Endocrinology and Metabolism

Original Articles

The Localization of Microadenoma with Sella Imaging Study and Inferior Petrosal Sinus Sampling in Cushing's Disease.: Jae Seok Jeon, Sang Jeon Choi, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hee Won Jung, Dae Hee Han, Moon Hee Han, Kee Hyun Chang; J Korean Endocr Soc. 1996;11(4):492-499. Published online November 7, 2019

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Abstract PDF: Background
Inferior petrosal sinus sampling(IPSS) is known to be useful for the differential diagnosis of ACTH-dependent Cushings syndrome and for the preoperative lateralization of pituitary microadenoma. We tried to analyze the relative value of IPSS in localization of microadenoma as compared with sella imaging study including computerized tomogram(CT) or magnet resonance imaging(MRI) in Cushings disease. Methods: We reviewed the clinical records of 21 patients with Cushings disease who underwent IPSS and the radiologic study such as sella CT or sella MRI preoperatively followed by transsphenoidal microsurgery. By pathologic examination including immunohistochemistry and postoperative clinical and biochemical evaluation we confirmed the diagnosis of Cushings disease due to pituitary microadenoma in all 21 cases. Results: Sella CT or sella MRI detected microadenoma in 57.1% of cases( =12/21), while recently available dynamic MRI did so in 7 out of S cases. With IPSS the diagnosis of Cushings disease was possible in 90.5% of cases(= 19/21), but accurate lateralization of microadenoma was achieved in only 63.2% of cases( =12/19). IPSS precisely localized the pituitary microadenoma in 6 out of 9 cases whose lesion were not detected by the radiologic study. Of 7 cases in which IPSS failed to localize microadenoma, the radiologic study detected the lesion in 6 cases. Of 5 cases in which IPSS and the radiologic study showed a discrepancy in location of microadenoma, the radiologic study correctly localizaed the lesion in 4 cases and IPSS did so in one case. Conclusion: IPSS is not more reliable than sella imaging study for preoperative localization of microadenoma in Cushings disease. However it might have a complementary role, especially when sella imaging study failed to visualize the lesion.

A Clinical study on the diagnesis and Treatment of Cushing's Disease - The significance of bilateral inferior petrosal sinus sampling -.: Seong Yeon Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Jae Seok Jeon, Hyeong Kyu Park, Chang Soon Koh, Hun Ki Min, Heu Won Jeong, Dae Hee Han, Moon Hee Han, Kee Hyun Jang; J Korean Endocr Soc. 1994;9(2):115-120. Published online November 6, 2019

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Abstract PDF: Bilateral inferior petrosal sinus sampling(IPSS) is known to be useful for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative localization of pituitary microadenomas.To evaluate the usefulness of IPSS, we performed the procedure in the 17 cases of ACTH-dependent Cushing's syndrome including 2 cases of macroadenomas, 6 of them with CRH stimulation test. A inferior petrosal sinus-to-peripheral ACTH ratio of 2:1 or greater(3:1 after CRH stimulation) indicates a pituitary source of ACTH hypersecretion, and a ratio of the ACTH level in one inferior petrosal sinus to the ACTH level in the other of 1:4 or greater lateralizes the microadenomas to that half of the pituitary gland.With these criteria, we diagnosed Cushing's disease in 15 of 17 cases of ACTH-dependent Cushing's syndrome, and localized the lesion in 8 of 13 cases of microadenoma.In conclusion, IPSS with CRH stimulation has high diagnostic accuracy in the differential diagnosis of ACTH-dependent Cushing's syndrome, but still has the limitations on the localization of microadenoma.

Clinical Study
Factors Associated with Resolution of Hypertension after Adrenalectomy in Patients with Primary Aldosteronism: Wann Jia Loh, Dawn Shao Ting Lim, Lih Ming Loh, Peng Chin Kek; Endocrinol Metab. 2018;33(3):355-363. Published online August 14, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.355

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Background

The aim of this study was to investigate the factors associated with resolution of hypertension after adrenalectomy in patients with primary aldosteronism. A secondary aim was to describe our use of the contralateral ratio in adrenal venous sampling (AVS) in the setting of suboptimal successful cannulation rates.

Methods

A retrospective review of patients who underwent AVS followed by unilateral adrenalectomy for primary aldosteronism was performed.

Results

Complete resolution of hypertension and hypokalemia was seen in 17 of 40 patients (42.5%), while a clinical improvement in hypertension was seen in 38 of 40 (95%). Shorter duration of hypertension, mean aldosteronoma resolution score (ARS), and a high ARS of 3 to 5 were associated with resolution of hypertension after adrenalectomy (P=0.02, P=0.02, and P=0.004, respectively). Of the individual components of ARS, only a duration of hypertension of ≤6 years was associated with resolution of hypertension after adrenalectomy (P=0.03).

Conclusion

A shorter duration of hypertension was significantly associated with resolution of hypertension after adrenalectomy in patients with primary aldosteronism.

Citations

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Clinical and biochemical outcomes after adrenalectomy for primary aldosteronism in tertiary and quaternary referral centers: data from SOPRANO study
Luigi Marzano, Claudio Ronco
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Catheter-based adrenal ablation: an alternative therapy for patients with aldosterone-producing adenoma
Fang Sun, Xiaoli Liu, Hexuan Zhang, Xunmei Zhou, Zhigang Zhao, Hongbo He, Zhencheng Yan, Yingsha Li, Qiang Li, Yaoming Li, Jun Jiang, Zhiming Zhu, Hongyun Miao, Zhiyong Li, Ping Wei, Min Long, Xiaoli Chen, Xiaoyun Fan, Wuquan Deng, Yangjie He, Qingbin Lia
Hypertension Research.2023; 46(1): 91. CrossRef
Prognostic models to predict complete resolution of hypertension after adrenalectomy in primary aldosteronism: A systematic review and meta‐analysis
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Long-term outcome success after operative treatment for primary aldosteronism
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Comparison of cystatin C-based and creatinine-based glomerular filtration rate in the prediction of postoperative residual hypertension in aldosterone-producing adenoma patients after adrenalectomy
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Long-term blood pressure outcomes of patients with adrenal venous sampling-proven unilateral primary aldosteronism
Xu Meng, Wen-Jun Ma, Xiong-Jing Jiang, Pei-Pei Lu, Ying Zhang, Peng Fan, Jun Cai, Hui-Min Zhang, Lei Song, Hai-Ying Wu, Xian-Liang Zhou, Ying Lou
Journal of Human Hypertension.2020; 34(6): 440. CrossRef
Update on the Aldosterone Resolution Score and Lateralization in Patients with Primary Aldosteronism
Eun-Hee Cho
Endocrinology and Metabolism.2018; 33(3): 352. CrossRef

Review Articles

Adrenal gland
Clinical Guidelines for the Diagnosis and Treatment of Cushing's Disease in Korea: Kyu Yeon Hur, Jung Hee Kim, Byung Joon Kim, Min-Seon Kim, Eun Jig Lee, Sung-Woon Kim; Endocrinol Metab. 2015;30(1):7-18. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.7

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Cushing's disease (CD) is a rare disorder characterized by the overproduction of adrenocorticotropic hormone due to a pituitary adenoma that ultimately stimulates excessive cortisol secretion from the adrenal glands. Prior to the detection of pituitary adenomas, various clinical signs of CD such as central obesity, moon face, hirsutism, and facial plethora are usually already present. Uncontrolled hypercortisolism is associated with metabolic, cardiovascular, and psychological disorders that result in increased mortality. Hence, the early detection and treatment of CD are not only important but mandatory. Because its clinical manifestations vary from patient to patient and are common in other obesity-related conditions, the precise diagnosis of CD can be problematic. Thus, the present set of guidelines was compiled by Korean experts in this field to assist clinicians with the screening, diagnoses, and treatment of patients with CD using currently available tests and treatment modalities.

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Usefulness of prolactin measurement in inferior petrosal sinus sampling with desmopressin for Cushing’s syndrome
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Hormonal aggressiveness according to the expression of cellular markers in corticotroph adenomas
Jung Soo Lim, Mi-Kyung Lee, Eunhee Choi, Namki Hong, Soo Il Jee, Sun Ho Kim, Eun Jig Lee
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Bone Metabolism
Diagnostic Modalities for FGF23-Producing Tumors in Patients with Tumor-Induced Osteomalacia: Seiji Fukumoto; Endocrinol Metab. 2014;29(2):136-143. Published online June 26, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.2.136

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Fibroblast growth factor 23 (FGF23) is a hormone that is produced by osteocytes and regulates phosphate and vitamin D metabolism through binding to the Klotho-FGF receptor complex. Excessive actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia. Tumor-induced rickets/osteomalacia (TIO) is a paraneoplastic syndrome caused by overproduction of FGF23 from the responsible tumors. Because TIO is cured by complete resection of the causative tumors, it is of great clinical importance to locate these tumors. Several imaging methods including skeletal survey by magnetic resonance imaging and octreotide scintigraphy have been used to identify the tumors that cause TIO. However, none of these imaging studies indicate that the detected tumors are actually producing FGF23. Recently, systemic venous sampling was conducted for locating FGF23-producing tumor in suspected patients with TIO and demonstrated that this test might be beneficial to a subset of patient. Further studies with more patients are necessary to establish the clinical utility of venous sampling in patients with TIO.

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Case Report

Adrenal gland
Adrenocorticotropic Hormone-Independent Cushing Syndrome with Bilateral Cortisol-Secreting Adenomas: Eu Jeong Ku, A Ram Hong, Ye An Kim, Jae Hyun Bae, Mee Soo Chang, Sang Wan Kim; Endocrinol Metab. 2013;28(2):133-137. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.133

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A 48-year-old woman was incidentally found to have bilateral adrenal masses, 2.8 cm in diameter on the right, and 2.3 cm and 1.7 cm in diameter on the left, by abdominal computed tomography. The patient had a medical history of hypertension, which was not being controlled by carvedilol, at a dose of 25 mg daily. She presented with signs and symptoms that suggested Cushing Syndrome. We diagnosed adrenocorticotropic hormone (ACTH)-independent Cushing Syndrome based on the results of basal and dynamic hormone tests. Adrenal vein sampling (AVS) was performed to localize a functioning adrenal cortical mass. AVS results were consistent with hypersecretion of cortisol from both adrenal glands, with a cortisol lateralization ratio of 1.1. Upon bilateral laparoscopic adrenalectomy, bilateral ACTH-independent adrenal adenomas were found. The patient's signs and symptoms of Cushing Syndrome improved after surgery just as the blood pressure was normalized. After surgery, the patient was started on glucocorticoid and mineralocorticoid replacement therapy.

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Original Articles

The Clinical Implication and Problems of Adrenal Vein Sampling in Patients with Primary Aldosteronism.: Jie Seon Lee, Mi Yeon Kang, Sang Wan Kim, Chan Soo Shin, Seong Yeon Kim, Jin Wook Chung; J Korean Endocr Soc. 2007;22(6):428-435. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.428

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Abstract PDF

BACKGROUND
Recently, the significance of primary aldosteronism is being recognized due to an increase in its incidence and its complications. However, it is difficult to differentiate primary aldosteronism based on radiological studies as the size of an aldosterone producing adenoma (APA) is small, and nonfunctioning adrenal incidentalomas are common. Adrenal vein sampling (AVS) has been considered as the gold standard for differentiating an aldosterone producing adenoma (APA) from bilateral idiopathic adrenal hyperplasia (BAH). The clinical implications and problems associated with AVS have not yet been reported in Korea. METHOD: Clinical data of 28 patients with primary aldosteronism who had undergone AVS in a hospital from 1995 to 2006 were retrospectively analyzed. RESULT: The study group comprised 13 males (46.4%) and 15 females (53.5%), with a mean age of 44.5 +/- 11.9 years. Clinical data indicated that 19 patients (67.9%) had APA and nine patients (32.1%) had BAH. AVS data demonstrated that 11 patients had APA and five patients had BAH. Two patients were not diagnosed despite successful AVS. AVS was not successful in 10 patients (37.5%); AV catheterization failed in two patients, was not selective in seven patients on the right side, and was not selective in one patient on the left side. CONCLUSION: AVS was helpful in primary aldosteronism patients with inconclusive CT and MRI findings. Selectivity of AVS should be appropriately assessed because of the technical problem of selective catheterization.

Citations

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Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently
Seung-Eun Lee, Jae Hyeon Kim, You-Bin Lee, Hyeri Seok, In Seub Shin, Yeong Hee Eun, Jung-Han Kim, Young Lyun Oh
Endocrinology and Metabolism.2015; 30(4): 607. CrossRef
Primary Aldosteronism
Sang Wan Kim
Korean Journal of Medicine.2012; 82(4): 396. CrossRef

Diagnostic Value of 1microgram Rapid ACTH Stimulation Test According to the Timing of Sampling of Serum Cortisol in Patients with Suspected Central Adrenal Insufficiency.: Sang Wan Kim, Young Min Cho, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2004;19(1):33-41. Published online February 1, 2004

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Abstract PDF: BACKGROUND
Traditional testing of the hypothalamic-pituitary-adrenal axis function has essentially relied upon the insulin tolerance test or the metyrapone test(both tests are not only uncomfortable, but are also dangerous). The standard ACTH stimulation test uses an extremely supra-physiologic amount(250f microgram) of ACTH to evaluate a physiological response, which may result in a false normal response. The 1microgram rapid ACTH stimulation test is more physiological and more sensitive than the standard test, but there exist much controversy about when the serum cortisol should be measured or what the most appropriate cut-off point is for normality or whether the 1microgram ACTH commercial solution is needed. The aims of this study were to investigate 1) whether 1microgram of ACTH is an appropriate amount to stimulate the adrenal gland of patients that have suspected central adrenal insufficiency compared with insulin tolerance test(ITT) and 2) the diagnostic value of the 1microgram rapid ACTH stimulation test according to timing of sampling of serum cortisol. METHODS: In order to evaluate the dose-response relationship between ACTH and cortisol, we performed the ITT in 77 patients with suspected central adrenal insufficiency with serial measurements of serum cortisol and plasma ACTH. We drew the blood samples in 10 min intervals between 10 and 60 min after the administration of 1microgram ACTH in 39 patients with central adrenal insufficiency and in 38 pituitary control patients with pituitary. ITT was used to confirm the diseases for the patients of central adrenal insufficiency, but for pituitary control patients, the ITT indicated normality in the patients. Also, all subjects underwent the 250microgram rapid ACTH stimulation test, and we compared the diagnostic value of the 1microgram ACTH stimulation test with the 250microgram test. RESULTS: 1) The plasma ACTH level after the 1microgram ACTH stimulation test, even if it was be assumed as approximately 300pg/mL, was expected to be sufficient enough to stimulate the adrenal cortex normally(serum cortisol levels >18microgram/dL) compared to the plasma ACTH level in the ITT. 2) The sensitivity and specificity of the 1microgram rapid ACTH stimulation test was highest with 92.3% and 84.2%, respectively, when serum cortisol levels were measured at 20, 30, and 40 min after the ACTH injection. The 1microgram rapid ACTH stimulation test was more sensitive than the 250microgram ACTH test(sensitivity: 92.3%, specificity: 71.8%). CONCLUSION: The 1microgram rapid ACTH stimulation test was more sensitive test in patients with suspected central adrenal insufficiency, and blood samples for cortisol levels should be drawn at 20, 30, and 40 min after ACTH administration.

Case Report

A Case of Raymond-Cestan Syndrome Caused by Inferior Petrosal Sinus Sampling.: Dong Hyeok Cho; J Korean Endocr Soc. 2003;18(1):73-78. Published online February 1, 2003

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Abstract PDF: Inferior petrosal sinus sampling (IPSS) plays an important role in the assessment of patients with ACTH-dependent Cushing's syndrome. IPSS has been described as an innocuous, essentially risk-free procedure. Neurological complications associated with IPSS are rare. Previously reported neurological complications include brain stem infraction, pontine hemorrhage and subarachnoid hemorrhage. A 26-year-old woman was admitted to the hospital because of a moon face and a buffalo hump. A MRI showed a suspicious, but uncertain, area on the left side of the sella turcica. IPSS was performed as an appropriate means of providing more information about the side of the ACTH source. Immediately after the procedure, the woman experienced double vision, caused by a complete sixth nerve palsy of the left eye, together with a contralateral hemiparesis. From a clinical point of view, abducens nerve palsy and contralateral hemiparesis corresponded to Raymond-Cestan syndrome. I report a case of Raymond-Cestan syndrome, following petrosal sinus sampling in a female patient with ACTH-dependent Cushing's syndrome. To the best of our knowledge, this complication associated with petrosal sinus sampling has only been described in one previous case report. Although IPSS may provide essential information in the investigation of Cushing's syndrome, the possibility of very occasional but devastating complications should be remembered.

Original Articles

Diagnosis of Cushing's Disease by Inferior Petrosal Sinus Sampling (IPSS): Evidence of False Negative Results.: Seon Hwa Lee, Hyeon Jeong Jeon, Sun Hee Park, Sun Wook Kim, Do Joon Park, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 1999;14(3):483-492. Published online January 1, 2001

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Abstract PDF: BACKGROUND
While inferior petrosal sinus sampling (IPSS) correctly diagnoses pituitary dependent Cushings syndrome if a significant ratio of plasma ACTH between the IPS and the peripheral blood is demonstrated, little has been said about the significance of a negative ratio in Cushings disease (e.g. false negative result). We evaluated the results of IPSS with Cushings disease, and compared them with imaging findings through transsphenoidal surgery. METHODS: 29 patients with Cushings disease underwent transsphenoidal examination of the pituitary gland from 1989 to 1998 at Seoul National University Hospital were evaluated. We compared the results of IPSS and imaging findings with sellar CT or dynamic MRI. The ratio of the ACTH concentrations at the IPS and in the peripheral blood (IPS:P ratio) and the ratio of the ACTH concentrations between the IPSs (interpetrosal ratio) were calculated before and after CRH infusion. RESULTS: With IPSS the diagnosis of Cushings disease was possible in 90% (26/29), and 3 cases in whom IPSS did not show significant IPS:P ACTH ratio were confirmed to be Cushings disease through hemihypophysectomy of lesion suspected by sellar dynamic MRI and achieved remission after operation (e.g. false negative result of diagnosis for Cushings disease by IPSS). However, accurate localization of microadenoma was achieved in only 59% (17/29). Imaging study detected microadenoma in 76% (22/29) and correctly localized in 66% (19/29). Both IPSS and imaging study precisely localized the pituitary microadenoma in 10 (34.5%) cases of 29 cases and a discrepancy between two studies existed in 7 (24.1%) cases in which the imaging study correctly localized microadenoma in 6 cases and IPSS in 1 case. CONCLUSION: Only when a significant IPS:P ACTH ratio is present can Cushings disease be established by IPSS. The absence of a significant IPS:P ACTH ratio does not necessarily imply ectopic secretion of ACfH, nor does it exclude Cushings disease. The results of lateralization by IPSS do not remove the need for transsphenoidal examination of the sella turcica because false negative result can be. IPSS and radiologic study should be complementary used in diagnosis of Cushings disease and localization of microadenoma, as IPSS can be used when sellar imaging study failed to visualize the lesion and hemihypophysectomy of suspected lesion by imaging study can be considered when IPSS did not show significant ratio of ACTH.

Primary Aldosteronism Due to Aldosterone Producing Adenama in the Presence of Contralateral Nonfunctioning Adenama.: Ho Young Son, Eun Ah Kim, Jin Il Kwon, Young Joon Kim, Won Ho Chung, Kyung Rim Choi, Sang Jin Choi, Hye Young Park, Moon Ho Kang; J Korean Endocr Soc. 1998;13(2):223-229. Published online January 1, 2001

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Abstract PDF: Primary aldosteronism is in most cases due either to a unilateral adrenal adenama or to a bilateral hyperplasia of the adrenal cortex. But, a few of bilateral adrena1 tumors in primary aldosteronism also have been reported. In these cases, it is important to differentiate the bilateral aldosterone producing adenomas from the unilateral aldosteronoma in the presence of a contralateral nonhmctioning adenoma for marking a treatment plan. We report a case of primary aldosteronism due to a unilateral aldosteronoma in the presence of a contralateral nonfunctioning adenoma. Abdominal CT sean revealed bilateral adrenal tumors, of which the functioning one was successfully localized using adrenal scintigraphy and selective adrenal venous sampling.

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