High Basal Growth Hormone Research Articles

Clinical profile of Laron dwarfism – experience from a tertiary care institute in Chennai

Laron dwarfism is a rare genetic disorder first reported among Israeli jewish children, subsequently about 350 cases cases have been reported worldwide. We aim to describe the clinical profile of nine children with Laron dwarfism from Institute of Child Health, Chennai. Analysis of case records from 2010 to 2018. Male:female ratio is 6:3. Mean age of the children at the time of diagnosis was 3 years. All children were extremely short, and mean height Z score (SD) was-7.7(0.8). All children had characteristic facies with no hypoglycaemic episodes. Microcephaly was present in four children out of which two had developmental delay. Three out of six boys had micropenis. All children had low insulin like growth factor-1 (IGF-1) and high basal growth hormone (GH) with a mean (SD) of 39.6 (11.2) ng/mL. Suspicion of Laron syndrome should be high when child presents with features of Growth Hormone Deficiency (GHD) with extreme stunting.

Evaluation of Factors Affecting Outcome in Growth Hormone–Secreting Pituitary Adenomas

Introduction Management of functioning pituitary adenomas is challenging as they can present with features of an intracranial mass, systemic effects, or a combination of both. In this series, one of the largest in available literature from our country, we have analyzed our experience with surgical management of growth hormone (GH)-secreting pituitary adenomas and factors influencing their hormonal remission. Materials and Methods The data of all functional pituitary adenomas operated at our institute from January 2002 to December 2011 were obtained from the case files of these patients. This was studied for various clinical-radiologic features, management stratagems, and clinical and hormonal outcomes. Results Ninety-three patients of GH-secreting pituitary adenomas with a mean age of 32.7 years were included in the study. Fifty-three (57%) patients had headache at presentation; 46 (49%) had visual complaints, whereas menstrual irregularity was seen in majority of females. Mean GH level was 52.05 ng/mL. Fifty (53%) patients had invasive adenoma; 32 had cavernous sinus extension. Among 80 patients with hormonal follow-up, 43 (53.75%) achieved remission of GH level < 5 ng/mL. Conclusion In this series, one of the largest of its kind, the main factors influencing unfavorable outcome include macroadenomas, invasiveness, high basal GH > 45 ng/mL levels, and mixed adenomas.

Growth hormone/insulin-like growth factor-1 axis: a possible non-nutritional factor for growth retardation in children with cerebral palsy

To assess growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis as a possible non-nutritional factor for growth retardation in children with cerebral palsy (CP). A case-control study was conducted at a tertiary university hospital. Thirty children with CP (seven children with normal growth [CP-N] and 23 with retarded growth [CP-R]), 30 children with protein energy malnutrition (PEM), and 30 healthy children (REF group) underwent an assessment of growth parameters, serum IGF-1, basal GH, and peak GH after stimulation with insulin. PEM patients had higher basal GH levels than CP-N, CP-R and REF groups (p = 0.026, p < 0.001, and p < 0.001 respectively). After insulin stimulation, CP-N, CP-R, and PEM patients had lower GH levels compared to the REF group (p = 0.04, p = 0.007, and p = 0.036 respectively). IGF-1 levels were lower in CP-R group compared to CP-N and REF groups (p = 0.037 and p < 0.001 respectively), and in PEM group compared to CP-N and REF groups (p < 0.001 and p < 0.001 respectively). CP-R patients failed to demonstrate the same high basal GH response as PEM patients, and responded inadequately to the insulin stimulation test, but they had IGF-1 levels comparable to those of PEM patients. On the other hand, CP-N patients behaved as controls regarding their basal GH and IGF-1 levels, but failed to respond adequately to the insulin stimulation test. The PEM group presented high basal GH and low IGF-1 levels. These findings suggest that non-nutritional factors contribute to growth retardation in CP children.

Epidermal Growth Factor‐Activated Extracellular Signal‐Regulated Kinase Suppresses Growth Hormone Expression and Stimulates Proliferation in MtT/ E Cells

The mechanism for the inhibition of growth hormone (GH) expression by the epidermal growth factor (EGF) was examined in two clonal cell lines, MtT/E and MtT/S. The former has a negligible basal level of GH, whereas the latter has a high basal GH. The treatment of MtT/E cells with retinoic acid resulted in a significant increase in GH mRNA and subsequently GH. This stimulatory response to retinoic acid was strongly suppressed by EGF. This suppression was associated with an increase in the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2). The MEK [mitogen-activated protein kinase (MAPK) kinases that activate ERK1 and ERK2] inhibitor, PD98059, clearly inhibited the phosphorylation of Erk1/2 and restored the stimulatory effects of retinoic acid. These results suggest that the inhibitory effects of EGF on GH expression are mediated by MAPK activation in these cells. By contrast to the GH-producing clones examined previously, EGF showed a marked stimulation of proliferation of the MtT/E cells through a mechanism dependent on MAPK activation. On the other hand, the inhibitory effect of EGF on GH expression was less pronounced and the stimulation of cellular proliferation was not seen in MtT/S cells, even though it induced Erk-phosphorylation similar to that seen in MtT/E. The distinct difference in the response to EGF between these two GH cell lines appears to be attributed to differences in the function of MAPK cascade in each cell line. This may reflect the developmental stage of the cells from which MtT/E and MtT/S are derived.

Secretion of Prolactin and Growth Hormone in Relation to Ovarian Activity in the Dog

In pregnant bitches an apparent increase in plasma prolactin concentrations is observed during the second half of pregnancy, mean plasma prolactin concentrations peak on the day of parturition, fall for the next 24-48 h and then rise again. During lactation, high plasma prolactin concentrations are observed. Plasma prolactin levels in non-pregnant bitches appear to be lower than in pregnant animals, particularly in the last part of the luteal phase. Pulsatile secretion of prolactin has been observed during the luteal phase and mid-anoestrus. Progression of the luteal phase is found to be associated with an increase in prolactin release. The association of a strong increase of prolactin release and a decrease of plasma progesterone concentrations has also been demonstrated in overtly pseudopregnant bitches. Elevated prolactin secretion during progression of the luteal phase in the bitch may play a role in mammogenesis and is important because of the luteotrophic action of prolactin. Acromegaly is a syndrome of tissue overgrowth and insulin resistance due to excessive growth hormone (GH) production. In the bitch, acromegaly can be induced either by endogenous progesterone or by exogenous progestagens. Progestagen-induced GH production in this species originates from foci of hyperplastic ductular epithelium of the mammary gland. Pulsatile secretion of GH has been observed in normal cyclic bitches. In contrast with the pulsatile GH secretion seen in healthy dogs, the progestagen-induced plasma GH levels in bitches with acromegaly do not have a pulsatile secretion pattern. Just as with prolactin, the plasma progesterone levels influence the secretion pattern of GH in the bitch. The pulsatile secretion pattern of GH changes during the progression of the luteal phase in healthy cyclic bitches, with higher basal GH secretion and less GH being secreted in pulses during the first part of the luteal phase. The progesterone-induced GH production may promote the proliferation and differentiation of mammary gland tissue during the luteal phase of the bitch by local autocrine/paracrine effects and may exert endocrine effects.

Children Born Small-for-Gestational Age: Postnatal Growth and Hormonal Status

It is generally recognized that children born small-for-gestational age (SGA) have a 5–7 times higher risk of short stature than children born at normal size. It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and is affected by intrauterine growth retardation. This study was undertaken to characterize the postnatal growth pattern and the final height of children born SGA, as part of a population- based study (n = 3,650), from birth to final height, and to evaluate the hormonal status in another group of prepubertal children born SGA (n = 134) without postnatal catch-up growth. The majority (88%) of ‘healthy’ full-term singleton SGA infants achieved catch-up growth during the first 2 years of life, and most of the increase in height occurred by 2 months of age. The SGA children who remained short at 2 years of age had a higher risk of short stature later in life. The risk of having a short final height (<–2 SDS) was five times higher for children with a low birth weight and seven times higher for those with a low birth length in comparison with children with a normal birth size. Moreover, about 20% of all children of short stature were born SGA. As a group, children born SGA will have a final height, expressed in SDS, as they had during the prepubertal years. This is in contrast to children, who became short postnatally. During puberty, these short children will have a mean height gain of 0.6 SDS for girls and 0.7 SDS for boys. The mean estimated secretion rate for growth hormone (GH) was lower in the short children born SGA compared with the reference groups born at an appropriate size for gestational age, of either short (p < 0.05) or normal stature (p < 0.001). Moreover, in the youngest children born SGA (2–6 years of age) a different pattern of GH secretion was found, with a high basal GH level, low peak amplitude, and high peak frequency. The majority of the children born SGA had levels of GH-binding protein within the range previously reported for normal children. However, the levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3) and leptin were significantly reduced compared with the reference values (p < 0.001, p < 0.01 and p < 0.001, respectively). In conclusion, the low spontaneous GH secretion rate and a disturbed GH secretion pattern, together with low serum levels of IGF-I, IGFBP-3 and leptin, might contribute to the reduced postnatal growth in some of the subgroup of children born SGA who remained short during childhood.

Factors predicting pituitary adenoma invasiveness in acromegalic patients.

Forty-four adult acromegalic patients carrying growth hormone-producing pituitary macroadenomas were investigated with neuroradiological and endocrinological techniques. Plasma growth hormone and somatomedin-C levels were repeatedly measured before surgical removal of tumors and during the follow-up period. Twenty-five patients presented preoperatively with an invasive adenoma that involved the cavernous sinus (CS). Diagnosis of tumor invasivity was made according to distinct neuroradiological criteria and was confirmed or rejected during surgery Significantly higher basal growth hormone levels were found in patients with CS invasion than in cases without tumor growth in the CS. Evidence is presented that plasma growth hormone level in acromegalics is a more sensitive indicator for predicting tumor invasiveness than somatomedin-C. Growth hormone basal values before surgery and the extent of their decrease after removal of tumor correlate with adenoma growth in the parasellar compartments and should be used as a prognostic factor to aid in planing adjuvant tumor treatment.

GH response to TRH in multicase families with schizophrenia

Can abnormal growth hormone (GH) response to TSH releasing hormone (TRH) differentiate between schizophrenic probands, their affected first degree relatives and phenotypicaily healthy family members? Five multicase families with schizophrenia were studied each family consisted of two chronic schizophrenic patients and one first degree healthy relative, TRH tests were performed between 8:00 9:00 am. Thirty minutes after IV line was inserted a basal blood sample was drawn, and thereafter synthetic TRH was administered. Additional blood samples were drawn at 15, 30 and 60 minutes. Plasma GH was carried out by double antibody RIA. The results were: One proband exhibited high basal GH levels (20 ng/ml) and was excluded. The mean baseline GH plasma levels did not differ significantly between the three groups and the controls. Abnormal GH response was observed in 3/4 probands; 3/5 schizophrenic relatives and 3/5 healthy relatives, but in 0/8 of the healthy non.related controls. The magnitude of the abnormal GH response did not differ significantly between the three groups of the families. The frequency of abnormal GH response was significantly higher in the schizophrenic patients (6/9) when compared to healthy non-related control subjects. A trend towards increased frequency of abnormal GH response was observed in healthy family members (3/5) as compared to control subjects. This study confirmed our previous observation of abnormal GH release after TRH challenge in about 50% of the schizophrenic patients with positive family history. The additional finding is increased frequency of GH response to TRH in healthy related controis.

Hepatic insulin action in adolescents with insulin-dependent diabetes mellitus: Relationship with long-term glycemic control

The relationship between hepatic insulin action and long-term glycemic control was assessed in 20 adolescents with insulin-dependent diabetes mellitus (IDDM) and five healthy matched controls using a two-step (0.8 and 1.6 mU/kg/min) hyperinsulinemic-euglycemic clamp and [6,6- 2H 2]glucose. The night before the study, diabetic patients received variable-rate intravenous insulin in an attempt to normalize fasting plasma glucose concentrations. In the postabsorptive state, hepatic glucose production (HGP) was similar in IDDM patients and controls (593 ± 40 v 518 ± 27 μmol/m 2/min); however, plasma glucose and free insulin concentrations were higher in IDDM patients than in controls (6.5 ± 0.4 v 5.4 ± 0.1 mmol/L [ P = .01], and 207 ± 21 v 104 ± 10 pmol/L [ P < .001], respectively). There was a positive correlation ( r = .62 P = .002) between basal HGP and glucohemoglobin level (HbA 1). Separation of the patients at the median HbA 1 (group no. 1 < and group no. 2. > 11.4% HbA 1) revealed two distinct patient populations with regard to hepatic and peripheral insulin action and plasma free fatty acid (FFA) suppression. During hyperinsulinemia, the percent suppression of HGP was lower in group no. 2 compared with group no. 1 (65.7% ± 9.8% v 94.4% ± 3.8%; P = .018). Rates of glucose disposal were lower in group no. 2 compared with controls and with group no. 1. Postabsorptive FFA levels were similar between group no. 2 and group no. 1 (0.45 ± 0.03 and 0.43 ± 0.04 mmol/L) despite higher free-insulin concentrations in group no. 2 (260 ± 30 v 171 ± 25 pmol/L; P = .04). Hyperinsulinemia in group no. 2 did not produce a significant decrease in FFA levels, unlike group no. 1 and controls. Group no. 2 patients compared with group no. 1 patients had higher basal growth hormone (GH) levels (8.5 ± 1.6 v 3.0 ± 0.9 μg/L; P = .008). We conclude that (1) poorly controlled adolescents with IDDM have significant degrees of hepatic insulin resistance, (2) insulin action in suppressing FFA levels in impaired in these adolescents, and (3) long-term glycemic/metabolic control adversely affects hepatic insulin action, possibly through elevated GH levels.

Serum growth hormone-binding protein, insulin-like growth factor-I, and growth hormone in patients with liver cirrhosis

We determined serum growth hormone-binding protein (GHBP), insulin-like growth factor-I (IGF-I), and growth hormone (GH) levels in patients with cirrhosis and in age-matched control subjects, and investigated their relationships. Serum GHBP levels in cirrhotic patients (14.6% ± 3.9%) (means ± SD) were significantly lower than those in normal subjects (20.4% ± 4.7%). GHBP levels had positive correlations with cholinesterase ( r = .58, P < .001) and Normotest ( r = .66, P < .001), both of which represent liver function in cirrhotic patients. Basal GH levels in cirrhotic patients (range, 0.35 to 13.0 μg/L; median, 3.9 μg/L) were significantly higher than those in normal subjects (0.015 to 6.0 μg/L; 0.19 μg/L). GHBP levels in cirrhotic patients correlated positively with IGF-I levels ( r = .39, P < .01), and negatively with GH levels ( r = −.33, P < .01). These results may indicate that the serum GHBP level reflects the number of hepatic GH receptors, and that the high basal GH level observed in cirrhotic patients is, at least in part, attributable to decreased clearance of GH by these receptors.

Blunted growth hormone responses to clonidine in adolescent girls with early anorexia nervosa: Evidence for an early hypothalamic defect

We studied growth hormone (GH) levels in 14 adolescents with anorexia nervosa (AN), 12–20 years of age. All had amenorrhea and the duration of symptoms ranged from 2–24 months. There was no difference in unstimulated GH between the girls with AN and endocrinologically normal girls. However, the GH response to the α-adrenergic agent clonidine was blunted (<10 ng/ml) in 11 of 14 girls with AN. Our results of a normal basal GH level and blunted response to stimulation is in contrast to some reports of high basal GH levels and an exaggerated response to pituitary stimulation although it agrees with other studies. Our patient population was younger and at an earlier stage of the disease (12 with symptoms for less than 1 year) than the AN patients previously reported to have elevated GH secretion. In view of studies that report an elevated GH response to growth hormone releasing factor, our results suggest that the AN patient's abnormalities in GH secretion may result from an abnormal hypothalamic response to adrenergic stimuli. This hypothalamic abnormality might also contribute to the growth failure seen in adolescent girls with AN.

Glucose intolerance in liver cirrhosis

Glucose intolerance and hyperinsulinemia frequently occur in patients with chronic liver failure. To investigate the importance of glucose counterregulating factors, an oral glucose tolerance test was performed on 18 patients with compensated liver cirrhosis, matched for liver function tests and degree of portal hypertension, and 10 healthy controls. Blood glucose, immunoreactive insulin, C-peptide, immunoreactive glucagon, glucagon like immunoreactivity, growth hormone, cortisol and free fatty acids were determined in both groups at 30 min intervals for 240 min. Despite the similarity in the severity of liver damage five cirrhotic patients showed normal glucose tolerance, eight impaired glucose tolerance and five overt diabetes. Immunoreactive insulin was significantly higher in cirrhotic patients than in controls both before and during the oral glucose tolerance test. As basal C-peptide values were significantly higher and C-peptide/immunoreactive insulin ratio was significantly lower in cirrhotic patients than in the control subjects, both hyperproduction and hypodegradation seem to be responsible for the high insulin levels. Immunoreactive glucagon and cortisol showed no statistical differences between cirrhotic patients and control subjects whereas high basal growth hormone and free fatty acids values were observed in the cirrhotic group. Basal values and maximum increase or decrease of all the factors examined were tested by a correlation analysis with the blood glucose at 120 min and evaluated by a stepwise linear regression analysis. Only basal blood glucose, basal free fatty acids and immunoreactive insulin increment correlated significantly with blood glucose at 120 min. By the stepwise procedure these factors were found to account for 86% of the variance of the glucose level at 120 min. In chronic liver disease we failed to establish a pathogenetic role of hormones involved in the glucose counterregulating system. Free fatty acids may play an important role in glucose intolerance in chronic liver failure.