[Show abstract][Hide abstract] ABSTRACT: In addition to impaired physical activity, adult GH deficiency (GHD) can decrease quality of life (QOL). Hence, assessment of QOL is important to evaluate the efficacy of GH replacement therapy. This study aimed to identify factors that may be predictive of long-term improvement in QOL among clinical/laboratory variables during GH replacement therapy. The analysis included 83 Japanese adults with GHD who participated in the Hypopituitary Control and Complications Study (HypoCCS). Correlations between the change from baseline in clinical/laboratory variables at 6 months and the change from baseline in Quality of life (Short-Form 36 [SF-36] component scores) at 12 months were examined. Unexpectedly, all component scores were negatively correlated with the change in fasting plasma glucose concentration (FPG) (physical component summary [PCS], r = -0.456; mental component summary [MCS], r = -0.523; role/social component summary [RCS], r = -0.433). The change in MCS was positively correlated with the change in insulin-like growth factor-1 standard deviation score (IGF-1 SDS) (r = 0.417). The change in PCS was positively correlated with the change in body fat (r = 0.551). The change in RCS was positively correlated with the change in waist circumference (r = 0.528). Short-term changes in several clinical/laboratory variables, most notably FPG and IGF-1 SDS, were correlated with long-term changes in QOL. The clinical importance of these correlations for predicting GH replacement treatment efficacy warrants further investigation.
[Show abstract][Hide abstract] ABSTRACT: Table 3 contains some typographical errors. Median (IQR) of FT4 should be median (5-95th percentile) and the median (IQR) values of TSH are replaced with median (5-95th percentile) values.
No preview · Article · Jan 2014 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: This large-scale observational study examined the long-term effectiveness and safety of growth hormone (GH) replacement therapy for adult GH deficiency (GHD) in Japanese clinical practice using the Hypopituitary Control and Complications Study database. The study included 402 GHD patients for safety analyses and a subset of 209 patients (149 adult-onset and 60 childhood-onset GHD patients) who had not previously received GH replacement therapy for the efficacy analyses. Data on clinical, metabolic, quality of life (QoL) characteristics, and all adverse events (AEs) were collected at baseline (start of GH treatment), 6 months, 1 year and 2 years. Over the observation period, there were improvements from baseline in insulin-like growth factor-I standard deviation scores (P < 0.001), although the changes in metabolic parameters were minimal. QoL (Short Form-36) Z-scores significantly increased from baseline in both onset-type groups for several subscale domains (P < 0.05). A total of 145 (36.1%) patients experienced ≥1 AE. Common AEs were hyperlipidaemia (2.7%) and hyperinsulinaemia (2.2%). Some patients experienced recurrent hypothalamic/pituitary tumour (events per 1000 patient-years: 2.78), new benign (0.93), malignant tumour (10.28) or other new tumour (0.93), new diabetes mellitus (7.45), and new stroke (3.71). Seven patients died during the observation period. Our safety findings are inconclusive about the associations between GH replacement and AEs, although the incidence of diabetes mellitus and cardiovascular events are similar to those reported in the Japanese general population. In conclusion, the key beneficial effects of GH replacement therapy for GHD are observed in routine clinical practice in Japan.
No preview · Article · Jul 2013 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: Iodine is an essential nutrient for thyroid hormone synthesis, and iodine deficiency especially in pregnant and lactating women results in serious damage to their infants. To characterize iodine nutrition throughout gestation by using a food frequency questionnaire (FFQ) and urinary iodine concentration (UIC) measurement, and to establish appropriate gestational age-specific reference ranges for serum TSH and FT4 in thyroid autoantibody (ThAb) negative euthyroid Japanese women, a total number of 563 pregnant women including 422 subjects with negative ThAbs, 105 postpartum women and their 297 newborn infants were included in the study. Dietary iodine intake (DII) was evaluated by FFQ. Serum TSH, FT4 and UIC were sequentially determined in the three trimesters of pregnancy and at the 31st postpartum day. The overall median UICs throughout pregnancy and in the postpartum period were 224.0 and 135.0μg/L, respectively, suggesting sufficient iodine nutrition. The median DII was 842.4μg/day in pregnant women. The median UIC in the first trimester (215.9μg/L) significantly decreased in the second trimester (136.0μg/L). The prevalence of pregnant women with a UIC below 150μg/L was 31.6% and that in lactating women with a UIC below 100μg/L was 33.3%. The pattern of gestational change in serum TSH and FT4 was comparable to that in iodine-sufficient areas. A substantial percentage of women might be at risk for iodine deficiency if there is a restriction of iodine-rich foods. However, iodine supplementation for pregnant women must be carefully balanced against the risk of iodine excess particularly in Japan. Further research in larger samples is needed.
No preview · Article · Jun 2013 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: Growth hormone (GH) affects body composition and atherogenic risk factors. Severe hyperlipidemia may develop in GH-deficient adults as a consequence of continuous GH deficiency. We investigated changes in lipid profiles in 158 Japanese children (103 boys and 55 girls) with GH deficiency who had been enrolled in the Pfizer International Growth Database Japan during 3 yr of GH replacement therapy to evaluate whether GH treatment has beneficial effects on atherogenic risk factors. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and atherogenic index were evaluated before treatment and then once a year during treatment. The mean baseline TC was within the normal range in both boys and girls. Seventeen (16.5%) of the 103 boys and 18 (32.7%) of the 55 girls, however, had a TC level over 200 mg/dl before treatment. The mean TC level showed a significant decrease in girls. In a separate analysis, patients of both sexes with a TC level > 200 mg/dl showed significantly decreased TC. LDLC decreased significantly only in girls, while HDLC showed no change in either sex. The atherogenic index decreased significantly in girls. GH replacement therapy in children with GH deficiency had beneficial effects on lipid metabolism and atherogenic risk in both sexes. Early GH treatment would produce lipid metabolism benefits in these patients.
[Show abstract][Hide abstract] ABSTRACT: Iodine deficiency in pregnant and lactating women results in serious damage to their fetuses, newborns, and weaning infants. The effect of dietary iodine intake on maternal and infantile thyroid function has not been well studied in iodine-sufficient areas, and there are few data on appropriate gestational age-specific reference ranges for urinary iodine excretion during pregnancy and lactation.
The aim of the study was to characterize the gestational change of urinary iodine excretion in Japanese women and to assess the effects of iodine status on thyroid function in mother and infant.
A total of 934 Japanese women and their 722 newborn infants were enrolled in the study. Iodine and creatinine concentrations were determined in spot urine samples in the three trimesters of pregnancy and the postpartum period at 34.0 d after delivery. Serum thyroperoxidase antibody and thyroglobulin antibody, TSH, and free T(4) were measured in each trimester, and neonatal TSH was measured on postnatal d 4.
The overall median urinary iodine concentration (UIC) during pregnancy was 219.0 μg/liter, higher than that in postpartum women (135.0 μg/liter). The prevalence of pregnant women with low UIC less than 100 μg/liter or high UIC greater than 500 μg/liter was 16.1 and 22.2%, respectively. Urinary iodine excretion decreased from 221.0 μg/liter in the first trimester to 208.0 μg/liter in the second trimester to 193.0 μg/liter in the third trimester, and then remained at 135.0 μg/liter postpartum. [corrected]. The maternal UIC correlated positively with serum TSH during pregnancy. There was no significant difference in UIC between subjects with positive thyroid autoantibodies and those with negative antibodies.
Iodine intake assessed by UIC in Japanese pregnant women is regarded as sufficient and not excessive according to World Health Organization criteria. Although the data are local, our results provide additional information on the reference range for UIC throughout gestation in iodine-sufficient areas.
No preview · Article · Sep 2011 · The Journal of Clinical Endocrinology and Metabolism
[Show abstract][Hide abstract] ABSTRACT: To identify factors affecting adult height in Japanese patients with idiopathic growth hormone deficiency (GHD), who received growth hormone (GH) treatment during childhood.
A retrospective pharmaco-epidemiological study of the effect of GH treatment on adult height standard deviation scores (SDS) was conducted in 374 Japanese patients with idiopathic GHD. During childhood, GH (0.146 +/- 0.023 mg/kg/week) was administered for a mean of 6.4 +/- 2.6 years.
The mean adult height was 160.6 +/- 6.3 cm (-1.75 SD; n = 232) in boys and 146.9 +/- 7.3 cm (-2.20 SD; n = 158) in girls after GH therapy. The mean increases in height SDS in boys and girls with severe GHD were 2.13 SD and 1.66 SD, respectively (p < 0.05). These increases were greater than those observed in patients with moderate GHD and mild GHD. The mean adult height of male patients with GHD and gonadotropin deficiency (166.8 cm) was significantly higher (p < 0.05) than that of isolated GHD patients who were either receiving (159.1 cm) or not receiving (160.5 cm) gonadal suppression therapy. The mean adult heights of female patients were 149.6, 146.7, and 146.9 cm, respectively, and these values did not significantly differ.
Linear multiple regression analyses of Japanese patients with severe GHD (n = 61) revealed three independent variables that influenced adult height: gonadotropin deficiency, initial height SDS and height velocity during the first year after the initiation of GH therapy.
No preview · Article · Aug 2011 · Journal of pediatric endocrinology & metabolism: JPEM
[Show abstract][Hide abstract] ABSTRACT: Iodine deficiency disorders (IDDs) are serious global public health problems and approximately 2 billion people are at risk of IDD complications. Urine iodine and thyroid size by ultrasound in school-age children are important indicators for assessing IDD in a population. Interpretation of sonographically measured thyroid volume requires valid reference criteria from iodine-sufficient populations, and in 2003 WHO (World Health Organization)/ICCIDD (International Council for the Control of Iodine Deficiency Disorders) proposed new international reference values for thyroid volume in children aged 6-12 years. To establish a normative reference of thyroid volume and characterize the current status of iodine nutrition in Japanese schoolchildren in Tokyo, where iodine deficiency has never existed, a total of 654 subjects aged 6-12 years (317 girls and 337 boys) in three primary schools were enrolled in the study in 2002. Thyroid volume was determined by using the standardized method recommended by WHO/ICCIDD and the iodine concentration in spot urine samples and the anthropometric measurements were evaluated. Thyroid volume was positively correlated with the children's age, height, weight, or BSA. Regardless of gender the computed median and 97th percentile thyroid volumes based on age or BSA in Japanese children were generally lower than the corresponding values recently reported in iodine-sufficient areas, although these values were slightly higher (5-13%) than those in the 2003 WHO/ICCIDD international reference. The computed median value of urinary iodine concentration was 281.6 microg/L (303.7 microg/gCre) and extremely high values exceeding 1,000 microg/L were found in 16% of the subjects. The present study clearly indicated a high iodine intake in Japanese schoolchildren and also established reference values for thyroid volume that might be applicable to countries in the Far East as a population-specific local reference.
[Show abstract][Hide abstract] ABSTRACT: Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48 (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.
No preview · Article · Dec 2006 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: Turner syndrome is a common sex chromosome anomaly. Human growth hormone (hGH) is effective for treating short stature, which is a major characteristic of the disease. In this report, we analyzed the results of low-dose GH treatment for short stature in 212 Turner syndrome patients with growth hormone deficiency. These patients were enrolled in KIGS Japan. After 5 years of treatment, change in height was more than the mean growth curve in many patients, and the standard deviation (SD) for stature improved by +1.22 SDS. As the treatment progressed, the weight-for-height index (WHI) decreased in patients aged 8.1 years or older but not more than 14.8 years at the commencement of the treatment.
No preview · Article · Nov 2006 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: Patients with growth hormone deficiency (GHD), both Japanese and Caucasian, have an abnormal body composition with pronounced abdominal obesity. This study aimed to evaluate changes in trunk fat with GH treatment.
Double-blind, placebo-controlled study.
Sixty-one Japanese adult GH deficient patients (mean age 37 years) were randomised to either GH, titrated to 0.012 mg/kg/day, (n = 30) or placebo (n = 31) for 24 weeks. Body composition, by dual-energy X-ray absorptiometry (DXA), was evaluated at a central laboratory for trunk fat, total body fat and lean body mass. Serum lipid levels were also determined centrally.
At baseline, 26 (42.6%) patients had a body mass index (BMI) > or = 25 kg/m(2), the threshold for obesity-related complications for Japanese subjects. Median trunk fat mass (FM) was > or = 9.0 kg for each treatment and gender group, higher than the cut-off for increased age-adjusted risk for cardiovascular complications reported in the normal Japanese population. After 24 weeks of GH treatment, the change in percentage trunk FM was -3.4 +/- 0.6%, versus 0.4 +/- 0.6% with placebo (p < 0.001). Change in total body FM was -2.8 +/- 0.5% with GH and 0.0 +/- 0.5% with placebo, indicating that the decrease in trunk fat was more pronounced than for total body fat. Total and low density lipoprotein (LDL)-cholesterol were both significantly (p < 0.001) decreased compared with placebo. One patient discontinued due to a subdural haematoma and one had GH dose reduced due to hyperglycaemia.
Japanese patients with GHD have abnormal central fat accumulation, which is reduced by GH treatment over 24 weeks. This may reduce cardiovascular risk but the GH dose should be individualised to maintain IGF-I in the normal range.
No preview · Article · Oct 2006 · Current Medical Research and Opinion
[Show abstract][Hide abstract] ABSTRACT: The Growth Hormone (GH) and Its Related Factors Study Committee of the Foundation for Growth Science, Japan, has been conducting a quality control study for 15 years to improve the equality of diagnosis of GH deficiency. It found that the greatest differences in measured GH values were due to the different potencies of the kit standards, which were primarily adjusted to WHO standards for human GH of pituitary origin. With the collaboration of kit makers and the Study Group of Hypothalamo-Pituitary Disorders of the Ministry of Health, Labor and Welfare, all GH kits in Japan have begun using the same recombinant human GH standard since April 2005. As a result the diagnostic cut-off peak GH has changed from 10 to 6 ng/ml.
No preview · Article · Feb 2005 · Hormone Research
[Show abstract][Hide abstract] ABSTRACT: It has been reported that adult patients with growth hormone deficiency (GHD) have increased risk factors for cardiovascular disorders in Western countries. However, data on this issue in Japan have not been fully investigated. To clarify the situation on this issue in Japan, a nationwide questionnaire survey was conducted by Study Group of Hypothalamo-Pituitary Disease, and medical records of 863 adult patients were recruited. The incidences of complications and risk factors for cardiovascular diseases were compared between GH deficient patients (GHD, n = 494) and GH intact patients (GHI, n = 369). The incidence of myocardial infarction was higher in GHD (1.2%) than in GHI (0.8%), but not significantly. The incidences of angina pectoris and liver dysfunction were significantly higher in GHD than in GHI (2.8 vs 0.8%, p = 0.048, and 11.9 vs 5.5%, p<0.0001, respectively). The prevalences of obesity and hyperlipidemia (HL) were significantly higher in GHD (p = 0.004, p<0.001, respectively). Combinations of HL plus diabetes mellitus (DM) or hypertension (HT) were more common in GHD than in GHI (HL + DM; 7.2 vs. 2.9%, HL + HT; 10.9 vs. 2.9%). These results indicated that GH deficiency have an increased prevalence of cardiovascular risk factors in Japanese similar to Western countries, and suggested that GH supplement therapy may be needed to reduce those complications.
No preview · Article · Oct 2004 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: The biological effects of 20-kDa human GH (20K-hGH), which is produced in the pituitary by alternative splicing of GH mRNA and comprises approximately 6% of all GH in serum, have not been reported. We have investigated the metabolic effects of recombinant 20K-hGH in adult patients with GH deficiency in an exploratory study. Three doses of 20K-hGH (0.006, 0.012, and 0.024 mg/kg.d), were administered for 16 wk to three groups (consisting of 18 or 19 subjects), respectively. The 20K-hGH dose-dependently increased serum IGF-I and IGFBP-3 levels, and the lowest dose (0.006 mg/kg) was enough to normalize both hormones by wk 4. Serum osteocalcin levels and urinary deoxypyridinoline excretion were also dose-dependently increased. There was a significant decrease in body fat mass with an increase of lean body mass at the lowest dose of 0.006 mg/kg.d. Blood glucose and serum insulin were increased significantly at 4 wk only in the high-dose group (0.024 mg/kg). Glucose tolerance was slightly impaired in 26-39% of patients in all treatment groups as judged by oral glucose tolerance tests, but there was no development of overt diabetes. The major adverse event in the 20K-hGH treatment was peripheral edema, similar to the incidence reported for 22K-hGH. The data demonstrated that 20K-hGH had metabolic effects comparable to those of 22K-hGH in humans. The results suggest that 20K-hGH could be used to treat GH-deficient patients, although further studies may be required to investigate the optimum dose and superiority of 20K-hGH over 22K-hGH in a comparative study.
Full-text · Article · May 2004 · Journal of Clinical Endocrinology & Metabolism
[Show abstract][Hide abstract] ABSTRACT: Although endemic goiter had been recognized in most parts of the country, there are few available data on iodine-deficiency disorders (IDDs) in Mongolia. This study aimed to characterize the current status of iodine deficiency in Ulaan Baatar, Mongolia's capital city.
Cross-sectional, observational study designed and performed according to the surveillance methods for IDD prevalence recommended by WHO/UNICEF/ICCIDD.
A total of 505 schoolchildren aged 9-14 years (237 girls and 268 boys) and 138 mothers and their neonatal infants were selected to clinical and biochemical examination of the thyroid in 1996 and 1999.
The anthropometric measurements, thyroid volume determined by ultrasound, blood TSH and FT4 concentrations, urinary iodine concentration and iodine content of salt consumed in households.
Median thyroid volumes based on age were generally higher than those in iodine-sufficient areas and comparative to those reported in mild iodine-deficiency areas. Application of the updated WHO/ICCIDD reference values in iodine-replete European schoolchildren to the Mongolian children aged 10-12 years resulted in a goiter prevalence of 43.3%. The median value of urinary iodine concentration was 152.5 micro g/l (1.20 micro mol/l) and 40.3% of children excreted iodine below 100 micro g/l. Iodized salt (> 40 ppm) was consumed in 63.1% of households and in the children using noniodized salt their urinary iodine concentration was lower than those using ionized salt. In postpartum women, median thyroid volume and urinary iodine concentration were 11.3 ml and 107 micro g/l (0.84 micro mol/l), respectively, and 46% of women excreted less than 100 micro g/l (0.79 micro mol/l) of iodine. Of their neonates, 17.8% had elevated blood TSH levels (> 5 mU/l). In a 1999 survey, the goiter prevalence and ratio of low iodine excretion in schoolchildren decreased to 29.8% and 31.3%, respectively, while median urinary iodine concentration remain unchanged (160 micro g/l; 1.26 micro mol/l).
The present study clearly indicates the presence of mild iodine deficiency in Mongolia. Enlarged thyroid gland and normal iodine excretion observed in schoolchildren living in Ulaan Baatar may result from the residual effects of iodine deficiency previously and presumably still exist in the city. Slight reduction in the rate of children with enlarged thyroid and low urinary iodine excretion after the onset of national iodinization programme suggests incomplete normalization of thyroid volume in children and that the correction of iodine deficiency is now in progress in Ulaan Baatar. Further nationwide surveys together with monitoring the progress of the national programme eliminating IDD are required in suburban areas surrounding the city and also in rural areas.
No preview · Article · Sep 2003 · Clinical Endocrinology
[Show abstract][Hide abstract] ABSTRACT: The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises approximately 10% of all GH in the pituitary. The physiological role of 20K hGH remains to be determined partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunoadsorbent assays (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight fasting was 118 +/- 178 pg/mL (N=282) in normal women, significantly higher than in normal men (64 +/- 170 pg/mL, N=226). However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 +/- 2.6%, N=176) and women (6.3 +/- 2.1%, N = 263). No correlation was detected between the ratio of 20K hGH and age, body height, body weight or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P < 0.001) higher in patients with active acromegaly (9.2 +/- 2.2%, N=33) and in patients with anorexia nervosa (9.0 +/- 1.9, N=8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of the 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic excess of 22K hGH altering the metabolic clearance rate of 20K hGH. The values in patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests such as insulin tolerance test and GRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH.
No preview · Article · Apr 2000 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: We previously demonstrated that individual subjects have fairly constant ratios of serum concentrations of 20 kDa- (20K) and 22 kDa-GH (22K). The aim of this study is to demonstrate the possibility of utilizing the changes in the ratio of 20K/22K for detecting the exogenous administration of 22K. A male patient with idiopathic dilated cardiomyopathy (age 51) received 22K (4U, s.c.) every other day. The concentrations of 20K and 22K in serum and urine were measured using enzyme-linked immunosorbent assays before and after administration. The administration of 22K increased total GH concentration, and markedly decreased the ratio of 20K/22K in serum, especially 2-10 h after the administration. From calculations, it became clear that the concentration of exogenous 22K reached a peak between 2-4 h after the administration and decreased to a negligible level after 24 h. The ratio of 20K/22K in the 0-24 h urine was 5 times lower than that in the 24-48 h urine. These data suggest that, by monitoring the ratio of 20K/22K in serum or urine, it is possible to determine whether or not GH has been externally administered and to calculate the serum GH that has been administered.
No preview · Article · Mar 2000 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises approximately 10% of all GH in the pituitary. The physiological role of 20K hGH remains to be determined partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunoadsorbent assays (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight fasting was 118+/-178 pg/mL (N=282) in normal women, significantly higher than in normal men (64+/-170 pg/mL, N=226). However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3+/-2.6%, N=176) and women (6.3+/-2.1%, N=263). No correlation was detected between the ratio of 20K hGH and age, body height, body weight or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P<0.001) higher in patients with active acromegaly (9.2+/-2.2%, N=33) and in patients with anorexia nervosa (9.0+/-1.9, N=8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of the 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic excess of 22K hGH altering the metabolic clearance rate of 20K hGH. The values in patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary hypothyroidism, or CH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests such as insulin tolerance test and GRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH.
No preview · Article · Mar 2000 · Endocrine Journal
[Show abstract][Hide abstract] ABSTRACT: Several GH isoforms have been identified in pituitary and serum, the most abundant of which is the 22K human GH (hGH) isoform. The 20K hGH isoform is produced by alternative splicing of GH messenger ribonucleic acid and comprises approximately 10% of all GH in the pituitary. The physiological role of 20K hGH remains to be determined, partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunosorbent assays (ELISAs) specific to 20K and 22K hGH. To determine whether regulation of 20K hGH secretion is the same as that for 22K hGH, we measured serum concentrations of both species of hGH in normal subjects and patients with a variety of endocrine disorders. The serum levels of 20K hGH after overnight fasting was 118 +/- 178 pg/mL (n = 282) in normal women, significantly higher than that in normal men (64 +/- 170 pg/mL; n = 226). However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 +/- 2.6%, mean +/- SD; n = 176) and women (6.3 +/- 2.1%; n = 263). No correlation was detected between the ratio of 20K hGH and age, body height, body weight, or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P < 0.001) higher in patients with active acromegaly (9.2 +/- 2.2%; n = 33) and patients with anorexia nervosa (9.0 +/- 1.9; n = 8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or that a chronic excess of 22K hGH alters the MCR of 20K hGH. The values in patients with adult GH deficiency, hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests, such as the insulin tolerance test and the GHRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH. This new assay may provide a tool for understanding the physiological or pathophysiological role of the 20K hGH isoform.
Preview · Article · Feb 1999 · Journal of Clinical Endocrinology & Metabolism