Clinical predictors of GH deficiency in surgically cured acromegalic patients

Ku, Cheol Ryong,Hong, Jae Won,Kim, Eui Hyun,Kim, Sun Ho,Lee, Eun Jig European Federation of Endocrine Societies 2014 European journal of endocrinology Vol.171 No.3

<P><B>Objective</B></P><P>Even in patients with cured acromegaly, GH deficiency (GHD) after transsphenoidal adenomectomy (TSA) adversely affects body composition and inflammatory biomarkers of cardiovascular risk. In this study, clinical parameters for predicting GHD after TSA in 123 cured acromegalic patients were investigated.</P><P><B>Design and methods</B></P><P>GH levels were measured at 6, 12, 18, 24, 48, and 72 h after TSA and serial insulin tolerance tests were conducted at 6 months, 2 years, and then every 2 years after TSA.</P><P><B>Results</B></P><P>GHD was found in 12 patients (9.8%) at 4.1 (range: 0.5–4.1) years after TSA. IGF1 levels were significantly lower at 6 months after TSA in GHD group than intact GH group (175.9 vs 316.8 μg/l, range: 32.0–425.0 and 96.9–547.3 respectively, <I>P</I>=0.008). Adenomas involving both sides of the pituitary gland were significantly more frequent in GHD patients (29.7 vs 83.3%; <I>P</I>=0.002). Furthermore, immediate postoperative 72-h GH levels after TSA were significantly lower (0.17 vs 0.45, range: 0.02–0.93 and 0.02–5.95 respectively, <I>P</I>=0.019) in GHD patients. In multiple logistic regression analysis, bilaterality of tumor involvement (odds ratio (OR)=10.678, <I>P</I>=0.003; 95% CI=2.248–50.728) and immediate postoperative 72-h GH level (OR=0.079, <I>P</I>=0.047; 95% CI=0.006–0.967) showed significant power for predicting GHD.</P><P><B>Conclusions</B></P><P>These data suggest that bilateral involvement of a pituitary adenoma and severely decreased immediate postoperative serum GH levels at 72 h after TSA may be independent risks factor for accelerated GHD in acromegalic patients.</P>

Intestinal Glycolysis Visualized by FDG PET/CT Correlates With Glucose Decrement After Gastrectomy

Ku, Cheol Ryong,Lee, Narae,Hong, Jae Won,Kwon, In Gyu,Hyung, Woo Jin,Noh, Sung Hoon,Lee, Eun Jig,Yun, Mijin,Cho, Arthur American Diabetes Association 2017 Diabetes Vol.66 No.2

<P>Gastrectomy method is known to influence glucose homeostasis. F-18-fluoro-2-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) images acquired after gastrectomy often reveals newly developed physiological small bowel uptake. We correlated newly developed small bowel FDG uptake and glucose homeostasis in postgastrectomy gastric cancer patients. We retrospectively analyzed 239 patients without diabetes who underwent staging and follow-up FDG PET/CT scanning before and after gastrectomy for gastric cancer. Postoperative small bowel glycolysis was quantified by recording intestinal total lesion glycolysis (TLG). TLG was assessed with regard to surgical method (Billroth I, Billroth II [BII], Roux-en-Y [RY]), fasting glucose decrement (>= 10 mg/dL), and other clinical factors. Patients' weight, fasting glucose, cholesterol, TLG, and body fat levels significantly decreased after surgery. The glucose decrement was significantly associated with fasting glucose, surgical methods, total cholesterol, TLG, and total body fat on univariate analysis. Multivariate analysis showed that BlI surgery (odds ratio 6.51) and TLG (odds ratio 3.17) were significantly correlated with glucose decrement. High small bowel glycolysis (TLG >42.0 g) correlated with glucose decrement in RY patients. Newly developed small bowel glycolysis on postgastrectomy FDG PET/CT scanning is correlated with a glucose decrement. These findings suggest a potential role of FDG PET/CT scanning in the evaluation of small bowel glycolysis and glucose control.</P>

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement

진상욱,Cheol Ryong Ku,김병준,김성운,박경혜,송기호,오승준,윤현구,이은직,이정민,임정수,김정희,김광준,진흥용,김대중,이경애,문성수,임동준,신동엽,김세화,권민정,김하영,김진화,김동선,김종화 대한내분비학회 2019 Endocrinology and metabolism Vol.34 No.1

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, thenumber of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements ininsurance 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 theKorean 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 ofacromegaly. 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.

Clinical Parameters to Distinguish Silent Corticotroph Adenomas from Other Nonfunctioning Pituitary Adenomas

Kim, Daham,Ku, Cheol Ryong,Park, Se Hee,Moon, Ju Hyung,Kim, Eui Hyun,Kim, Sun Ho,Lee, Eun Jig Elsevier 2018 World neurosurgery Vol.115 No.-

<P><B>Background</B></P> <P>It is difficult to distinguish silent corticotroph adenomas (SCAs) from other nonfunctioning pituitary adenomas (NFPAs) preoperatively. This study aimed to determine the preoperative clinical parameters associated with SCAs.</P> <P><B>Methods</B></P> <P>This was a retrospective single-center study of patients who underwent surgery for NFPAs during 2011–2016 in our tertiary hospital and who had preoperative combined pituitary function test (CPFT) and immunohistochemical staining results available. After we excluded patients with increased 24-hour urinary free cortisol to preclude overt Cushing's disease, 341 patients were finally enrolled. The medical records, including the CPFT and immunohistochemistry results, of the patients were reviewed.</P> <P><B>Results</B></P> <P>The age and tumor size were similar between patients with SCAs and other NFPAs. The SCA group had a greater proportion of women (89.2% vs. 57.6%, <I>P</I> < 0.001), cavernous sinus invasion (35.1% vs. 20.7%, <I>P</I> = 0.047), and intratumoral hemorrhage on preoperative sella magnetic resonance imaging (32.4% vs. 9.2%, <I>P</I> < 0.001) compared with the NFPA group. In the preoperative CPFT, the cortisol response was not significantly different between groups. However, the peak adrenocorticotropic hormone (ACTH) (67.80 ± 49.83 vs. 85.67 ± 78.97 pg/mL, <I>P</I> = 0.061) tended to be lower, and the ΔACTH (53.71 ± 50.14 vs. 72.67 ± 75.82 pg/mL, <I>P</I> = 0.046) was significantly lower in SCAs. After we excluded patients with preoperative hypopituitarism caused by mass effects, the peak ACTH (69.39 ± 39.45 vs. 119.75 ± 89.84 pg/mL, <I>P</I> = 0.001) and ΔACTH (58.58 ± 36.51 vs. 107.66 ± 86.05 pg/mL, <I>P</I> = 0.001) were significantly lower in SCAs than in other NFPAs.</P> <P><B>Conclusions</B></P> <P>Female sex, cavernous sinus invasion, intratumoral hemorrhage on sella magnetic resonance imaging, and decreased ACTH response in the CPFT are independent indicators of SCAs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> SCAs are difficult to distinguish from other NFPAs preoperatively. </LI> <LI> We determined the preoperative clinical parameters associated with SCA. </LI> <LI> Patients (<I>N</I> = 341) who underwent surgery for NFPA were evaluated retrospectively. </LI> <LI> Indicators include female sex, cavernous sinus invasion, and intratumoral hemorrhage. </LI> <LI> Decreased ACTH response in the CPFT also was an independent indicator. </LI> </UL> </P>

A case of fugitive acromegaly, initially presented as invasive prolactinoma.

Lim, Jung Soo,Ku, Cheol Ryong,Lee, Mi-Kyung,Kim, Tai Seung,Kim, Sun Ho,Lee, Eun Jig Macmillan Press 2010 Endocrine Vol.38 No.1

<P>Fugitive acromegaly is most commonly caused by pituitary acidophil stem cell adenomas, and is characterized by a relatively short clinical history, a large and locally invasive tumor, and relatively low hormonal activity. Here, we report an unusual case of fugitive acromegaly that initially presented as invasive prolactinoma. A 48-year-old man with a huge pituitary mass extending to the suprasellar area was referred to our hospital in December 2007. He had undergone transsphenoidal surgery in November 1999 because of a large invasive prolactinoma. The tumor had grown progressively, despite therapy with dopamine agonists. Subtle features of acromegaly were noted and serum IGF-1 levels were high (733 ng/ml). An oral glucose tolerance test revealed that basal and nadir levels of growth hormone (GH) were 1.56 and 1 ng/ml, respectively. As a therapeutic trial, long-acting octreotide (20 mg IM, monthly) was added, and the tumor size markedly reduced within 6 months on magnetic resonance imaging examination. Immunohistochemical staining of the tumor tissue obtained at the surgery in 1999 showed positive staining for GH and prolactin (PRL). Double immunofluorescence staining showed a mixed positivity for GH and PRL in the majority of tumor cells; however, the two hormones colocalized in a minority of tumor cells, indicating that the tumor was composed of three different cell types (GH, PRL, and GH/PRL). The diagnosis of fugitive acromegaly was initially overlooked in this patient because of normal serum GH levels and a lack of acromegalic features, although histological evidence for GH production was present. IGF-1 determinations would be helpful for the diagnosis of fugitive acromegaly.</P>

Thyroid Dysfunction in Malignant Lymphoma

Jae Hoon Moon,Cheol Ryong Ku,Si Hoon Lee,Sung Kil Lim,Jee Sook Hahn 대한내과학회 2005 대한내과학회 추계학술대회 Vol.2005 No.1

Therapeutic Effects of Water Soluble Danshen Extracts on Atherosclerosis

Cho, Yoon Hee,Ku, Cheol Ryong,Hong, Zhen-Yu,Heo, Ji Hoe,Kim, Eun Hee,Choi, Dong Hoon,Kim, Dongkyu,Kim, Ae-Jung,Lee, Cheol Soon,Jung, Mankil,Lee, Hyun Chul,Seo, MiRan,Lee, Eun Jig Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>Danshen is a traditional Chinese medicine with many beneficial effects on cardiovascular diseases. The aim of this study was to evaluate the mechanisms responsible for the antiatherogenic effect of water soluble Danshen extracts (DEs). Rat vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were treated with DE. To evaluate the effects of DE <I>in vivo</I>, carotid balloon injury and tail vein thrombosis were induced in Sprague-Dawley (SD) rats and iliac artery stent was induced in New Zealand white rabbits. The inhibitory action of DE on platelet aggregation was confirmed with an impedance aggregometer. DE inhibited the production of reactive oxygen species, and the migration and proliferation of platelet-derived growth factor-BB stimulated VSMCs. Furthermore, DE prevented inflammation and apoptosis in HUVECs. Both effects of DE were reconfirmed in both rat models. DE treatment attenuated platelet aggregation in both <I>in vivo</I> and <I>ex vivo</I> conditions. Pretreatment with DE prevented tail vein thrombosis, which is normally induced by <I><I>κ</I></I>-carrageenan injection. Lastly, DE-treated rabbits showed decreased in-stent restenosis of stented iliac arteries. These results suggest that water soluble DE modulates key atherogenic events in VSMCs, endothelial cells, and platelets in both <I>in vitro</I> and <I>in vivo</I> conditions.</P>

Slide Session : OS-END-35 ; Endocrinology : The Effect of Pregnancy and Lactation on Prolactinoma

( Won Jin Kim ),( Cheol Ryong Ku ),( Jae Won Hong ),( Eun Jig Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Prolactinoma predominantly occurred in young women of reproductive age. But there are limited data about the effect of pregnancy and lactation on prolactinoma progression. We evaluated the safety of dopamine agonists including bromocriptine and cabergoline and pregnancy outcome in prolactinoma patients. Methods: Patients diagnosed with prolactinoma who experienced pregnancies were included. Sellar MRI and serum prolactin levels were performed before and after pregnancy and lactation. Total 46 patients with 62 pregnancies were included. Results: Among 62 pregnancies, spontaneous pregnancies analyzed 61 (98.3 %) and only one pregnancy was made by in vitro fertilization. Live births were in 51 (82.3 %), while spontaneous abortions occurred in 11 (17.7%). Twenty-one were treated with cabergoline at the time of conception, whereas twenty-eight with bromocriptine. We divided patients into two groups by their changes of adenoma size after delivery; increased (n = 22) or decreased (n = 15). Patients with bigger adenoma size before pregnancy showed significantly increased after childbirth. However, the enlarged adenoma did not cause any clinical problems. Of all, breast-feeding was performed in 38 pregnancies. Mean duration of lactation was 4.9 ± 4.4 months. Among those 38, 16 patients had done MRI follow-up after the lactation. There were decreased adenoma sizes in 9 patients, no changes in 5 patients, while increased only in two patients. Conclusions: In conclusion, breast-feeding is not contraindicated in patients with prolactinoma, especially those who had smaller adenoma.

Age- and Sex-Specific Differences as Predictors of Surgical Remission Among Patients With Acromegaly

Park, Se Hee,Ku, Cheol Ryong,Moon, Ju Hyung,Kim, Eui Hyun,Kim, Sun Ho,Lee, Eun Jig Issued for the Endocrine Society by the Williams & 2018 The Journal of clinical endocrinology & metabolism Vol.103 No.3

Spontaneous Non-Traumatic Stress Fractures in Bilateral Femoral Shafts in a Patient Treated with Bisphosphonates

( Dong Yeob Shin ),( Cheol Ryong Ku ),( Kyung Min Kim ),( Han Seok Choi ),( Yumie Rhee ),( Eun Jig Lee ),( Sung Kil Lim ) 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.1

Bisphosphonates are potent inhibitors of bone resorption and widely used to treat osteoporosis. Extensive studies have shown that therapy with bisphosphonates improves bone density and decreases fracture risk. However, concerns have been raised about potential over-suppression of bone turnover during long-term use of bisphosphonates, resulting in increased susceptibility to and delayed healing of non-spinal fractures. We report a patient who sustained non-traumatic stress fractures in bilateral femoral shafts with delayed healing after long-term bisphosphonate therapy. She underwent open reduction and surgical internal fixation. Although bisphosphonates effectively prevent vertebral fractures, and their safety has been tested in randomized trials, we must emphasize the need for awareness of the possibility that long-term suppression of bone turnover with bisphosphonates may eventually lead to an accumulation of fatigue-induced damage and adverse skeletal effects such as delayed fracture healing.