Growth hormone response to exercise in asthmatic and normal children

Maximal growth hormone (GH) increments following exercise were compared in asthmatic (n=14) and normal (n=8) children. Exercise, which consisted of 6 min ergometer cycling while breathing cold dry (CD) air, induced asthma in all asthmatic patients but not in normal subjects. Baseline plasma GH levels were similar in both groups. Following exercise, however, asthmatic patients had significantly higher mean GH increments than normal subjects (14.8 vs 4.9 ng/ml,P<0.025). To evaluate the possible role of bronchoconstriction in the GH response all subjects exercised again, this time while breathing warm humid (WH) air. Despite the absence of exercise-induced asthma (EIA) while breathing WH air, asthmatic patients still had significantly higher mean GH increments than normal subjects (9.2 vs 2.3 ng/ml,P<0.05). We conclude that some asthmatic children show excessive GH secretion after exercise regardless of inspired air conditions or the development of EIA.     

Prolactin response to thyrotropin-releasing hormone in children with Turner's syndrome and hyperthyroidism

Plasma prolactin (PRL) response to synthetic thyrotropin-releasing hormone (TRH) was studied in 26 prepubertal and 19 pubertal children with constitutional short stature, 7 patients with Turner's syndrome and 10 patients with hyperthyroidism. The mean basal concentrations of plasma PRL did not differ among groups. In prepubertal children PRL responses to TRH were comparable in both sexes, while pubertal children plasma PRL levels after TRH in females were significantly higher (P<0.05) than those in age-matched males. Plasma PRL levels after TRH in patients with Turner's syndrome were significantly higher (P<0.05) than those in age-matched males, but were not significantly different from those in age-matched females. Plasma PRL response to TRH was markedly suppressed in patients with hyperthyroidism before treatment, but it returned to normal after treatment when patients became euthyroid. A significant correlation (P<0.05) between peak concentrations of plasma PRL after TRH stimulation and plasma T₃ but not T₄ levels was observed.These data suggest that a sex difference in TRH-stimulated PRL secretion appears around puberty and that plasma PRL response to TRH is suppressed in children with hyperthyroidism. The magnitude of plasma PRL response to TRH is closely correlated with the severity of hyperthyroidism when judged by plasma T₃ but not T₄ concentrations.     

Prolactin response to arginine in children with hyperthyroidism and primary hypothyroidism

Plasma prolactin (PRL) response to arginine was examined in 16 prepubertal and 18 pubertal children with constitutional short stature, 5 patients with hyperthyroidism and 4 patients with primary hypothyroidism. The mean basal concentration of plasma PRL was significantly higher (P<0.01) in primary hypothyroidism than in other groups. Arginine infusion elicited significant (P<0.05) rises in plasma PRL in all groups. The maximal increment of plasma PRL above the baseline level after arginine stimulation was significantly larger (P<0.05) in pubertal than in prepubertal females and was significantly smaller (P<0.05) in patients with hyperthyroidism than in age- and sex-matched controls. There was no sex difference in arginine-stimulated PRL secretion. These data suggest that arginine produces a significant increase in plasma PRL and the PRL response to arginine was greater in pubertal than in prepubertal children. Plasma PRL response to arginine is suppressed in children with hyperthyroidism and the basal plasma PRL is markedly elevated in primary hypothyroidism.     

Pattern of growth hormone response to insulin,arginine and haemodialysis in uraemic children

Plasma growth hormone (GH) concentrations after insulin and arginine stimulation were estimated in 11 dialyzed and 6 non-dialyzed children with chronic renal failure. Twenty healthy children served as controls. Plasma GH peak concentration and estimation of the total area under the plasma GH concentration-time curve by the trapezoidal rule were used to evaluate results. Elevated basal GH levels and an exaggerated response to the stimuli were seen in several of the patients. The causes of the abnormal GH secretion and the role of high GH levels in carbohydrate intolerance are discussed. No consistent pattern was seen in GH secretion during haemodialysis without glucose in the dialysate. In children undergoing haemodialysis with a fluid containing glucose, plasma GH fell considerably.Supported by the Deutsche Forschungsgemeinschaft     

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6–16.3 years) and a mean relative height score of –3.2 SD (range –5.0–2.1 SD) were investigated. The children were divided into prepubertal (n=35) and pubertal (n=11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH<10 g/l in both test); (2) discordant responders (maximal GH<10 g/l in one test and 10 g/l in the other); and (3) normal responders (maximal GH10 g/l in both test). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older, than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH<10 g/l). These subjects had increased basal plasma ir-GHRH concentrations. All of them had a decreased GH response to IIH and/or clonidine. Pubertal children had higher circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r=–0.46;P<0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observations suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating complementary evaluation of their spontaneous GH secretion; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH responses in pharmacological tests respond normally to GHRH and (4) the pituitary sensitivity to GHRH decreases with increasing age. Peripheral ir-GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature. The GHRH test is of limited value in the diagnosis of GHD, since a normal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.     

Defective growth hormone secretion and hypogonadism in the new syndrome of congenital hypoparathyroidism,growth failure and dysmorphic features

A child with extreme growth failure, dysmorphic features, hypoparathyroidism, and abnormal skeletal survey was studied. He was a product of first degree consaguineous marriage who had intrauterine growth retradation and presented at 14 days of age with hypocalcemic tetany with normal cardiovascular system and immune function. Endocrine evaluation after infancy revealed defective growth hormone (GH) secretion in 2 provocation tests and lack of clinical and testosterone response to human chorionic gonadotrophin (HCG) therapy.     

Comparative HGH response to i.v. glucagon and i.v. arginine stimulation tests in children and adolescents

Thirty-seven children and adolescents of several diagnostic entitites (constitutional growth retardation, diabetes mellitus and pituitary insufficiency) were tested with an i.v. bolus injection of glucagon for plasma human growth hormone (HGH) response. Most of the subjects were also tested for the same purpose by the arginine stimulation test, and the data were compared.It was found that i.v. glucagon is a potent stimulus of human growth hormone release. The HGH is released in two peaks, the first one occuring within 30 min, most probably by a direct effect. The second peak occurs after 120 min, most probably as a secondary effect caused by the drop in blood glucose after its initial rise, which is induced by glucagon. The peak concentrations of HGH induced by glucagon, were very similar to those provoked by i.v. arginine in the same subjects.     

Short stature and growth hormone

Normal growth and development is a prime concern during childhood. Accurate assessment is essential for differentiating between normal and abnormal growth. Increased accessibility to growth hormone has equipped the pediatrician and pediatric endocrinologist to treat and improve growth in many clinical scenarios. At the same time, there is added responsibility to use this tool judiciously. This review summarizes the basics of proper growth assessment, differentiation of normal and abnormal growth causes of and works up of short stature, and delineation of indications for growth hormone treatment.     

Mean 24-hour growth hormone and testosterone concentrations in relation to pubertal growth spurt in boys with normal or delayed puberty

The mean growth hormone concentration during a 24-hour period in 7 boys of short familial stature and a growth rate of 3.2–5.4 cm/year was between 1.0 and 4.6 ng/ml serum. In 7 boys with pubertal growth spurt and familial tallness (growth rate 7.2–11.0 cm/year) it varied from 0.97 to 4.4 ng/ml and in 6 boys with constitutional delay of puberty (a growth rate of 4.2–5.2 cm/year prior to puberty) from 1.3 to 4.3 ng/ml.No correlation was found between the 24-hour mean growth hormone concentration and the mean 24-hour testosterone concentration in serum or the growth rate, but a correlation was found between testosterone and the growth rate.It is concluded that the growth spurt in puberty is not due to a change in growth hormone concentration but rather to the increase of androgen production in puberty.Supported by Deutsche Forschungsgemeinschaft, SFB 51.     

Growth hormone in T-lymphocyte thymic and postthymic development: a study in HIV-infected children

OBJECTIVES: Growth hormone (GH) plays a role in thymic function, and recombinant GH may stimulate thymopoiesis in HIV-infected individuals. We performed immunologic analyses in 26 antiretroviral-treated children matched for age, pubertal status, clinical parameters, and antiretroviral exposure who did or did not show an impaired response to GH-release stimulation tests with arginine + GH-releasing hormone. RESULTS: The following abnormalities were found in GH-deficient compared with GH-nondeficient children after >4 years of therapy: CD4 count ( P = .02) and percentage ( P = .03), CD4 as percentage of normal cells for age ( P = .003), serum interleukin-7 concentration ( P = .02), and thymic volume ( P = .01). Naive CD4 (4+62+RA+ and 4+CCR7+RA+) and CD8 (8+CCR7+RA+) lymphocytes were lower in GH-deficient children ( P = .003; P = .007; and P = .02, respectively). Postthymic pathways were also impaired in GH-deficient children. Thus, central memory (4+CCR7+RA-) CD4+ cells were reduced ( P = .006), whereas effector memory (4+CCR7-RA-) CD4+ cells ( P = .002) and late effector CD8+ lymphocytes (8+CCR7-RA+ and 8+27-28-) ( P = .009 and P = .002, respectively) were increased in these children. CONCLUSIONS: Growth hormone plays a role in thymic and postthymic pathways, and defective GH production may be associated with incomplete immunoreconstitution. Immunomodulant agents (including GH) could be useful in patients with defective GH production.     

Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology,quality of life,and radiographic response

Background

Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel–Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM.

Procedure

A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed.

Results

Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus.

Conclusion

Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.