Endocrinology and Metabolism

Case Report

A Case of Malignant Insulinoma Resistant to Octreotide and Combination Chemotherapy.: Duk Kyu Kim, Hyuk Chan Kwon, Ju Il Lee, Do Young Kang, Jae Seok Kim, Hyo Jin Kim, Jong Seong Kim; J Korean Endocr Soc. 1994;10(3):300-305. Published online November 6, 2019

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Abstract PDF: Insulinoma is insulin-secreting tumor that almost all originate in the pancreas and cause symptoms related to hypoglycemia. The documentation of metastatic lesions by imaging studies, is only accurate mean of diagnosing malignant insulinoma before surgical exploration. We experienced a case of malignant insulinoma with liver, adrenal glands, regional lymph nodes and multiple bone metastasis. Abdominal ultrasonography, computed tomography and liver, bone scanning were used to evaluate the disease. Tissue diagnosis was obtained by percutaneous needle biopsy of liver metastasis. The patient was treated with Octreotide therapy and combination chemotherapy(Streptozocin and 5-FU), but she did not respond to these regimen. Now, we present this case with the brief review of literatures.

Special Article

Hypothalamus and Pituitary gland
Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement: Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong Jun Lim, Dong Yeob Shin, Se Hwa Kim, Min Jeong Kwon, Ha Young Kim, Jin Hwa Kim, Dong Sun Kim, Chong Hwa Kim; Endocrinol Metab. 2019;34(1):53-62. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.53

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The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Citations

Citations to this article as recorded by

Hydrogel-fiber-mesh-based 3D cell cultures: A new method for studying pituitary tumors
Wooju Jeong, Sungrok Wang, Yumin Kim, Soohyun Lee, Minhu Huang, Jaeil Park, Myung-Han Yoon, Chang-Myung Oh, Cheol Ryong Ku
Smart Materials in Medicine.2024;[Epub] CrossRef
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association
A Ram Hong, Ho-Cheol Kang
Endocrinology and Metabolism.2023; 38(2): 175. CrossRef
Growth Hormone Excess: Implications and Management
Suneela Dhaneshwar, Shrishti Shandily, Vatsalya Tiwari
Endocrine, Metabolic & Immune Disorders - Drug Targets.2023; 23(6): 748. CrossRef
Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly
Montserrat Marques-Pamies, Joan Gil, Elena Valassi, Marta Hernández, Betina Biagetti, Olga Giménez-Palop, Silvia Martínez, Cristina Carrato, Laura Pons, Rocío Villar-Taibo, Marta Araujo-Castro, Concepción Blanco, Inmaculada Simón, Andreu Simó-Servat, Gemm
Frontiers in Endocrinology.2023;[Epub] CrossRef
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: a Position Statement from the Korean Thyroid Association
A Ram Hong, Hwa Young Ahn, Bu Kyung Kim, Seong Hee Ahn, So Young Park, Min-Hee Kim, Jeongmin Lee, Sun Wook Cho, Ho-Cheol Kang
International Journal of Thyroidology.2022; 15(1): 1. CrossRef
Octreotide in the treatment of acromegaly – the possibilities of high-dose therapy
I. A. Ilovayskaya
Meditsinskiy sovet = Medical Council.2022; (10): 148. CrossRef
Approach of Acromegaly during Pregnancy
Alexandru Dan Popescu, Mara Carsote, Ana Valea, Andreea Gabriela Nicola, Ionela Teodora Dascălu, Tiberiu Tircă, Jaqueline Abdul-Razzak, Mihaela Jana Țuculină
Diagnostics.2022; 12(11): 2669. CrossRef
Left to themselves: Time to target chronic pain in childhood rare diseases
Christine B. Sieberg, Alyssa Lebel, Erin Silliman, Scott Holmes, David Borsook, Igor Elman
Neuroscience & Biobehavioral Reviews.2021; 126: 276. CrossRef
Severe respiratory failure in a patient with COVID-19 and acromegaly: rapid improvement after adding octreotide
Jacob Luty, LesleAnn Hayward, Melanie Jackson, P Barton Duell
BMJ Case Reports.2021; 14(8): e243900. CrossRef
Precision Therapy in Acromegaly Caused by Pituitary Tumors: How Close Is It to Reality?
Cheol Ryong Ku, Vladimir Melnikov, Zhaoyun Zhang, Eun Jig Lee
Endocrinology and Metabolism.2020; 35(2): 206. CrossRef
Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong
The Korean Journal of Medicine.2019; 94(6): 485. CrossRef

Case Reports

The Effect of Octreotide LAR on GH and TSH Co-Secreting Pituitary Adenoma.: Nam Keong Kim, Yu Jin Hah, Ho Young Lee, Sang Jin Kim, Mi Kyung Kim, Keun Gyu Park, Ealmaan Kim, Hyukwon Chang, Hye Soon Kim; Endocrinol Metab. 2010;25(4):378-381. Published online December 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.4.378

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Abstract PDF: Growth hormone (GH) and thyroid stimulating hormone (TSH)-secreting pituitary adenomas are very rare and they account for only 0.5% for all pituitary adenomas. These adenomas are usually treated with surgery, but this surgery is not easy because the tumor is usually huge and invasive. We reported here on a case of a GH-TSH-secreting adenoma in a 23-year-old male patient who was initially treated with octreotide LAR. He presented with symptoms of headache, palpitation and a visual defect that he had for the 3 months. He had hypertrophy of the frontal bone and enlargement of both the hands and feet. The visual field test showed bitemporal hemianopsia. The laboratory examinations showed high serum levels of free T4, TSH and free alpha-subunit. Additionally, the serum levels of GH and insulin-like growth factor-I (IGF-I) were increased. GH was not suppressed below 1microg/L by an oral 75g glucose loading test, and TSH was not stimulated by thyrotropin-releasing hormone (TRH). Because sellar MRI showed invasive macroadenoma encasing the vessels, we initially tried octreotide LAR for treatment. A year later, the IGF-I and thyroid function tests were normalized and the size of the tumor was reduced with cystic change. The symptoms of palpitation and headache were improved without a change of the visual field defect.

Sustained Maintenance of Normal Insulin-like Growth Factor-I during Pregnancy and Successful Delivery in an Acromegalic Patient with Octreotide-LAR(R) Treatment.: Soo Kyoung Kim, Jung Hwa Jung, Jae Hyeon Kim, Kyu Yeon Hur, Alice Hyun Tan, Hee Kyung Kim, Ji In Lee, Hye Soo Chung, Kwang Won Kim; Endocrinol Metab. 2010;25(3):213-216. Published online September 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.3.213

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Abstract PDF: We report here on a 34-year-old Korean woman with active acromegaly and who received Octreotide-LAR(R) for 12 months following transsphenoidal pituitary surgery. During Octreotide-LAR(R) treatment, the clinical improvement was paralleled with the decrease of the growth hormone levels to 1.1 ng/mL and the insulin-like growth factor-I (IGF-I) levels to 345.5 ng/mL. Octreotide-LAR(R) was discontinued when the patient was found to be at the 12th week of pregnancy. During pregnancy, the patient experienced clinical well-being and she maintained her IGF-I levels within the normal range for her age-matched despite discontinuation of Octreotide-LAR(R) treatment at early gestation. She delivered a full-term healthy male infant. The serum IGF-I levels of the patient increased progressively increased after delivery. This report describes a successful pregnancy in an acromegalic woman who was exposed to Octreotide-LAR(R) during the early gestational period. She and who showed an unexpected pattern of persistently normal IGF-I levels through the pregnancy despite discontinuation of Octreotide-LAR(R) therapy.

Acromegaly with Diabetes Insipidus after Pituitary Tumor Removal: Successful Pregnancy and Delivery.: Sei Hyun Kim, Joo Il Kim, Yae Min Park, In Sik Won, Kwen Chul Shin, Yunjeong Jo, Sihoon Lee, Yeun Sun Kim, Ki Young Lee, Ie Byung Park; J Korean Endocr Soc. 2010;25(1):56-60. Published online March 1, 2010; DOI: https://doi.org/10.3803/jkes.2010.25.1.56

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Abstract PDF: A 33-year-old woman visited our hospital because of oligomenorrhea. Acromegaly was diagnosed based on elevated insulin like growth factor-I (IGF-I) and paradoxical growth hormone (GH) rise in oral glucose tolerance test. Pituitary macroadenoma was detected on magnetic resonance imaging (MRI). The pituitary tumor was removed. Still, diabetes insipidus developed. We prescribed desmopressin and bromocriptine. Two months post-surgery, IGF-I was decreased and a combined pituitary function test was normal, except for the follicle stimulating hormone response. Residual tumor was detected on MRI. The bromocriptine dose was increased and treatment with the long-acting somatostatin analogue octreotide long acting release (LAR) was begun. After the fifth round of octreotide LAR, IGF-I was normalized. After the seventh round of octreotide LAR, the patient became pregnant. Bromocriptine and octreotide LAR were stopped, and desmopressin was continued. Successful delivery occurred at week 38 of pregnancy. The patient was discharged without any complications. Acromegaly is a disease caused by chronic GH hypersecretion, generally related to a somatotroph adenoma. Amenorrhea and menstrual irregularities are common in acromegaly. Pregnancy rarely occurs because chronic anovulation usually exists. When gonadotroph axis was preserved, the possibility of pregnancy in a woman of child-bearing age with acromegaly should be considered.

Two Cases of Acromegaly with Empty Sella Syndrome Treated by Long-Acting Release Octreotide.: Dong Jin Kim, Young Jin Seo, Nam Hoon Kim, Hye Soo Chung, Chai Ryoung Eun, Hye Jung Choi, Hye Sook Kim, Sae Jeong Yang, Juri Park, Hye Jin Yoo, Soo Yeon Park, Yun Jeong Lee, Ohk Hyun Ryu, Kye Won Lee, Hee Young Kim, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi; J Korean Endocr Soc. 2007;22(2):135-141. Published online April 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.2.135

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Abstract PDF: Two cases of typical acromegaly with empty sella syndrome presented to our institution. In the natural course of untreated pituitary adenoma, empty sella syndrome may result from necrosis by infarction or from hemorrhage of the pituitary gland. In our patients, the secretion of growth hormone continued in spite of the existence of empty sella syndrome. In one case, we confirmed the hypersecretion of growth hormone from sella by jugular vein sampling. Medical therapy with somatostatin analogue was attempted because there was no obvious mass in the sella. After 6~12 months of treatment with long-acting release octreotide, clinical features in our patients were improved, and the level of growth hormone and IGF-1 were also normalized.

Original Articles

Efficacy of Octreotide LAR in Acromegalic Patients.: Ji Youn Kim, Jae Hwan Jee, Chan Ho Yoon, Yun Jae Chung, Byung Wan Lee, Gun Yong Cho, Sang Young Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; J Korean Endocr Soc. 2005;20(4):344-352. Published online August 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.4.344

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Abstract PDF

BACKGROUND
Octreotide(OC)-LAR is a long-acting preparation of octreotide which has been effectively used to suppress GH/IGF-1 hypersecretion in acromegalic patients. The clinical response, biochemical outcomes, and safety of OC-LAR were evaluated in 27 active acromegalic patients. METHOD: 27patients with an active disease status (according to the clinical picture, GH >5microgram/L and elevated age-matched IGF-1), and previously treated with bromocriptine after surgery, comprised the study population. OC-LAR was given(20mg, i.m., every 4 week for 3 injections, then the doses were titrated individually) and the acromegalic symptoms and adverse reactions recorded. The serum levels of GH and IGF-1 were evaluated every 12 week. The acromegalic symptoms including headache, fatigue and arthralgia, improved in all patients. RESULTS: Gastrointestinal side effects were transient and mild. The levels of GH significantly decreased, from 8.9+/-3.5 to 2.9+/-2.2 microgram/L at 12 weeks(P<0.001, vs. baseline), to 2.9+/-2.1microgram/L after 24 weeks(P<0.001) and to 2.5 +/-1.3microgram/L at 48 weeks(P<0.001). The levels of IGF-1 significantly decreased, from 753.7+/-213.6 to 429.7+/-253.4 microgram/L at 12 weeks(P<0.001, vs. at baseline), to 405.7+/-213.3microgram/L at 24 weeks(P <0.001) and to 348.9+/-144.7microgram/L at 48 weeks(P<0.001). The safelevel of GH is less than 2.5microgram/L and normal age-matched IGF-1 levels were achieved in 63 and 52% of the patients, respectively. CONCLUSION: Octreotide-LAR was well tolerated and effective as an adjuvant treatment in lowering the levels of GH and IGF-1 in active acromegalic patients.

Citations

Citations to this article as recorded by

Letter: Comparison of the Efficacy of Octreotide Long-acting Repeatable and Lanreotide Autogel in Acromegalic Patients (J Korean Endocr Soc 25:37-45, 2010)
Yu-Bae Ahn
Endocrinology and Metabolism.2010; 25(2): 157. CrossRef
The Effect of Octreotide LAR on GH and TSH Co-Secreting Pituitary Adenoma
Nam Keong Kim, Yu Jin Hah, Ho Young Lee, Sang Jin Kim, Mi Kyung Kim, Keun Gyu Park, Ealmaan Kim, Hyukwon Chang, Hye Soon Kim
Endocrinology and Metabolism.2010; 25(4): 378. CrossRef
Comparison of the Efficacy of Octreotide Long-acting Repeatable and Lanreotide Autogel in Acromegalic Patients
Seul young Kim, Dohee Kim
Journal of Korean Endocrine Society.2010; 25(1): 37. CrossRef
Response: Comparison of the Efficacy of Octreotide Long-acting Repeatable and Lanreotide Autogel in Acromegalic Patients (J Korean Endocr Soc 25:37-45, 2010)
Seul Young Kim, Dohee Kim
Endocrinology and Metabolism.2010; 25(2): 159. CrossRef

Gene Expression of Somatostatin Receptor (Subtype 2 & 5), Gi2 alpha and Pit-1 in GH-secreting Pituitary Adenomas.: Mee sook Ryu, In myung Yang, Cheol young Park, Jeong taek Woo, Sung woon Kim, Jin Woo Kim, Young seoul Kim, Young kil Choi, En hee Kim, Seung joon Park, Kook gi Kim; J Korean Endocr Soc. 2002;17(2):158-169. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Mutation of Gs protein subunit (gsp oncogene), detected in about 30~40% of growth hormone (GH)-secreting pituitary tumors, is associated with an increased long-acting somatostatin analog octreotide sensitivity. However, the mRNA expression of somatostatin receptor (sst) was not changed in the GH-secreting pituitary tumor, regardless of whether they were gsp oncogene positive or negative. This suggests that the expression of genes coding for Gi2 alpha , Pit-1 and the other factors involved in the regulation of secretory activity in somatotrophs is likely to be altered in gsp oncogene positive tumors. We observed the impact of the gsp oncogene on the expression of the genes coding for Gi2 alpha, Pit-1 and sst (2&5) in GH-secreting pituitary tumors. METHODS: The GH response to octreotide was examined in 13 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were extracted from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gs gene. Sst2, sst5, Gi2 alpha and Pit-1 mRNA levels were measured by semi-quantitative RT-PCR. RESULTS: Sst2 and sst5 mRNA transcripts were detected in all tumors (7 gsp +, 6 gsp-). The amount of sst transcripts varied considerably varied between the tumors. There were no significant differences in sex, age, tumor size, grade or basal GH levels. Pit-1 and sst2 mRNA levels were not different. In contrast, Gi2 alpha mRNA levels were significantly higher in gsp (+) while sst5 mRNA levels were higher in gsp (-). CONCLUSION: These data suggests that gsp oncogene may increase Gi2 alpha levels but decrease sst5 mRNA levels. However, Pit-1 and sst2 mRNA expression may not be affected by gsp oncogene. The increased expression of the Gi2 alpha gene might be an inhibitory compensatory response to the action of gsp oncogene.

Changes of Glucose Tolerance in Acromegaly Patients with 24 Hour Continuous Subcutaneous Infusion of Octreotide.: Ki Hyun Baik, Kun Ho Yoon, Jeong Min Lee, Chang Wook Kim, Paek Sun Kim, Sang Aha Jang, Soon Jib Yoo, Hyun Sik Son, Moo II Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; J Korean Endocr Soc. 1999;14(4):636-644. Published online January 1, 2001

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Abstract PDF: BACKGROUND
An important metabolic feature of acromegaly is a reduced action of insulin on hepatic gluconeogenesis and peripheral glucose disposal which mediated by growth hormone hypersecretion. Octreotide, a synthetic octapeptide somatostatin analogue exerts complex effects on hormonal and metabolic regulations affecting glucose homeostasis. This study was designed to ascertain the shorterm effect of octreotide on glucose tolerance in acromegaly. METHODS: 10 patients (five men and five women, age 47.9+/-11.8) were injected subcutaneously with octreotide, 100 micrograms for 24 hours. Patients were assessed with respect to growth hormone, glucose, and insulin response to a standard 100 g oral glucose tolerance test (OGTT) before and during the last 2 hour of octreotide infusion. RESULTS: During the therapy, there was significant decrease in mean blood glucose response to OGTT (678.4+/-51.9 vs 581.9+/-47.3 mg/dL/2hr: mean areas under the glucose curve, p=0.01) and mean serum insulin response to oral glucose load was significantly reduced in all patients (339.2+/-106.2 vs 256.7+/-111.3 U/mL/2hr: mean areas under the insulin curve, p=0.01). Using glucose tolerance test criteria three patients of 10 had normal glucose tolerance, four and three had impaired glucose tolerance and diabetes, respectively, at base line. While on octreotide these composition was changed to six patients of NGT, three of IGT and one diabetes. CONCLUSION: We conclude that insulin resistance mediated by GH hypersecretion was improved by shorterm octreotide treatment.

Case Report

A Case of Cughing's Disease which Responded to the Combined Treatment of Ketoconazole and Octreotide.: Chan Soo Shin, Chang Hoon Yim, Jae Jun Koh, Sung Yeon Kim, Bo Yeon Cho, Hong Gyu Lee; J Korean Endocr Soc. 1998;13(1):94-98. Published online January 1, 2001

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Abstract PDF: The treatment of choice for Cushing's disease is surgical removal of tumor, the source of ACTH overproduction. In occasional patients in whom a surgical approach including total adrenalectomy is not feasible or surgical removal of tumor is not complete, medical treatment may be necessary because pituitary irradiation requires a long 1ag time to remission. Although ketoconazole, an imidazole derivative with inhibitory activity on adrenal steroidogenesis has been reported to be effective in the treatment of Cushing's disease, the limited effectiveness in lowering very high level of cortisol and occasional hepatotoxicity restrains its wide use. In this report, we describe a woman with Cushing's disease due to pituitary microadenoma. Transsphenoidal pituitary adenomeetomy followed by ketoconzole treatment had been unsuccessful in achieving remission of the disease, but combined treatment with ketoconazole and octreotide accomplished successful reduction in cortisol production.

Original Article

Gene Expression of Somatostatin Receptor Subtype 2 and 5 in GH-Secreting Pituitary Adenomas.: Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Seung Joon Park, In Myoung Yang, Jung Taek Woo, Kook Ki Kim; J Korean Endocr Soc. 1997;12(4):508-517. Published online January 1, 2001

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Abstract PDF: BACKGROUND
SSTR2 and SSTR5 are most frequently observed in GH-secreting pituitary tumors, and SSTR5 is believed to be more specific to mammosomatotroph lineage. Octreotide binds with high affinity to those two types. There is no report that investigates the quantitative comparison of the two subtype gene expressions, and the correlation between their gene expressions and GH response to octreotide in GH-secreting pituitary adenomas. METHOD: GH response to octreotide was examined in 8 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were prepared from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gas gene. mRNAs of SSTR2 and SSTRS were quantitated by the comparative RT-PCR and in vitro transcription. RESULTS: The in vitro transcripts of SSTR2 and SSTR5 cDNA were detected in all tumors. The amount of SSTR transcripts was considerably variable between the tumors. The amount of SSTR5 transcript was significantly smaller than that of SSTR2 transcript (0.07+-0.02 vs. 0.87+-0.10), and they did not show any correlation . There was no signicant difference in sex, age, tumor size and grade, basal GH levels, and the GH responses to octreotide between the group with high and low SSTR gene expression. No significant correlation was found between the GH response to octreotide and the amount of SSTR2 transcript, wherease the amount of SSTR5 transcripts showed a tendency of negative correlation with the octreotide response. Tumors with gsp oncogene showed significantly higher response to octreotide than those without the oncogene. The amount of SSTRS transcript in gsp-positive tumors was significantly smaller than in gsp-negative tumors (0.03+-0.01 vs. 0.12+-0.03). CONCLUSION: These results suggest that SSTRS gene expression is lower than that of SSTR2 in GH-secreting adenomas. It is probably attributed to the binding of somatostatin to SSTR5 which has a higher affinity to the hypothalamic somatostatin, Tumors with gsp-oncogene is likely to express a higher density of SSTR5 than those without the oncogene.

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