Endocrinology and Metabolism

Original Articles

Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis: A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Deep Dutta, Thanikai Sasikanth, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra; Received September 29, 2024 Accepted November 14, 2024 Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2164 [Epub ahead of print]

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Abstract PDF: Background
Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.
Methods
RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.
Results
Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.
Conclusion
Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study: Eu Jeong Ku, Won Sang Yoo, Yu Been Hwang, Subin Jang, Jooyoung Lee, Shinje Moon, Eun Kyung Lee, Hwa Young Ahn; Received July 13, 2024 Accepted November 11, 2024 Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2101 [Epub ahead of print]

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Abstract PDF: Background
The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group.
Methods
This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006–2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated.
Results
Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures.
Conclusion
In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.

Deep Learning Technology for Classification of Thyroid Nodules Using Multi-View Ultrasound Images: Potential Benefits and Challenges in Clinical Application: Jinyoung Kim, Min-Hee Kim, Dong-Jun Lim, Hankyeol Lee, Jae Jun Lee, Hyuk-Sang Kwon, Mee Kyoung Kim, Ki-Ho Song, Tae-Jung Kim, So Lyung Jung, Yong Oh Lee, Ki-Hyun Baek; Received June 3, 2024 Accepted September 23, 2024 Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2058 [Epub ahead of print]

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Abstract PDF: Background
This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules.
Methods
This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images.
Results
Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity.
Conclusion
CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

Triiodothyronine Is Associated with Incidence/Resolution of Steatotic Liver Disease: Longitudinal Study in Euthyroid Korean: Hye In Kim, Jun Young Kim, Jung Hwan Cho, Ji Min Han, Sunghwan Suh, Ji Cheol Bae, Tae Hyuk Kim, Sun Wook Kim, Jong Ryeal Hahm, Jae Hoon Chung; Received May 11, 2024 Accepted July 19, 2024 Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2040 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design.
Methods
This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models.
Results
During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR,1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD.
Conclusion
In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Thyroid
Association of the Preoperative Controlling Nutritional Status (CONUT) Score with Clinicopathological Characteristics in Patients with Papillary Thyroid Carcinoma: Doohwa Kim, Myungsoo Im, Soree Ryang, Mijin Kim, Yun Kyung Jeon, Sang Soo Kim, Bo Hyun Kim; Endocrinol Metab. 2024;39(6):856-863. Published online November 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.2006

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Abstract PDF Supplementary Material PubReader ePub: Background
The Controlling Nutritional Status (CONUT) score is an immunonutritional test tool based on serum albumin, total cholesterol, and lymphocyte counts. It has been studied as a simple prognostic predictor for various carcinomas. This study aimed to investigate the association between preoperative CONUT scores and the clinicopathological characteristics in papillary thyroid carcinoma (PTC) patients.
Methods
This study included 2,403 PTC patients who underwent total thyroidectomy between 2012 and 2016 at a single tertiary medical center. The CONUT scores were calculated based on preoperative blood tests. The clinicopathological characteristics were retrospectively reviewed. The patients were categorized by the CONUT score (relatively low, 0–2; relatively high, 3–5).
Results
Among the 2,997 PTC patients who underwent total thyroidectomy at Pusan National University Hospital between 2012 and 2016, those without preoperative blood test were excluded (n=149). Finally 2,403 patients were analyzed after excluding 439 patients taking lipid-lowering drugs and six patients without available T stage data after surgery. Based on the CONUT score, the relatively high score group had a lower body mass index (23.7±3.3 kg/m² vs. 21.9±2.9 kg/m², P<0.001), more advanced T stage (T stage 3/4, 5.9% vs. 11.4%, P=0.045), and higher extrathyroidal extension (2.1% vs. 7.6%, P=0.005).
Conclusion
Patients included in this large, single-center study all had a preoperative CONUT score of 0–5, but this study demonstrated that higher preoperative CONUT scores were significantly associated with advanced T stage and extrathyroidal extension. The CONUT score, which can be easily used in clinical practice, is thought to be helpful in predicting the aggressiveness of PTC.

Thyroid
A Neglected Point: Frailty in Older Adults with Differentiated Thyroid Cancer: Meric Coskun, Esra Cataltepe, Hacer Dogan Varan, Eda Ceker, Yasemin Bektas, Yasemin Kuscu, Mehmet Muhittin Yalcin, Mujde Akturk, Fusun Balos Toruner, Mehmet Ayhan Karakoc, Alev Eroglu Altinova; Endocrinol Metab. 2024;39(6):899-907. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2046

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Abstract PDF PubReader ePub: Background
This study investigated the risk of frailty in older adults with differentiated thyroid cancer (DTC) and the effect of thyroid- stimulating hormone (TSH) levels on frailty.
Methods
This single-center, cross-sectional study included 70 DTC patients aged ≥60 years with stable TSH levels during the previous year while receiving levothyroxine. Frailty was assessed using the fried frailty phenotype (FFP). Anterior thigh muscle thickness was measured by ultrasound, and the sonographic thigh adjustment ratio (STAR) index was calculated. Muscle strength was measured using a hand dynamometer. Physical activity was determined by the physical activity scale for the elderly (PASE).
Results
The median (interquartile range) age and follow-up time were 65 years (62 to 71) and 11 years (7.0 to 14.2), respectively. The median TSH level was 1.10 μIU/mL (0.49 to 1.62), and 58.6% of patients were prefrail/frail. Muscle mass and strength were reduced in 35.7% and 17.2% of patients, respectively. TSH levels were lower in those with prefrailty/frailty (P=0.002), low muscle mass (P=0.014), and low strength (P=0.037) than in their normal counterparts. TSH levels correlated negatively with FFP (P= 0.001) and positively with the STAR index (P=0.034). TSH below 1.325 μIU/mL was associated with an increased frailty risk (area under the curve=0.719; P=0.001). Low TSH, female sex, low handgrip strength, and low PASE leisure time scores emerged as independent predictors of frailty (P<0.05).
Conclusion
Older adults with lower TSH levels due to DTC are at high frailty risk and have low muscle mass and strength. Therefore, TSH targets should be set based on a comprehensive evaluation with consideration of the risk-benefit ratio.

Thyroid
Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma: Moon Young Oh, Kyong Yeun Jung, Hoonsung Choi, Young Jun Chai, Sun Wook Cho, Su-jin Kim, Kyu Eun Lee, Eun-Jae Chung, Do Joon Park, Young Joo Park, Han-Kwang Yang; Endocrinol Metab. 2024;39(6):877-890. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2027

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Abstract PDF Supplementary Material PubReader ePub: Background
Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.
Methods
Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed.
Results
The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group.
Conclusion
Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Thyroid
Prevalence of Subclinical Hypothyroidism in a Non-Diabetic Young Female Population and Its Impact on Diabetes and Cardiometabolic Risk: Nawoda Hewage, Udaya Wijesekara, Rasika Perera; Endocrinol Metab. 2024;39(6):864-876. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2015

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Abstract PDF PubReader ePub: Background
We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes.
Methods
This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese).
Results
The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk.
Conclusion
SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

Review Article

Thyroid
Long-Term Antithyroid Drug Therapy in Smoldering or Fluctuating-Type Graves’ Hyperthyroidism with Potassium Iodide: Ken Okamura; Endocrinol Metab. 2024;39(6):827-838. Published online October 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.2079

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Abstract PDF PubReader ePub: Graves’ hyperthyroidism is characterized by stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibodies (TRAbs). Antithyroid drug (ATD) continuation is recommended as long as the thyroid gland is stimulated. Goiter size, thyroidal ¹²³I uptake, serum thyroglobulin level, and TRAb positivity are reliable markers of thyroid stimulation. Attention must also be paid to the responsiveness of the thyroid gland due to the high prevalence of painless thyroiditis and spontaneous hypothyroidism during treatment. TRAbs disappeared at <5 years entering remission in 36.6% of patients (smooth-type), while re-elevation of TRAb activity occurred in 37.7% (fluctuating-type) and remained positive for >5 years in 21.1% (smoldering-type). Seven percent of patients remained positive for TRAbs for >30 years, requiring life-long ATD treatment. Remission occurred after median 6.8 years (interquartile range, 4.0 to 10.9) of ATD treatment in 55% of patients. However, late relapse may occur after stressful events (dormant type). In apparently intractable Graves’ disease (GD) with a large goiter (>40 g), ¹³¹I therapy should be considered. For initial and long-term ATD treatment, we must choose effective, safe, and economical drugs such as 100 mg potassium iodide (KI), although KI sensitivity varies in patients with GD. Thionamide, which has notorious side effects, is added only during the KI-resistant period.

Original Article

Thyroid
In Vitro Investigation of HIF-1α as a Therapeutic Target for Thyroid-Associated Ophthalmopathy: Jeongmin Lee, Jinsoo Lee, Hansang Baek, Dong-Jun Lim, Seong-Beom Lee, Jung-Min Lee, Sang-Ah Jang, Moo Il Kang, Suk-Woo Yang, Min-Hee Kim; Endocrinol Metab. 2024;39(5):767-776. Published online October 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1952

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Abstract PDF Supplementary Material PubReader ePub: Background
Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression.
Methods
OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia.
Results
TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia.
Conclusion
Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.

Review Article

Thyroid
Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease: Rohit A. Sinha; Endocrinol Metab. 2024;39(5):686-692. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.2068

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Abstract PDF PubReader ePub: The influence of thyroid hormone (TH) on liver metabolism has attracted the attention of pharmacologists seeking new treatments for metabolic dysfunction-associated steatotic liver disease (MASLD), an increasingly common metabolic disorder. In this context, the selective induction of autophagy by TH in preclinical models has been identified as a promising mechanism. In this process, TH clears intrahepatic fat through lipophagy while protecting against inflammation and mitochondrial damage in hepatocytes via mitophagy. Furthermore, TH-induced aggrephagy may represent a protective mechanism to mitigate the development of MASLD-associated hepatocellular carcinoma. Considering the defects in autophagy observed during the progression of human MASLD, the induction of autophagy by TH, its metabolites, and its analogs represent a novel strategy to combat hepatic damage across the MASLD spectrum.

Original Articles

Thyroid
Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules: Moon Young Oh, Hye-Mi Choi, Jinsun Jang, Heejun Son, Seung Shin Park, Minchul Song, Yoo Hyung Kim, Sun Wook Cho, Young Jun Chai, Woosung Chung, Young Joo Park; Endocrinol Metab. 2024;39(5):777-792. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.2034

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Abstract PDF Supplementary Material PubReader ePub: Background
We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules.
Methods
Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group).
Results
In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P<0.001), and indeterminate nodules (23.5% vs. 68.2%, P<0.001). Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules.
Conclusion
Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

Thyroid Big Data Articles (National Health Insurance Service Database)
Rising Incidence and Comorbidities of Endogenous Hypothyroidism in Republic of Korea from 2004 to 2018: A Nationwide Population Study: Chae Won Chung, Hwa Young Ahn, Sun Wook Cho, Ka Hee Yi; Endocrinol Metab. 2024;39(6):891-898. Published online September 23, 2024; DOI: https://doi.org/10.3803/EnM.2024.1996

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Abstract PDF Supplementary Material PubReader ePub: Background
Hypothyroidism, a prevalent endocrine disorder, results from insufficient thyroid hormone production or release, affecting metabolism. However, disparities in comorbidities and treatment trajectories may exist between endogenous and exogenous hypothyroidism.
Methods
Data from the Korean National Health Insurance Service from 2004 to 2018. Endogenous hypothyroidism was defined as cases with two or more diagnostic codes for hypothyroidism coupled with a history of thyroid hormone intake exceeding 60 days. To eliminate iatrogenic hypothyroidism, individuals with diagnosis codes for thyroid cancer, treatment codes for thyroid surgery, or radiotherapy were excluded. Hypothyroidism-related comorbidities were defined as new occurrences of the corresponding diagnosis code after the diagnosis of hypothyroidism during the entire study period.
Results
The age-standardized incidence of endogenous hypothyroidism among men was 0.2 per 1,000 person-years in 2004, increasing to 0.8 in 2018. Among women, the incidence increased from 1.6 per 1,000 person-years in 2004 to 3.7 in 2018. When comparing age groups of 20s–50s and 60s–90s, both sexes in the 60s–90s demonstrated a more rapid increase in incidence than those in the 20s–50s age range. Patients with endogenous hypothyroidism demonstrated a higher incidence of mood disorders across all age groups and cerebrovascular disease in individuals ≥60 years old, regardless of sex.
Conclusion
In Republic of Korea, endogenous hypothyroidism incidence has been increased in recent years. The incidence of endogenous hypothyroidism is increasing more rapidly in men than in women, especially in the elderly. Patients with endogenous hypothyroidism seem to have a heightened risk for cerebrovascular disease and mood disorders.

Thyroid
Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer: Hyun Jin Ryu, Min Sun Choi, Hyunju Park, Tae Hyuk Kim, Jae Hoon Chung, So Young Park, Sun Wook Kim; Endocrinol Metab. 2024;39(4):615-621. Published online August 7, 2024; DOI: https://doi.org/10.3803/EnM.2023.1896

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Abstract PDF PubReader ePub

Background
The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT.
Methods
The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (μg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age.
Results
In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m² (n=46), ≥23 and <25 kg/m² (n=30), and ≥25 kg/m² (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 μg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011).
Conclusion
The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

Citations

Citations to this article as recorded by

Levothyroxine Dosing for Thyroid-Stimulating Hormone Suppression in Patients with Differentiated Thyroid Cancer after Total Thyroidectomy
Mijin Kim
Endocrinology and Metabolism.2024; 39(4): 576. CrossRef

Thyroid
Prognosis of Poorly Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis: Ji Young Kim, Jae Kyung Myung, Soyun Kim, Kyung Tae, Yun Young Choi, Soo Jin Lee; Endocrinol Metab. 2024;39(4):590-602. Published online June 27, 2024; DOI: https://doi.org/10.3803/EnM.2024.1927

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Background
Poorly differentiated thyroid carcinoma (PDTC) accounts for a small portion of thyroid carcinomas but contributes to a significant proportion of thyroid carcinoma-associated deaths. The clinicopathological prognostic factors and clinical outcomes of PDTC remain unclear. We aimed to evaluate the clinical outcomes of patients with PDTC after curative treatment.
Methods
A comprehensive search was performed up to September 2023. We included studies investigating treatment outcomes in patients with PDTC who underwent initial surgery. The 5-year disease-free survival (DFS) and overall survival (OS) were extracted. In this meta-analysis, the enrolled PDTC histological criteria included 3rd, 4th, and 5th World Health Organization (WHO) and Memorial Sloan Kettering Cancer Center (MSKCC) classification. A random-effects model was used for the pooled proportion analysis. Meta-regression analysis was conducted to evaluate the prognostic factors.
Results
Twenty retrospective studies published between 2007 and 2023, including 1,294 patients, met all inclusion criteria. Studies that diagnosed PDTC based on various histological criteria including 3rd WHO (n=5), 4th WHO (n=12), 5th WHO (n=2), and MSKCC (n=1) were included. Overall, 5-year DFS and 5-year OS were 49.4% (95% confidence interval [CI], 42.3 to 56.4) and 73.8% (95% CI, 66.5 to 79.9), with moderate heterogeneity of 58% and 55%, respectively. In meta-regression analysis, extrathyroidal extension (ETE) was a prognostic factor for OS.
Conclusion
The meta-analysis of DFS and OS in patients with PDTC show the moderate heterogeneity with a variety of histological criteria. ETE appears to have a significant impact on OS, regardless of histological criteria.

Citations

Citations to this article as recorded by

Aggressive Types of Malignant Thyroid Neoplasms
Maria Boudina, Eleana Zisimopoulou, Persefoni Xirou, Alexandra Chrisoulidou
Journal of Clinical Medicine.2024; 13(20): 6119. CrossRef

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