Biomedical subjects

A T Soliman

Publications and source records attributed to A T Soliman.

At least 19 recordsLinked to original sources

PubMed2001

Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy.

Pycnodysostosis is a rare hereditary bone abnormality with an autosomal recessive mode of inheritance. We report the clinical, radiologic, and endocrine status of 8 children with this rare disease. All patients had the characteristic phenotype of the disorder including short stature (8 of 8), increased bone density (7 of 8), separated cranial sutures (8 of 8), large fontanel with delayed closure (8 of 8), obtuse mandibular angle (8 of 8), delayed teeth eruption (8 of 8), enamel hypoplasia (7 of 8), dysplastic acromial ends of the clavicles (6 of 8), frontal bossing (6 of 8), ocular proptosis (8 of 8), and dysplastic nails (8 of 8). Developmental evaluation according to the revised Denever developmental screening showed normal motor, fine motor-adaptive language, and personal social abilities in all the children. All had normal hepatic and renal functions. Serum calcium and phosphorus concentrations were normal. Two children had low serum alkaline phosphatase concentration. Short stature is a characteristic feature of pycnodysostosis. Seven of the 8 children were born short (length standard deviation score [SDS] = -3 to -1.5). Deceleration of linear growth was significant during the first 3 years of life. All the children had height SDS below -3 at the end of their third year of life. Although short stature is a feature of this genetic disorder, defective growth hormone (GH) secretion in response to provocation with clonidine and glucagon was found in 4 of the 8 patients. These 4 patients had pituitary hypoplasia on the magnetic resonance imaging (MRI) of their brain. In addition, 3 of these 4 patients had demyelination of the cerebrum. Patients with pycnodysostosis (n = 8) had low circulating concentrations of insulin-like growth factor-1 (IGF-1) compared with normal age-matched short children with constitutional short stature (CSS). IGF-I increased significantly after injecting GH for 3 days in these patients. Physiologic replacement with GH (18 U/m(2)/week) divided in daily evening doses subcutaneously increased IGF-1 concentration and improved linear growth velocity and height standard deviation scores (HtSDS) in the 4 children with GH deficiency. These data ruled out GH resistance and proved the usefulness of GH therapy in the management of short stature in these patients. In summary, some patients with pycnodysostosis have partial GH deficiency and low IGF-1 concentration. GH therapy markedly increases IGF-I secretion and improves their linear growth. MRI study of the brain including the hypothalamic-pituitary area is recommended in these children because of the high incidence of pituitary hypoplasia and cerebral demyelination.

Adolescent↗

PubMed2001

Growth parameters and endocrine function in relation to echocardiographic parameters in children with ventricular septal defect without heart failure.

To determine the effect of ventricular function, size of ventricular septal defect (VSD), and endocrine function on linear growth in children with VSD, we studied 88 children with VSD over a period of 1 year. Growth was assessed by determining the height standard deviation scores (HtSDS) and growth velocity (GV) every 4 months. Two hundred age-matched normal children served as controls for the growth data. Endocrine evaluation was performed in 30 randomly selected children with VSD, and 20 age-matched children with constitutional delay of growth (CSS). Growth hormone (GH) response to clonidine provocation was evaluated and circulating free thyroxine (FT4) and insulin-like growth factor-I (IGF-I) concentrations measured. Echocardiographic evaluation of the different cardiac parameters including shunt size and shunt fraction (Qp/Qs) was performed using a colour-coded echodoppler. The HtSDS, body mass index (BMI), and mid-arm circumference (MAC) of children with VSD were significantly decreased compared to those for the normal control group. The dietary intake evaluated by the recall method, appeared to be adequate in the majority of these children (83/88). IGF-I concentrations were reduced in children with VSD (87.5 +/- 29 ng/ml) versus normal age-matched children (169 +/- 42 ng/ml). Basal and clonidine-stimulated GH concentrations were significantly higher in children with VSD (4.6 +/- 2.1 microg/l and 28.8 +/- 7.9 microg/l respectively) versus controls (17.8 +/- 4.2 microg/l). In these patients (n = 88) the HtSDS was correlated negatively with the size of the shunt (r = -0.793, p < 0.001), shunt fraction (Qp/Qs) (r = -0.76, p < 0.001), pulmonary mean gradient (r = -0.4, p = 0.006), and pulmonary maximum velocity (r = -0.32, p = 0.02). Growth velocity (GV) was correlated negatively with pulmonary maximum gradient (r = -0.3, p = 0.02), pulmonary maximum velocity (r = -0.37, p = 0.007), and pulmonary stroke volume (Qp) (r = -0.345, p = 0.01). The BMI and IGF-I concentrations were correlated significantly with the size of the shunt (r = -0.453, p < 0.01), Qp/Qs (r = -0.432, p < 0.01), HtSDS (r = 0.565, p < 0.01), and BMI (r = 0.435, p < 0.01). It appears that in patients with VSD, the size of the left-to-right shunt and the abnormal hemodynamics in the pulmonary circulation are important factors in the etiology of impaired growth. It is suggested that the hypermetabolic status of these patients compromise nutrition and this decreases IGF-I synthesis with subsequent slowing of linear growth and weight gain.

Body Mass Index↗

PubMed2000

Serum leptin concentrations during severe protein-energy malnutrition: correlation with growth parameters and endocrine function.

Circulating leptin, insulin, insulin-like growth factor-I (IGF-I), cortisol, and albumin concentrations and the growth hormone (GH) response to provocation were measured in 30 children with severe protein-energy malnutrition (PEM), 20 with marasmus and 10 with kwashiorkor, as well as 10 age-matched normal children (body mass index [BMI] >50th and <90th percentile for age and sex) and 10 prepubertal obese children (BMI >95th percentile for age and sex). Patients with PEM had a significantly lower BMI, midarm circumference (MAC), and skinfold thickness (SFT) compared with the age-matched control group. Basal cortisol and GH concentrations were significantly higher in the malnourished groups versus controls. Leptin and IGF-I were significantly lower in the marasmic and kwashiorkor groups versus normal children. Fasting insulin levels were significantly decreased in the kwashiorkor group compared with marasmic and normal children. The BMI correlated significantly with leptin (r = .77, P < .001), basal insulin (r = .61, P < .001), and IGF-I (r = .77, P < .001) and negatively with basal GH (r = -.52, P < .001). These findings suggest that during prolonged nutritional deprivation, the decreased energy intake, diminished subcutaneous fat mass, and declining insulin (and possibly IGF-I) concentration suppress leptin production. In support of this view, serum leptin levels were positively correlated with triceps, scapular, and abdominal SFT (r = .763, .75, and .744, respectively, P < .0001) in all of the children. Moreover, basal insulin and circulating IGF-I were correlated significantly with leptin concentrations (r = .47 and .62, respectively, P < .001). Basal levels of cortisol and GH were significantly elevated in the 2 groups with severe PEM. It is suggested that low leptin levels can stimulate the hypothalamic-pituitary-adrenal (HPA) axis and possibly the hypothalamic-pituitary-GH axis to maintain the high cortisol and GH levels necessary for effective lipolysis to ensure a fuel (fatty acids) supply for the metabolism of brain and peripheral tissue during nutritional deprivation. In summary, during prolonged PEM, the decreased synthesis of IGF-I and the low level of insulin and/or its diminished effect due to an insulin-resistant status in the presence of high circulating GH and cortisol levels ensure substrate diversion away from growth toward metabolic homeostasis. Leptin appears to be an important signal in the process of metabolic/endocrine adaptation to prolonged nutritional deprivation.

Child, Preschool↗

PubMed2000

Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty.

To elucidate whether the cause of sexual maturation arrest in thalassaemia is of gonadal or pituitary etiology, 10 males with thalassaemia and delayed puberty and 10 with constitutional delay of growth and pubertal maturation (CSS) were extensively studied. Their spontaneous nocturnal gonadotropin secretion and gonadotropin response to intravenous 100 micrograms gonadotropin-releasing hormone (GnRH) were evaluated. Circulating testosterone concentration and clinical response were evaluated after 3 days, 4 weeks and 6 months of intramuscular administration of human chorionic gonadotropin (HCG) (2500 U/m2/dose). Thalassaemic boys had significantly lower circulating concentrations of testosterone compared to those with constitutional delay of growth and sexual maturation (CSS) at the same pubertal stage. Short- and long-term testosterone response to administrations of HCG was markedly decreased in thalassaemic boys. After 6 months of HCG administration 50 per cent (5/10) of the boys did not show significant testicular enlargement or genital changes. Despite the low circulating concentrations of testosterone, none of the patients had high basal or exaggerated gonadotropin response to gonadotropin releasing hormone (GnRH) stimulation. Luteinizing hormone (LH) peak responses to GnRH were significantly lower as compared to controls. Follicle-stimulating hormone (FSH) peak responses to GnRH did not differ among the two study groups. The mean nocturnal LH and FSH secretion was significantly decreased in all thalassaemic boys as compared to boys with CSS at the same pubertal stage (testicular volume). These data proved that hypogonadotropic hypogonadism is the main cause of delayed/failed puberty in adolescents with thalassaemia major. MRI studies revealed complete empty sella (n = 5), marked diminution of the pituitary size (n = 5), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 8) in thalassaemic patients, denoting a high incidence of structural abnormalities (atrophy) of the pituitary gland. Moreover, in many of the thalassaemic boys, the defective testosterone response to long-term (6 months) HCG therapy denoted significant testicular atrophy and/or failure secondary to siderosis. It appears that testosterone replacement might be superior to HCG therapy in these patients. This therapy should be introduced at the proper time in these hypogonadal patients to induce their sexual development and to support their linear growth spurt and bone mineral accretion.

Adolescent↗

PubMed1999

Growth and pubertal development in transfusion-dependent children and adolescents with thalassaemia major and sickle cell disease: a comparative study.

Despite regular blood transfusion and desferrioxamine treatment, growth impairment and pubertal delay are commonly seen in children and adolescents with transfusion-dependent thalassaemia and sickle cell disease (SCD). We evaluated growth parameters and sexual maturation in a large cohort of children and adolescents with SCD (n = 110) and thalassaemia (n = 72) receiving nearly the same protocol of transfusion and chelation, and compared them with those for 200 normal age-matched children, 30 children with constitutional delay of growth (CSS), and 25 children with growth hormone deficiency (GHD). Before transfusion, haemoglobin concentration had not been less than 9 g/dl in the past 7 years; desferrioxamine was administered for 7-10 years, including by the intramuscular and subcutaneous routes, three times or more per week. The height standard deviation score (HtSDS), growth velocity (GV) (cm/yr), and growth velocity standard deviation score (GVDSD) of children and adolescents with thalassaemia and SCD were significantly decreased compared to normal children (p < 0.01). Forty-nine per cent of thalassaemic patients and 27 per cent of patients with SCD had HtSDS less than -2, and 83 per cent of thalassaemic patients and 67 per cent of SCD patients had HtSDS less than -1. Fifty-six per cent of thalassaemic children and 51 per cent of children with SCD had GVSDS less than -1. The GV of thalassaemic children was significantly slower than that for children with SCD. Children with thalassaemia and SCD had HtSDS and GVSDS comparable to those for children with CSS but higher than those for patients with GHD. Serum ferritin concentration was correlated significantly with the linear GV in all patients (r = 0.45, p < 0.001). The bone age delay did not differ among the three groups with thalassaemia, SCD and CSS, but the delay was significant in the group with GHD. The mid-arm circumference was significantly smaller in children with thalassaemia and SCD than in normal children. The triceps skin-fold thickness of patients with SCD was significantly decreased compared to thalassaemic and normal children. The upper/lower segment ratio was significantly lower in thalassaemic and SCD patients than in normal children. In thalassaemic patients between the ages of 13 and 21 years a complete lack of pubescent changes was present in 73 per cent of boys and 42 per cent of girls. Seventy-four per cent of the thalassaemic girls had primary amenorrhoea. Girls with SCD aged between 13 and 21 years had markedly delayed breast development and menarche. Twenty-five per cent of boys with SCD above the age of 14 years had absence of testicular development. Males with thalassaemia and SCD who had spontaneous testicular development had significantly smaller testicular volume than did normal controls. Short children with thalassaemia and SCD had significantly decreased serum insulin-like growth factor 1 (IGF-1) concentrations compared to children with CSS. Collectively, these data confirm the high prevalence of impaired growth and pubertal delay/failure in children and adolescents with thalassaemia and SCD. The aetiology of impaired growth includes the contributions of lack of pubertal growth spurt due to delayed/absent puberty, decreased synthesis of IGF-1 which might be secondary to a disturbed GH-IGF-1 axis and/or under nutrition, probably due to the hypermetabolic status of these children. It is suggested that newer protocols of treatment, in addition to optimization of transfusion and chelation requirements, should increase the caloric intake of these patients and properly manage their pubertal delay-failure in order to improve their adult height.

Adolescent↗

PubMed1999

Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth.

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.

Adolescent↗

PubMed1998

Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data.

Patients with beta-thalassemia major (beta-thalassemia) frequently have bone disorders of multifactorial etiology. We attempted to analyze the relationship between the bone mineral density ([BMD] measured by dual-photon absorptiometry) and auxanologic parameters, degree of siderosis, function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 (IGFBP3) axis, calcium-phosphate balance, parathyroid hormone (PTH), and cytokines (interleukin-1beta [IL-1] and tumor necrosis factor-alpha [TNF-alpha]) in 30 prepubertal children with beta-thalassemia major and 15 age-matched children with constitutional short stature (CSS), who have normal glucose tolerance and thyroid function. Children with beta-thalassemia had a significantly decreased BMD and mean BMD% for age and sex (0.75+/-0.24 g/cm2 and 71%+/-10%, respectively) versus children with CSS (1.06+/-0.3 g/cm2 and 92%+/-7%, respectively). Thalassemic patients had significantly lower circulating concentrations of IGF-I and IGFBP3 (49+/-21 ng/mL and 1.2+/-0.25 mg/L, respectively) compared with control children (153+/-42 ng/mL and 2.1+/-0.37 mg/L, respectively). The GH response to provocation by clonidine and glucagon was defective (peak GH < 7 microg/L) in 12 of the 30 thalassemic children. Serum concentrations of IL-1beta and TNF-alpha did not differ among the two study groups. Hypocalcemia was detected in five of the 30 thalassemic patients: hypoparathyroidism was diagnosed in two of the five and rickets in the other three. BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, weight, height, height standard deviation score [HSDS], and body mass index [BMI]). It is suggested that increasing the circulating IGF-I concentration through aggressive nutritional therapy and/or GH/IGF-I therapy with supplementation with vitamin D and/or calcium might improve bone growth and mineralization and prevent the development of osteoporosis and consequent fractures in these patients. Such therapy requires blinded controlled trials.

Absorptiometry, Photon↗

PubMed1998

Recessive Robinow syndrome: with emphasis on endocrine functions.

We present the characteristic features of 14 children with the recessive form of Robinow syndrome and the growth hormone (GH) response to provocation with clonidine and the serum insulin-like growth factor-I (IGF-I) concentration in 12 of these children. The gonadotropin (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) response to gonadotropin-releasing hormone (GnRH) was evaluated in early pubertal and pubertal patients, and the testosterone response to human chorionic gonadotropin (HCG) was evaluated in males. Children with Robinow syndrome, born at full-term, were short at birth (length, 41.4+/-2.1 cm) and had markedly slow growth velocity (GV) during the first year (13.1+/-2.1 cm/yr); consequently, they were significantly short at the end of the first year of life (length, 54.4+/-2.9 cm). This intrauterine and early extrauterine growth delay reflected low growth potential. During childhood, the GV standard deviation score (GVSDS) remained low (-2.17+/-0.83). Despite the presence of empty sella in all of the patients, they had an adequate GH response to clonidine provocation (peak, 19.3+/-5.8 microg/L) and a normal serum IGF-I concentration (309+/-142 ng/mL) for their age. During childhood and early adolescence, boys with Robinow syndrome had low basal testosterone and a low testosterone response to HCG stimulation (3,000 IU/m2/d intramuscularly [IM] for 3 days). However, their basal and GnRH-stimulated FSH concentrations were normal. Two girls (Tanner II breast development) had a normal serum estradiol (E2) concentration but high LH and FSH responses to GnRH stimulation. This suggested either defective feedback of E2 on the hypothalamic-pituitary axis or hyporesponsiveness of the ovaries to gonadotropin. Four weeks of HCG therapy (2,500 IU/m2 IM twice weekly) in three boys with Robinow syndrome increased the penile length and testicular volume, denoting a significant Leydig cell response to prolonged HCG stimulation and the presence of functioning androgen receptors. It is suggested that HCG and/or testosterone therapy during infancy may improve the severe micropenis in these patients.

Abnormalities, Multiple↗

PubMed1998

Decreased bone mineral density in prepubertal children with sickle cell disease: correlation with growth parameters, degree of siderosis and secretion of growth factors.

Patients with sickle cell disease (SCD) frequently have bone disorders of multifactorial aetiology. We attempted to analyse the relationships between bone mineral density (BMD) on the one hand and auxologic parameters, degree of siderosis, function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein 3 (IGFBP3) axis, and calcium-phosphate balance in 28 prepubertal children with SCD and 15 age-matched children with constitutional short stature (CSS). Children with SCD had significantly decreased BMD (77.9 +/- 11.9 per cent of normal BMD for age and sex) and circulating concentrations of IGF-I (91 +/- 31 ng/ml) and IGFBP3 (1.7 +/- 0.44 mg/l) compared with the control group (BMD = 93.5 +/- 8.2 per cent of normal BMD for age and sex, IGF-I = 221 +/- 48 ng/ml, and IGFBP3 = 2.3 +/- 0.34 mg/ml). GH response to provocation was defective (peak below 10 micrograms/l) in 40 per cent of children with SCD. Those with SCD with defective GH secretion had significantly lower circulating IGF-I concentration and BMD than those with normal GH secretion. Serum calcium, phosphate and alkaline phosphatase concentrations were normal in all children with SCD. BMD was correlated significantly with height, weight, and body mass index as well as with the circulating concentrations of IGF-I and IGFBP3. It is suggested that increasing the circulating IGF-I concentration, either through increasing the caloric intake of subjects and/or via GH/IGF-I therapy, may improve growth and bone mineralization in these patients.

Anemia, Sickle Cell↗

PubMed1998

GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia.

The causes of growth retardation of children with thalassaemia major are multifactorial. We studied the GH response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, IGF-I, IGF-binding protein-3 (IGFBP-3) and ferritin, and evaluated IGF-I generation after a single dose of GH (0.1 mg/kg per dose) in 15 prepubertal patients with thalassaemia, 15 age-matched children with constitutional short stature (CSS) (height standard deviation score less than -2, with normal GH response to provocation) and 11 children with isolated GH deficiency (GHD). Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (6.2 +/- 2.3 and 6.8 +/- 2.1 microg/l respectively) than the CSS group (18.6 +/- 2.7 and 16.7 +/- 3.7 microg/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP-3 (47.5 +/- 19 ng/ml and 1.2 +/- 0.27 mg/l respectively) compared with those with CSS (153 +/- 42 ng/ml and 2.06 +/- 0.37 mg/l respectively), but the IGF-I and IGFBP-3 concentrations were not different from those with GHD (56 +/- 25 ng/ml and 1.1 +/- 0.32 mg/l respectively). These data demonstrate that the GH-IGF-I-IGFBP-3 axis in thalassaemic children is defective. Serum ferritin concentration correlated significantly with GH peak response to provocation (r = -0.36, P < 0.05) and circulating IGF-I (r = -0.47, P < 0.01) and IGFBP-3 (r = -0.42, P < 0.01) concentrations. In the IGF-I generation test, after GH injection, the thalassaemic children had significantly lower IGF-I and IGFBP-3 levels 86.7 +/- 11.2 ng/ml and 2.05 +/- 0.51 mg/l respectively) than those in the CSS group (226 +/- 45.4 ng/ml and 2.8 +/- 0.43 mg/l respectively). The IGF-I response was significantly higher in children with GHD (158 +/- 50 ng/ml) than in thalassaemic children. Six short (height standard deviation score less than -2) thalassaemic children who had defective GH response to provocation (< 10 microg/l), all the children with GHD and eight short normal children (CSS) were treated for 1 year with human GH (18 units/m2 per week divided into daily s.c. doses). After 1 year of GH therapy there was a marked acceleration of growth velocity in both thalassaemic children (from 3.8 +/- 0.6 cm/year to 7.2 +/- 0.8 cm/year) and controls. However, the linear acceleration of growth velocity on GH therapy was significantly slower in thalassaemic children (3.3 +/- 0.3 cm/year increment) compared with those with CSS (5.3 +/- 0.4 cm/year increment) and GHD (6.9 +/- 1.2 cm/year increment) (P < 0.05). Their circulating IGF-I concentration (105 +/- 36 ng/ml) was significantly lower than those for CSS (246 +/- 58 ng/ml) and GHD (189 +/- 52 ng/ml) after 1 year of GH therapy. These data prove that some children with beta-thalassaemia major have a defective GH-IGF-I-IGFBP-3 axis and suggest the presence of partial resistance to GH.

Adolescent↗

PubMed1997

Congenital adrenal hyperplasia complicated by central precocious puberty: linear growth during infancy and treatment with gonadotropin-releasing hormone analog.

Some children with congenital adrenal hyperplasia (CAH) develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have seen six such children who had the diagnosis of CAH with late initiation of corticosteroid treatment and/or poor compliance who developed central precocious puberty (CPP). These patients were treated with standard-dose hydrocortisone and fludrocortisone. Administration of depot leuprorelin (3.75 mg subcutaneously every 28 days) for 2 years or longer was effective in arresting the manifestations of puberty, decelerating the pretreatment growth velocity ([GV] 10.8 +/- 1.5 v3.65 +/- 0.95 cm/yr), increasing the predicted adult height ([PAHT] 147.5 +/- 7.8 v 153.4 +/- 8.3 cm), and decreasing the bone age to statural age ratio (1.26 +/- 0.13 v 1.16 +/- 0.09). Analysis of auxanological data during the first 2 years of life showed that linear growth was significantly accelerated and bone age was advanced in patients who developed CPP compared with 11 age-matched patients. It appears that proper glucocorticoid replacement to achieve adequate control of hyperandrogenemia during early life might prevent development of CPP in these patients. Gonadotropin-releasing hormone agonist (GnRHa) therapy can improve the final adult height, bringing it closer to that expected from the genetic potential.

Adrenal Hyperplasia, Congenital↗

PubMed1997

Growth hormone secretion and circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3 concentrations in children with sickle cell disease.

Impaired growth involving both height and weight accompanying sickle cell disease (SCD) poses diagnostic and therapeutic problems. We undertook this study to test the hypothesis that this impaired growth is associated with abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF binding protein-3 (IGFBP-3) axis in 21 children with SCD and that SCD is associated with GH resistance. Nine of 21 children with SCD had a defective GH response to both clonidine and glucagon provocation (peak < 10 micrograms/L); these children differed from the 12 others in having slower linear growth velocity (GV and GVSDS), lower circulating concentrations of IGF-I and IGFBP-3, and either partial or complete empty sellae in computed tomographic scans of the hypothalamic-pituitary area. In this group of patients with SCD, it appears that defective GH secretion and consequent low IGF-I production are the major etiological factors causing the slow growth. The two groups with SCD did not differ significantly in dietary intake, body mass index (BMI), midarm circumferences, skinfold thickness, serum albumin concentration, or intestinal absorption of D-xylose. A single injection of GH produced a smaller increase in circulating IGF-I in children with SCD with or without defective GH secretion versus 10 age-matched children with idiopathic short stature (ISS) and 11 children with isolated GH deficiency (GHD), suggesting partial GH resistance in the SCD group. The presence of defective GH secretion, decreased IGF-I synthesis, and partial resistance to GH in short children with SCD suggests that treatment with IGF-I may be superior to GH therapy for improving growth.

Adrenergic alpha-Agonists↗

PubMed1997

Growth parameters and endocrine function in relation to echocardiographic parameters in children and adolescents with compensated rheumatic heart disease.

To determine the effect of left ventricular and endocrine functions on linear growth in children with rheumatic heart disease (RHD) we studied 100 children and adolescents with RHD over a period of 1 year. The mean +/- SD for age of onset and duration of RHD were 7.3 +/- 3.8 years and 4.4 +/- 2.8, respectively. The cardiac lesions were mitral incompetence (n = 31), combined mitral and aortic incompetence (n = 64), and mitral stenosis (n = 5). Growth was assessed by determining both height standard deviation scores (HtSDS) and growth velocity standard deviation score (GVSDS) every 4 months, and sexual maturity was assessed according to Tanner's criteria. Two-hundred age-matched normal children served as controls for the growth data. Endocrine evaluation was performed in the 30 children with RHD who had age above 14 years (mean age 15.4 +/- 1.5 years), 20 age- and sex-matched normal children, and 20 age-matched children with constitutional delay of growth (normal variant short stature) (NVSS). Circulating concentrations of estradiol (E2) in girls, testosterone (T) in boys, and free T4 (FT4) were measured. Growth hormone (GH) response to clonidine provocation, LH and FSH response to LHRH stimulation, and in boys testosterone (T) response to HCG were evaluated. Echocardiographic evaluation of the left ventricular parameters was performed using a colour-coded echodoppler. The HtSDS and GVSDS of children with RHD were significantly lower than those for the normal control group. Delayed onset of puberty was evident in 16/30 of the children with RHD, and 6/ 30 more had sexual maturity score below 10th percentile for age and gender. In comparison with the age-matched normal group, those with RHD had significantly lower sexual maturity score (1.8 +/- 0.4 v. 3.25 +/- 0.8). All the children had normal GH response to clonidine provocation and normal FT4 concentrations. Basal and HCG stimulated T concentrations were significantly low in adolescents with RHD and E2 levels were non-significantly lower in girls with RHD compared to normal controls. LH response to LHRH was significantly decreased in RHD patients v. controls denoting delayed maturation of the hypothalamic-pituitary gonadal axis. HtSDS and GVSDS were correlated significantly with the left ventricular echocardiographic parameters, including left ventricular end diastolic diameter (LVEDD) (r = 0.57, and 0.617, respectively; P < 0.01), left ventricular end systolic diameter (LVESD) (r = 0.49, and 0.546, respectively; P < 0.01), left ventricular end diastolic volume (LVEDV) (r = 0.33 and 0.31, respectively; P < 0.05), left ventricular end systolic volume (LVESV) (r = 0.325 and 0.33, respectively; P < 0.05), peak velocity of circumferential fibres (Vcf) (r = 0.25 and 0.38, respectively; P < 0.05), and with pre-ejection period/ejection time (PEP/ET) (r = 0.14 and 0.47, respectively; P < 0.05). It appears that linear growth of children with RHD, without heart failure, depends on the left ventricular function. In addition, they have high incidence of delayed sexual development secondary to delayed maturation of their hypothalamic-pituitary gonadal axis.

Adolescent↗

PubMed1997

Mode of presentation and progress of childhood diabetes mellitus in the Sultanate of Oman.

We surveyed the clinical presentation, initial management and subsequent course of a prospectively registered cohort of 60 children with insulin-dependent diabetes mellitus (IDDM) diagnosed before age 15 years in the Sultanate of Oman between January 1990 and December 1993. Clinical details from the time of diagnosis were available on all the children. At diagnosis 9 (15 per cent) presented with severe ketoacidosis (DKA) with pH less than 7.1 or plasma bicarbonate less than 10 mmol/l, and 16 (27 per cent) had mild to moderate ketoacidosis with pH 7.1-7.35 or plasma bicarbonate 10-18 mmol/l. During DKA electrolyte disturbances included: hypokalemia (K < 3.5 mmol/l) 25 per cent), hyperkalemia (K > 5.5 mmol/l) (18 per cent) and hyponatremia (Na < 130 mmol/l) (40 per cent). Serum creatinine concentrations were high in 25 per cent of children with DKA. Within the first year of diagnosis, 17 of the 60 children (28 per cent) experienced symptomatic hypoglycaemia, which in six (10 per cent) led to one or more admissions. Re-admission for unstable glycaemic control, excluding acute hypoglycaemia occurred at least once in six children (10 per cent) within 1 year of diagnosis and in 10 (17 per cent) within 2 years. Statural growth velocity (GV) and GVSDS (6.9 +/- 0.85 cm/year and 0.75, respectively) were significantly higher in the group of children with good glycaemic control (HbA1C = 7.9 +/- 0.4 per cent) compared to those children (3.7 +/- 0.44 cm/ year and -1.6, respectively) with bad glycaemic control (HbA1C = 12.5 +/- 1.5 per cent). Insulin-like growth factor-I (IGF-I) concentrations were significantly higher (260 +/- 21 ng/ml) in the group with good glycemic control v. the group with bad control (149 +/- 15 ng/ml). In summary, greater public and medical awareness of the presenting features of diabetes in young children is needed to reduce the frequency of DKA at presentation, and improvement of patient and family education is necessary to reduce the incidence of DKA and hypoglycaemia in children with IDDM.

Adolescent↗

PubMed1997

Growth hormone secretion and serum insulin-like growth factor-I concentration in X-linked hypophosphatemic rickets before and after treatment.

The aetiology of growth retardation in children with X-linked hypophosphatemic rickets (HPR) has not been totally defined. We evaluated growth hormone (GH)/insulin-like growth factor-I (IGF-I) changes in relation to linear growth and biochemical parameters in seven children with X-linked hypophosphatemic rickets before and after treatment with 1,25-dihydroxyvitaminD3 and phosphate therapy for a year or more. Moreover, we compared patients' growth data and GH/IGF-I changes with those for 20 age-matched children with normal variant short stature (NVSS)[with normal GH secretion and height standard deviation score (HtSDS) before -2]. Before treatment, all children with HPR secreted normal GH in response to clonidine provocation (> 10 microgram/l) and their IGF-I concentration was significantly lower than those with NVSS. The HtSDS and growth velocity (GV) of children with HPR improved significantly after (-3.05, 8.9 cm/year, respectively) v. before (-3.9 and 4.1 cm/year, respectively) therapy. Their serum IGF-I concentration increased significantly from 76.7 ng/ml before to 99.6 ng/ml after treatment. In summary children with HPR had no abnormality of GH secretion but improvement of their linear growth was associated with significant increase of circulating IGF-I concentration after treatment.

Child↗

PubMed1996

Epidemiology of childhood insulin-dependent diabetes mellitus in the Sultanate of Oman.

This study assessed the updated incidence of IDDM in 0 to 14-year-old children in the Sultanate of Oman, which is located in the southern-eastern part of the Arabian peninsula. Incident cases were recorded prospectively from January 1993 to the end of December 1994. Incidence rates were standardized on the basis of the National Population Census. The degree of ascertainment was above 96% from the primary source. During two full calendar years, 31 new cases of IDDM in children were diagnosed in Oman (10 health regions). The standardized incidence rates were 2.45 and 2.62/100,000 per year during 1993 and 1994, respectively. The sex-specific rates among males and females were 3.23 and 1.99/100,000, respectively, in 1993 and 2.91 and 1.95/100,000, respectively in 1994. The age-specific incidence rates during the 2 years were higher in the 10-14 age group (3.69 and 4.22/100,000, respectively) vs those in the 5-9 age group (2.32 and 2.79/100,000, respectively) and 0.4 age group (1.54 and 0.97/100,000 respectively). The number of new cases/month was markedly higher in the relatively cooler months (September through March) of the year. The incidence rate of IDDM in children under the age of 15 years in Oman was lower than the reported incidence in Kuwait (another gulf country located north-west to Oman) which might reflect the north-south gradient reported in several previous studies. However this incidence rate was higher than those reported for many countries in Asia.

Adolescent↗

PubMed1996

Empty sellae, impaired testosterone secretion, and defective hypothalamic-pituitary growth and gonadal axes in children with Bardet-Biedl syndrome.

We evaluated growth parameters and hypothalamic-pituitary-gonadal and growth functions in five children with Bardet-Biedl syndrome (BBS). Three of the five children had stature below the fifth percentile for age. Their growth hormone (GH) response to provocation was defective, and computed tomographic (CT) scanning revealed empty sellae in all of them. All the children were obese (body mass index [BMI] > 95th percentile for age). Three had hypercholesterolemia. Their basal serum testosterone concentration and testosterone response to 3-day human chorionic gonadotropin (HCG) stimulation were significantly lower than the levels in 12 age-matched obese normal children. Testosterone secretion failed to respond to HCG therapy for 4 weeks. Both basal gonadotropin levels (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and gonadotropin responses to LH-releasing hormone (LHRH) stimulation were normal and did not differ among the two study groups. It appears that primary hypogonadism is a cardinal feature of BBS, and it may be accompanied by hypothalamic and pituitary abnormalities.

Adolescent↗

PubMed1996

Radiological, biochemical, and hormonal changes in malnourished children with rachitic manifestations.

We evaluated the radiological, biochemical and growth hormone (GH)/insulin-like growth factor-I (IGF-I) changes in 10 children with severe protein-energy malnutrition (PEM) who had rachitic manifestations (group 1), 10 children with severe PEM without clinical signs of rickets (group 2), and 10 children with normal body weight-for-length and -age, suffering from vitamin-D-deficiency with signs of florid rickets (group 3) and 10 normal age-matched children (group 4). Serum calcium (Ca2+), phosphorus (PO4), and albumin concentrations were markedly decreased in the two groups with PEM. Malnourished children with rickets had significantly higher serum alkaline phosphatase (ALP) concentrations compared to the malnourished group without rachitic manifestations. Radiological evaluation of the two groups who had rachitic manifestations revealed demineralization of long bones, thinning of the bony cortex, increased formation of osteoid tissue, and metaphyseal changes including cupping, fraying, and flaring. The incidence of these radiological findings did not differ among the well-nourished and the malnourished groups with clinical signs of rickets. However, the incidence of fracture of the shaft was higher (40 per cent) in the malnourished group compared to the well-nourished group (10 per cent) with rickets. In the malnourished group without clinical evidence of rickets, demineralization and cortical thinning was detected in 40 per cent without significant metaphyseal changes. Basal concentrations of GH and peak GH response to clonidine were significantly elevated and IGF-I concentrations were significantly depressed in the malnourished groups v. the other two groups. There were no significant differences in the fasting and the clonidine provoked GH levels or IGF-I concentrations between the rachitic children (group 3) and the normal children. These data suggest that in rachitic children there is not a major role for circulating GH (and by implication IGF-I) on bone mineralization. However, during malnutrition decreased IGF-I production can slow or stop epiphyseal growth and might contribute to the demineralization of the cortex of long bones.

Bone and Bones↗