1c value for detecting diabetes by Youden's index was at HbA1c 6.2%. Thai CV risk score was much higher among the OGTT-defined diabetes group when compared with the NGT group (median score 10 vs. 3, p-value < 0.001). CONCLUSIONS: Despite the practicality and validity of HbA1c as a diagnostic test, our study suggested that HbA1c as a screening tool for diabetes in high-risk Thai patients is much inferior to OGTT. With limitations of HbA1c, physicians should continue to advocate OGTT as a screening tool for the identification of dysglycemic status in high-risk Thai patients.

Hemorrhagic necrosis of small bowel following small bowel obstruction as a late complication of sex reassignment surgery-a gap in transgender care.

For decades, Thailand has been at the forefront of sex reassignment surgeries. The neovagina created by recto-sigmoid vaginoplasty is much more complex procedure when compared with penile skin version technique, but yielded more satisfactory functional outcomes. We reported an unusual case of life-threatening small bowel obstruction following previously successful recto-sigmoid vaginoplasty in a transgender woman. Transgender individuals have unique healthcare needs. However, various gaps still exist to provide multi-disciplinary care for these patients. The rate of adhesive small bowel obstruction is highest in the early period of any intra-abdominal post-operative surgeries, but the risk remains life-long. Transgender women receiving complicated vaginoplasty should be instructed to continue long-term follow-up to ensure early detection and management of post-operative complications.

A Novel Mutation in Thyroid Peroxidase Gene Causing Congenital Goitrous Hypothyroidism in a German-Thai Patient.

Thyroid dyshormonogenesis is responsible for 10-15% of all cases of congenital hypothyroidism and is usually inherited. We report a 26-year-old German-Thai male with congenital hypothyroidism caused by a compound heterozygous mutation in the thyroid peroxidase (TPO) gene. He was diagnosed with congenital goitrous hypothyroidism at 4 months of age and had been treated with levothyroxine replacement therapy. His goiter size had increased due to poor compliance to treatment. Ultrasonography of the thyroid gland showed a pattern suspicious for malignancy. The patient later underwent near-total thyroidectomy. Pathologic examination results were consistent with a multinodular goiter and no malignancy. Genetic analyses by direct sequencing of the entire exons and flanking regions of the TPO gene were performed in the index case and family members. The analyses revealed a compound heterozygote of novel TPO mutation of c.1727C>T in exon 10 resulting in amino acid substitution (p.Ala576Val) and c.2268_2269insT in exon 13 causing a frameshift mutation which introduced a stop codon after the insertion site. The latter has been reported in Chinese subjects. However, there is no previous report of c.1727C>T mutation in the literature. We found the allele contained a novel exon 10 mutation inherited from the patient's German mother and an exon 13 mutation from his Thai father. Analysis using two bioinformatic software programs indicated that this variant was likely to cause damage in the resulting protein molecule. The present report emphasizes the importance of regular follow-up and patient compliance to levothyroxine replacement in patients with goitrous congenital hypothyroidism to avoid prolonged stimulation of thyroid tissue by thyroid-stimulating hormone.