Endocrinology and Metabolism

Original Article

Clinical Study
Gender-Dependent Reference Range of Serum Calcitonin Levels in Healthy Korean Adults: Eyun Song, Min Ji Jeon, Hye Jin Yoo, Sung Jin Bae, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Hong-Kyu Kim, Won Gu Kim; Endocrinol Metab. 2021;36(2):365-373. Published online April 7, 2021; DOI: https://doi.org/10.3803/EnM.2020.939

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Background
Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults.
Methods
Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638).
Results
This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively.
Conclusion
Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.

Citations

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Determinants of circulating calcitonin value: analysis of thyroid features, demographic data, anthropometric characteristics, comorbidities, medications, and smoking habits in a population with histological full exclusion of medullary thyroid carcinoma
Pierpaolo Trimboli, Giuseppe Peloni, Dorotea Confalonieri, Elena Gamarra, Tommaso Piticchio, Francesco Frasca, Petra Makovac, Arnoldo Piccardo, Lorenzo Ruinelli
Frontiers in Oncology.2024;[Epub] CrossRef
Surgical treatment of solid variant of papillary thyroid carcinoma: Fifteen-year experience of a tertiary center
Katarina Tausanović, Marina Stojanović, Milan Jovanović, Boban Stepanović, Jovan Ilić, Sara Ivaniš, Vladan Živaljević
Medicinska istrazivanja.2024; 57(1): 121. CrossRef
Some genetic differences in patients with rheumatoid arthritis
Hosam M. Ahmad, Zaki M. Zaki, Asmaa S. Mohamed, Amr E. Ahmed
BMC Research Notes.2023;[Epub] CrossRef
Presence or severity of Hashimoto’s thyroiditis does not influence basal calcitonin levels: observations from CROHT biobank
M. Cvek, A. Punda, M. Brekalo, M. Plosnić, A. Barić, D. Kaličanin, L. Brčić, M. Vuletić, I. Gunjača, V. Torlak Lovrić, V. Škrabić, V. Boraska Perica
Journal of Endocrinological Investigation.2022; 45(3): 597. CrossRef
Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels
Mirjana Babić Leko, Nikolina Pleić, Ivana Gunjača, Tatijana Zemunik
International Journal of Molecular Sciences.2021; 23(1): 44. CrossRef

Review Article

Hypothalamus and Pituitary gland
Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations: Ahmed Al-Sharefi, Richard Quinton; Endocrinol Metab. 2020;35(3):526-540. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.760

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Male hypogonadism—rebadged by some as testosterone deficiency syndrome—is a clinical and biochemical diagnosis of increasing worldwide interest. Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lower serum testosterone levels; principally due to burden of extra-gonadal comorbidities such as obesity, diabetes and metabolic syndrome, but with an underlying intact hypothalamo-pituitary-testicular (HPT) axis capable of springing back into operation once comorbidities are addressed. Despite encouraging observational data and plausible theoretical underpinning, evidence for efficacy and safety of testosterone in this “aging” group of men is lacking; addressing comorbid illnesses remains the key priority instead. Nevertheless, in recent years, accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Despite this, many men with organic hypogonadism remain undiagnosed or untreated; many more face a diagnostic odyssey before achieving care by the appropriate specialist. As testosterone therapy is not without risk several clinical practice guidelines have been published specialist societies to guide physicians on best practice. However, these are heterogeneous in key areas, reflecting divergent approaches to the same evidence basis. Herein, we navigate the major clinical practice guidelines on male hypogonadism and test their respective recommendations against current best evidence.

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Сибирский научный медицинский журнал.2022; 42(2): 18. CrossRef
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Recommendations on the diagnosis, treatment and monitoring of testosterone deficiency in men
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Original Articles

Clinical Study
Changes in Body Composition According to Age and Sex among Young Non-Diabetic Korean Adults: The Kangbuk Samsung Health Study: Seul-Ki Kim, Yu-Hyun Kwon, Jung Hwan Cho, Da Young Lee, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2017;32(4):442-450. Published online November 21, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.4.442

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Background

Age-related decreases in lean mass represent a serious health problem. We aimed to analyze the risks of rapid decreases in lean mass by age and sex in relatively young Korean adults during a 4-year follow-up study.

Methods

A total of 65,856 non-diabetic participants (59.5% men, mean age 39.1 years) in a health screening program were subjected to bioimpedance body composition analyses and metabolic parameter analyses at baseline and after 4 years. The participants were sub-divided according to age, and additionally to six groups by age and the degree of body weight change over the 4-year period. The actual changes in body weight, lean mass, and fat mass and the percent changes over the 4-year period were assessed.

Results

The percent change in lean mass decreased and the percent change of fat mass increased with increasing age in every age and sex group. However, the annual percent decrease in lean mass and percent increase in fat mass were significantly higher among women than among men (−0.26% vs. −0.15% and 0.34% vs. 0.42%, respectively; P<0.01). Participants who were older than 50 years and had a weight loss <−5% during the 4 years had significantly greater decreases in lean mass and smaller decreases in fat mass, compared to those who were younger than 50 years. An odds ratio analysis to determine the lowest quartile of the percent change in lean mass according to age group revealed that participants older than 60 years had a significantly increased risk of a rapid decrease in the lean mass percentage (2.081; 95% confidence interval, 1.678 to 2.581).

Conclusion

Even in this relatively young study population, the lean mass decreased significantly with age, and the risk of a rapid decrease in lean mass was higher among women than among men. Furthermore, the elderly exhibited a significantly more rapid decrease in lean mass, compared with younger participants.

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Obesity and Metabolism
Sex Factors in the Metabolic Syndrome as a Predictor of Cardiovascular Disease: Sunghwan Suh, Jongha Baek, Ji Cheol Bae, Kyoung-Nyoun Kim, Mi Kyoung Park, Duk Kyu Kim, Nam H. Cho, Moon-Kyu Lee; Endocrinol Metab. 2014;29(4):522-529. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.522

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Background

Metabolic syndrome (MetS) is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the impact of MetS on CVD.

Methods

A total of 8,898 subjects (4,241 males and 4,657 females), 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up).

Results

The prevalence of MetS at baseline was 22.0% (932/4,241) and 29.7% (1,383/4,657) in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD; hazard ratio [HR], 1.818; 95% confidence interval [CI], 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to 2.404 in females) and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686; 95% CI, 1.007 to 2.192 in females). Specifically, MetS was associated with risk of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192). Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk.

Conclusion

MetS is a significant risk factor for the development of CVD although its impact varies between sexes.

Citations

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Rate and risk factors of metabolic components and component combinations according to hypertension status in Tibetans in a cross-sectional study
Jihong Hu, Brian Thompson, Shuxia Wang, Minhao Guo, Chunjuan Yan, Fengfeng Ding, Peng Guo, Li Chen, Zhuoma Cao, Jianzong Wang
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Six Cases of Congenital Adrenal Hyperplasia That Were Due to 17alpha-hydroxylase/17,20-lyase Deficiency.: Dong Hoon Shin, Sung Hoon Yu, Young Min Choi, Jung Gu Kim, Sang Wan Kim, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim; J Korean Endocr Soc. 2009;24(2):109-115. Published online June 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.2.109

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Abstract PDF

17alpha-hydroxylase/17,20-lyase deficiency is a rare phenotype of congenital adrenal hyperplasia (CAH), and this is characterized by hyporeninemic hypertension, primary amenorrhea and abnormality of the secondary sexual characteristics (pseudohermaphroditism in men). This type of CAH is usually misdiagnosed at first as mineralocorticoid induced hypertension with primary aldosteronism, but primary amenorrhea with deficient sex hormone is a clue for making the correct diagnosis. The authors experienced 6 cases of 17alpha-hydroxylase/17,20-lyase deficiency in patients who ranged from 15 to 42 years of age. 4 cases were diagnosed according to the investigation of their mineralocorticoid-induced hypertension and 2 cases their primary amenorrhea and sexual infantilism. All of them had hypokalemia, hyporeninemic hypertension and an atrophied uterus and ovaries. In the genotypic male (46 XY), the testicles were atrophied in the abdominal cavity. The levels of cortisol, estrogen and dehydroepiandrosterone sulfate (DHEAS) were low, but the levels of progesterone and 11-deoxycorticosterone were high. Therefore, the diagnosis of 17alpha-hydroxylase/17,20-lyase deficiency should be considered in female patients who present with both sexual infantilism and mineralocorticoid hypertension. We report on these cases with a brief review of the literature.

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Functional Identification of Compound Heterozygous Mutations in the CYP17A1 Gene Resulting in Combined 17α-Hydroxylase/17,20-Lyase Deficiency
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The Korean Journal of Medicine.2016; 91(2): 191. CrossRef

Case Report

A Case of 45,X Turner's Syndrome with Iron Deficiency Anemia due to Menometrorrhagia and Spontaneous Sexual Development.: Mi Kwang Kwon, Suk Chon, Gwan Pyo Koh, Seung Jun Oh, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; J Korean Endocr Soc. 2005;20(2):160-167. Published online April 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.2.160

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Abstract PDF

Short stature and gonadal dysgenesis are two characteristic clinical features of Turners syndrome. Very rarely, patients with Turners syndrome may menstruate and even be fertile. We experienced a case of Turners syndrome with spontaneous sexual development and menstruation. A 16-year-old girl was referred for severe anemia and menometrorrahgia. She had nearly normal features, with the exception of a short stature and a single right kidney. Also, she had spontaneous development of secondary sexual characteristics. We performed and anemia study and evaluated her short stature. In chromosomal study of her bone marrow and peripheral blood lymphocytes, she was revealed to have monosomy 45,X. Herein, this case is reported, with a brief review of literature

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Original Articles

Sex Hormone-Binding Globulin and Oxidative Stress in Korean Premenopausal Women.: Young Ju Choi, Jee Young Oh, Young Sun Hong, Yeon Ah Sung; J Korean Endocr Soc. 2004;19(1):48-57. Published online February 1, 2004

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Abstract PDF: BACKGROUND
Low levels of sex hormone-binding globulin(SHBG), an indirect index of androgenicity, are associated with insulin resistance and cardiovascular risk factors. The risk factors of the cardiovascular disease are known to be related to oxidative stress. In recent reports, sex hormones were associated with oxidative stress in women with polycystic ovarian syndrome(PCOS), which is characterized by increased androgenicity and insulin resistance. METHODS: To investigate the relationship between sex hormones and oxidative stress, we examined the association of malondialdehyde(MDA), total antioxidant status(TAS), oxidized low density lipoprotein cholesterol(ox-LDL), and SHBG in 46 Korean premenopausal women. RESULTS: 1. SHBG and MDA levels were not significantly different among the women with NGT and IGT. But, TAS was significantly lower(p=0.034) in the subjects with IGT than in the subjects with NGT. 2. The SHBG level was significantly lower(p=0.036) in obese women than in non-obese women. 3.The SHBG level was significantly inversely correlated with BMI(r=-0.394, p=0.007), post challenge glucose(r=-0.326, p=0.027), waist size(r=-0.323, p=0.029), waist-to-thigh ratio(WTR) (r=-0.308, p=0.037), fasting insulin level(r=-0.387, p=0.008), visceral fat area(VFA)(r=-0.339, p=0.021), and was significantly positively correlated with SI(r=0.397, p=0.008). 4. The SHBG level was significantly inversely correlated with levels of MDA(r=-0.357, p=0.015) and ox-LDL(r=-0.367, p=0.014). 5. In a multiple linear regression analysis, the SHBG level was a significant and independent factor for both MDA and ox-LDL. For TAS, the fasting insulin level and post challenge glucose were significant and independent factors. CONCLUSION: Increased androgenicity assessed by the decrease in serum SHBG levels is associated with the increase in MDA and ox-LDL. These results suggest that increased androgenicity in premenopausal women can contribute to the development of cardiovascular diseases via increased oxidative stress.

Clonical Experience on Non-Scrotal Testosterone Transdermal Patch in the Middle Aged Male.: Young Chan Kim, Jong Ho Park, Suk Ki Lee, Young Jin Lee, Chul Young Bae, Yong Wook Cho, Myung Seo Kang, Jung Hoon Kim; J Korean Endocr Soc. 1999;14(1):102-121. Published online January 1, 2001

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Abstract PDF: BACKGROUND
To evaluate metabolic effects of testosterone on whole bodily systems, non-scrotal testosterone transdermal patch was given to middle aged men. METHODS: Sixteen impotent patients with serum testosterone levels between 300 and 500 ng/dL, were recruited for 6 month of treatment with non-scrotal testosterone transdermal delivery system, and six patients dropped during the study. All patients have a non-organic impotence (mean age:48 +/- 7). After 1 month placebo patch running period, patients were given 1 or 2 patches. The parameters were evaluated at each stage; before treatment, after placebo patch, and after testosterone patch for 3 months and 6 months. The evaluation parameters included body weight, blood pressure, heart rate, body mass index (BMI), body fat, haemoglobin, haematocrit, RBC, lipid profiles, Prostatic Specific Antigen (PSA), Transrectal Ultrasonography (TRUS), International Prostatic Symptom Score (IPSS), bone markers such as osteocalcin and Deoxypyridinoline (dPyr), Bone Mineral Density (BMD), psychological evaluation with Questionnaire and hormones such as cortisol, Dehydroepiandrosterone sulfate (DHEA-S), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), prolactin, testosterone and Sex Hormone Binding Globulin (SHBG). Sexual functions were evaluated by means of sexual Questionnaire which has grade systems (high grade means good response) on each domain. RESULTS: Hormonal, hematopoietic, lipid and prostatic parametem were not changed with statistical insignificance. There were no significant changes in BMD. But mean osteocalcin values increased about 31.5% (p<0.05). Bone resorption marker, D-Pyr values were also decreased significantly about 18.6% after 4 montbs treatment, but such changes were not shown after 6 months. Tendencies of improvement in all domains of Sexual Questionnaire were noticed, even though they were not statistically significant except in frequency of coitus and satisfaction with ejaculation (p<0.05), CONCLUSION: Decreased bone resorption was noticed while persistent increased bone formation occurred after 4 months treatment of testosterone. Testosterone supplementation has a beneficial effects on mood and sexual function in the impotent patients with lower borderline testosterone level. And it can be concluded that 6 months testosterone treatment dose not produce any adverse reactions on bodily system.

Prevalence Thyroid Cancer in Patients with Cold Thyroid Nodules in Relation to Sex, Age, And Multinodularity.: Won Bae Kim, Hyun Kyung Chung, Chang Hoon Yim, Do Joon Park, Sung Yeon Kim, Bo Yeon Cho, Hong Gyu Lee; J Korean Endocr Soc. 1998;13(3):366-372. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We evaluated the prevalence of thyroid cancer in patients with cold thyroid nodules and the impact of sex, age, hardness of nodule, and multinodularity as factors able to predict the probability of malignancy in patients with nodular thyroid diseases. METHODS: We examined a 728 patients who visited Seoul National University Hospital with one or more cold thyroid nodules between Jan. 1996 and Dec. 1997. After clinical evaluations including medical history, physical examinations(size, hardness and multiplicity of nodule), fine needle aspiration biopsies and cytologic examinations were carried out. RESULTS: Among the 728 cases, 76 cases(10.4%) were diagnosed as cancer and 602 cases (82.6%) were diagnosed as benign nodule. The prevalence of cancer was significantly lower in female patients with cold nodules(9.4%, 62/662) than in males(17.5%, 11/63)(p=0.041). Age was an important factor in both sexes. The proportion of nodules that were malignant was lower in patients of 20-60 years old(8,9%, 56/632) than patients younger than 20 years old(1S.1%, 2/11) or older than 60 years old(18.3%, 15/82)(p=0.019). The prevalence of cancer was significantly higher in hard nodules(36.3%, 41/113) than firm(5.2%, 30/574) or soft nodules(5.3%, 2/38)(p= 0.001). There was no size difference between malignant(25.2 +- 13.7mm) and benign nodules(25.3 +- 8.9mm)(p=0.9425). The prevalence of thyroid cancer in solitary nodule(10.6%, 63/593) was not different from that in multiple nodules(7.6%, 10/132)(p=0.293). CONCLUSION: Our data suggest that thyroid nodules of the patients who are younger than 20 years old or older than 60 years old, male, as well as hard nodule require more careful evaluation for the risk of thyroid malignancies.

The Effect of Sex Steroid Hormone on the Expression of Insulin-Like Growth Factor Binding Preteins mRNA in the Explant Cultured from Human Uterine Myoma and Adjacent Normal Myometrium.: Jin Yong Lee, Jung Koo Kim, Chang Seok Seo, Seok Hyun Kim, Young Min Choi, Shin Yong Moon; J Korean Endocr Soc. 1998;13(1):34-44. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Sex steroid hormones are believed to play an important role in the genesis and growth of uterine myoma. Several studies suggest a possible role of insulin-like growth factor(IGF) as a mediator of estradiol in uterine myama. We have recently demonstrated that some IGF binding proteins(IGFRPs) messenger ribonucleic acid(mRNA) expressions in myoma are dependent on the in vivo esttogen status. The purposes of this study are to evaluate the in vitro effects of sex steroid hormones including estrogen on the IGFBPs gene expression in tissues from uterine myoma and adjacent normal myometrium. METHODS: Tissues from myoma and adjacent normal myometrium of patients with uterine myoma during early proliferative phase of menstrual cycle were cultured in the absence(control) and presence of 17b-estradiol(10M/L) or/and progesterone(10M/L) for 3 days. The IGFBPs mRNA expressions in these explants were analyzed by Nothern blot using specific human complementary deoxyribonucleic acid(cDNA) probes. RESULTS: The addition of 17b-estradiol, progesterone alone and in combination to conditioned media of explants from myoma and adjacent normal myornetrium did not result in any changes in the expression of IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 mRNA. With progesterone addtion, lGFBP-3 rnRNA expression was significantly reduced in myoma explant but not in adjacent ncemal myometrium explant. There was no significant change in the IGFBP-3 mRNA expression with 17b-estradiol and with the combination of both 17b-estradiol and progesterone. CONCLUSION: 17b-estradiol does not affect IGFBPs gene expression in the myoma and adjacent normal myometrium explant regardless of the presence of progesterone in vitro. However progesterone alone induces a decrease in IGFBP-3 synthesis in myoma explant.

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