No abstract available.
Diabetes Mellitus, Type 2*

PURPOSE: Adults with GH deficiency(GHD) have abnormal body composition, reduced physical performance, altered lipid metabolism, increased cardiovascular diseases, and reduced quality of life. Administration of GH to these patients reduce clinical abnormalities to normal ranges. Therefore, patients with childhood-onset GHD might need to continue GH replacement after the attainment of final height. Recently studies have shown that a high proportion of patients with childhood-onset GHD are no longer GHD when retested at young adult. METHODS: GH secretion was reevaluated with insulin and clonidine after completion of GH treatment in 29 young adult patients(21.3+/-2.8 yrs, 17 men, 12 women) with childhood-onset GHD diagnosed at a mean age of 11.4+/-3.5 yr. The mean duration of GH treatment was 3.7+/-3.0 yrs. Eleven(11 men) with idiopathic patients presented in 2(18%) isolated GHD and 9(82%) in multiple pituitary hormonal deficiencies. Eighteen(6 men, 12 women) with organic patients presented in 4(22%) isolated GHD and 14(88%) in multiple pituitary hormomal deficiencies, which was caused from craniopharyngioma, germinoma & other lesions. Blood sampling were done as usual method for checking LH, FSH and TSH concentration after injection of gonadotropin releasing hormone & thyrotropin releasing hormone. Serum cortisol levels were also checked after insulin injection and all hormonal concentrations were measured with radioimmunoassay method. Total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein(LDL)-cholesterol concentrations were measured by standard techniques. Bone density was measured in the level of lumbar spine and femur with DEXA. M-mode, two-dimensional and pulsed Doppler echocardiographic studies were performed. Quality of life was assessed from Beck depression inventory questionnaire with age-matched control. RESULTS: All patients with idiopathic and organic GHD were confirmed as GHD through combined pituitary function retesting at young adult. The additional pituitary hormonal deficiencies were increased in numbers. Their total cholesterol and triglyceride levels were increased especially in patients with organic GHD. There were no specific abnormal findings in echocardiographic findings compared to normal reference. Bone density with DEXA showed osteopenia(T score <-1) was found in 20/24(83%) and osteoporosis(T score <-2.5) in 8/24(33%) in young adult GHD. Quality of life was evaluated with BDI questionnaire and showed mild depression in 32% and moderate to severe depression in 11%. CONCLUSION: 82% of patients with idiopathic and 88% of organic GHD have additional pituitary hormonal deficiencies in childhood, showing multiple pituitary hormonal deficiencies rather than isolated GHD and has GHD permanently in all young adults with idiopathic and organic GHD and that is a little different findings from other foreign reports and needs to follow up in future.
Adult ; Body Composition ; Bone Density ; Cardiovascular Diseases ; Cholesterol ; Clonidine ; Craniopharyngioma ; Depression ; Echocardiography ; Femur ; Germinoma ; Gonadotropin-Releasing Hormone ; Humans ; Hydrocortisone ; Insulin ; Lipid Metabolism ; Lipoproteins ; Male ; Quality of Life ; Surveys and Questionnaires ; Radioimmunoassay ; Reference Values ; Spine ; Thyrotropin-Releasing Hormone ; Triglycerides ; Young Adult*

PURPOSE: This study is designed to find out the clinical characteristics, growth status, and response to growth hormone treatment in children with organic growth hormone deficiency(GHD) after treatment of brain tumors. METHODS: Fifty-three children with organic GHD were evaluated for pituitary function, serum insulin-like growth factor-1(IGF-1), and insulin-like growth factor binding protein-3(IGFBP-3) concentrations. We also observed their growth status and corresponding change with or without growth hormone treatment. RESULTS: The causes of organic GHD were craniopharyngioma(47%), germinoma (19%), and medulloblastoma(17%), and 18 children(35%), diagnosed with brain tumors, presented with symptoms suggesting hormonal deficit. Initial height was -2.5+/-.2 SDS in craniopharyngioma, -1.7+/-.1 SDS in germinoma, and -2.1+/-.6 SDS in medulloblastoma, and children with craniopharyngioma showed the highest obesity rate, at 21.4+/-9.3%. After treatment for brain tumors, children with craniopharyngioma had the lowest values of peak GH, IGF-1, and IGFBP-3 concentrations, which were 1.1+/-.3 ng/mL, 74.1+/-6.6 ng/mL(-1.7+/-.2 SDS), and 1.9+/-.0 mg/L(-2.0+/-.1 SDS) respectively. The numbers of deficient hormones increased from 2.4+/-.1 to 3.2+/-.2 after treatment of brain tumors(P<0.05). Nine children showed normal or accelerated growth velocity(growth velocity 7.0+/-.8 cm/yr) without GH replacement and they had higher body mass index(BMI), IGF-1 concentrations, and IGFBP-3 SDS(P<0.05) compared to the others(growth velocity 1.9+/-.9 cm/yr). Height SDS increased every year during the first three years of GH treatment(P<0.05), 0.5+/-.4 SDS(n=20) for the first year, 0.4+/-.4 SDS(n=14) for the second, and 0.3+/-.5 SDS(n=11) for the third, and it increased by 1.1+/-.9 SDS(n=11) in total. CONCLUSION: The numbers of deficient pituitary hormones were increased after operation, irradiation, and/or chemotherapy. Children with GHD showed good response to GH replacement. Some children grew normally in spite of growth hormone deficiency, and their BMI, serum levels of IGF-1 and IGFBP-3 SDS were increased compared to those of the decreased growth group. This study suggests that further studies are needed to determine the mechanism of growth with low GH concentrations.
Brain Neoplasms* ; Brain* ; Child* ; Craniopharyngioma ; Drug Therapy ; Germinoma ; Growth Hormone* ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Medulloblastoma ; Obesity ; Pituitary Hormones

PURPOSE:Craniopharyngioma is one of the most common causes of organic growth hormone deficiency leading to pituitary hormonal insufficiency. However, some growth hormone(GH)-deficient children with craniopharyngioma may grow normally or even show accelerated growth. This study was designed to evaluate several factors associated with growth of patients with craniopharyngioma. METHODS:Forty children operated on for craniopharyngioma were evaluated for their pituitary function, serum insulin like growth factor-I(IGF-I), serum insulin like growth factor binding protein-3(IGFBP-3) and serum prolactin levels. We also observed their growth status and corresponding changes with or without GH treatment. RESULTS:Among 40 patients, one had normal pituitary hormonal status and one had isolated GHD(GH deficiency). The other patients showed multiple pituitary hormone deficiency including GH(98%), LH, FSH(75%), TSH(65%), ACTH(62%), and ADH(38%) deficiencies. Patients with GHD were categorized into 2 groups. Group 1 consisted of children who showed normal growth, thus had not received GH treatment(n=14) and Group 2, those who showed subnormal growth(n=25). Patients in Group 2 were subdivided into Group 2A, when the patients had not received GH treatment in spite of subnormal growth(n=9) and Group 2B, when GH treatment had been added later on(n=16). There were no differences in the age at diagnosis of GHD, initial height standard deviation score(Ht SDS), body mass index(BMI), peak GH concentration between Group 1 and Group 2. Height velocities in Group 1, 2A, and 2B were 8.1+/-.2 cm/yr, 2.4+/-.2 cm/yr, 2.7+/-.2 cm/yr during the first year of endocrinologic follow-up, 7.1+/-.8 cm/yr, 1.2+/-.1 cm/yr, 7.6+/-.7 cm/yr during the second year, 5.9+/-.0 cm/yr, 2.8+/-.9 cm/yr, 7.3+/-.7 cm/yr during the third year, respectively. BMI changes during the first year of endocrinologic follow-up and postoperative prolactin levels were not significantly different between Group 1 and Group 2A. Postoperative IGF-I and IGFBP-3 levels in Group 1 were significantly higher than those in Group 2A(P<0.05). Both IGFBP-3 and prolactin levels correlated significantly with height velocity in Group 1 and 2A(P=0.004 r=0.64 and P= 0.035 r=0.74 , respectively). CONCLUSION: In this study, growth in children with craniopharyngioma was likely to be associated with IGF-I, IGFBP-3 and prolactin levels. Further studies are needed to unravel other growth promoting factors related to GH independent growth.
Child* ; Craniopharyngioma* ; Diagnosis ; Follow-Up Studies ; Growth Hormone ; Humans ; Insulin ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Prolactin

PURPOSE: Ginseng has been reported to reduce blood glucose levels in diabetic animals and patients, and it is also reported to slow the aging process by acting as an anti-atherosclerotic agent or as an anti-oxidant. This study was designed to investigate whether ginseng and irbesartan can prevent the development of diabetic nephropathy in streptozotocin-induced diabetic rats. METHODS: Diabetes was induced in 7 week-old male Sprague-Dawley rats by intravenous injection of 60 mg/kg streptozotocin. Ginseng(1 g/kg/day) or irbesartan (20 mg/kg/day) was given to diabetic rats for 25 weeks. Blood glucose and body weight were checked weekly and urinary albumin excretion was evaluated every 6 weeks. At the end of the experiment, the kidneys were weighed and sliced for microscopic examination. Glomerular size and hyaline deposition were measured on light microscopy(on Masson' trichrome stain and PAS stain) and thickness of glomerular basement membrane(GBM) on electron microscopy. Renal histologic findings of ginseng or irbesartan treated rats were compared with those of normal control and diabetic control groups. RESULTS: The weight gain in diabetic rats was significantly reduced, and the final body weight of diabetic rats was lower than that of normal control rats. There was no significant difference in body weights between the diabetic control, ginseng, and irbesartan treated groups. Mean levels of blood glucose were significantly increased in diabetic rats compared to normal rats, but there was no significant difference in blood glucose among the three groups of diabetic rats. Urinary albumin excretion was increased in the diabetic groups compared to the normal control group, and it was significantly decreased in the irbesartan treated group compared to the diabetic control group at 13th week of treatment. At the end of the experiment, the kindeys of the diabetic rats were examined and showed significantly enlarged than those of the normal rats, and the ratio of kidney weight to body weight was decreased in the ginseng treated group compared to the diabetic control and irbesartan treated group. There was no significant difference in the size of glomerulus, the thickness of GBM, and glomerular hyaline deposition among the three diabetic groups. CONCLUSION: There was no significant hypoglycemic effect of ginseng in streptozotocin-induced diabetic rats. Renal hypertrophy was relatively milder in the ginseng-treated group, but there was no difference in findings of renal histology between the treatment groups.
Aging ; Animals ; Blood Glucose ; Body Weight ; Diabetic Nephropathies* ; Humans ; Hyalin ; Hypertrophy ; Hypoglycemic Agents ; Injections, Intravenous ; Kidney ; Male ; Microscopy, Electron ; Panax* ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Weight Gain

Skin atrophy is one of the most common side effects of topical steroid use and results from decreased skin proalphaI collagen mRNA production due to specific alterations in collagen gene transcription or from reduced collagen mRNA stability. This report describes a case of a 8 year-old-girl who visited our hospital with a complaint of ambiguous genitalia. She was observed to have atrophic labia majora and atrophic striae resembling scrotal rugae. However, her serum levels of FSH, LH, 17-KS, 17-OHCS, 5-DHT, DHT and DHEA-S were all in normal range and her karyotype was 46,XX. Abdominal and pelvic ultrasonogram showed a normal uterus and ovaries. Careful history taking revealed frequent use of steroid ointment due to vulvar pruritus for 2 years and she was finally diagnosed to have atrophy of external genitalia induced by long-term use of topical steroid.
Atrophy* ; Collagen ; Disorders of Sex Development ; Female ; Genitalia* ; Karyotype ; Ovary ; Pruritus ; Reference Values ; RNA Stability ; RNA, Messenger ; Skin ; Ultrasonography ; Uterus

McCune-Albright syndrome, which consists of cafe-au lait spots, multiple fibrous dysplasia, sexual precocity and endocrinal dysfunction such as pituitary, thyroid and adrenal aberrations, has been increasingly recognized recently. The etiology is now suggested that activating mutations on the gene that encodes the alpha subunit of stimulatory G protein cause McCune-Albright syndrome. The child presented with sexual precocity and elevated estrogen level was still persisted after left oophorectomy and right partial oophorectomy due to misdiagnosed as ovarian granulosa-theca cell tumor. Whole body bone scan revealed abnormal radiotracer uptake on left facial bone and left proximal femur. Facial bone MRI showed marked thickening of facial bone from fibrous dysplasia. And the patient had cafe-au-lait pigmentations on neck and buttock area. Other endocrine function was normal. Pathologic finding of ovary was finally confirmed with cystic follicles. Skull biopsy revealed fibrous dysplasia. And she was finally diagnosed McCune-Albright syndrome.
Biopsy ; Buttocks ; Cafe-au-Lait Spots ; Child ; Estrogens ; Facial Bones ; Female ; Femur ; Fibrous Dysplasia, Polyostotic* ; GTP-Binding Proteins ; Humans ; Magnetic Resonance Imaging ; Neck ; Ovariectomy ; Ovary ; Pigmentation ; Skull ; Thyroid Gland

Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of insulin producing beta cells, and theoretically, it can be cured by replacement of the lost beta cells. The limitations along with successes of pancreas transplantation opened the door for stem cell therapy for T1DM. For clinical application, regenerated beta cells have to show robust glucose-responsiveness to maintain euglycemia. It is also important to protect the new beta cells from autoimmune destruction as well as graft rejection. Studies using embryonic stem cells (ESCs) are encouraging, but there are ethical concerns on destroying human embryo to harvest ESCs. Researches using bone marrow stem cells (BMSCs), induced pluripotent stem cells (iPSCs), umbilical cord blood, pancreatic and hepatic cells are also promising, and they can circumvent the ethical issues on using human ESCs. BMSCs are probably the most promising because of their proven ability to promote the regeneration of beta cells, and immune modulating effect that may prevent autoimmune destruction of beta cells. IPSCs, reprogrammed from skin fibroblasts or spermatogonial stem cells, are also good candidates for stem cell therapy. Although there are major challenges to overcome, with rapid progress of science, stem cell therapy has the potential to realize a permanent cure for T1DM in the future.
Bone Marrow ; Diabetes Mellitus, Type 1 ; Embryonic Stem Cells ; Embryonic Structures ; Fetal Blood ; Fibroblasts ; Graft Rejection ; Hepatocytes ; Humans ; Induced Pluripotent Stem Cells ; Insulin ; Pancreas Transplantation ; Regeneration ; Skin ; Stem Cells

Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of insulin producing beta cells, and theoretically, it can be cured by replacement of the lost beta cells. The limitations along with successes of pancreas transplantation opened the door for stem cell therapy for T1DM. For clinical application, regenerated beta cells have to show robust glucose-responsiveness to maintain euglycemia. It is also important to protect the new beta cells from autoimmune destruction as well as graft rejection. Studies using embryonic stem cells (ESCs) are encouraging, but there are ethical concerns on destroying human embryo to harvest ESCs. Researches using bone marrow stem cells (BMSCs), induced pluripotent stem cells (iPSCs), umbilical cord blood, pancreatic and hepatic cells are also promising, and they can circumvent the ethical issues on using human ESCs. BMSCs are probably the most promising because of their proven ability to promote the regeneration of beta cells, and immune modulating effect that may prevent autoimmune destruction of beta cells. IPSCs, reprogrammed from skin fibroblasts or spermatogonial stem cells, are also good candidates for stem cell therapy. Although there are major challenges to overcome, with rapid progress of science, stem cell therapy has the potential to realize a permanent cure for T1DM in the future.
Bone Marrow ; Diabetes Mellitus, Type 1 ; Embryonic Stem Cells ; Embryonic Structures ; Fetal Blood ; Fibroblasts ; Graft Rejection ; Hepatocytes ; Humans ; Induced Pluripotent Stem Cells ; Insulin ; Pancreas Transplantation ; Regeneration ; Skin ; Stem Cells

Sitosterolemia is an autosomal recessive disorder characterized by increased plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, severe hypercholesterolemia have been reported in patients with sitosterolemia, especially in children. Sitosterolemia is caused by increased intestinal absorption and decreased biliary excretion of sterols resulting from biallelic mutations in either ABCG5 or ABCG8, which encode the sterol efflux transporter ABCG5 and ABCG8. Patients with sitosterolemia show extreme phenotypic heterogeneity, ranging from almost asymptomatic individuals to those with severe hypercholesterolemia leading to accelerated atherosclerosis and premature cardiac death. Hematologic manifestations include hemolytic anemia with stomatocytosis, macrothrombocytopenia, splenomegaly, and abnormal bleeding. The mainstay of therapy includes dietary restriction of both cholesterol and plant sterols and the sterol absorption inhibitor, ezetimibe. Foods rich in plant sterols include vegetable oils, wheat germs, nuts, seeds, avocado, shortening, margarine and chocolate. Hypercholesterolemia in patients with sitosterolemia is dramatically responsive to low cholesterol diet and bile acid sequestrants. Plant sterol assay should be performed in patients with normocholesterolemic xanthomas, hypercholesterolemia with unexpectedly good response to dietary modifications or to cholesterol absorption inhibitors, or hypercholesterolemia with poor response to statins, or those with unexplained hemolytic anemia and macrothrombocytopenia. Because prognosis can be improved by proper management, it is important to find these patients out and diagnose correctly. This review article aimed to summarize recent publications on sitosterolemia, and to suggest clinical indications for plant sterol assay.
Absorption ; Anemia, Hemolytic ; Atherosclerosis ; Bile ; Cacao ; Child ; Cholesterol ; Death ; Diagnosis* ; Diet ; Food Habits ; Hemorrhage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Intestinal Absorption ; Margarine ; Nuts ; Persea ; Phytosterols ; Plant Oils ; Plants ; Population Characteristics ; Prognosis ; Splenomegaly ; Sterols ; Triticum ; Xanthomatosis