Endocrinology and Metabolism

Original Articles

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; Received March 28, 2024 Accepted July 15, 2024 Published online September 23, 2024; DOI: https://doi.org/10.3803/EnM.2024.1996 [Epub ahead of print]

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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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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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Abstract PDF Supplementary Material PubReader ePub: 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.

Review Articles

Calcium & bone metabolism
Parathyroid Gland Generation from Pluripotent Stem Cells: Mayuko Kano; Endocrinol Metab. 2024;39(4):552-558. Published online June 10, 2024; DOI: https://doi.org/10.3803/EnM.2024.1989

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Abstract PDF PubReader ePub: Patients with permanent hypoparathyroidism require lifelong treatment. Current replacement therapies sometimes have adverse effects (e.g., hypercalciuria and chronic kidney disease). Generating parathyroid glands (PTGs) from the patient’s own induced pluripotent stem cells (PSCs), with transplantation of these PTGs, would be an effective treatment option. Multiple methods for generating PTGs from PSCs have been reported. One major trend is in vitro differentiation of PSCs into PTGs. Another is in vivo generation of PSC-derived PTGs by injecting PSCs into PTG-deficient embryos. This review discusses current achievements and challenges in present and future PTG regenerative medicine.

Thyroid
Metabolic Reprogramming in Thyroid Cancer: Sang-Hyeon Ju, Minchul Song, Joung Youl Lim, Yea Eun Kang, Hyon-Seung Yi, Minho Shong; Endocrinol Metab. 2024;39(3):425-444. Published online June 10, 2024; DOI: https://doi.org/10.3803/EnM.2023.1802

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Abstract PDF PubReader ePub: Thyroid cancer is a common endocrine malignancy with increasing incidence globally. Although most cases can be treated effectively, some cases are more aggressive and have a higher risk of mortality. Inhibiting RET and BRAF kinases has emerged as a potential therapeutic strategy for the treatment of thyroid cancer, particularly in cases of advanced or aggressive disease. However, the development of resistance mechanisms may limit the efficacy of these kinase inhibitors. Therefore, developing precise strategies to target thyroid cancer cell metabolism and overcome resistance is a critical area of research for advancing thyroid cancer treatment. In the field of cancer therapeutics, researchers have explored combinatorial strategies involving dual metabolic inhibition and metabolic inhibitors in combination with targeted therapy, chemotherapy, and immunotherapy to overcome the challenge of metabolic plasticity. This review highlights the need for new therapeutic approaches for thyroid cancer and discusses promising metabolic inhibitors targeting thyroid cancer. It also discusses the challenges posed by metabolic plasticity in the development of effective strategies for targeting cancer cell metabolism and explores the potential advantages of combined metabolic targeting.

Original Articles

Thyroid
Diagnostic Accuracy of Preoperative Radiologic Findings in Papillary Thyroid Microcarcinoma: Discrepancies with the Postoperative Pathologic Diagnosis and Implications for Clinical Outcomes: Ying Li, Seul Ki Kwon, Hoonsung Choi, Yoo Hyung Kim, Sunyoung Kang, Kyeong Cheon Jung, Jae-Kyung Won, Do Joon Park, Young Joo Park, Sun Wook Cho; Endocrinol Metab. 2024;39(3):450-460. Published online May 27, 2024; DOI: https://doi.org/10.3803/EnM.2023.1872

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Abstract PDF Supplementary Material PubReader ePub: Background
The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups.
Methods
In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed.
Results
The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery.
Conclusion
Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.

Thyroid
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration: Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim; Endocrinol Metab. 2024;39(4):579-589. Published online May 23, 2024; DOI: https://doi.org/10.3803/EnM.2024.1918

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Abstract PDF Supplementary Material PubReader ePub: Background
Changes in thyrotropin receptor antibody (TRAb) levels are associated with the clinical outcomes of Graves’ hyperthyroidism. However, the effects of the patterns of TRAb changes on patient prognosis according to the treatment duration of antithyroid drugs (ATDs) are not well established.
Methods
In this retrospective cohort study, 1,235 patients with Graves’ hyperthyroidism who were treated with ATDs for more than 12 months were included. Patients were divided into two groups according to treatment duration: group 1 (12–24 months) and group 2 (>24 months). Risk prediction models comprising age, sex, and either TRAb levels at ATD withdrawal (model A) or patterns of TRAb changes (model B) were compared.
Results
The median treatment duration in groups 1 (n=667, 54%) and 2 (n=568, 46%) was 17.3 and 37.1 months, respectively. The recurrence rate was significantly higher in group 2 (47.9%) than in group 1 (41.4%, P=0.025). Group 2 had significantly more goiter, thyroid eye disease, and fluctuating and smoldering type of TRAb pattern compared with group 1 (all P<0.001). The patterns of TRAb changes were an independent risk factor for recurrence after adjusting for other confounding factors in all patients, except in group 1. Integrated discrimination improvement and net reclassification improvement analyses showed that model B performed better than model A in all patients, except in group 1.
Conclusion
The dynamic risk model, including the patterns of TRAb changes, was more suitable for predicting prognosis in patients with Graves’ hyperthyroidism who underwent longer ATD treatment duration.

Thyroid
Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis: Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung; Endocrinol Metab. 2024;39(3):468-478. Published online May 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.1923

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Abstract PDF PubReader ePub: Background
Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished.
Methods
This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm² were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery.
Results
Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm² was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT.
Conclusion
This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

Review Article

Calcium & bone metabolism
Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease: Yosuke Nakagawa, Hirotaka Komaba; Endocrinol Metab. 2024;39(3):407-415. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1978

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Abstract PDF PubReader ePub: Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.

Original Articles

Thyroid
Clinical Manifestations of Malignant Struma Ovarii: A Retrospective Case Series in a Tertiary Hospital in Korea: Hyun Jin Ryu, Da Eun Leem, Ji Hyun Yoo, Tae Hyuk Kim, Sun Wook Kim, Jae Hoon Chung; Endocrinol Metab. 2024;39(3):461-467. Published online May 9, 2024; DOI: https://doi.org/10.3803/EnM.2023.1863

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Abstract PDF PubReader ePub: Background
Malignant struma ovarii (MSO) is a very rare disease in which thyroid cancer originates from the ovary. Because it is rare for endocrinologists to encounter patients with MSO, endocrinologists may have a limited understanding of the disease. Therefore, we analyzed and introduced its incidence and clinical course in a tertiary hospital in Korea.
Methods
We retrospectively investigated the clinical data of 170 patients who underwent surgery for struma ovarii at the Department of Obstetrics and Gynecology of Samsung Medical Center from 1994 to May 2023.
Results
Among 170 patients with struma ovarii, 15 (8.8%) were diagnosed with MSO. The median age of patients with MSO was 48 years (range, 30 to 74), and the median tumor size was 3.3 cm (range, 0.5 to 11.0). Papillary thyroid carcinoma (46.7%) was the most common subtypes followed by follicular thyroid carcinoma (26.7%). All patients were diagnosed after surgery, with no predictions from preoperative imaging. The surgical extent of gynecological surgery was variable. Four patients (26.7%) underwent thyroidectomy for thyroid cancer, while one underwent total thyroidectomy and radioactive iodine therapy for MSO with peritoneal metastasis. Except for one patient who underwent hemithyroidectomy, thyroid stimulating hormone suppression therapy was performed in four patients. Only 53% of MSO patients were consulted by an endocrinologist. With a median follow-up period of 33 months (range, 4 to 156), 11 patients remained disease-free, one experienced progression with peritoneal seeding, and the remaining one was in treatment. There have been no recurrences or deaths due to MSO.
Conclusion
An endocrinologist should be involved in establishing a therapeutic plan for MSO, for which the overall prognosis is generally favorable.

Thyroid Thyroid Cancer Screening
Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population: Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chul-Min Kim; Endocrinol Metab. 2024;39(2):310-323. Published online April 9, 2024; DOI: https://doi.org/10.3803/EnM.2023.1870

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Abstract PDF Supplementary Material PubReader ePub: Background
There is debate about ultrasonography screening for thyroid cancer and its cost-effectiveness. This study aimed to evaluate the cost-effectiveness of early screening (ES) versus symptomatic detection (SD) for differentiated thyroid cancer (DTC) in Korea.
Methods
A Markov decision analysis model was constructed to compare the cost-effectiveness of ES and SD. The model considered direct medical costs, health outcomes, and different diagnostic and treatment pathways. Input data were derived from literature and Korean population studies. Incremental cost-effectiveness ratio (ICER) was calculated. Willingness-to-pay (WTP) threshold was set at USD 100,000 or 20,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address uncertainties of the model’s variables.
Results
In a base case scenario with 50 years of follow-up, ES was found to be cost-effective compared to SD, with an ICER of $2,852 per QALY. With WTP set at $100,000, in the case with follow-up less than 10 years, the SD was cost-effective. Sensitivity analysis showed that variables such as lobectomy probability, age, mortality, and utility scores significantly influenced the ICER. Despite variations in costs and other factors, all ICER values remained below the WTP threshold.
Conclusion
Findings of this study indicate that ES is a cost-effective strategy for DTC screening in the Korean medical system. Early detection and subsequent lobectomy contribute to the cost-effectiveness of ES, while SD at an advanced stage makes ES more cost-effective. Expected follow-up duration should be considered to determine an optimal strategy for DTC screening.

Review Article

Calcium & bone metabolism
Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone: Lars Rejnmark; Endocrinol Metab. 2024;39(2):262-266. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.1916

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Abstract PDF PubReader ePub

The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.

Citations

Citations to this article as recorded by

Hypoparathyroidism update
Cherie Chiang
Current Opinion in Endocrinology, Diabetes & Obesity.2024;[Epub] CrossRef
Potential of Calcilytics as a Novel Treatment for Post-Surgical Hypoparathyroidism
Han Seok Choi
Endocrinology and Metabolism.2024; 39(3): 534. CrossRef

Original Articles

Thyroid
Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: Jinsun Lim, Han Sai Lee, Jin-Hyung Heo, Young Shin Song; Endocrinol Metab. 2024;39(2):324-333. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1885

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Abstract PDF Supplementary Material PubReader ePub: Background
The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development.
Methods
We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining.
Results
Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group.
Conclusion
Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.

Thyroid
Prognostic Roles of Inflammatory Biomarkers in Radioiodine-Refractory Thyroid Cancer Treated with Lenvatinib: Chae A Kim, Mijin Kim, Meihua Jin, Hee Kyung Kim, Min Ji Jeon, Dong Jun Lim, Bo Hyun Kim, Ho-Cheol Kang, Won Bae Kim, Dong Yeob Shin, Won Gu Kim; Endocrinol Metab. 2024;39(2):334-343. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1854

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Abstract PDF Supplementary Material PubReader ePub: Background
Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers.
Methods
This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers.
Results
No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039).
Conclusion
Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

Calcium & bone metabolism
Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality: Sung Hye Kong, Jeong Mo Bae, Jung Hee Kim, Sang Wan Kim, Dohyun Han, Chan Soo Shin; Endocrinol Metab. 2024;39(2):375-386. Published online March 21, 2024; DOI: https://doi.org/10.3803/EnM.2023.1827

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Abstract PDF Supplementary Material PubReader ePub: Background
Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses.
Methods
We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis.
Results
The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations.
Conclusion
Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

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