Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 50 , Issue 6
Showing 1-29 articles out of 29 articles from the selected issue
ORIGINALS
  • Ji-Hyun PARK, Kyung-Pyo KANG, Sung-Joong LEE, Chong-Hwa KIM, Tae-Sun P ...
    2003 Volume 50 Issue 6 Pages 653-656
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Although the spontaneous rupture of adrenal pheochromocytoma is rare, it can be lethal because it can induce serious changes in the circulation. We describe a 32 year old man with bilateral pheochromocyroma presenting as abdominal pain. In the emergency room, an abdominal MRI showed an aneurysmal vessel in the right adrenal mass and accompanying hemorrhage around the tumor capsule. The bleeding site was found by transfemoral abdominal angiography. Coil embolization was done in the bleeding vessels, specifically branches of the right adrenal artery. The hemorrhage was successfully controlled and vital signs of the patient were restored. Following emergency care, biochemical and imaging studies showed compatible findings of a bilateral adrenal pheochromocytoma. Postoperative histologic findings confirmed these observations. A ruptured pheochromocytoma should be considered as a cause of acute abdomen in cases of a concomitant adrenal mass. Intratumoral aneurysmal bleeding may be a cause of ruptured tumor, and careful angiographic intervention will help to ensure safe control of bleeding in such an emergency situation, even in cases of bilateral tumor.
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  • Gurcan KISAKOL, Ahmet KAYA, Sait GONEN, Recep TUNC
    2003 Volume 50 Issue 6 Pages 657-661
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Bone turnover is reported to increase in favour of resorption in overt hyperthyroidism and the rate of resorption is associated with the levels of thyroid hormones. Hypothyroidism, on the other hand, was shown to cause no disturbance of calcium kinetics and found to associate lower trabecular resorption surfaces and increased bone cortical thickness. Similar studies are very rare in subclinical thyroid disorders and consequently we aimed to examine calcium and bone metabolism in subclinical thyroid disorders. Thirteen patients with subclinical hyperthyroidism secondary to untreated Graves' disease, 20 patients with subclinical hypothyroidism and 10 healthy subjects participated in this survey. Briefly calcium, phosphorus, and creatinine (Cre), urinary deoxypyridinoline (U-DPD) and serum osteocalcin (OC) were measured as biochemical markers for calcium metabolism. Concerning serum Ca and phosphorus levels, there were no differences between three of the groups, but urinary Ca excretion was higher in subclinical hyperthyroid patients compared to control and hypothyroid subjects. Hypothyroid patients had similar U-DPD levels with control subjects (p = 0.218). Serum OC and U-DPD were higher in subclinical hyperthyroid compared to control subjects (p<0.001 and p<0.001 respectively). We demonstrated a higher bone turnover and greater calcium excretion in subclinical hyperthyroid patients. Additionally, we found that subclinical hypothyroidism is not associated with disturbed calcium metabolism. As persistent increase in bone turnover is responsible for accelerated bone loss, patients with Graves' disease may have increased risk for osteoporosis.
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  • Nilgun GUVENER, Neslihan Bascil TUTUNCU, Sule AKCAY, Fusun EYUBOGLU, A ...
    2003 Volume 50 Issue 6 Pages 663-667
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    The present study has been conducted to quantify and compare the capacity of gas exchange in patients with type 2 diabetes mellitus (DM) and healthy controls and also to investigate the effects of various factors on alveolar capillary permeability. A total of 37 subjects, 25 patients with DM and 12 healthy controls were recruited for the study. All the participants were evaluated with simple spirometric tests and simple breath carbonmonoxide (CO) diffusion test (DLCO). The ratio of DLCO value to the alveolar ventilation (VA) was used to assess alveolar membrane permeability. Diabetic patients were also evaluated in detail with respect to degenerative diabetic complications including the presence of microalbuminuria, advanced nephropathy, sensorial and autonomic neuropathy, retinopathy, hypertension and macrovascular disease. The results of simple spirometric tests which determined lung capacity were similar in the diabetic patients and the healthy controls. Ratio of DLCO/VA, which determines alveolar membrane permeability, revealed statistically significant decline in pulmonary gas exchange in the diabetic group (p: 0.037). Pearson correlation analysis revealed statistically significant correlation between duration of diabetes mellitus, age and urinary albumin excretion with DLCO/VA values (Pearson: -0.726, p: 0.001; Pearson: -0.438, p: 0.036; Pearson: -0.472, p: 0.023 respectively). This study demonstrated the decreased alveolar gas exchange capacity in diabetic patients compared with healthy controls. Detrimental effects of DM on alveolar capillaries were found to be correlated with age, duration of DM and urinary albumin excretion. Microalbuminuria was the only significant predictor of DLCO/VA.
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  • Takashi MISAKI, Yasuhiro IIDA, Kanji KASAGI, Junji KONISHI
    2003 Volume 50 Issue 6 Pages 669-672
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Objective: Controversy abounds on the issue of seasonal variation in new onset of Graves' disease, partly due to the difficulty of precisely dating the exact start of symptoms. To address the possible relationship between climatic changes and disease activity from a different perspective, we reviewed time of relapse during regular follow-up after successful drug treatment with thionamides. Design: Retrospective analysis of a case series in a university clinic. Patients and measurements: We consecutively registered patients who experienced re-emergence of hyperthyroidism between 1992 and 2001 after successful antithyroid drug therapy. Excluded were subjects with superimposing painless thyroiditis, in postpartum, on immunomodulatory drugs, or off thionamides prematurely on their own volition. Results: Fifty-two patients recurred 2 to 36 months after drug cessation. The frequency was higher in spring and summer (March to August) than in autumn and winter (September to February). With a new coated-tube radioreceptor assay, TSH binding inhibitor immunoglobulin activity was detected in sera from 87.5% of the reworsened patients. Conclusions: Graves' disease tends to relapse more frequently in spring and summer. Further clinical studies are warranted to clarify underlying mechanism (s) for this seasonal variation.
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  • Hiroshi IWAI, Yasuhiro OHNO, Norihiko AOKI
    2003 Volume 50 Issue 6 Pages 673-680
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Adipocytokines and nitric oxide (NO) play important roles in type 2 diabetes; however, the regulatory mechanism has not been fully clarified. To investigate the role of adipocytokines and NO production on insulin resistance in type 2 diabetes, the LETO rats and the OLETF rats were fed a control diet or a high-fat diet for 4 weeks. After 4 weeks the blood levels of leptin, tumor necrosis factor-α (TNF-α), and NO were measured. As an indicator of insulin resistance, the homeostasis model assessment for insulin resistance (HOMA-R) was applied. Food intake in high-fat diet group rats was lower than in control diet group rats. The high fat diet increased body weight (BW), but did not significantly affect the HOMA-R and blood pressure (BP). Leptin and TNF-α levels were significantly higher in the OLETF rats than in the LETO rats, while NO levels did not change between the two groups. The high-fat diet elevated blood leptin levels, but not TNF-α and NO levels. The HOMA-R in the OLETF rats was correlated with leptin, but not with BP, BW, TNF-α or NO. NO showed an inverse correlation with BP. In conclusion, leptin, TNF-α, and NO may each regulate insulin sensitivity through their own unique pathways. The elucidation of the regulatory mechanism of adipocytokines and NO may give a clue to clarify the pathophysiology of insulin resistance.
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  • Yusuke TSUKAMOTO, Tatsuhiko WATANABE, Tetsuo NAKAGAMI, Kaoru MORISHITA
    2003 Volume 50 Issue 6 Pages 681-687
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    The aim of this study was to investigate the effect of daily oral administration of calcitriol on calcium metabolism in Japanese postmenopausal women. For this purpose, we administered 0.5 μg of daily calcitriol to 18 Japanese postmenopausal women for up to 24 weeks. During the first 28 days, daily administration of 0.5 μg of oral calcitriol increased fasting serum 1,25(OH) 2D levels significantly in 9 women (Group B) (p<0.005), while no significant change was seen in another 9 women without calcitriol administration (Group A). The first 28-day calcitriol supplement increased fasting urinary calcium excretion (urinary Ca/Cr) from 0.133 ± 0.072 to 0.171 ± 0.089 (p<0.05) and fractional excretion of calcium (FECa) without changing serum Ca2+. Urinary NTx/Cr excretion, an index of bone resorption, decreased significantly from 64.8 ± 24.5 to 50.3 ± 27.2 nMBCE/mMCr in Group B. Following the 28-day control period, 0.5 μg of oral calcitriol was also administered to women in Group A for another 20 weeks. At the end of the 24-week investigation period, the effects of oral calcitriol on urinary calcium excretion and bone resorption were still significant in both Group A and B. A positive correlation was found between urinary Ca/Cr and NTx/Cr excretion at the start (r = 0.657, p<0.05), but this correlation was lost by calcitriol treatment (r = 0.135). These results indicated that calcitriol supplement was effective in suppressing bone resorption in postmenopausal women, and that an increased fasting urinary calcium excretion due to calcitriol supplement was predominantly caused by increased intestinal calcium absorption in these women.
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  • Barna VÁSÁRHELYI, Péter BENCSIK, András TR ...
    2003 Volume 50 Issue 6 Pages 689-695
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Several data support that adrenal hyperandrogenism affects women with low birth weight (LBW). We also found an association between serum dehydroepiandrosterone (DHEA) and fasting insulin levels. The aim of our study was to detect the acute effects of reactive hyperinsulinemia during oral glucose tolerance test (OGTT) on DHEA(S) levels in LBW men and women. Fifty three men and 47 women (of those, 37 men and 33 women were LBW) were enrolled. DHEA, DHEAS, and insulin levels were measured before and during OGTT. Cortisol was also measured. DHEA/cortisol ratio during OGTT was calculated to analyze the acute effect of hyperinsulinemia on DHEA levels. During OGTT, DHEA and cortisol levels decreased in each individual, independently of gender and birth weight. Serum DHEAS decreased to a minor (but significant) extent only in LBW women (p<0.05). The rate of DHEA/cortisol increased in both gender, independently of birth weight. The increase of the rate of DHEA/cortisol during OGTT was associated with maximal insulin response (r = 0.45, p<0.05) and with the insulinAUC (r = 0.48, p<0.05) in women. Our results suggest that reactive hyperinsulinemia during OGTT might activate the androgen pathway of adrenal cortex including DHEA production. Therefore acute hyperinsulinemia might counterbalance to some extent the diurnal decrease of DHEA during OGTT.
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  • Susumu TANAKA, Ke-ita TATSUMI, Toru TAKANO, Yoshio MURAKAMI, Toshihiro ...
    2003 Volume 50 Issue 6 Pages 697-702
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    A previous study reported a high prevalence of autoantibodies to alpha-enolase in lymphocytic hypophysitis and these antibodies efficiently distinguished lymphocytic hypophysitis from pituitary tumors. To confirm this, we examined autoantibodies to alpha-enolase in patients with lymphocytic hypophysitis (n = 17), pituitary non-functioning adenoma (n = 13), other pituitary diseases (n = 17) and other autoimmune diseases (n = 30), and compared to healthy controls (n = 46). Autoantibodies were found in 41.2%, 46.2%, 23.5%, 20.0% and 4.3%, respectively. Our findings indicate that detection of anti-alpha-enolase antibodies is not suitable for specific diagnosis of lymphocytic hypophysitis.
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  • Yuki NAKATSUJI, Yukihiro NISHIO, Naoyuki TANI, Kazushige ADACHI, Masah ...
    2003 Volume 50 Issue 6 Pages 703-714
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    The trophoblast, an important component of the mammalian placenta, has several essential biological roles in the maintenance of pregnancy. First, trophoblast cells must attach to the uterine endometrium, and then they must invade to a depth at which the vascular network exists. Here, we investigated the effects of epidermal growth factor (EGF) on α2 integrin expression, adhesiveness to collagen, and invasive activity using human BeWo choriocarcinoma cells. EGF induced the expression of α2 integrin mRNA and protein, as shown by Northern blotting, Western blotting, and flow cytometry. Human chorionic gonadotropin (hCG) secretion was enhanced by the addition of EGF, which suggests that the BeWo cells functionally differentiated similarly to normal trophoblasts. EGF also dose-dependently stimulated the invasiveness of BeWo cells. Antibody against α2 integrin inhibited this effect, suggesting that it may be mediated by an increase of cell surface integrin. EGF had no effect on the adhesiveness of BeWo cells to collagen, whereas it stimulated the chemokinetic activity in a dose-dependent manner. The increase of chemokinetic activity was suppressed by antibody against α2 integrin. These results suggest that EGF may induce α2 integrin expression in trophoblast cells, thereby enhancing their invasiveness into the endometrium via an increase of their chemokinetic activity.
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  • Manabu OGURA, Ikuyo KUSAKA, Shoichiro NAGASAKA, Toshimitsu YATAGAI, Sa ...
    2003 Volume 50 Issue 6 Pages 715-721
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered to be a standard therapy for AIMAH, although lifetime replacement of glucocorticoids is necessary after the procedure. This paper describes a subject with AIMAH who underwent unilateral adrenalectomy of the predominantly enlarged gland and subsequently displayed an improvement in insulin resistance and diabetes mellitus, the cardinal symptoms before the operation, concomitant with alleviation of abnormal cortisol secretion. The patient was a 61-year-old man with a body mass index of 25.6 kg/m2. He was diagnosed as having diabetes mellitus, hypertension, and hyperlipidemia at 50 years of age. Eight years after diagnosis, bilateral enlargement of the adrenal glands was revealed by chance upon computed tomography of the abdomen. Typical manifestations of Cushing's syndrome were not demonstrated. Basal levels of serum and urinary cortisol had not increased, although the serum cortisol level displayed no circadian rhythm and no response to the administration of dexamethasone. Despite sulfonylurea treatment, the patient's HbA1C level was as high as 7.6% (normal range 4.3-5.8%). Fasting insulin concentration was increased to 42.6 μU/ml, and the homeostasis model insulin resistance index (HOMA-R) was calculated to be 15.5 (with a normal range of less than 2.5), indicating severe insulin resistance. Unilateral adrenalectomy of the predominantly enlarged gland revealed that the resected gland consisted of multiple nodules of various sizes. Based on endocrinological, radiological, and pathological findings, a diagnosis of AIMAH was made. Ten months after the unilateral adrenalectomy, cortisol circadian rhythms were restored, and serum cortisol concentration was suppressed in response to the administration of low doses of dexamethasone, suggesting an improvement in the cortisol secretory pattern. Levels of HbA1C, fasting insulin, and HOMA-R decreased to 5.7%, 12.7μU/ml, and 2.2, respectively. An improvement in hyperlipidemia was also observed. Insulin resistance and glucose intolerance are recognized as features of mild hypercortisolism. In the present case, unilateral adrenalectomy was effective in ameliorating insulin resistance and improving glycemic control. Unilateral adrenalectomy might be an alternative therapy for improvement of glucose and lipid metabolism in subjects with AIMAH.
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  • Ayhan KOYUNCU, Hatice Sebila DÖKMETAS, Mustafa TURAN, Cengiz AYDI ...
    2003 Volume 50 Issue 6 Pages 723-727
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Extent of thyroidectomy in the management of benign thyroid disease remains controversial. In this clinical study, three different thyroidectomy techniques were compared by means of the complication, short period recurrence and L-thyroxin requirement rates. Two hundred consecutive patients who had bilateral subtotal thyroidectomy (BST) (n = 71), unilateral total lobectomy + contralateral subtotal lobectomy (Dunhill Procedure (DP)) (n = 71), or total thyroidectomy (TT) (n = 58) for benign thyroid disorders were included in this study. One patient was re-operated due to bleeding in BST group. Wound infection was observed in 1 patient both in BST and DP group and 2 patients in TT group. Temporary hypocalcaemia was seen in 14 (19.7%) of BST group, in 19 (26.7%) of DP group, and in 14 (24.1%) patients of TT group (p>0.05). Transient recurrent laryngeal nerve palsy developed in 1 patient both in DP and TT group. One patient of DP group had secondary thyroidectomy due to postoperative diagnosis of papillary carcinoma. There was no significant difference in the mean durations of hospitalization between the groups. Mean postoperative follow-up periods were 27.7 months (6-56), 34.8 months (8-55), 26.5 months (6-54) in BST, DP and TT groups, respectively. While all patients were administered L-thyroxin in TT group, 26 (36.6%) patients in DP group and 34 (47.8%) patients in BST group needed no L-thyroxin supplementation and L-thyroxin requirement rates were not different in either group. We think that total thyroidectomy should be adopted for benign thyroidal diseases, because its complications are no different than those for BST and DP. If individual factors and patient's preference are not in favor of lifelong L-thyroxin supplementation, however, DP may be carried out for benign thyroidal diseases instead of BST.
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  • Hideki YAMASAKI, Tsutomu DOUCHI, Yukihiro NAGATA
    2003 Volume 50 Issue 6 Pages 729-731
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    A 31-year-old regularly menstruating Japanese female was referred to our outpatient clinic by a psychiatrist. She had been diagnosed as having gender identity disorder by detailed counseling and clinical intervention 3 years earlier. After obtaining fully informed written consent, we treated her with 125 mg of testosterone enanthate, intramuscularly, every 2 weeks for 4 months. Serum testosterone levels increased to the normal male value (from 28 to 432 ng/dL). Although menstrual cycle remained regular, her voice became lower after 4 months of therapy. Body weight, body mass index, and lean body mass increased, while body fat mass and percentage of body fat decreased. However, trunk-leg fat ratio did not change during the observation period. During testosterone therapy, a disproportionate increase in lean body mass and decrease in body fat mass are early onset events, while the shift toward upper body fat distribution may be a late onset event along with increase in BMD.
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  • Koji SHIRAISHI, Katsusuke NAITO
    2003 Volume 50 Issue 6 Pages 733-737
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Fertile eunuch syndrome is caused by isolated LH deficiency, but its pathophysiology still remains controversial. We report a case of fertile eunuch syndrome with homozygous Trp8Arg and Ile15Thr mutations in the LH β subunit gene. An 18-year-old man was admitted to our hospital for hypogonadism. Examination of genitalia revealed Tanner G1PH1, whereas both testes were elastically palpated and developed up to 18 ml. Endocrinological evaluations revealed normogonadotropic hypogonadism and there were normal responses after GnRH and hCG stimulation. Intratesticular testosterone concentration was almost normal (1.34 × 103 ng/g). By PCR direct sequencing, homozygous Trp (8) Arg and Ile (15) Thr mutations in exon 2 of LH β were detected. Normal virilization and improved semen parameters were achieved after hCG supplementation. To our knowledge, this is the first case of fertile eunuch syndrome with homozygous Trp (8) Arg and Ile (15) Thr mutations in β subunit of LH gene.
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  • Hyoung Chul OH, Jung-Min KOH, Min Seon KIM, Joong Yoel PARK, Young Kee ...
    2003 Volume 50 Issue 6 Pages 739-744
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Ectopic ACTH syndrome is rarely caused by pheochromocytoma. We report a case of a 28-year-old woman with Cushing's syndrome due to ACTH-producing adrenal pheochromocytoma. She had delivered preterm baby at 32nd week of gestation with `severe preeclampsia'. After delivery, persistent hypertension accompanied by severe headache led her to being misdiagnosed as Cushing's syndrome due to right adrenal adenoma (normal plasma ACTH level) and cerebral vasculitis of unknown etiology. She was referred to our hospital for surgical treatment. Repeated biochemical studies suggested coexistence of ectopic ACTH syndrome and pheochromocytoma. To reverse her clinical deterioration, right total and left subtotal adrenalectomy was performed with presumptive diagnosis of 1) right adrenal pheochromocytoma causing ectopic ACTH syndrome or 2) coexistence of ACTH-dependent Cushing's syndrome and right adrenal pheochromocytoma. Pathologic examination of right adrenal mass revealed pheochromocytoma which showed strong immunostaining for ACTH. Plasma ACTH and urinary cortisol excretion normalized after surgery, but she succumbed to multiple cerebral infarcts and disseminated intravascular coagulation. Pregnancy and inappropriately low plasma ACTH at initial evaluation might have hampered early diagnosis. To our knowledge, this is the first description of a case with ectopic ACTH syndrome due to pheochromocytoma associated with pregnancy.
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  • Kazue OMORI, Kaoru NOMURA, Satoru SHIMIZU, Nariko OMORI, Kazue TAKANO
    2003 Volume 50 Issue 6 Pages 745-752
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Patients with adrenal insufficiency have a life-threatening risk of adrenal crisis, thus preventing adrenal crisis is an important clinical issue. In order to clarify the risk factors for adrenal crisis, the medical records of 137 patients with established adrenal insufficiency were retrospectively investigated. The explanatory variables analyzed were gender, etiology of hypoadrenalism, class of adrenocortical hormone replaced, duration of steroid replacement, age at time of survey, age at time of diagnosis of hypoadrenalism, state of other hormone deficiencies (growth hormone and sex steroids), diabetes insipidus, and mental disorder. Diagnosis of adrenal crisis was based on physical and laboratory findings. Forty (29%) of the 137 patients had at least one episode of adrenal crisis. Based on the Akaike Information Criterion (AIC), steroid replacement therapy of more than 4 yrs' duration was the largest single contributor to the occurrence of an adrenal crisis, followed by mental disorder and sex steroid deficiency. In the subclass of patients with secondary adrenal insufficiency (N = 115), sex steroid deficiency was the greatest risk factor. Patients with untreated hypogonadism had a significantly higher relative risk of 3.70 (95% confidential interval: 1.71-7.98) compared to those without hypogonadism or with treated hypogonadism. Furthermore, among patients with hypogonadism aged younger than 50 yrs, those treated with sex hormone (5/51: 10%) suffered less frequently from adrenal crisis than those untreated (7/11: 64%, p = 0.0004). In conclusion, the present study has, for the first time, clarified the risk factors of adrenal crisis. Among them, sex hormone deficiency has an especially important implication because it can be treated by hormone replacement therapy with the hope of reducing the risk of adrenal crisis.
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  • Kazunori KAGEYAMA, Takako MORIYAMA, Naomi HIZUKA, Satoru SAKIHARA, Shi ...
    2003 Volume 50 Issue 6 Pages 753-758
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    We describe a rare case of hypoglycemia associated with a high molecular weight form of insulin-like growth factor II (big IGF-II) produced during the development of malignant fibrous histiocytoma (MFH). A 66-year-old man was referred to our department for further evaluation of hypoglycemia. At the age of 59, he had been diagnosed as having a MFH in the retroperitoneum, and underwent incomplete resection of the tumor. He had no symptoms of hypoglycemia at that time. Within the last few years, he developed symptoms of hypoglycemia in the early morning. Computerized tomography scans of the abdomen showed multiple tumors around the peritoneum and the liver. Serum insulin levels were decreased although no other hormonal deficiencies were observed. Serum IGF-II levels were elevated as a result of big IGF-II production. Taken together, these results indicated that hypoglycemia in this patient was associated with the production of big IGF-II by the MFH. The most effective therapeutic modality in patients with non-islet cell tumor hypoglycemia is resection of the tumor. In our case, as complete resection was impossible, dexamethasone and glucagon were administered and proved to be effective for preventing hypoglycemia.
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  • Yoshio MURAKAMI, Yuzuru KATO
    2003 Volume 50 Issue 6 Pages 759-765
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Dyslipidemia and obesity are common in adult patients with hypopituitarism. Possible contributions of age, sex and hormone deficiencies to hypercholesterolemia and obesity in adult hypopituitary patients were analyzed in 1, 272 Japanese cases based on a database of a national survey on adult hypopituitarism. In patients on routine hormone replacement therapy, 30.5% of male and 40.7% of female subjects were considered hypercholesterolemic. In univariate analysis, hypercholesterolemia was more prevalent in female, aged, untreated Gn-deficient and TSH-deficient groups. In multivariate analysis, sex of female, age older than 40 yr and TSH deficiency were the independent contributing factors to hypercholesterolemia. Obesity (body mass index (BMI) ≥25 kg/m2) was more prevalent in male, TSH-deficient and ADH-deficient groups. Severe obesity (BMI ≥30) was observed in high prevalence in the youngest group. These findings suggest that hypercholesterolemia and obesity were prevalent in different age and gender groups in Japanese adult patients with hypopituitarism. Insufficient replacement of thyroid hormone and possibly gonadotropin deficiency might contribute to hypercholesterolemia. In contrast, hypothalamic dysfunction as well as hormone deficiencies might play roles in obesity in these patients.
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  • Michiaki ABE, Kouki MORI, Ken-ichi NAGAI, Sadayoshi ITO
    2003 Volume 50 Issue 6 Pages 767-770
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    We describe a patient with right adrenal tumor detected incidentally. The tumor was diagnosed as pheochromocytoma by endocrinological and radiological studies, and was removed surgically. Graves' disease, which had been in remission for more than two decades after discontinuation of antithyroid drug treatment, relapsed during preoperative evaluation of pheochromocytoma when the patient was treated with α-and β1-adrenergic antagonists. Administration of methimazole resulted in a rapid improvement of thyroid function and the patient remained euthyroid on small doses of methimazole. This case may suggest possible involvement of excessive catecholamine secretion and β2-adrenergic receptor activation by pheochromocytoma in the relapse of Graves' disease.
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  • Yi-Ming MU, Koichi OBA, Toshihiko YANASE, Takeshi ITO, Kenji ASHIDA, K ...
    2003 Volume 50 Issue 6 Pages 771-781
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [3H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21WAF1/CIP1 -dependent and -independent.
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  • Keiko HOMMA, Tomonobu HASEGAWA, Masami MASUMOTO, Eiko TAKESHITA, Kiyoa ...
    2003 Volume 50 Issue 6 Pages 783-792
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Urinary steroid profile analysis using gas chromatography/mass spectrometry (GC/MS) has been reported for the diagnosis of abnormal steroidogenesis in newborn infants with some success. We tried to establish the reference values of 63 urinary steroids in Japanese newborn infant, using GC/MS in selected ion monitoring (SIM) that utilizes two characteristic mass ions for each steroid for definitive identification. We studied 36 healthy full-term newborn infants (1-56 days of age) on spot urine samples to define the reference values (mg/g creatinine, median and 10-90 percentile range) and to investigate the possible difference between daytime and nighttime levels. We also studied 23 healthy adult females (20-24 years of age) on 24-hour-urine for the comparison of the reference values of newborn infants. Fifty metabolites of DHEA, pregnenolone, 17-hydroxypregnenolone, androstenedione, progesterone, 17-hydroxyprogesterone, 21-deoxycortisone, corticosterone, 18-hydroxycorticosterone, aldosterone, 18-hydroxycortisol, 11-deoxycortisol, cortisone, cortisol, and estrogen in each infant were measurable without interference, but 13 metabolites of 11-hydroxyandrostenedione, pregnenolone, 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, 21-deoxycortisol, 11-deoxycortisol and cortisol were unmeasurable in each infant due to the interference of fetal cortex steroids as confirmed by abnormal peak area ratios of two mass ions. All 63 metabolites in each control adult were measurable without interference. 16α-, 16β-, and 15β-hydroxy metabolites of 3β-hydroxy-5-en-steroids, and 6β-, 18-hydroxy and 11-oxo-metabolites of corticosteroids were significantly higher in full-term newborn infants than those in adults as previously reported. Urinary steroids showed little circadian variation in the newborn infants, indicating that spot urine can substitute for 24-hour urine.
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NOTES
  • Anil BHANSALI, Bhawani S SHARMA, Polupoina SREENIVASULU, Paramjit SING ...
    2003 Volume 50 Issue 6 Pages 793-799
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    The McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies including growth hormone (GH) excess. Polyostotic bone lesions and café-au-lait macules are common while monostotic bone lesions are rare. Similarly, acromegaly as a manifestation of endocrine hyperfunction with MAS is uncommon and in most of the instances somatotropinoma has not been documented. We report 3 patients, two of them had monostotic lesion, none had café-au-lait macules and all had GH secreting pituitary macroadenoma. All of them underwent transfrontal pituitary adenomectomy and had histopathological confirmation of GH secreting pituitary adenoma. A brief review of literature is also presented.
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  • Seikoh NISHIDA, Tamaki SASAKI, Hisashi KIMURA, Junji TANAKA, Tsutomu N ...
    2003 Volume 50 Issue 6 Pages 801-807
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    In normal New Zealand white rabbits, immunization with rabbit lung ACE (angiotensin converting enzyme) induced atherosclerotic retinal changes, and glomerular changes similar to those seen in diabetic nephropathy. Also, in genetically diabetogenic rats, immunization with the rabbit lung ACE induced diabetic nephropathy and retinopathy.
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  • Masashi MIYAKOSHI, Kyuzi KAMOI, Shinichi UCHIDA, Sei SASAKI
    2003 Volume 50 Issue 6 Pages 809-814
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    We describe a case of a novel mutant vasopressin 2 receptor (V2R)-dependent nephrogenic diabetes insipidus (NDI) with bilateral non-obstructive hydronephrosis in a middle aged man. This could be distinguished from aquaporin 2 (AQP2)-dependent NDI by the response of factor VIII and von Willebrand factor (vWF) to 1-deamino-8-D-arginine vasopressin (DDAVP) administration. A 47-year-old man was admitted to hospital because of polyuria, which had been present from infancy and was suspected of causing non-obstructive hydronephrosis. His mother's father, the older brother of his mother and his second daughter also all had polyuria. Sodium concentration, osmolality and vasopressin in blood were high, while sodium concentration and osmolality in urine were low. There were no changes in urine osmolality, factor VIII and vWF in response to DDAVP infusion. Neither was heart rate, diastolic blood pressure nor facial flushing affected. These findings suggested this case was V2R-dependent NDI rather than AQP2-dependent NDI. Molecular genetic analysis demonstrated that the patient had a V2R missense mutation involving a substitution of cysteine for arginine at position 104 (R104C) located in the first extracellular loop of the V2R. It was also found that the patient's mother and his second daughter were heterozygous for this R104C mutation.
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  • Nuri KAMEL, Vedia TONYUKUK, Rifat EMRAL, Demet ÇORAPÇIOG ...
    2003 Volume 50 Issue 6 Pages 815-823
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    Late onset congenital adrenal hyperplasia (LO CAH) can be seen in association with polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). The study aimed to find out the prevalence of LO CAH in Central Anatolia among hirsute women. Sixty-three patients with hirsutism were evaluated to determine the frequency of LO CAH by comparing them with their age and body mass index matched 28 healthy controls. Of those 63 hirsute women, 43 were diagnosed as PCOS, and 20 were diagnosed as IH. Following basal hormonal evaluation, all subjects underwent ACTH stimulation test and ACTH stimulated 17-hydroxyprogesterone (17-OH P), 11-desoxycortisol (11-DOC), cortisol (F), and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in all subjects. ACTH stimulated 17-OH P, 11-DOC, and DHEA-S levels did not differ between groups. However, stimulated F levels were found to be higher in hirsute women (p<0.001). Six out of 63 (9.52%) patients with hirsutism met the criterion for 21 hydroxylase deficiency. We found no subject presumed to have 11-β hydroxylase deficiency, but one subject in control group (3.57%) and two patients among PCOS subjects (4.65%) had exaggerated DHEA-S response which was suggestive of mild 3-β hydroxysteroid dehydrogenase deficiency. In conclusion, the most frequent form of LO CAH seems to be due to 21 OH deficiency among women with PCOS and IH in Central Anatolia. Mild 3-β HSD deficiency may also be an underlying cause for hirsutism and it may be seen without any clinical presentation. Adrenal hyperactivity is likely to be the main reason of hyperandrogenemia in women with hirsutism.
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  • Kanae NISHIMURA, Toshihiro TAKAO, Tomoko MIMOTO, Akinori MATSUMORI, At ...
    2003 Volume 50 Issue 6 Pages 825-829
    Published: 2003
    Released: December 27, 2003
    JOURNALS FREE ACCESS
    We report a case of anterior hypopituitarism showing recurrent pituitary mass associated with central diabetes insipidus. A 76-year old woman was hospitalized with general fatigue and 5 kg body weight loss. Endocrinological examinations and pituitary provocative tests demonstrated hypopituitarism and central diabetes insipidus. T1-weighted image of magnetic resonance imaging (MRI) revealed an intrasellar cystic mass with ring enhancement suggesting pituitary abscess. MRI films subsequently obtained from another hospital and studied retrospectively showed intrasellar cystic mass with ring enhancement 4 years earlier, and a mass shape that was decreased after 2 years. Over the subsequent years, the patient has remained asymptomatic with hormone replacement therapy only. Cystic pituitary adenoma or Rathke's cleft cyst with repeated infection may be involved in the repeated change of pituitary mass shape although neither pituitary surgery nor a pituitary biopsy was performed because of the patient's age and condition. It is reported that apparent recurrence of Rathke's cleft cysts after initially successful surgery was higher than suggested by previous reports, and that long-term follow-up with pituitary imaging and neuroophthalmological assessment is essential. Careful evaluation by follow-up brain MRI is needed in the present case to prevent future recurrence of pituitary abscess.
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