A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by 22q13 deletions including SHANK3 or pathogenic sequence variants in SHANK3 and is among the more common rare genetic findings in autism spectrum disorder (ASD). SHANK3 is critical for synaptic function, and preclinical and clinical studies suggest that insulin-like growth factor-1 (IGF-1) can reverse a range of deficits in PMS. IGF-1 release is stimulated by growth hormone secretion from the anterior pituitary gland, and this study sought to assess the feasibility of increasing IGF-1 levels through recombinant human growth hormone (rhGH) treatment, in addition to establishing safety and exploring efficacy of rhGH in children with PMS. METHODS: rhGH was administered once daily for 12 weeks to six children with PMS using an open-label design. IGF-1 levels, safety, and efficacy assessments were measured every 4 weeks throughout the study. RESULTS: rhGH administration increased levels of IGF-1 by at least 2 standard deviations and was well tolerated without serious adverse events. rhGH treatment was also associated with clinical improvement in social withdrawal, hyperactivity, and sensory symptoms. LIMITATIONS: Results should be interpreted with caution given the small sample size and lack of a placebo control. CONCLUSIONS: Overall, findings are promising and indicate the need for larger studies with rhGH in PMS. Trial registration NCT04003207. Registered July 1, 2019, https://clinicaltrials.gov/ct2/show/NCT04003207 .

Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS. METHODS: Ten children aged 5-9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N = 19). RESULTS: Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events. LIMITATIONS: The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results. CONCLUSION: IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity  in children with PMS. Trial registration NCT01525901.

Histocompatibility studies in a closely bred colony of dogs. II. Influence of the DL-A system of canine histocompatibility upon the survival of cardiac allografts.

The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days. Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens. Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions. The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration.

Demographics and anthropometrics impact benefits of health intervention: data from the Reduce Obesity and Diabetes Project.

OBJECTIVE: To determine the efficacy of a 4-month school-based health, nutrition and exercise intervention on body fatness and examine possible effects of demographic and anthropometric covariates. METHODS: Height, weight, waist circumference and body composition were measured in a diverse population of 644 NYC middle school students (mean ± SD age 12.7 ± 0.9 years; 46% male; 38% Hispanic, 17% East Asian, 15% South Asian, 13.5% African American, 8.5% Caucasian, 8% other) during the fall and spring semesters. Year 1 participants (n = 322) were controls. Experimental participants (year 2, n = 469) received a 12-session classroom-based health and nutrition educational programme with an optional exercise intervention. RESULTS: Groups were demographically and anthropometrically similar. The intervention resulted in significant reductions in indices of adiposity (ΔBMI z-scores [-0.035 ± 0.014; p = 0.01], Δ% body fat [-0.5 ± 0.2; p < 0.0001] and Δwaist circumference [-0.73 ± 0.30 cm; p < 0.0001]). Intervention effects were greater (p = 0.01) in men (ΔBMI z-score = -0.052 ± 0.015) versus women (0.022 ± 0.018), participants who were obese (ΔBMI z-score -0.083 ± 0.022 kg m-2) versus lean (-0.0097 ± 0.020 kg m-2) and South Asians (Δ% body fat -1.03 ± 0.35) versus total (-0.49 ± 0.20%) participants (p = 0.005). CONCLUSION: A 4-month school-based health intervention was effective in decreasing measures of adiposity in middle school students, particularly in men, participants who were obese and South Asians.

Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society.

OBJECTIVE: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies. PARTICIPANTS: There were 42 participants chosen for their expertise in obstetrics, peri- and neonatal medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and pharmacology. EVIDENCE: Written materials were exchanged, reviewed, revised, and then made available to all. This formed the basis for discussions at the meeting. Where published data were not available or adequate, discussion was based on expert clinical opinions. CONSENSUS PROCESS: Each set of questions was considered by all and then discussed in plenary sessions with consensus and unresolved issues identified. The consensus statement was prepared in plenary sessions and then edited by the group chairs and shared with all participants. CONCLUSIONS: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference. We recommend early surveillance in a growth clinic for those without catch-up. Early neurodevelopment evaluation and interventions are warranted in at-risk children. Endocrine and metabolic disturbances in the SGA child are recognized but infrequent. For the 10% who lack catch-up, GH treatment can increase linear growth. Early intervention with GH for those with severe growth retardation (height sd score, <-2.5; age, 2-4 yr) should be considered at a dose of 35-70 microg/kg x d. Long-term surveillance of treated patients is essential. The associations at a population level between low birth weight, including SGA, and coronary heart disease and stroke in later life are recognized, but there is inadequate evidence to recommend routine health surveillance of all adults born SGA outside of normal clinical practice.

New-onset IDDM presenting with diabetic ketoacidosis in a pregnant adolescent.

OBJECTIVE: To describe the presentation of insulin-dependent diabetes mellitus (IDDM) as ketoacidosis during pregnancy in a teenager. CASE: A 14-year-old pregnant girl presented with ketoacidosis (bicarbonate 14 nM, 14 meq/l, pH 7.27, glucose 67 mM, 1,208 mg/dl) during the last month of pregnancy with a fetal demise. Two years of follow-up has confirmed that she has IDDM. CONCLUSIONS: Diabetes presenting in pregnant adolescents is likely due to IDDM. Immediate insulin therapy and proper education about managing diabetes should be initiated to hopefully prevent the outcome described in this patient.

The 21-hydroxylase activity in the glomerulosa and fasciculata of the adrenal cortex in congenital adrenal hyperplasia.

In the two clinical syndromes of congenital adrenal hyperplasia due to a 21-hydroxylation defect of adrenal steroidogenesis, the simple virilizing and the salt-wasting forms, the 21-hydroxylase activity was studied considering the zona fasciculata and the zona glomerulosa of the adrenal cortex as two separate glands under different regulation. To test this hypothesis, we stimulated adrenal steroidogenesis by ACTH infusion or dietary sodium restriction in eight patients with congenital adrenal hyperplasia (four patients with the simple virilizing form and four with the salt-wasting form of congenital adrenal hyperplasia) and in six normal children. Both the 17-hydroxy and 17-deoxy pathways of adrenocortical steroid biosynthesis were examined by measuring serum concentrations of 17-hydroxyprogesterone, cortisol, progesterone, deoxycorticosterone, corticosterone, and aldosterone and the excretion of free deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, cortisol, and aldosterone. We considered the steroids 18-hydroxycorticosterone and aldosterone to be primarily of zona glomerulosa origin. These studies indicated that the zona fasciculata of both the salt-wasting and the simple virilizing forms is defective in 21-hydroxylation of 17-hydroxy and 17-deoxy steroids. The zona glomerulosa demonstrated deficient 21-hydroxylation only in the salt-wasting form, whereas in the simple virilizing form, the glomerulosa was spared this defect.

Effect of treatment with biosynthetic human growth hormone (GH) on peripheral blood lymphocyte populations and function in growth hormone-deficient children.

GH influences the immune response. The mechanism is not known; however, the presence of receptors for GH on human lymphocytes as well as its ability to influence and modulate immune responses in animals suggest an association between GH and immune function in man. We evaluated the effect of recombinantly derived natural sequence human GH (hGH) on lymphocyte surface antigen expression, response to mitogenic stimulation, expression of interleukin-1 receptors, and production of anti-hGH antibodies in GH-deficient children. The only observed changes were a decrease in the percentage of B-cells and a transient increased reactivity to phytohemagglutinin stimulation. It appears from the results of our studies that the administration of hGH has a selective effect on lymphocyte immune function; however, we cannot eliminate a role for hGH in the initiation or regulation of antigen-mediated immune responses.

A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome.

Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 families with triple A syndrome. The proband with IGD was a homozygote for an A-->G substitution, changing tyrosine 254 to cysteine in the third extracellular loop of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome.

Detection of human growth hormone receptors on IM-9 cells and peripheral blood mononuclear cell subsets by flow cytometry: correlation with growth hormone-binding protein levels.

We have developed a method using flow cytometry to identify fluorescein-conjugated GH receptors (GHR) on IM-9 lymphocytes and circulating peripheral blood mononuclear cell subsets. Binding to IM-9 cells and peripheral blood mononuclear cells was concentration dependent and could be competitively blocked by the addition of unlabeled human GH, but not by the addition of rat or bovine GH or human insulin or PRL. Using two-color flow cytometric analysis, fluorescein-conjugated human GHR were readily detected on more than 90% of B lymphocytes and monocytes, but only variably on T lymphocytes. B Lymphocytes and monocytes had approximately 6000 GHR/cell. Using two-color flow cytometry, we identified GHR on circulating B lymphocytes in subjects with GH deficiency (n = 9), precocious puberty (n = 6), and Turner syndrome (n = 5) and in seven subjects with miscellaneous disorders, including familial short stature, bone dysplasia, Crohn disease, congenital adrenal hyperplasia, and acromegaly. The percentage of B lymphocytes expressing GHR in subjects with GH deficiency (mean +/- SD, 95 +/- 9%), precocious puberty (91 +/- 15%), and Turner syndrome (84 +/- 15%) was not different from that in normal volunteers (90 +/- 12%; n = 14). In 10 subjects, serum GH-binding protein levels were assayed simultaneously with B lymphocyte GHR. GH-binding protein was normal in all (mean, 1255 pmol/L; range, 773-1809). There was a good correlation between GHR expression on B lymphocytes and GH-binding protein levels (r = 0.75; P = 0.01). We postulate that GHR found on circulating B lymphocytes may contribute to the pool of receptors identified in serum as GH-binding proteins. Two-color flow cytometry appears to be an effective method for the detection of GHR on circulating peripheral blood mononuclear cell subsets. The evaluation of GHR on circulating B lymphocytes may prove to be a useful means of evaluating GH-GHR interactions in subjects with growth disorders.

New studies of the 11 beta-hydroxylase and 18-hydroxylase enzymes in the hypertensive form of congenital adrenal hyperplasia.

Studies in four children with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency provide evidence for two separate 11 beta-hydroxylating systems in the adrenal zona fasciculata and zona glomerulosa. In addition, these studies support the proposal that the adrenal 11 beta- and 18-hydroxylating activities are related and may involve the same enzyme protein and catalytic site. In the untreated or poorly treated state, despite elevation of deoxycorticosterone (DOC) and tetrahydrodeoxycorticosterone, urinary free 18-hydroxy-DOC was in the low normal range and did not increase normally with ACTH. PRA and urinary free 18-hydroxycorticosterone (18-OHB), tetrahydroaldosterone (TH Aldo), and pH 1 aldosterone were suppressed in the untreated and ACTH periods. Glucocorticoid administration suppressed plasma ACTH, and urinary tetrahydro-DOC and free DOC excretion decreased to the normal range. Concomitantly, there was a rise in PRA accompanied by parallel increase in urinary 18-OHB, urinary TH Aldo, and pH 1 aldosterone. While on dexamethasone, a low sodium diet (10 meq/day) resulted in prompt sodium retention, with a further rise in PRA and urinary 18-OHB, TH Aldo, and pH 1 aldosterone. These studies indicate the presence of both an 11 beta- and an 18-hydroxylase deficiency in the zona fasciculata and normal 11 beta- and 18-hydroxylase function in the zona glomerulosa, suggesting that these two enzymatic functions are related and that separate enzyme systems are present in the two zones.

Subcutaneous growth hormone-releasing hormone therapy in growth hormone-deficient children: first year of therapy.

The purpose of this study was to determine the efficacy and safety of GH-releasing Hormone [GHRH-(1-44)] therapy in GH-deficient children. Twenty previously untreated prepubertal children with GHRH deficiency were treated for 1 yr in a multicenter, open label, company-sponsored study with at least 20 micrograms/kg GHRH-(1-44), sc, half at bedtime and half upon awakening. The main effects were enhancement of linear growth, advancement in bone age, and alteration in general blood chemistries and hormonal values. The mean velocity of the entire group increased from 3.6 +/- 1.1 to 8.1 +/- 1.5 cm/yr (P < 10(-4)) at 1 yr of therapy. After 6 months of therapy, 16 were growing at a mean of 9.4 +/- 2.0 cm/yr and were continued on this dose. In 4 patients who were growing at a rate of 5.5 +/- 1.7 cm/yr, the dose was increased to 40 micrograms/kg daily for the second 6 months. The high dose group increased their mean linear growth velocity for the second 6 months while on the higher dose to 7.6 +/- 0.4 cm/yr (P < 10(-2)). This was equal to the mean velocity for the second 6 months of therapy of the 16 subjects who remained on the 20 micrograms/kg daily therapy (7.6 +/- 1.2 cm/yr). Mean advancement of bone age was 1.3 +/- 0.6 yr during the first year of therapy. No adverse changes in general biochemical, hormonal, or pituitary radiographic analyses were noted. No change in fasting glucose or insulin concentrations, or excessive generation of insulin-like growth factor-I concentrations occurred. We conclude that GHRH in a daily dose of 20-40 micrograms/kg for 1 yr was effective in increasing growth velocity in most GHRH-responsive GH-deficient patients. It was well tolerated without side-effects. Glucose intolerance was not noted.

Thyrotropin-releasing hormone stimulation tests in infants.

The TSH response to TRH administration (7 micrograms/kg) was measured in 68 infants (22 premature) who had abnormal thyroid screening tests by the filter paper method and whose serum thyroid function tests were only mildly abnormal. Twenty-eight infants (12 premature) had peak TSH values of 35 mU/L or less and were considered normal (group I). Forty infants (10 premature) had peak TSH values above 35 mU/L and were considered hyperresponsive (group II). The mean age at testing, screening T4, TSH levels that prompted the testing, as well as baseline T4, T3, and free T4 at the time of TRH testing were not different between the groups. The mean (+/- SD) baseline TSH value was greater in group II (6.8 +/- 2.3 mU/L) than in group I (4.4 +/- 2.2 mU/L; P < 0.001). However, there was a great deal of overlap in the individual TSH values (group I, 0.9-10 mU/L; group II, 1.9-10.6 mU/L). Mean peak TSH levels were significantly different in the two groups (group I, 24 +/- 7.7 mU/L; group II, 60.3 +/- 26.1 mU/L; P < 0.001). During long term follow-up, all 25 group I infants available for evaluation have been confirmed as clinically and biochemically normal. No infant diagnosed as normal was later found to have evidence of hypothyroidism. Fourteen infants in group II have had evidence of thyroid dysfunction. We conclude that the TSH response to TRH stimulation is a useful tool for the evaluation of infants suspected of having primary hypothyroidism. Whether hyperresponsiveness to TRH represents a form of neonatal hypothyroidism requiring treatment remains to be determined.

No apparent mineralocorticoid receptor defect in a series of sporadic cases of pseudohypoaldosteronism.

Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Although the mineralocorticoid receptor (MR) was suggested as a potential locus of the defect in this disease, no such abnormality was found in 3 recently reported cases, one of whom belongs to this series of 5 patients. Molecular studies of the MR complementary DNA and gene in this series of sporadic cases of pseudohypoaldosteronism are reported. Four of these patients had multiple mineralocorticoid target tissue resistance, whereas 1 had transient isolated resistance in the kidney. A nonconservative homozygous mutation (C944-->T944, Ala241-->Val241) was identified in the complementary DNA of 4 of the patients but was also found in 62 of 100 normal alleles. One of these 4 patients had an additional conservative heterozygous mutation (A760-->G760, Ileu180-->Val180), which was also present in 11 of 100 normal alleles. None of the patients had any abnormalities in the first untranslated exon and 0.9 kilobases of the 5'-regulatory region of the MR gene, which were fully sequenced and compared with the normal sequence. It is concluded that the mutations identified in 4 of these 5 patients with PHA are polymorphisms, which on their own have no apparent pathophysiological significance. It is hypothesized that the defect causing PHA might be in a post-MR step of aldosterone action or in an unsuspected nonclassic receptor for this hormone.

46,XX pure gonadal dysgenesis with growth hormone deficiency and impaired 3 beta-hydroxysteroid dehydrogenase activity.

Patients with 46,XX pure gonadal dysgenesis generally are of normal stature and have less than usual amounts of pubic and axillary hair. We report on a patient who presented at age 11.9 years with short stature, absence of breast development, and excessive pubic hair. Her karyotype in leukocytes, fibroblasts, and streak gonad was 46,XX. The patient was diagnosed as having growth hormone deficiency. Elevated ACTH stimulated levels of 17-hydroxypregnenolone and dehydroepiandrosterone and elevated ACTH stimulated ratio of 17-hydroxypregnenolone to 17-hydroxyprogesterone suggested inadequate adrenal 3 beta-hydroxysteroid dehydrogenase activity. Treatment with growth hormone resulted in improvement in growth velocity and replacement with estrogen in feminization. We suggest that the finding of short stature in patients with 46,XX pure gonadal dysgenesis should not be attributed to the syndrome, but rather requires investigation for possible growth hormone deficiency. The poor growth of our patient prior to growth hormone replacement implies that dehydroepiandrosterone, unlike testosterone and estrogen, is ineffective in promoting linear growth in the absence of adequate growth hormone.

Familial Pallister-Hall syndrome: case report and hormonal evaluation.

Pallister-Hall syndrome is a usually lethal dysplasia/malformation syndrome characterized by hypothalamic hamartoblastoma, hypopituitarism, postaxial polydactyly, craniofacial malformations, imperforate anus, and other malformations. We report a familial case in a male infant and his female sib fetus, suggesting autosomal recessive inheritance, or germinal mosaicism for an autosomal dominant mutation, or a segregating submicroscopic chromosome abnormality. Detailed endocrine evaluation on the surviving infant revealed documented pituitary function, pituitary deficit, and hypothalamic deficiency. We suggest that hypothalamic dysfunction contributes to the hypopituitarism seen in Pallister-Hall syndrome.

Modulating effect of human growth hormone on tumour necrosis factor-alpha and interleukin-1beta.

We measured serum tumour necrosis factor-alpha (TNF-alpha) as well as interleukin-1betta (IL-1beta) and GH concentrations in 15 children with isolated growth hormone deficiency (GHD), age range 5.1-13.9 years, before and 4 and 24h after the first GH injection (0.1 IU/kg s.c.). No differences were found in basal concentrations of serum TNF-alpha and IL-1beta between GHD children (10.01 +/- 1.55 pg/ml and 2.14 +/- .16 ng/ml respectively) and sex- and age-matched controls (11.57 +/- 2.16 pg/ml and 3.78 +/- 1.46 ng/ml respectively). In GHD children, serum TNF-alpha and IL-1beta values had significantly increased (P < 0.002) 4h (26.75 +/- 5.57 pg/ml and 2.99 +/- 0.21 ng/ml respectively) and decreased again 24 h after GH administration. Likewise, serum GH levels had significantly increased 4 h (from 1.29 +/- 0.69 to 48.71 +/- 13.35 ng/ml, P < 0.001) and decreased to basal values 24h after GH administration. A significant correlation was found between basal serum concentrations of GH and those of both TNF-alpha (P < 0.01) and IL-1beta (P < 0.05). However, no correlation was found between serum GH concentration and either TNF-alpha or IL-1beta levels 4 and 24h after GH administration. Our data suggest that GH plays a role in modulating TNF-alpha and IL-1beta release in humans.

Clonal analysis of peripheral T cell precursors in lpr mice.

MRL/Mp-lpr/lpr mice develop massive lymphadenopathy characterized by expansion of an unusual population of T cells with the Thy 1+, CD3+, CD4-, CD8- (double negative) phenotype. The role these cells play in accelerating the autoimmune syndrome seen in these mice is unknown. In order to better understand the origin of the expanded population of T cells, we have derived a panel hybridomas from double negative lpr lymph node cells. Surprisingly, eleven of twelve hybridomas selected for the absence of surface CD4 and CD8 do not express CD3. Six of eleven confirmed to have inherited the MRL T cell receptor locus have rearrangement at that locus, suggesting commitment to a T cell lineage. Only hybridoma 2.4, which expresses CD3, responds to ConA, anti-CD3 monoclonal antibody, and induces antibody production. The presence of CD3-, CD4-, CD8- T cells in the periphery of lpr mice confirms aberrant T cell development in these mice and suggests an intrinsic cell defect which is expressed early in lymphopoiesis.

Negatively charged quantum well polaritons in a GaAs/AlAs microcavity: An analog of atoms in a cavity

The negatively charged exciton (X-) is observed to strongly couple with the microcavity- (MC-)confined photons in a GaAs quantum well containing a two-dimensional electron gas with 0

Effects of human growth hormone on immune functions: in vitro studies on cells of normal and growth hormone-deficient children.

We have studied the in vitro effects of human growth hormone on cell surface markers and mitogenic responses of peripheral blood lymphocytes (PBL) of normal and growth hormone-deficient children before, during and after treatment with growth hormone. Growth hormone resulted in a decrease in B cell expression but it did not affect expression of T cell subsets. Growth hormone depressed the proliferation of PBL of normal and untreated growth hormone-deficient children. The proliferative responses to phytohemagglutinin (PHA) versus PHA with growth hormone were not statistically different, though the responses of most normal and on treatment children were diminished by the addition of growth hormone. PBL derived from growth hormone-deficient children during treatment with human growth hormone exhibited significantly greater spontaneous proliferation then the PBL of normal children. Growth hormone further significantly enhanced their proliferation. PHA and PHA with growth hormone resulted in significantly greater proliferation of these patients' PBL when compared to those of normal children. We demonstrated that human growth hormone had substantial in vitro effects on immune functions. These effects, some of which depend on the treatment status of the children, may need to be considered in the clinical use of human growth hormone.