Endocrinology and Metabolism

Original Articles

Endocrine Research
Suppression of Fibrotic Reactions of Chitosan-Alginate Microcapsules Containing Porcine Islets by Dexamethasone Surface Coating: Min Jung Kim, Heon-Seok Park, Ji-Won Kim, Eun-Young Lee, Marie Rhee, Young-Hye You, Gilson Khang, Chung-Gyu Park, Kun-Ho Yoon; Endocrinol Metab. 2021;36(1):146-156. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.879

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Background
The microencapsulation is an ideal solution to overcome immune rejection without immunosuppressive treatment. Poor biocompatibility and small molecular antigens secreted from encapsulated islets induce fibrosis infiltration. Therefore, the aims of this study were to improve the biocompatibility of microcapsules by dexamethasone coating and to verify its effect after xenogeneic transplantation in a streptozotocin-induced diabetes mice.
Methods
Dexamethasone 21-phosphate (Dexa) was dissolved in 1% chitosan and was cross-linked with the alginate microcapsule surface. Insulin secretion and viability assays were performed 14 days after microencapsulation. Dexa-containing chitosan-coated alginate (Dexa-chitosan) or alginate microencapsulated porcine islets were transplanted into diabetic mice. The fibrosis infiltration score was calculated from the harvested microcapsules. The harvested microcapsules were stained with trichrome and for insulin and macrophages.
Results
No significant differences in glucose-stimulated insulin secretion and islet viability were noted among naked, alginate, and Dexa-chitosan microencapsulated islets. After transplantation of microencapsulated porcine islets, nonfasting blood glucose were normalized in both the Dexa-chitosan and alginate groups until 231 days. The average glucose after transplantation were lower in the Dexa-chitosan group than the alginate group. Pericapsular fibrosis and inflammatory cell infiltration of microcapsules were significantly reduced in Dexa-chitosan compared with alginate microcapsules. Dithizone and insulin were positive in Dexa-chitosan capsules. Although fibrosis and macrophage infiltration was noted on the surface, some alginate microcapsules were stained with insulin.
Conclusion
Dexa coating on microcapsules significantly suppressed the fibrotic reaction on the capsule surface after transplantation of xenogenic islets containing microcapsules without any harmful effects on the function and survival of the islets.

Citations

Citations to this article as recorded by

Engineering superstable islets-laden chitosan microgels with carboxymethyl cellulose coating for long-term blood glucose regulation in vivo
Haofei Li, Weijun He, Qi Feng, Junlin Chen, Xinbin Xu, Chuhan Lv, Changchun Zhu, Hua Dong
Carbohydrate Polymers.2024; 323: 121425. CrossRef
Investigation of encapsulation of pancreatic beta cells and curcumin within alginate microcapsules
Zahra Hosseinzadeh, Iran Alemzadeh, Manouchehr Vossoughi
The Canadian Journal of Chemical Engineering.2024; 102(2): 561. CrossRef
Advancements in innate immune regulation strategies in islet transplantation
Kehang Duan, Jiao Liu, Jian Zhang, Tongjia Chu, Huan Liu, Fengxiang Lou, Ziyu Liu, Bing Gao, Shixiong Wei, Feng Wei
Frontiers in Immunology.2024;[Epub] CrossRef
A Case for Material Stiffness as a Design Parameter in Encapsulated Islet Transplantation
Courtney D. Johnson, Helim Aranda-Espinoza, John P. Fisher
Tissue Engineering Part B: Reviews.2023; 29(4): 334. CrossRef
Improved membrane stability of alginate-chitosan microcapsules by crosslinking with tannic acid
Li Chen, Fang Jiang, Haidan Xu, Yaoyao Fan, Cunbin Du
Biotechnology Letters.2023; 45(8): 1039. CrossRef
Advances in alginate encapsulation of pancreatic islets for immunoprotection in type 1 diabetes
Dinesh Chaudhary, Tiep Tien Nguyen, Simmyung Yook, Jee-Heon Jeong
Journal of Pharmaceutical Investigation.2023; 53(5): 601. CrossRef
Emerging strategies for beta cell transplantation to treat diabetes
Jesus Paez-Mayorga, Izeia Lukin, Dwaine Emerich, Paul de Vos, Gorka Orive, Alessandro Grattoni
Trends in Pharmacological Sciences.2022; 43(3): 221. CrossRef
Layer-by-Layer Cell Encapsulation for Drug Delivery: The History, Technique Basis, and Applications
Wenyan Li, Xuejiao Lei, Hua Feng, Bingyun Li, Jiming Kong, Malcolm Xing
Pharmaceutics.2022; 14(2): 297. CrossRef
β cell replacement therapy for the cure of diabetes
Joonyub Lee, Kun‐Ho Yoon
Journal of Diabetes Investigation.2022; 13(11): 1798. CrossRef
Modern pancreatic islet encapsulation technologies for the treatment of type 1 diabetes
P. S. Ermakova, E. I. Cherkasova, N. A. Lenshina, A. N. Konev, M. A. Batenkin, S. A. Chesnokov, D. M. Kuchin, E. V. Zagainova, V. E. Zagainov, A. V. Kashina
Russian Journal of Transplantology and Artificial Organs.2021; 23(4): 95. CrossRef

Adrenal gland
Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease: A Ram Hong, Jung Hee Kim, Eun Shil Hong, I Kyeong Kim, Kyeong Seon Park, Chang Ho Ahn, Sang Wan Kim, Chan Soo Shin, Seong Yeon Kim; Endocrinol Metab. 2015;30(3):297-304. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.297

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Abstract PDF PubReader

Background

Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level.

Methods

We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured.

Results

Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively.

Conclusion

Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

Citations

Citations to this article as recorded by

Development of diagnostic algorithm for Cushing’s syndrome: a tertiary centre experience
A. Efthymiadis, H. Loo, B. Shine, T. James, B. Keevil, J. W. Tomlinson, A. Pal, R. Pofi
Journal of Endocrinological Investigation.2024;[Epub] CrossRef
Eurasian clinical guidelines for the diagnosis and treatment of secondary (symptomatic) forms of arterial hypertension (2022)
I. E. Chazova, N. M. Chikhladze, N. V. Blinova, Zh. E. Belaya, N. M. Danilov, E. M. Elfimova, A. Yu. Litvin, L. Ya. Rozhinskaya, N. Yu. Sviridenko, M. Yu. Shvetsov, V. A. Azizov, E. A. Grigorenko, N. P. Mit’kovskaja, I. I. Mustafaev, A. G. Polupanov, A. S
Eurasian heart journal.2023; (1): 6. CrossRef
Diagnosis and Management of Pituitary Adenomas
Nicholas A. Tritos, Karen K. Miller
JAMA.2023; 329(16): 1386. CrossRef
Distinct serum steroid profiles between adrenal Cushing syndrome and Cushing disease
Chang Gao, Li Ding, Xiaona Zhang, Menghua Yuan, Shaofang Tang, Wei Li, Yuanyuan Ye, Ming Liu, Qing He
Frontiers in Endocrinology.2023;[Epub] CrossRef
The Importance of DHEA-S Levels in Cushing’s Syndrome; Is There a Cut-off Value in the Differential Diagnosis?
Sema Ciftci, Ozlem Soyluk, Alev Selek, Selvinaz Erol, Zeliha Hekimsoy, Ayse Esen, Huseyin Dursun, Serdar Sahin, Gonca Oruk, Meral Mert, Huseyin Soylu, Banu Sarer Yurekli, Melek Eda Ertorer, Tulay Omma, Mehtap Evran, Mine Adas, Seher Tanrikulu, Kadriye Ayd
Hormone and Metabolic Research.2022; 54(04): 232. CrossRef
Epidemiology and Comorbidity of Adrenal Cushing Syndrome: A Nationwide Cohort Study
Chang Ho Ahn, Jung Hee Kim, Man Young Park, Sang Wan Kim
The Journal of Clinical Endocrinology & Metabolism.2021; 106(3): e1362. CrossRef
Metabolic changes in serum steroids for diagnosing and subtyping Cushing’s syndrome
Chang Ho Ahn, Chaelin Lee, Jaeyoon Shim, Sung Hye Kong, Su-jin Kim, Yong Hwy Kim, Kyu Eun Lee, Chan Soo Shin, Jung Hee Kim, Man Ho Choi
The Journal of Steroid Biochemistry and Molecular Biology.2021; 210: 105856. CrossRef
Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean Patients
Insoon Jang, Su-jin Kim, Ra-Young Song, Kwangsoo Kim, Seongmin Choi, Jang-Seok Lee, Min-Kyeong Gwon, Moon Woo Seong, Kyu Eun Lee, Jung Hee Kim
Endocrinology and Metabolism.2021; 36(6): 1287. CrossRef
Clinical Parameters to Distinguish Silent Corticotroph Adenomas from Other Nonfunctioning Pituitary Adenomas
Daham Kim, Cheol Ryong Ku, Se Hee Park, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Eun Jig Lee
World Neurosurgery.2018; 115: e464. CrossRef
Cushing's syndrome: a practical approach to diagnosis and differential diagnoses
Joseph M Pappachan, Christian Hariman, Mahamood Edavalath, Julian Waldron, Fahmy W Hanna
Journal of Clinical Pathology.2017; 70(4): 350. CrossRef

Case Report

Thyrotoxic Periodic Paralysis Induced by Dexamethasone.: Eun Ju Lee, Tae Kyoon Kim, Min Jeong Kwon, Soon Hee Lee, Jeong Hyun Park; Endocrinol Metab. 2012;27(4):299-302. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.299

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Abstract PDF

Thyrotoxic periodic paralysis (TPP) is a disease characterized by sudden onset and muscle paralysis. It occurs in the setting of hypokalemia of thyrotoxicosis. Cases of TPP induced by a glucocorticoid such as prednisolone or methylprednisolone have been reported. We report on two patients, each of whom received a dexamethasone injection and subsequently developed TPP. Both patients experienced sudden, flaccid paralysis of both extremities after the injection but recovered completely after receiving a potassium replacement. Laboratory results revealed thyrotoxicosis. The patients were diagnosed with Graves' disease and discharged after receiving treatment with methimazole and propranolol. This report provides the clinical description of TPP induced by dexamethasone injection. These cases suggest that clinicians must consider the presence of hyperthyroid disease in patients who develop acute paralysis after treatment with a glucocorticoid, even in the absence thyrotoxic symptoms. Furthermore, physicians should be aware that TPP can occur even in response to dexamethasone used for treatment of thyrotoxic crisis or Graves' ophthalmopathy.

Citations

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Glucocorticoid-Induced Hypokalemic Periodic Paralysis after Short-Term Use of Tenofovir with Hypophosphatemia: A Case Report
Yujin Shin, Yonglee Kim, Kyong Young Kim, Jong Ha Baek, Soo Kyoung Kim, Jung Hwa Jung, Jong Ryeal Hahm, Min Young Kim, Jaehoon Jung, Hosu Kim
Medicina.2021; 58(1): 52. CrossRef

Original Article

Search for Materials that Influence Human Medullary Thyroid Carcinoma Cell Proliferation.: Hyun Won Shin, Hye Won Jang, Keun Sook Kim, Ji In Lee, Ji Young Park, Sun Wook Kim, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Jae Hoon Chung; J Korean Endocr Soc. 2009;24(2):93-99. Published online June 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.2.93

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Abstract PDF

BACKGROUND
Surgical excision is the only effective treatment of medullary thyroid carcinoma (MTC) and there is no certain treatment for recurrence or distant metastasis. Materials that influence MTC cell proliferation were recently reported. Presently, we evaluated the influence of dexamethasone, somatostatin, progesterone, estradiol-17-beta, forskolin and gastrin on MTC cell proliferation and calcitonin secretion. METHODS: Genomic DNA was extracted and sequenced from untreated thyroid TT cells and cells treated with 10-5~10-10 M dexamethasone, somatostatin, progesterone, estradiol-17-beta, forskolin or gastrin, and cultured for 1~6 days. Cell proliferation was assessed using a BrdU assay at days 1, 2, 3, and 6. Calcitonin in the culture medium from dexamethasone-treated TT cells was measured at days 1~3. RESULTS: Replacement of cysteine with tryptophan at codon 634 of exon 11 was evident in treated TT cells. There was no significant difference in cell proliferation at days 1~3 in cells treated with somatostatin, progesterone, estradiol-17-beta, gastrin and forskolin, while proliferation was inhibited in dexamethasone-treated cells in a concentration-dependent manner from 10-5~10-8 M with no inhibition evident at 10-10 M. Calcitonin levels in 10-5~10-8 M dexamethasone-treated cells were decreased. CONCLUSION: Dexamethasone is a potentially useful compound to suppress MTC cell proliferation. Further studies are necessary to explore this potential further prior to clinical use.

Citations

Citations to this article as recorded by

Identification of Growth Regulatory Factors in Medullary Thyroid Carcinoma Cell Line
Young Suk Jo, Minho Shong
Journal of Korean Endocrine Society.2009; 24(2): 84. CrossRef

Case Report

A Case of Bilateral Macronodular Adrenal Hyperplasia with Cushing's Syndrome Treated by Unilateral Adrenalectomy.: Si Hoon Lee, Kwang Eun Lee, Eun Seok Kang, Sang Su Chung, Dae Jung Kim, Yun Mi Jin, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh; J Korean Endocr Soc. 2002;17(4):596-602. Published online August 1, 2002

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Abstract PDF: In order to differentiate the causes of Cushing's syndrome; whether it is pituitary or adrenal-dependent, a high dose dexamethasone suppression test is usually performed but this does not always correlated with the imaging diagnosis. We report a case of bilateral macronodular adrenal hyperplasia, which was thought to be independent to adrenocorticotrophin (ACTH) stimulation. At first we thought it was pituitary-dependent Cushing's syndrome, due to its suppression by high dose dexamethasone. However, we found no abnormal findings on the brain sella magnetic resonance image (MRI). A significant finding, however, we found bilateral adrenal masses on the abdominal computed tomography (CT). We performed percutaneous selective adrenal venous sampling (PSAVS), and confirmed hypercortisolism of the left adrenal mass only. Therefore, we decided to remove the left adrenal gland to preserve the residual function of the right adrenal gland. After the left adrenalectomy, the patient became normotensive, and their buffalo hump disappeared, and her 24 hour urinary free cortisol level returned to normal.

Randomized Controlled Trial

Effect of Dexamethasone and 1,25(OH)2D3 on Proliferation and Osteogenic Differentiation of Cultured Human Bone Marrow Stromal Cells.: Hye Soo Kim, Il Woo Lee, Jong Min Lee, Chang Hwan Han, Jin Hyung Sung, Min Young Park, Gil Son Khang, Hai Bang Lee; J Korean Endocr Soc. 2002;17(2):206-217. Published online April 1, 2002

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Abstract PDF: BACKGROUND
It is crucial, in the case of regenerating bone by tissue-engineering technique, that osteoblast progenitors are proliferated and induced to differentiate to osteoblasts sequentially at the proper time. Osteoblasts can be obtained from bone itself or from osteoblast progenitors in bone marrow, even though the amount of human marrow stromal cells in marrow aspirate is usually scanty. These cells, however, have been known demonstrate the potential to easily proliferate and differentiate in osteoblasts, chondroblasts or adipocytes according to different microenvironmental factors. We evaluated the effect of dexamethasone and 1,25(OH)2D3 on the proliferation, differentiation, and mineralization of human marrow stromal cells in vitro. METHODS: We used twelve bone marrow aspirates obtained from different healthy bone marrow donors. Culture plates were randomly divided into the following four experimental groups; group 1 was cultured with control medium only, group 2 with control medium containing 1,25(OH)2D3, group 3 with control medium containing dexamethasone, and group 4 with control medium containing both 1,25(OH)2D3 and dexamethasone. 3H-thymidine uptake, protein content of cell lysates, alkaline phosphatase activities and alkaline phosphatase histochemistries were measured. Alizarin Red-S staining and quantification of dissolved dye were also performed. RESULTS: Combined stimulation of marrow stromal cells with both 1,25(OH)2D3 and dexamethasone was found to be effective to maintain stable long-term culture of the cells and to increased differentiation and mineralization of the cells. Synthesis and mineralization of matrix were highest when the cells were stimulated with 1,25(OH)2D3 alone during the early culture phase. However, 1,25(OH)2D3 shortened the lifespan of the cells. Interestingly, mineralization was higher in female donor cells than in male donor cells when stimulated with dexamethasone alone or with both dexamethasone and 1,25(OH)2D3. Neither 1,25(OH)2D3 nor dexamethasone affected cell proliferation. CONCLUSION: Our results suggest that the synergistic effect of dexamethasone and 1,25(OH)2D3 is important in maintaining long-term culture and differentiation of human marrow stromal cells. It is preferable to administer 1,25(OH)2D3 after the attachment of cultured osteoblasts to biomaterials has been established, since it could shorten cell survival despite the great increase of mineralization at the early culture phase.

Original Article

Adrenal Myelolipoma Confirmed by Fine Aspiration Biopsy.: Young Sik Jung, Jun Ho Whang, Jeon Ho Yang, Hyeon Soo Shin, Ih Geun Kim, Ki Sung Ahn, Sung Gug Chang, Sang Chae Lee, Jung Dong Bae, Ho Sang Shon, Mi Ok Park, Jae Bok Park, Yeong Hwan Lee; J Korean Endocr Soc. 1997;12(1):105-110. Published online January 1, 2001

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Abstract PDF: Adrenal myelolipomas are rare, benign tumors cornposed of mature fat and bone marrow elements. Most are small, asymptomatic tumors found incidentally at postmortem examination, Fine needle aspiration biopsy can be used to confirm the diagnosis and avoid an unnecessary operation. We report a case of adrenal myelolipoma confirmed by fine needle aspiration biopsy. A 77-year-old woman with complaining of upper abdominal pain for 2 days was found to have an adrenal mass. She took dexamethasone frequently for 3 years due to multiple arthralgia. Ultrasono-graphy showed a 6cm-sized, suprarenal mass and a stone in the gall bladder with thickened wall. Computed tomography and magnetic resonance imaging scan also presented a suprarenal mass. Endocrinologic results were within normal limits. Adrenal myelolipoma was confirmed by computed tomography-guided fine needle aspiration biopsy without surgery.

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