Endocrinology and Metabolism

Original Article

Clinical Study
Comparison of the Efficacy and Safety of Insulin Detemir Administered Once Daily According to Two Titration Algorithms (3-0-3 and 2-4-6-8) in Patients with Type 2 Diabetes Mellitus: Hea Min Yu, Kang Seo Park, Jun Hwa Hong, Keun Yong Park, Jong Min Lee, Bon Jeong Ku, Yeo Joo Kim, Tae Kun Oh; Endocrinol Metab. 2020;35(1):142-148. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.142

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Background

This study was conducted to compare glycaemic control with insulin detemir administered according to two titration algorithms (3-0-3 and 2-4-6-8) after 20 weeks of treatment in subjects with type 2 diabetes mellitus inadequately controlled on metformin.

Methods

This was a 20-week, randomised, multicentre, open-labelled, treat-to-target trial. Forty-six patients were randomised in a 1:1 manner to either the 3-0-3 (G3, n=23) or 2-4-6-8 (G2, n=23) algorithm. The primary endpoint was change of haemoglobin A1c (HbA1c), and the secondary safety endpoint included hypoglycaemic events.

Results

After 20 weeks, HbA1c decreased similarly in the G3 and G2 groups, with a mean change of −0.9% from baseline. The mean change in fasting plasma glucose was numerically similar in both groups. The hypoglycaemia event rate per 100-patient-years of exposure (r) in the G2 group (r=1,427) was higher than that in the G3 group (r=807).

Conclusion

Both treatment groups had numerically similar HbA1c reductions. A trend towards fewer hypoglycaemia episodes after dose stabilisation was seen with the simpler G3. Clinically, this may be an important observation, as a simpler titration algorithm may support self-management and maintenance of insulin therapy.

Citations

Citations to this article as recorded by

Time for Using Machine Learning for Dose Guidance in Titration of People With Type 2 Diabetes? A Systematic Review of Basal Insulin Dose Guidance
Camilla Heisel Nyholm Thomsen, Stine Hangaard, Thomas Kronborg, Peter Vestergaard, Ole Hejlesen, Morten Hasselstrøm Jensen
Journal of Diabetes Science and Technology.2022; : 193229682211459. CrossRef
Efficacy and safety of patient-led versus physician-led titration of basal insulin in patients with uncontrolled type 2 diabetes: a meta-analysis of randomized controlled trials
Marco Castellana, Filippo Procino, Rodolfo Sardone, Pierpaolo Trimboli, Gianluigi Giannelli
BMJ Open Diabetes Research & Care.2020; 8(1): e001477. CrossRef

Case Report

A Case of 17a-Hydroxylase Deficiency in 17-Year-Old Girl.: Keun Yong Park, Ki Lack Park, Jung Ho Rhee; J Korean Endocr Soc. 1996;11(1):102-107. Published online November 7, 2019

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Abstract PDF: The single enzyme P-450c17 hydroxylase catalyzes the 17a-hydroxylation of both pregnenolone and progesterone and the side-chain cleavage of 17a-hydroxypregnenolone and 17a-hydroxypro- gesterone to dehydroepiandrosterone and androstenedione. This enzyme is located in the endoplasmic reticulum and consists of a P-450c17 and a specific flavoprotein NADPH-cytochrome P-450 reductase. The clinical picture and hormonal pattern in 17a-hydroxylase deficiency have been consistent in both genotypic sexes with hypergonadotropic hypogonadism in whom the virtual absence of gonadal steroids results in a female phenotype with primary amenorrhea and pseudohermaphro- ditism in the male and underdeveloped secondary sex characteristics and hypermineralocorticoidism with hypertension, hypokalemia, suppressed renin-angiotensin system and extremely reduced aldo-sterone production. A 17-year-old girl visited endocrine clinic because of amenorrhea, absence of pubic and axillary hair, and hypertension. she had elevated levels of serum corticosterone, deoxycorticosterone(DOC), 18-hydroxycorticosterone(18-OHB). Stumulation with ACTH effected minimal increase in the elevated steroids and the ACTH-stimulated 18-OHB to aldosterone ratio was more than 280. These hormonal patterns appear to be homozygote in 17a-hydroxylase deficiency.

Original Articles

Estrogen Replacement Therapy Continuously Combined with Progesterone; Effect on Bone Mineral Density and Lipid Metabolism.: Keun Yong Park; J Korean Endocr Soc. 1995;10(4):411-417. Published online November 7, 2019

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Abstract PDF: A study in 51 healthy postmenopausal women was performed to assess the effect of estrogen replacement therapy continuously combined with progesterone for 6 months on bone mineral density and lipid metabolism.Seventeen hysterectomized women were treated with conjugated estrogen(0.625mg/D), 33 nonhysterectomized women with conjugated estrogen(0.625mg/D) and medroxyprogesterone(2.5mg/D), and 1500mg/day calcium supplementation was given to all patients.After 6 month-treatment, serum total cholesterol and LDL-cholesterol levels were reduced significantly (p<0.01) between the two groups. But lumber BMD and other lipid profiles were not changed significantly between the two groups. Our data suggest that continuously applied progesterone in combined hormone replacement therapy dose not annihilate the beneficial effects on bone mineral density and lipid metabolism induced by estrogen.

Correlation between Serum Levels of ICAM-1 and Serum Levels of Thyroid Hormones, TSH - Receptor Antibodies or Levels of IL-6 of Peripheral Blood Monocyte in Graves' Disease.: Keun Yong Park, Deok Jun Kim; J Korean Endocr Soc. 1995;10(4):405-410. Published online November 7, 2019

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Abstract PDF: Lymphocytic infiltration of the thyroid gland is a hallmark of the human thyroid autoimmune disease. Enhanced expression of immunoglobulin and adhesion molecules are consistently found in patients with autoimmune thyroid diseases. And cytokines are implicated in enhancing the expression of adhesion molecules.It has been suggested that adhesion-molecule expression within thyroid glands mediates lymphocyte homing events to the target of the autoimmune process. The expression of ICAM-1 was shown to be up-regulated on thyroidal perifollicular endothelial cells and thyrocytes in autoimmune thyroid diseases both in vitro and in vivo.Therfore, we investigated the correlation between thyroid hormone, TSH receptor antibodies, Interleukin-6 and soluble ICAM-1 in patients with Graves' disease before and 2 months after treatment with prophylthiouracil(PTU).Serum concentrations of soluble intercellular adhesion molecule-1(sICAM-1), T_3, T_4, TSH-receptor antibodies(TSH-R-Ab) and Interleukin-6(IL-6) of peripheral blood monocytes were measured in patients with Graves' disease.Serum levels of sICAM-1 were elevated in patients with Graves' disease before treatment with PTU, but serum levels of sICAM-1 did not correlate with the serum concentration of thyroid hormone and TSH-R-Ab before and after treatment. In addition, no correlation between serum levels of sICAM-1 and IL-6 of peripheral blood monocyte.We conclude that although the elevated serum levels of sICAM-1 may contribute to the autoimmune process in Graves' disease, we need more future studies for the role of sICAM-1 and correlation between adhesion molecule and thyroid hormone or cytokines in patients with Graves' disease.

Analysis of Cytokine Gene Expression in Thyroid Aspirates and Peripheral Blood Mononuclear Cell and in vitro Production of Interferon - Gamma by Peripheral Blood Mononuclear Cell Culture.: Sung Rae Cho, Keun Yong Park, Young June Jeon, Hong Suk Song, Ki Young Kwon, Yun Nyun Kim, Seung Beom Han, In Kyu Lee; J Korean Endocr Soc. 1995;10(1):13-25. Published online November 6, 2019

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Abstract PDF: Cytokine production was studied in thyroid fine needle aspirates and peripheral blood and the production of interferon-gamma by peripheral blood mononuclear cell(PBMC) culture in response to interleukin-2(IL-2) stimulation was also studied from patients with hyperthyroidism, non toxic goiter, thyroid nodule. The expression of glycer aldehyde 3-phosphate dehydrogenase(GAPDH), interleukin-1beta(IL-1beta), IL-2, interleukin-8(IL-8), platelet- derived growth factor-A(PDGF-A) and interferon-gamma(IFN-gamma) chain was assessed by RT-PCR(reverse transcriptase polymerase chain reaction) in fine needle aspirates of thyroid and peripheral blood mononuclear cell : the samples were obtained from 7 patients with hyperthyroidism, 6 patients with non toxic goiter, 7 patients with thyroid nodule. A dose of IL-2(25 U/ml) was utilized to induce IFN-gamma production by PBMC from all patients.The results were as follows:1) In case of cytokine expression of fine-needle aspirates, GAPDH and IL-1beta, IL-8 were expressed highly but IFN-gamma, IL-2 were not expressed in hyperthyroidism and non-toxic goiter, thyroid nodule. PDGF-A was expressed in hyperthyroidism and thyroid nodule but not in non toxic goiter. 2) In case of cytokine expression of PBMC, GAPDH, IL-1beta were expressed in hyperthyroidism and non toxic goiter, thyroid nodule and highly expressed after IL-2 stimulation than before. But PDGF-A was more expressed in non toxic goiter and thyroid nodule than hyperthyroidism. Also, IFN-gamma was less expressed in thyroid nodule than hyperthyroidism and non toxic goiter. 3) The incremental increase in IFN-gamma value in supernatants of PBMC culture was significantly higher in patients with non toxic goiter than that in PBMC from hyperthyroidism and thyroid nodule(p<0.05).Therefore it seems that the cytokine production was found in hyperthyroidism and non toxic goiter and thyroid nodule. There were variability in their distribution each other, in general, higher expressed in hyperthyroidism than non toxic goiter. And RT-PCR Method that employed should be sufficiently sensitive to permit the analysis of cytokine gene expression in fine needle aspiration biopsies from patients with thyroid disease.

Changes of Interleutin-6 Level Ofter Treatment of Radioactive Iodine in Graves' Disease.: Keun Yong Park; J Korean Endocr Soc. 1994;10(3):214-219. Published online November 6, 2019

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Abstract PDF: Interleukin-6(IL-6) is a cytokine secreted from lymphocytes or non-lymphoid cell(monocyte, fibroblast, osteoblast, vascular endothelial cell, or synoviocytes). Increased serum IL-6 concentrations have recently been reported in patients with subacute thyroiditis, possibly because of cytokine release damaged thyroid cells. In this study, IL-6 levels serum T_3, T_4, Thyroglobulin(Tg) and TSH were determined by an radioimmunoassay method in 14 patients treated with radioactive iodine(10mci) for Graves' disease. IL-6 levels were as follows: 23.9+-0.8 fmol/ml(at baseline), 25.4+-1.1 fmol/ml(1hour), 24.7+-0.6 fmol/ml(24hours), 76.8+-2.0 fmol/ml(48hours), 22.8+-0.5 fmol/ml(72hours). There was significant increase in IL-6 values at 48hours after RAI treatment(p<0.01). Serum Tg, T_3 and T_4 also increased after RAI treatment, but no significant correlation could be demonstrated with the increase in L-6. The results of this study support the concept that IL-6 can be regarded as a useful marker of thyroid-destructive processes.

Amyloid Goiter.: Sung Rae Cho, Keun Yong Park, In Kyu Lee, Ki Lack Park, Seung Yeup Han, Young Woo Kang, Sung Bae Park, Hyun Chul Kim, Sang Pyo Kim, Kun Young Kwon; J Korean Endocr Soc. 1994;10(2):125-130. Published online November 6, 2019

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Abstract PDF: Amyloidosis is a systemic disorder of unknown etiology, The pathophysiological precess is caused by deposition of amyloid fibrils in tissues of the body. Almost any organ in the body can be affected, but amyloid goiter is a very rare presentation.A definitive diagnosis of amyloidosis requires tissue examination using special stains and electron microscopy. We had recently experienced a case of 62 year-old man who was found to have amyloid goiter after thyroid surgery.The patient was admitted Keimyung University Medical Center for evaluation of rapid growing thyroid mass and lobectomy of right thyroid gland was performed.The light microscopic finding showed eosinophilic hyalinized stroma containing one thick-walled blood wessel in the hematoxyline and eosin stain. Congo-red stain on polarized light showed apple-green birefringence of amyloid in thyroid and abdominal fat tissues. Using the PAP method, nodular deposits of amyloid in the stroma and blood vessels are stained positively with anti-AA serum. Electron microscopic finding showed randomly arranged and nonbranching fibrillary rods in the stroma.

Case Reports

A Case Of Transient Hyporeninemic Hypoaldosteronism After Unilateral Adrenalrectomy for Aldosterone-Producing Adenoma.: Jungho Suh, Gwanpyo Koh, Keun Yong Park, Jongwook Hong, Suk Chon, Seungjoon Oh, Jeong taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; J Korean Endocr Soc. 2005;20(5):502-506. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.502

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Abstract PDF

Primary aldosteronism is due to either a unilateral adrenal adenoma or bilateral hyperplasia of the adrenal cortex in most cases. A unilateral adrenalectomy in hypertensive and hypokalemic patients, with a well-documented adrenal adenoma, is usually followed by the correction of hypokalemia in all subjects, with the cure of hypertension in 60 to 87% of patients. Here, a unique case, in which a unilateral adrenalectomy for the removal of an adrenal adenoma was followed by severe hyperkalemia, low levels of plasma renin activity and serum aldosterone, suggestive of chronic suppression of the renin-aldosterone axis, is reported. In a follow-up Lasix stimulation test on the 70th day after surgery, the suppression of the renin-aldosterone axis was resolved, indicating the suppression was transient. Patients undergoing a unilateral adrenalectomy for an aldosterone-producing adenoma should be closely followed up to avoid severe hyperkalemia.

Citations

Citations to this article as recorded by

A Case of Persistent Hyperkalemia After Unilateral Adrenalectomy for Aldosterone-Producing Adenoma
Min Jae Yang, Seung Jin Han, Min Seok Lee, Eun Kyung Kim, Hae Jin Kim, Dae Jung Kim, Yoon Sok Chung, Tae Hee Lee, Jang Hee Kim, Kwan Woo Lee
Journal of Korean Endocrine Society.2009; 24(3): 201. CrossRef

A Case of Thyroid Abscess Associated with Lymphocytic Thyroidits.: Hyoun Jung Chin, Mi Kwang Kwon, Yeehuung Kim, Gwanpyo Koh, Keun Yong Park, Suk Chon, Seungjoon Oh, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Moon Ho Yang; J Korean Endocr Soc. 2005;20(4):385-389. Published online August 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.4.385

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Abstract PDF: No Abstract available.

A Case of Graves' Disease associated with Idiopathic Thrombocytopenic Purpura.: Wan Ho Kim, Eun Kyoung Choi, Se Hee Yoon, In Beom Jeong, Do Yeun Cho, Keun Yong Park; J Korean Endocr Soc. 2005;20(3):289-293. Published online June 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.3.289

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Abstract PDF: The association of Graves' disease and idiopathic thrombocytopenic purpura(ITP) is a rather rare, but well documented condition, and has also been reported a few times in Korea. At present, two main hypothetical mechanisms are used to explain the association of the two diseases; the presence of autoimmunity, which leads to both diseases, and activation of the reticuloendothelial system by thyroid hormone. A 33 year old female patient visited our hospital with mucosal bleeding and purpura over her entire body of 3 days duration. Her initial platelet count was 2x109/L, and the thyroid function tests showed a suppressed TSH level of 0.09 mU/L(0.4~3.1) and elevated levels of triiodothyronine and free thyroxine. The levels of anti-thyroglobulin Ab anti-TPO Ab, and anti-TSH receptor Ab were also elevated. The clinical, laboratory and bone marrow findings were compatible with Graves' disease associated with ITP. She was treated with methylprednisolone and propylthiouracil, after which her platelet count increased and thyroid function normalized. We report a case of Graves' disease associated with ITP, which was treated well by glucocorticoid and antithyroid medications

A Case of Pericardiocentesis in Myxedema with Pericardial Effusion.: Min Su Kim, Dong Woo Shin, Seong Jong Kim, Seong Wook Han, Jang Ho Bae, Keun Yong Park, Kwon Bae Kim; J Korean Endocr Soc. 1999;14(1):165-170. Published online January 1, 2001

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Abstract PDF: Myxedema is the nonpitting edema caused by the accumulation of glycosaminoglycans in subcutaneous and other interstitial tissue that occurs in hypothyroid patients. It is most often present in long-standing or severe primary hypothyroidism. While pericardial effusion appears to be a frequent occurrence in patients with myxedema, the development of cardiac tamponade in hypothyroid patients is distinctly unusual because of the slow formation of the pericardial effusion and the ability of the pericardium to distend. Recently we experienced a case of myxedema with pericardial effusion. The patient was 39-year-old female who was admitted due to aggrevated dyspnea for 1 month. She was obese and myxedematous. Chest X-ray revealed marked cardiomegaly. Two-dimensional echocardiography imaged massive pericardial effusion, especially left ventricular posterior wall and right ventricular side. The thyroid function test showed an obvious hypothyroid state. The patient was intubated and given controlled ventilation because of labored breathing, hypoxemia, and hypercapnea. After one half liter of straw-colored fluid was removed by pericardiocentesis, and she was given thyroid hormone replacement therapy, progressive clinical improvement was noted over course of next few weeks. We report this case with reviews of the literatures.

Original Articles

Changes of Bone Mineral Density and Levels of Cytokines in the Culture Media of Bone Marrow Monocytes after Ovariectomy in Rats.: Keun Yong Park; J Korean Endocr Soc. 1997;12(2):215-221. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although the mechanism of the increase in bone resorption induced by estrogen deficiency is still controversial, recent studies have suggested that estrogen may modulate the secretion of bone resorption cytokines that are produced in the bone microenvironment and influence bone remodeling. Among them, IL-1 and TNF-a promote bone resorption by stimulating the activity of mature osteoclasts and the differentiation of osteoclast precursors and the production of these cytokines are mediated by estrogen. We performed this study to evaluate the effect of ovariectomy on bone mineral density and levels of cytokines in the culture media of bone marrow monocytes. METHODS: The experimental animals were 23 female Sprague-Dawley rats that were 8 weeks of age and weighed an average of 176.8 gm at the beginning of the study. Bilateral ovariectomy (n=13) and sham-operation (n=10) were performed in all rats from a ventral approach. Bone mineral density (BMD) of the total body and levels of IL-1 and TNF-a of culture media of bone marrow monocytes were measured before and 8 weeks after operation with using DPX-L and ELISA assay, respectively. Serum levels of LH, FSH, E2 were measured by RIA assay. RESULTS: BMD of total body was lower after ovriectomy (0.24+-0.04g/cm) than before ovariectomy (0.27+-0.03g/cm), but there was no statistically significant difference in sham-operation group. Serum levels of LH, FSH were higher after ovariectorny (0.87+-0.36 mIU/mL, 9.47+-1.26 mIU/mL) than before ovariectomy (0.10+-0.06mIU/mL, 2.09+-0.41mIU/mL) (p<0.01) and serum level of E was lower after ovariectomy (10.98+-8.71pg/mL) than before ovariectomy (7350.77+-417.29 pg/mL) (p<0.01), respectively. Levels of IL-1 and TNF-a in culture media of bone marrow monocytes were higher after ovariectomy (23.48+-3.98pg/mL, 52.64+-5.31 pg/mL) than before ovariectomy (9.72+0.94pg/mL, 24.37+-3.39pg/mL) (p<0.01), but there were no statistically significant differences in the sharn-operation group. CONCLUSION: It is possible that increased production of IL-1 and TNF-a in estrogen deficiency induced by ovariectomy occures in the bone microenvironment and these cytokines may play a critical causal role in inducing bone loss.

The incidence and causes of hypercalcemia in a hospital population.: Jeong Mo Park, Gyeong Lyae Kim, Ho Young Pyun, Sung Rae Cho, Jun Ki Yeo, Keun Yong Park, Jeong Wook Hur, In Kyu Lee; J Korean Endocr Soc. 1993;8(1):72-77. Published online January 1, 2001

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Abstract PDF: No abstract available.

Adrenal function in active pulmonary tuberculosis.: Jae Suk Hwang, Keun Yong Park, Seung Beom Han, In Kyu Lee, Young June Jeon; J Korean Endocr Soc. 1992;7(1):61-65. Published online January 1, 2001

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Abstract PDF: No abstract available.

Therapeutic effect of suppressive therapy for solitary thyroid nodule.: Jung Mo Park, Jun Ki Yeo, Keun Yong Park, Seung Beom Han, In Kyu Lee, Seong Ku Woo; J Korean Endocr Soc. 1992;7(1):39-45. Published online January 1, 2001

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Abstract PDF: No abstract available.

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