Background: Dutasteride, a 5-alpha reductase inhibitor, is prescribed for male androgenetic alopecia (AGA) in Korea and Japan. Despite its efficacy, its use is limited by its long half-life, potent dihydrotestosterone suppression, and adverse effects. Objective: To investigate the efficacy and safety of 0.2 mg dutasteride for male AGA. Methods: Patients with male AGA were randomized to receive 0.2 mg dutasteride, placebo, or 0.5 mg dutasteride (2:2:1) once daily for 24 weeks. Safety and efficacy endpoints were assessed. Results: Overall, 139 men were analyzed. At week 24, the change in hair count within the target area at the vertex from baseline was significantly higher in the 0.2 mg dutasteride group than in the placebo group (21.53 vs. 5.96, p=0.0072). Dutasteride (0.2 mg) treatment led to greater hair growth improvement, as assessed by investigators at week 24 (p=0.0096) and an independent panel at weeks 12 and 24 (p=0.0306, p=0.0001). For all efficacy endpoints, 0.2 mg dutasteride was as effective as 0.5 mg dutasteride. The incidence of adverse events was low and not statistically different between the 0.2 mg dutasteride and placebo groups. The limitation of this study is the limited number of participants. Conclusion Low-dose (0.2 mg) dutasteride for male AGA showed significant efficacy and favorable safety profile.Trial Registration: ClinicalTrials.gov Identifier: NCT04825561

Background: Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. Methods: A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). Results: NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025);nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. Conclusion We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic.Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker. Methods: LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results. Results: LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages. Conclusion LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Background and Objectives: Although thyroid hormones affect human cancer progression, the regulatory mechanism of thyroid hormone receptors in carcinogenesis has not been elucidated. This study aimed to evaluate the expression pattern of the thyroid hormone receptor (TR) and its corepressors, and to investigate the clinical and biological functions of TR. Materials and Methods: Transcriptomic and clinical data for thyroid cancer were downloaded from The Cancer Genome Atlas. Paraffin-embedded tissue sections from patients who underwent thyroidectomy were used for immunohistochemistry. BCPAP cells were treated with T3 to investigate the thyroid hormone target genes. Thyroid hormone receptor alpha (THRA) and Thyroid hormone receptor beta (THRB) were knocked down by transient siRNA transfection. Results: THRA and THRB expression was lower in thyroid cancer tissues than in normal tissues. However, strong focal staining of TRβ was observed in the invasive front. High THRB expression was associated with high Silencing Mediator for Retinoid or Thyroid hormone receptor (SMRT) expression, older age, a high MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) score, more aggressive histological subtypes, more frequent extra-thyroidal extension, and advanced TNM stage. THRB expression was positively correlated with Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), L1 Cell Adhesion Molecule (L1CAM), and Lysyl Oxidase (LOX) expression. Thyroid hormone-induced HIF1A, L1CAM, and LOX upregulation was abolished by siTHRB but not siTHRA in BCPAP cells. High SMRT and high THRB groups (SMRT/THRB) presented more aggressive clinical features and showed an upregulation of HIF1A, L1CAM, and LOX, as well as of epithelial-mesenchymal transition (EMT)-related genes, causing changes in the tumor microenvironment. Conclusion Cooperative subtype switching from NCOR1/THRA to SMRT/THRB was thus related to aggressive clinical and molecular features, possibly related to EMT and EMT-related tumor microenvironment.

Purpose: Paragangliomas (PGL) are rare neuroendocrine tumors derived from chromaffin cells of the autonomic nervous system. We aim to describe our experience and the long-term outcome of abdominal PGL over the last decade. Methods: A retrospective review of patients diagnosed with PGL in our hospital between November 2005 and June 2017 was conducted. All nonabdominal PGL were excluded and the clinicopathological features and long-term outcomes of the patients were analyzed. Results: A total of 46 patients were diagnosed with abdominal PGL. The average age of diagnosis was 55.4 years and there was no sex predilection. The average tumor size was 5.85 cm and they were predominantly located in the infrarenal position (50%). The mean follow-up period was 42 months (range, 1.8–252 months). All patients with metastases had Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) of ≥4. One patient presented with synchronous metastases while 2 developed local recurrence and distant metastases. One presented with only local recurrence. One patient died 5 years after diagnosis. Conclusion Abdominal PGL is a rare tumor with excellent long-term prognosis. Recurrence although uncommon, can occur decades after initial diagnosis. Long-term follow-up is therefore recommended for all patients with PGL, especially in patients with PASS of ≥4.

Background: Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features. Methods: Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort. Results: In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of human cancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets. Conclusion The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

PURPOSE: Recently, posterior retroperitoneoscopic adrenalectomy (PRA) has been reported to have some advantages over laparoscopic transperitoneal adrenalectomy (LTA). The objectives of this study were to report our experience over 12 years with laparoscopic adrenalectomy for primary hyperaldosteronism (PHA) and to examine surgical outcomes of PRA compared with LTA in patients with PHA. METHODS: The medical records of 527 patients who underwent minimally invasive adrenalectomy, including LTA or PRA, from January 2006 until May 2017 were reviewed at Severance Hospital (Seoul, Korea). Clinicopathologic characteristics and surgical outcomes of 146 patients with PHA who underwent LTA (19 patients) or PRA (127 patients) were analyzed retrospectively by complete chart review. RESULTS: The overall rates of biochemical and clinical cure were 91.1% and 93.1%, respectively. The mean operation time of the PRA group was significantly shorter than that of the LTA group (72.3 ± 24.1 minutes vs. 115.7 ± 69.7 minutes, P = 0.015). The length of hospital stay in the PRA group was significantly shorter than in the LTA group (3.5 ± 1.3 days vs. 4.2 ± 1.6 days, P = 0.029), and the first meal after surgery came earlier in the PRA group (0.3 ± 0.5 days vs. 0.6 ± 0.5 days, P = 0.049). The number of pain-killers used was also significantly smaller in the PRA group (2.3 ± 2.1 vs. 4.3 ± 2.3, P < 0.001). CONCLUSION: PRA offers an alternative or likely superior method for treatment of small adrenal diseases such as PHA, with improved surgical outcomes.
Adrenalectomy ; Humans ; Hyperaldosteronism ; Laparoscopy ; Length of Stay ; Meals ; Medical Records ; Methods ; Retrospective Studies

PURPOSE: Recently, the American Thyroid Association (ATA) dynamic risk stratification (DRS) has been verified to be more valuable than the static anatomical staging system for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The purpose of this retrospective study was to compare the clinical usefulness of DRS, which is based on the response to initial treatment, with that of ATA initial risk stratification in pediatric patients. METHODS: A total of 144 pediatric patients underwent thyroid operation from August 1982 to December 2013 at Yonsei University Hospital (Seoul, Korea). Among them, 128 patients with complete clinical data were enrolled in this study. Clinicopathologic features and surgical outcomes were retrospectively analyzed by medical chart review. The mean follow-up duration was 11.5 years. RESULTS: The mean tumor size was 2.1 cm; 80.4% of patients were diagnosed with conventional papillary thyroid carcinoma, and 7.0% of patients were diagnosed with follicular thyroid carcinoma. Low-risk patients had the highest probability of an excellent response to initial treatment (66.6%). High-risk patients had the highest probability of a structural incomplete response (100%) and the lowest probability of an excellent response (11.1%). The ATA risk stratification and the DRS system were independent risk factors for disease-free survival (DFS) (P = 0.041 and P < 0.001, respectively). CONCLUSION: The DRS system, which is based on the response to initial treatment, can offer more useful prognostic information compared with ATA risk stratification in pediatric patients with DTC.
Adenocarcinoma, Follicular ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Pediatrics ; Prognosis ; Retrospective Studies ; Risk Factors ; Thyroid Gland* ; Thyroid Neoplasms*

PURPOSE: Postoperative hypocalcemia is a common complication of thyroidectomy. This study evaluated the incidence and predisposing risk factors for postoperative permanent hypocalcemia after total thyroidectomy. METHODS: There were 1,247 consecutive patients undergoing total thyroidectomy and complete treatment and observation for differentiated thyroid cancer between January 2012 to December 2012 who were enrolled in this study. Patients were divided into two groups, those remaining normalcalcemic (Group I-824 pts) and those who had hypocalcemia requiring treatment (Groups II-423 pts). Group II was subdivided into a transient hypocalcemic group (Group IIA-409 pts) and a permanent hypocalcemic group (Group IIB-14 pts). RESULTS: Female gender, thyroiditis, preserved parathyroid number, lateral lymph node metastasis, RAI treatment, preoperative parathyroid hormone and preoperative vitamin D were significantly associated with the development of postoperative hypocalcemia by multivariate analysis. Comparing patients with transient versus permanent hypocalcemia, tumor size and multiplicity were significantly related to the development of permanent hypocalcemia by multivariate analysis. RAI treatment and parathyroid hormone level on the postoperative third day were significantly related to recovery from transient hypocalcemia to normo-calcemia. CONCLUSION: Risk factors of postoperative hypocalcemia were associated with preoperative patient factors and advanced thyroid cancer. Advanced thyroid cancer was a risk factor for permanent hypocalcemia. To prevent postoperative hypocalcemia, we should focus on patient condition and need to preserve parathyroid gland more carefully in thyroid surgery.
Female ; Humans ; Hypocalcemia* ; Incidence ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Parathyroid Glands ; Parathyroid Hormone ; Risk Factors* ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy* ; Thyroiditis ; Vitamin D

Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is generally encouraging, a diagnostic dilemma is posed when an increasing level of serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using conventional imaging tools such as the iodine-131 whole-body scanning (the [131I] scan) or neck ultrasonography (US). The objective of the present study was to evaluate the diagnostic value of [124I]-PET/CT and [18F]-FDG-PET/CT in terms of accurate detection of both iodine- and non-iodine-avid recurrence, compared with that of conventional imaging such as the [131I] scan or neck ultrasonography (US). Between July 2009 and June 2010, we prospectively studied 19 DTC patients with elevated thyroglobulin levels but who do not show pathological lesions when conventional imaging modalities are used. All involved patients had undergone total thyroidectomy and radioiodine (RI) treatment, and who had been followed-up for a mean of 13 months (range, 6-21 months) after the last RI session. Combined [18F]-FDG-PET/CT and [124I]-PET/CT data were evaluated for detecting recurrent DTC lesions in study patients and compared with those of other radiological and/or cytological investigations. Nine of 19 patients (47.4%) showed pathological [18F]-FDG (5/19, 26.3%) or [124I]-PET (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients, disease management was modified in six (66.7%) and disease was restaged in seven (77.8%). In particular, the use of the described imaging combination optimized planning of surgical resection to deal with locoregional recurrence in 21.1% (4/19) of patients, who were shown to be disease-free during follow-up after surgery. Our results indicate that combination of [18F]-FDG-PET/CT and [124I]-PET/CT affords a valuable diagnostic method that can be used to make therapeutic decisions in patients with DTC who are tumor-free on conventional imaging studies but who have high Tg levels.
Adult ; Aged ; Aged, 80 and over ; Carcinoma/metabolism/*radionuclide imaging/surgery ; Female ; Fluorodeoxyglucose F18/chemistry/diagnostic use ; Follow-Up Studies ; Humans ; Iodine Radioisotopes/chemistry/diagnostic use ; Male ; Middle Aged ; Neck/ultrasonography ; Positron-Emission Tomography and Computed Tomography ; Prospective Studies ; Radiopharmaceuticals/chemistry/*diagnostic use ; Recurrence ; Thyroglobulin/blood ; Thyroid Neoplasms/metabolism/*radionuclide imaging/surgery ; Thyroidectomy ; Whole Body Imaging