Background: Acromegaly leads to various skeletal complications, and fragility fractures are emerging as a new concern in patients with acromegaly. Therefore, this study investigated the risk of fractures in Korean patients with acromegaly. Methods: We used the Korean nationwide claims database from 2009 to 2019. A total of 931 patients with acromegaly who had never used an osteoporosis drug before and were treated with surgery alone were selected as study participants, and a 1:29 ratio of 26,999 age- and sex-matched osteoporosis drug-naïve controls without acromegaly were randomly selected from the database. Results: The mean age was 46.2 years, and 50.0% were male. During a median follow-up of 54.1 months, there was no difference in the risks of all, vertebral, and non-vertebral fractures between the acromegaly and control groups. However, hip fracture risk was significantly higher (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.32 to 5.65), and non-hip and non-vertebral fractures risk was significantly lower (HR, 0.40; 95% CI, 0.17 to 0.98) in patients with acromegaly than in controls; these results remained robust even after adjustment for socioeconomic status and baseline comorbidities. Age, type 2 diabetes mellitus, cardio-cerebrovascular disease, fracture history, recent use of acid-suppressant medication, psychotropic medication, and opioids were risk factors for all fractures in patients with acromegaly (all P<0.05). Conclusion Compared with controls, patients surgically treated for acromegaly had a higher risk of hip fractures. The risk factors for fracture in patients with acromegaly were consistent with widely accepted risk factors in the general population.

Background: The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. Methods: We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. Results: GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). Conclusion GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

Background: The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. Methods: We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. Results: GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). Conclusion GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

OBJECTIVE: Silent corticotroph adenomas (SCA) are endocrine-inactive pituitary adenomas with positive immunohistochemistry staining for adrenocorticotropic hormone (ACTH). We investigated whether SCA-associated clinical profiles were more aggressive than hormonally negative adenomas (HNA).METHODS: Among 627 patients with pathologically proven endocrine-inactive pituitary adenomas between 2004 and 2013, positive immunohistochemistry revealed 55 SCAs and 411 HNAs. Surgical outcomes and radiological and endocrinological characteristics were compared.RESULTS: Strong female predominance was observed in the SCA group (p<0.001). Cavernous sinus invasion was identified in 22 (40%) SCA patients and 72 (17.6%) HNA patients (p<0.001). There were no differences in ACTH or cortisol levels between the two groups. The incidence of preoperative hypopituitarism and postoperative hormonal outcome did not differ between two groups. Total resection was achieved in 35 patients (63.7%) with SCA and 332 patients (80.8%) with HNA (p=0.007). When tumors were completely removed, recurrence rates were not statistically different between two groups (p=0.60). When complete resection was not achieved, tumors regrew from these remnants in seven patients (35.0%) with SCA and 12 patients (15.2%) with HNA (p=0.05).CONCLUSION: Total surgical resection for SCA is often challenging as these tumors frequently invade a cavernous sinus. Early remnant tumor intervention is justified, because untreated residual pituitary tumors regrow when patients were followed up for a long time. Prophylactic radiotherapy is not warranted for completely resected SCAs as tumor recurrence is uncommon.
ACTH-Secreting Pituitary Adenoma ; Adenoma ; Adrenocorticotropic Hormone ; Cavernous Sinus ; Corticotrophs ; Female ; Humans ; Hydrocortisone ; Hypopituitarism ; Immunohistochemistry ; Incidence ; Pituitary Neoplasms ; Radiotherapy ; Recurrence

PURPOSE: Chemerin has been suggested to be linked to insulin resistance and type 2 diabetes mellitus (T2DM). However, the relationship between visceral adiposity and chemerin levels remains unclear in subjects with T2DM. In this study, we investigated the relationship between serum chemerin levels and visceral adiposity. MATERIALS AND METHODS: This study included 102 subjects newly diagnosed with T2DM. The relationships between serum chemerin levels and clinical and biochemical parameters were examined. Multiple linear regression analysis was performed to determine the predictable factors of serum chemerin levels. RESULTS: Serum chemerin levels showed significant positive correlations with body mass index (BMI), waist circumference (WC), visceral fat thickness (VFT), insulin levels, the homeostasis model assessment of insulin resistance, and levels of triglycerides (log-transformed) and high-sensitivity C-reactive protein, while showing significant negative correlations with high-density lipoprotein cholesterol. After adjusting for BMI and WC, VFT showed a significant relationship with serum chemerin levels (r=0.222, p=0.027). Moreover, VFT was an independent predictive factor of serum chemerin levels (β=0.242, p=0.041). CONCLUSION: We demonstrated that chemerin is linked to metabolic syndrome components. Moreover, serum chemerin levels were associated significantly with obesity, especially visceral adipose tissue, in subjects with T2DM.
Adiposity* ; Body Mass Index ; C-Reactive Protein ; Cholesterol ; Diabetes Mellitus, Type 2 ; Homeostasis ; Insulin ; Insulin Resistance ; Intra-Abdominal Fat ; Linear Models ; Lipoproteins ; Obesity ; Triglycerides ; Waist Circumference*

BACKGROUND: Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. OBJECTIVE: This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. METHODS: The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. RESULTS: Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4+ Foxp3+ regulatory T cells in thermomineral balneotherapy compared with distilled water bath. CONCLUSION: Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.
Balneology* ; Baths ; Cell Count ; Dermatitis ; Dermatitis, Atopic* ; Humans ; Immunomodulation ; Interleukins ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; T-Lymphocytes, Regulatory ; Water*

Background: The beneficial clinical effects of Korean hot spring spa therapy, as well as their underlying mechanisms are still poorly understood. We performed a series of clinical and laboratory investigations for better understanding of the clinical effects as well as possible mechanisms of their beneficial effects. Methods: HaCaT cells were prepared and treated with TLR agonist in the presence or absence of HS water for quantification of IL-6, IL-8, GM-CSF, and TNF-α levels. The serum levels of IFN-ɤ, IL-4, IL-5, and IgE were measured. CD4+ naïve cells were allowed to polarize into Th1, Th2, Th17, and Treg cells, and CD4+ and CFSE+ cells were measured for the degree of proliferation. Total RNA from the lesional skin was transcribed into cDNA using a reverse transcription system, and RT-PCR was performed subsequently. Confocal microscopy and RT-PCR were utilized to evaluate the target skin localization of Th cell subsets and associated inflammatory cytokine milieu. Results: Treatment with agonists of TLR 1 through 6 induced attenuation of cytokine production in the exposure to HS water. HS water suppressed the proliferation of Th1, Th2, and Th17 cells with anti-CD3 stimulation, while proliferation and differentiation to Treg cells were promoted under HS water treatment. On RT-PCR of the lesional skin, thymic stromal lymphopoietin (TSLP) mRNA decreased dramatically after bathing with HS. IL-33 mRNA decreased markedly in HS water group as compared to control group. Foxp3 mRNA expression, same as in confocal microscopic finding, showed tendency to increase more in HS. Conclusions: HS water suppressed the proliferation of Th1, Th2, and Th17 cells. In contrast, proliferation and differentiation to Treg cells were promoted under HS water treatment. These results indicate that HS water may affect the distribution of the helper T cells in the immune response, by suppressing the polarization of the Th1, Th2, and Th17 cells. Also, APC induced TNF-α and IL-6 levels were reduced in the presence of HS water. These results showed that TLR-triggered inflammatory responses in APCs might also be modulated under HS water treatment. Overall, our findings suggest that HS spa therapy could be an effective and safe modality for the management of adult AD.

We report two cases of ectopic epididymal ducts and efferent ductules in the testicular appendices (TAs) of adult men with normally descended testes. In both cases, a sessile TA was incidentally found at the upper pole of the right testis during the scrotal hydrocelectomy. Microscopically, a few closely arranged tubules were detected within the TA. In the first case, the tubules were lined with a pseudostratified columnar epithelium with numerous, long microvilli, and were surrounded by a smooth muscle coat. In contrast, in the second case, the tubules had a wavy luminal surface, because ciliated columnar cells alternated with groups of cuboidal cells. In both cases, strong CD10 immunoreactivity was observed in the luminal border of the lining epithelium. Surgical pathologists should be aware of the presence of both ectopic epididymal ducts and efferent ductules that can occur in TAs, in order to avoid misinterpretation as transected, functional reproductive structures.
Adult ; Choristoma ; Epididymis ; Epithelium ; Female ; Humans ; Male ; Microvilli ; Muscle, Smooth ; Parovarian Cyst ; Phenobarbital ; Testis ; Wolffian Ducts

BACKGROUND: Medical skin care is essential for the treatment of skin diseases all over the world. Medical skin care is also part of medical practice and this must be differentiated from the simple skin care that is given for normal healthy skin. OBJECTIVE: We wanted to discuss medical skin care and the related medical devices and legal issues. METHODS: We reviewed the related laws and regulations, we consulted experts and associations and we analyzed the result of the survey. RESULTS: Legally, medical skin care and simple skin care are well classified. However, many illegal procedures are still performed by non-medical personnel and many adverse effects have been reported as a result. Furthermore, there are no legal restrictions for the performer based on the grade of each medical skin care procedure. CONCLUSION: For the best results and safe procedures, medical skin care must be performed by approved medical equipment under the supervision of a physician or medical personnel. Continuous control and guidance by the government is strongly needed.
Jurisprudence ; Organization and Administration ; Skin ; Skin Care ; Skin Diseases ; Social Control, Formal

A 66-year-old man underwent surgery to remove an incidentally discovered non-tender intrascrotal mass. Ultrasonography revealed an irregular-margined, heterogeneous mass-like lesion in the epididymal tail. The mass was relatively well circumscribed but unencapsulated, irregular and firm; it consisted of expansile, increased smooth muscle fascicles originating from the epididymal muscular coat. Its cellular growth pattern lacked the cohesive, well-circumscribed proliferation pattern typical of a leiomyoma. A diagnosis of smooth muscle hyperplasia of the epididymis was made. Although ultrasonography is the imaging modality of choice for evaluating suspected intrascrotal masses, there are times when it cannot reliably identify the character of the masses and distinguish malignant from benign lesions. Ill-defined, solid extratesticular masses, that are ultrasonographically ambiguous, should be excised and confirmed histopathologically and smooth muscle hyperplasia of the epididymis should be included in the differential diagnosis of solid extratesticular masses.
Aged ; Diagnosis, Differential ; Epididymis ; Humans ; Hyperplasia ; Leiomyoma ; Male ; Muscle, Smooth