• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.353-357
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• 2009

As a synthetic analog of the naturally occurring hormone somatostatin, octreotide has been commercially formulated in poly(lactide-co-glycolide) (PLGA) microspheres for the treatment of acromegaly. The purpose of this study was to evaluate stability of octreotide acetate in aqueous solutions at various pH values and PLGA films. Stability-indicating reversed-phase high-performance liquid chromatographic method was developed with good precision and accuracy, and it was applied to the stability studies. In aqueous solutions at pH 2.5-9.0, the degradation of octreotide followed approximately first order kinetics and the most favorable stability was found at pH 4. In PLGA films, the formation of acylated octreotides reached approximately 55% of the released octreotides. Various acylated octreotides was structurally identified by liquid chromatography-mass spectrometric analysis.

• Journal of Korean Neurosurgical Society
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• 제30권5호
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• pp.567-574
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• 2001

Objective : As for growth hormone(GH) secreting pituitary adenoma, it's remission should be declared on the basis of satisfactory controlling of the tumor, normalization of hormonal level, and symptomatic improvement of the patient. Several modalities of treatment have been applied and administered, and yet, this disease still remains as inveterate one to be fully treated. The purpose of this study is to evaluate the outcome of gamma knife radiosurgery(GKRS) for GH secreting pituitary adenoma, and to identify various factors affecting the outcome of the treatment. Method : A group of 24 out of 35 patients, treated by Leksell gamma knife unit during the period of March of 1992 through October of 1997, had been observed for more than two years. The mean target volume of microadenoma was $449.3mm^3(range 216-880mm^3)$, and that of macroadenoma was $3183.1mm^3(range 1456-13125mm^3)$. The tumor margin was covered with 50% isodose profile, and mean marginal dose was 25.2Gy(range 15-32.4Gy). The mean number of isocenter was 4.3(range 1-6). The exposed dose to the optic apparatus was less than 8Gy. The mean follow-up period was 37.8months(range 24-102months). Result : No patients showed any increase in the tumor volume during the follow-up period. And definite shrinkage of tumor volume(tumor volume reduction rate, TVRR : more than 50%) was obtained in 10 patients(41.7%). Twenty one patients(87.5%) had reduced hormonal level compared than pre-treatment level. Among them, normalization of the hormonal level was achieved in 12 patients(50%). Clinicoendocrinological remission was seen in 3 patients (12.5%). According to the results of statistical analysis, tumor volume(p=0.016),duration of symptoms(p=0.046), initial GH level(p=0.017), and the invasion of cavernous sinus(p=0.036) were significantly favorable to post-radiosurgical outcome. The TVRR was significantly related to post-radiosurgical reduction of serum GH level. Permanent complication was not seen. Conclusion : The authors concluded that GKRS is a safe and effective treatment modality for acromegaly. To otain the better outcome of GKRS in GH secreting pituitary adenoma, more careful and sophisticated treatment-planning is recommended.

• Radiation Oncology Journal
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• 제29권3호
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• pp.156-163
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• 2011

Purpose: To evaluate long-term local control rate and toxicity in patients treated with external beam radiotherapy (EBRT) for pituitary adenomas. Materials and Methods: We retrospectively reviewed the medical records of 60 patients treated with EBRT for pituitary adenoma at Korea University Medical Center from 1996 and 2006. Thirty-five patients had hormone secreting tumors, 25 patients had non-secreting tumors. Fifty-seven patients had received postoperative radiotherapy (RT), and 3 had received RT alone. Median total dose was 54 Gy (range, 36 to 61.2 Gy). The definition of tumor progression were as follows: evidence of tumor progression on computed tomography or magnetic resonance imaging, worsening of clinical sign requiring additional operation or others, rising serum hormone level against a previously stable or falling value, and failure of controlling serum hormone level so that the hormone level had been far from optimal range until last follow-up. Age, sex, hormone secretion, tumor extension, tumor size, and radiation dose were analyzed for prognostic significance in tumor control. Results: Median follow-up was 5.7 years (range, 2 to 14.4 years). The 10-year actuarial local control rates for non-secreting and secreting adenomas were 96% and 66%, respectively. In univariate analysis, hormone secretion was significant prognostic factor (p = 0.042) and cavernous sinus extension was marginally significant factor (p = 0.054) for adverse local control. All other factors were not significant. In multivariate analysis, hormone secretion and gender were significant. Fifty-three patients had mass-effect symptoms (headache, dizziness, visual disturbance, hypopituitarism, loss of consciousness, and cranial nerve palsy). A total of 17 of 23 patients with headache and 27 of 34 patients with visual impairment were improved. Twenty-seven patients experienced symptoms of endocrine hypersecretion (galactorrhea, amenorrhea, irregular menstruation, decreased libido, gynecomastia, acromegaly, and Cushing's disease). Amenorrhea was abated in 7 of 10 patients, galactorrhea in 8 of 8 patients, acromegaly in 7 of 11 patients, Cushing's disease in 4 of 4 patients. Long-term complication was observed in 4 patients; 3 patients with cerebrovascular accident, 1 patient developed dementia. Of these patients, 3 of 4 received more than 60 Gy of irradiation. Conclusion: EBRT is highly effective in preventing recurrence and reducing mass effect of non-secreting adenoma. Effort to improve tumor control of secreting adenoma is required. Careful long-term follow-up is required when relatively high dose is applied. Modern radiosurgery or proton RT may be options to decrease late complications.

• 대한핵의학회지
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• 제13권1_2호
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• pp.31-36
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• 1979

The TRH stimulation test was known as a highly diagnostic method in hypothalamopituitary disorders. To evaluate the location and the extension of the lesion, we estimated TSH response to TRH test in 27 patients. Correlation between volume of sella and TSH response was also studied. The results obtained were as follows: 1. In Sheehan's syndrome, TSH response after TRH test were not observed in all of 12 patients. 2. All 2 acromegaly patients showed normal TSH response. 3. In 4 cases of chromophobe adenoma, 2 cases showed no TSH response. In 2 responded cases, one patient whose tumor mass extended to suprasella region was hypothyroid state. 4. In craniopharyingioma 3 cases, the tumor which extended to intrasella showed hypothyroid and no TSH response. 5. Correlation between volume of sella and TSH response were valuable in 2 cases, but no diagnostic significance. 6. In diabetes inspidus, TSH response were all absent. 7. In primary amenorrhea, TSH response observed in 1 case, which conformed with isolated FSH deficiency.

• Journal of Korean Neurosurgical Society
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• 제45권3호
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• pp.157-163
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• 2009

Objective : In recent years, CyberKnife has emerged as an important treatment modality in the management of pituitary adenomas. Treatment results after performing CyberKnife and the complications of this procedure are reviewed. Methods : Twenty-six patients with pituitary adenomas received stereotactic radiosurgery with the CyberKnife (CKRS). The follow-up periods ranged from 7 months to 47 months (mean$\pm$SD : $30{\pm}12.7$ months). The patients consisted of 17 with non-functioning adenomas, 3 with prolactinomas and 6 with acromegaly. The change in the tumor volume, visual acuity, hormonal function, and complications by this therapy were analyzed in each case. Results : The tumor control rate was 92.3%. Hormonal function was improved in all of the 9 (100%) functioning adenomas. Hormonal normalization was observed in 4 of the 9 (44%) patients with a mean duration of 16 months. In two patients (7.6%), visual acuity worsened due to cystic enlargement of the tumor after CKRS. No other complications were observed. Conclusion : CyberKnife is considered safe and effective in selected patients with pituitary adenomas. However, longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.

• Journal of Korean Neurosurgical Society
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• 제45권5호
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• pp.271-274
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• 2009

Objective: We retrospectively analyzed the surgical outcomes of 42 patients with growth hormone (GH)-secreting pituitary adenoma to evaluate the clinical manifestations and to determine which preoperative factors that significantly influence the remission. Methods: Forty-two patients with GH-secreting pituitary adenoma underwent transsphenoidal surgery (TSS) between 1995 and 2007. The patient group included 23 women and 19 men, with a mean age of 40.2 (range 13-61) years, and a mean follow-up duration of 49.4 (range 3-178) months after the operation. For comparable radiological criteria, we classified parasellar growth into five grades according to the Knosp classification. We analyzed the surgical results of the patients according to the most recent stringent criteria for cure. Results: The overall rate of endocrinological remission in the group of 42 patients after primary TSS was 64% (26 of 42). The remission rate was 67% (8 of 12) for microadenoma and 60% (18 of 30) for macroadenoma. The remission rate was 30%(3 of 10) for the group with cavernous sinus invasion and 72% (23 of 32) for the group with intact cavernous sinus. Cavernous sinus invasion in Knosp grade III and IV was significantly correlated with the remission rate. There was a significant relationship between preoperative mean GH concentration and early postoperative outcome, with most patients in remission having a lower preoperative GH concentration. Conclusion: TSS is thought to be an effective primary treatment for GH-secreting pituitary adenomas according to the most recent criteria of cure. Because the remission rate in cases with cavernous sinus invasion is very low, early detection of the tumor before it extends into the cavernous sinus and a long-term endocrinological and radiological follow-up are necessary in order to improve the remission rate of acromegaly.

• Journal of Korean Neurosurgical Society
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• 제38권6호
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• pp.450-455
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• 2005

Objective : Pituitary apoplexy is a rare clinical syndrome caused by pituitary hemorrhage, hemorrhagic infarction, or ischemic infarction within a pituitary tumor or surrounding structure. We analyzed surgical outcomes of pituitary apoplexy. Methods : From 1995 to 2004, we reviewed our experience of 29 cases with pituitary apoplexy. In all patients, pre- and postoperative clinical presentation were checked and endocrine study were performed. Results : The most frequent symptoms were visual disturbance [24 cases, 82.8%] and headache [22 cases, 75.9%]. After surgery, headache improved in 86.4%, 88.9% among 18cases who had preoperative reduction in visual acuity and 75.0% among 12 cases who had preoperative reduction in visual field improved. In endocrine study, long-term steroid and thyroid hormone replacement therapy was necessary in 42.9% of 14 cases presenting preoperative hypopituitarism. Postoperative transient hypopituitarism developed in 5 cases [33.3%] and they all recovered in follow up study. Postoperative endocrinological recovery were in 77.9% of 9 cases with preoperative prolactinoma, 1 case in 2 cases with acromegaly and one case with Cushing disease. Postoperative complications were diabetes inspidus[DI] in 1 case [3.4%]. cerebrospinal fluid[CSF] leakage in 2 cases [6.8%] and death in 1 case [3.4%] due to sepsis, Conclusion : We report good results through surgery of pituitary apoplexy in a clinical and endocrine outcomes. The surgery should be performed as soon as possible to be a suitable method for treating pituitary apoplexy.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.101-108
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• 1998

We investigated the effect of ${\alpha}-subunit$ of the stimulatory GTP-binding protein ($G{\alpha}_s$) gene mutation on the expression of the thyrotropin-releasing hormone (TRH) receptor (TRH-R) gene in GH3 cells and in growth hormone (GH)-secreting adenomas of acromegalic patients. In the presence of cyclohexicmide, forskolin and isobutylmethylxanthine, cholera toxin, and GH-releasing hormone (GHRH) decreased rat TRH-R (rTRH-R) gene expression by about 39%, 43.7%, and 46.7%, respectively. Transient expression of a vector expressing mutant-type $G{\alpha}_s$ decreased the rTRH-R gene expression by about 50% at 24 h of transfection, whereas a wild-type $G{\alpha}_s$ expression vector did not. The transcript of human TRH-R (hTRH-R) gene was detected in 6 of 8 (75%) tumors. Three of them (50%) showed the paradoxical GH response to TRH and the other three patients did not show the response. The relative expression of hTRH-R mRNA in the tumors from patients with the paradoxical response of GH to TRH did not differ from that in the tumors from patients without the paradoxical response. Direct PCR sequencing of $G{\alpha}_s$ gene disclosed a mutant allele and a normal allele only at codon 201 in 4 of 8 tumors. The paradoxical response to TRH was observed in 2 of 4 patients without the mutation, and 2 of 4 patients with the mutation. The hTRH-R gene expression of pituitaty adenomsa did not differ between the tumors without the mutation and those with mutation. The present study suggests that the expression of TRH-R gene is not likely to be a main determinant for the paradoxical response of GH to TRH, and that $G{\alpha}_s$ mutation may suppress the gene expression of TRH-R in GH-secreting adenoma. However, a certain predisposing factor(s) may play an important role in determining the expression of TRH-R.

• Journal of Korean Neurosurgical Society
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• 제29권6호
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• pp.754-762
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• 2000

Objectives : The surgical results of 80 patients with growth hormone(GH)-producing pituitary adenoma were analyzed retrospectively to evaluate the clinical manifestations and to determine which preoperative factors significantly influenced the surgical outcome. Patients and Methods : The patients consisted of 39 men and 41 women and the age of patients at the time of initial operation ranged from 17 to 67 years(mean age, 40.5 years) Between January 1990 and June 1996, 77 patients underwent transsphenoidal surgery and 3 patients underwent craniotomy for GH-producing pituitary adenoma at our institution. Preoperative administration of octreotide was performed in 18 patients. Surgical control was defined as a postoperative serum basal level of GH less than 5ng/ml. A logistic regression model was used for univariate and multivariate analysis. Probability value of less than 0.05 was considered as statistically significant. Results : The most common presenting symptom was acromegaly, followed by headache, visual disturbance, and fatigability. Visual symptoms were present in 39% of the patients. Diabetes mellitus was associated in 24 patients and hypertension in 12. Preoperative mean basal level of GH was 93.2ng/ml(range 72-500ng/ml) which was closely related with tumor size(p<0.05). Grade II by Hardy's classification was the most common radiological type. Preoperative octreotide treatment significantly reduced the level of GH(p<0.05), but not enough to induce endocrinological remission. One patient died of cerebral infarction after craniotomy. The most common surgical complication was transient diabetes insipidus. The symptom of the earliest improvement after surgery was paresthesia and tightness of the hand and foot, followed by headache and easy fatigability. The preoperative visual symptom was improved in all patients. The patients who had hypertension or DM experienced alleviated symptoms in 67% and 92%, respectively. The overall rate of endocrinological remission was 44%. By multivariate logistic regression analysis, the size of tumor, extrasellar extension, and extent of removal were significant prognostic factors for endocrinologial remission. Conclusion : Early detection of a small tumor without extrasellar extension followed by a complete resection is highly recommended in order to achieve endocrinological cure of GH-producing pituitary adenomas.

• 대한핵의학회지
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• 제6권1호
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• pp.25-32
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• 1972

The plasma HGH concentrations were assayed in total 138 cases by the radioimmunoassay. The groups of control, typhoid fever, epidemic hemorrhagic fever, tuberculous meningitis and other febrile diseases were studied, also were the groups of hyperthyroidism, acromegaly and hypopitutarism. Insulin stimulation test was performed in control, typhoid fever and hypopituitarism. In the control group, the plasma HGH concentration in fasting (early morning) was $2.06{\pm}1.183m{\mu}g/ml$ and its upper limit was $4.5m{\mu}g/ml$. No sexual difference was observed. By the insulin stimulation, plasma HGH concentration had rised to the peak level of $24.1{\pm}15.71m{\mu}g/ml$, 60 min. after the intravenous insulin injection, then decreased to the normal level progressively. In typhoid fever, fasting HGH concentrations in febrile state and in defeverence were $2.5{\pm}1.35m{\mu}g/ml\;and\;2.2{\pm}3.32m{\mu}g/ml$ respectively, showing no significant difference with the control group. However, the levels of individual cases ranged widely, conpared with the control group. The response to the insulin stimulation test was similar to the control group. In epidemic hemorrhagic fever the HGH concentrations in oliguric phase, in diuretic phase and in convalescence were $4.2{\pm}3.71m{\mu}g/ml,\;2.2{\pm}1.30m{\mu}g/ml\;and\;3.4{\pm}3.01m{\mu}g/ml$ respectively. No significant differences were observe compared to the control, but they showed wide range of plasma HGH levels. In tuberculous meningitis, the fasting HGH concentration was $2.9{\pm}1.42m{\mu}g/ml$. In the other febrile diseases, the value was $2.5{\pm}2.23m{\mu}g/ml$. In 4 cases of hypopituitarism, the fasting HGH concentration was $2.3{\pm}0.42m{\mu}g/ml$ and ranged normally. However, the response to the insulin stimulation test was not observed. Very high plasma HGH concentrations were observed in acromegalic patients.