Growth hormone secretion in poorly growing children with renal hypophosphataemic rickets

We evaluated growth hormone (GH) secretion and baseline serum free insulin-like growth factor-I (IGF-I) levels in 12 poorly growing patients (5 males and 7 females; age 1.6–12.5 years, median 6.4) with renal hypophosphataemic rickets treated with 1,25-dihydroxy-vitamin D₃ plus inorganic oral phosphate salts. Eleven healthy normally growing children (6 males and 5 females age 3.1–10.8 years, median 6.6) were studied as control group. All patients had a normal GH response (GH peak 10 g/l) to at least one provocative pharmacological stimulus (levodopa or insulin tolerance test), as well as all the controls. Mean growth hormone concentrations (MGHC), mean pulse amplitude, number of GH peaks above 5 g/l, and IGF-I values overlapped between patients and controls, even though four patients had MGHC below the lower limit of MGHC of controls. In these patients, however, height-SDS, serum calcium, phosphate, alkaline phosphatase, intact parathyroid hormone, 1,25-dihydroxyvitamin D concentrations and maximum tubular phosphate reabsorption/glomerular filtration rate ratio did not differ in respect to the patients who showed MGHC in the range of controls (n = 6). MGHC, IGF-I and biochemical parameters of phospho-calcium metabolism did not differ when the patients were subdivided in two groups on the basis of the median (–2.4) of height-SDS. No relationship was found between MGHC or IGF-I and height-SDS or growth velocity-SDS. Height-SDS and years of treatment or age at which therapy was started were not related.     

Growth hormone deficiency impedes the rise in plasma insulin-like growth factor I levels associated with precocious puberty

We tested the hypothesis that growth hormone (GH) mediates the rise in insulin-like growth factor I (IGF-I) concentrations in children with precocious puberty. We studied three groups of patients. Group 1 included six children with GH deficiency and precocious puberty (precocious GH-deficient); group 2 included 10 GH-sufficient patients with idiopathic true precocious puberty (precocious GH-sufficient); and group 3 included 9 prepubertal children with GH deficiency (prepubertal GH-deficient). Growth rates, pubertal status, and plasma IGF-I concentrations were determined at regular intervals. The precocious children with GH deficiency had a mean (+/- SD) growth rate of 7.2 +/- 2.1 significantly below that of the precocious GH-sufficient patients (10.5 +/- 2.5 cm/yr, p less than 0.05) but above that of the prepubertal GH-deficient children (3.9 +/- 1.4 cm/yr, p less than 0.05). The mean IGF-I concentration in the precocious GH-deficient children was 0.77 +/- 0.39 U/ml, significantly lower than the mean level of 2.2 +/- 0.67 U/ml in the precocious GH-sufficient patients (p less than 0.01). However, precocious GH-deficient patients had significantly higher IGF-I values than the prepubertal GH-deficient children (0.24 +/- 0.10 U/ml, p less than 0.05). IGF-I values did not rise with the onset of precocious puberty in four of the precocious GH-deficient children evaluated before and after the development of precocious puberty. However, three patients who began GH treatment did have a rise in plasma IGF-I concentrations to levels of 1.2, 3.4, and 3.7 U/ml, respectively. These findings are compatible with the concept that sex steroids increase IGF-I levels in precocious puberty primarily by increasing GH production. A small but direct effect of sex steroids on IGF-I production may also exist. The onset of precocious puberty in children with organic GH deficiency may mask the abnormal growth pattern of these children and delay diagnosis; determinations of plasma IGF-I concentrations may be helpful in assessing the GH status of these patients.     

Basal and stimulated levels of growth hormone, insulin-like growth factor-I (IGF-I), IGF-I binding and IGF-binding proteins in beta-thalassemia major

A significant percentage of children with beta-thalassemia major shows retardation in longitudinal growth as they progress towards puberty due to skeletal dysplasia, endocrine gland hypofunction or trace element deficiencies. The aim of this study was to evaluate GH/IGF-I secretion and action in prepubertal patients with beta-thalas-semia major. Eight prepubertal patients with short stature (group A) and seven prepubertal patients with normal stature (group B) were studied. Basal and stimulated (after administration of the hexapeptide Hexarelin) GH levels were measured with IRMA (Nichols); IGF-I and IGFBP-3 levels were measured with RIA (Nichols). IGF-I binding proteins (IGFBPs) were analyzed qualitatively with Western ligand blot. IGF-I binding to B-lymphocytes of the patients was also measured with competitive binding studies using human recombinant IGF-I and 125I-IGF-I (Amersham). Basal GH levels did not differ statistically between the groups. Peak GH levels after Hexarelin stimulation test were higher in group A (A: 27.9 +/- 15.6 ng/ml vs B: 9.1 +/- 4.7 ng/ml) (Wilcoxon test, p < 0.05). IGF-I levels in the two groups were low-normal and comparable (A: 168.0 +/- 81.6 ng/ml vs B: 126.6 +/- 25.5 ng/ml). IGFBP-3 levels were low in both groups (A: 1.21 +/- 0.27 microg/ml vs B: 1.08 +/- 0.20 microg/ml). Western ligand blot did not reveal any discernible difference in IGFBPs. However, IGF-I binding on B-lymphocytes was at least 20% lower in group A compared to group B (t-test, p < 0.01). IGF-I binding inversely correlated with peak GH levels (r = -0.54, p < 0.05). Patients in group A were older and chronological age correlated with IGF-I levels (r = 0.53, p < 0.05) whereas it inversely correlated with IGF-I binding (r = -0.63, p < 0.05). Moreover, patients in group A had higher ferritin levels. No correlation was found between ferritin levels, desferrioxamine dose/compliance or liver enzyme levels and the parameters of the GH axis studied. However, desferrioxamine dose x years correlated with IGFBP-3 (r = 0.56, p < 0.05) and correlated inversely with IGF-I binding (r = -0.74, p < 0.01). In conclusion, we have shown adequate GH secretion, higher secretive capacity after the administration of Hexarelin and lower IGF-I binding in prepubertal beta-thalassemic patients with short stature. Whatever the cause, reduced IGF-I action has to be considered when treating beta-thalassemic patients with short stature.     

Height prognosis of children with true precocious puberty and growth hormone deficiency: effect of combination therapy with gonadotropin releasing hormone agonist and growth hormone.

We evaluated height prognosis and therapeutic efficacy of long-term, combination therapy with gonadotropin releasing-hormone agonist and growth hormone (GH) in five children (three girls) with coexistent precocious puberty and GH deficiency. Their clinical characteristics and growth response were compared with those of 12 girls with idiopathic true precocious puberty and eight prepubertal GH-deficient children (one girl). Precocious GH-deficient subjects were older than the precocious GH-sufficient children (9.5 +/- 1.8 years vs 6.5 +/- 1.3 years; mean +/- SD), but bone ages were comparable (12 +/- 3.7 years vs 10 +/- 0.9 years); their chronologic age was similar to that of the prepubertal GH-deficient children (9.6 +/- 2.1 years), but bone age was significantly more advanced (6.9 +/- 2.3 years). The mean height velocity of the prepubertal GH-deficient children (3.8 +/- 1.5 cm/yr) was lower than that of the precocious GH-deficient subjects (6.7 +/- 1.6 cm/yr) and the precocious GH-sufficient children (9.5 +/- 2.9 cm/yr). Baseline adult height prediction z scores were significantly lower in the precocious GH-deficient children (-3.7 +/- 1.0) than in either the precocious GH-sufficient children (-2.2 +/- 1.0) or the prepubertal GH-deficient subjects (-1.5 +/- 0.8). During therapy with gonadotropin releasing-hormone agonist, growth rates slowed to an average of 3.7 cm/yr in the precocious GH-deficient children but increased after the addition of GH to 7.4 cm during the first year of combination therapy. After 2 to 3 years of combination therapy, height predictions increased an average of 10 cm, compared with an increase of 2.8 cm in the precocious GH-sufficient group treated with gonadotropin releasing-hormone agonist alone. We conclude that combination treatment with gonadotropin releasing-hormone agonist and GH improves the height prognosis of children with coexistent true precocious puberty and GH deficiency, but falls short of achieving normal adult height potential.     

Three-Year Follow-up Study on Serum Leptin Levels in GH Deficient Children with GH Replacement Therapy

Interactions between GH and leptin have been extensively studied. However, results of long-term GH therapy on serum leptin levels in GH-deficient children were not consistent. Moreover, no such reports were available in Japanese children with this disease. We studied 35 Japanese patients with GH deficiency (26 boys and 9 girls, mean age: 9.8 ± 6.2 yr old), of whom 6 patients with complete and 29 with incomplete GH deficiency were identified by GH provocation test. Serum leptin levels, percent of ideal body weight (%IBW) and percent fat (%fat) were determined at 0, 1, 3, 6, 12, 18, 24, and 36 mo after beginning GH therapy. Baseline levels of %fat and leptin were significantly higher in girls than boys (P<0.05), though serum leptin did not change throughout the study period in either group. Further, %IBW did not change significantly, whereas %fat exhibited significant changes after 6 mo in boys and remained virtually constant thereafter for up to 3 yr. In summary, serum leptin levels did not change in GH-deficient boys and girls during the 3-yr period after the start of GH replacement therapy, despite a decrease in %fat after 6 mo of therapy in the boys. Thus, it is conceivable that long-term GH replacement therapy can be employed without an effect on normal leptin secretion.     

Growth hormone secretory pattern in non-obese children and adolescents with Prader-Willi syndrome

The aetiology of impaired growth hormone (GH) secretion in Prader-Willi syndrome (PWS) remains controversial due to the common occurrence of obesity. To further clarify whether suboptimal GH secretion in PWS is an artefact of excess weight, we evaluated both GH immunological activity and GH bioactivity after arginine administration in 23 non-obese PWS patients [seven females, aged 6.9 +/- 0.9 years, body mass index (BMI) SDS 0.63 +/- 0.26], in comparison with a control group of 32 healthy subjects, matched for age, gender and BMI (10 females, aged 7.9 +/- 0.3 years, BMI SDS 0.21 +/- 0.20). Serum GH concentration was measured with a time-resolved immunofluorometric assay (IFMA), while GH bioactivity was evaluated by the Nb2 cell bioassay. Serum IGF-I concentrations were measured by double-antibody RIA. GH mean peak after pharmacological stimulation was significantly lower in PWS individuals compared with controls when measured either by IFMA (6.05 +/- 1.23 microg/L vs. 23.7 +/- 1.06 microg/L, p < 0.0001) or by Nb2 (6.87 +/- 0.55 microg/L vs. 12.88 +/- 0.19 microg/L, p < 0.0001). Analysis of integrated GH secretion (AUC) confirmed that the PWS group differed significantly from the control subjects (387.9 +/- 76.1 microg/L/h vs. 1498.1 +/- 56.2 microg/L/h, p < 0.0001); the same result was obtained when the GH rise after arginine administration was expressed as nAUC (278.2 +/- 53.3 microg/L/h vs. 1443.6 +/- 52.5 microg/L/h, p < 0.0001). PWS patients had an IGF-I SDS significantly lower than those found in control subjects (p < 0.0001). Subnormal IGF-I values were present in 19 PWS individuals (82.6%) and two healthy controls (6.2%). These findings are in agreement with the hypothesis that a complex derangement of hypothalamus-pituitary axis occurs in PWS.     

Reduced pericellular sensitivity to IGF-I in fibroblasts from girls with Turner syndrome: a mechanism to impair clinical responses to GH

Girls with Turner syndrome (TS) are treated with supraphysiological doses of growth hormone (GH) to improve final height; however in some girls, the growth response can be poor. This may reflect aberrations in GH and/or IGF-I actions at the cellular level, and thus this study compared the response of skin fibroblasts from normal children (n = 5) and girls with TS (n = 8) to GH, IGF-I, or a combination, by assessing the IGF binding protein (IGFBP) profile of conditioned medium harvested over 7 d. The two cell types had a comparable IGFBP profile; IGFBP-3 and IGFBP-4 were the most abundant species. TS fibroblasts produced more IGFBP-3 (d 7, 51.4 ± 45 ng/mL versus 20 ± 22 ng/mL; p < 0.05) than control cells; levels of IGFBP-4 were similar (21 ± 12 ng/mL versus 30 ± 21 ng/mL). GH did not influence IGFBP production. IGF-I treatment did not affect IGFBP-4 levels but enhanced the production of IGFBP-3 by both cell types (p < 0.05). However, the response of TS fibroblasts to IGF-I was approximately half that observed in normal cells (p < 0.05). Altered IGF-I activity, because of reduced bioavailability and/or reduced sensitivity, could contribute to the need for high GH doses in TS and for the poor response to GH in some girls with TS.     

Favorable Impact of Growth Hormone Treatment on Cholesterol Levels in Turner Syndrome

Background: Patients with Turner syndrome (TS) are prone to having metabolic abnormalities, such as obesity, dyslipidemia, hypertension, hyperinsulinemia and type 2 diabetes mellitus, resulting in increased risks of developing atherosclerotic diseases. Objective: To determine the effect of growth hormone (GH) therapy on serum cholesterol levels in prepubertal girls with TS enrolled in the Turner syndrome Research Collaboration (TRC) in Japan. Patients and methods: Eighty-one girls with TS were enrolled in the TRC, and their total cholesterol (TC) levels before GH therapy were compared with reported levels of healthy school-aged Japanese girls. TC levels after 1, 2 and 3 yr of GH treatment were available for 28 of the 81 patients with TS. GH was administered by daily subcutaneous injections, 6 or 7 times/wk, with a weekly dose of 0.35 mg/kg body weight. Results: Baseline TC levels revealed an age-related increase in TS that was in contrast to healthy girls showing unchanged levels. During GH therapy, TC decreased significantly after 1 yr of GH treatment and remained low thereafter. Conclusions: Girls with untreated TS showed an age-related increase in TC that was a striking contrast to healthy girls, who showed unchanged levels. GH therapy in girls with TS brought about a favorable change in TC that indicates the beneficial impact of GH on atherogenic risk.     

Estradiol levels in girls with Turner's syndrome compared to normal prepubertal girls as determined by an ultrasensitive assay

Based on growing evidence that estradiol is produced in small amounts even in the prepubertal ovary, we hypothesized that estradiol levels in girls with Turner's syndrome (TS) are lower than in normal prepubertal girls secondary to the lack of normally functioning ovaries. Estradiol levels in untreated girls with TS have not been previously well defined because of the lack of adequate sensitivity of previously available estradiol assays. We utilized an ultrasensitive assay to study estradiol levels in 34 girls with TS and 34 normal age-matched prepubertal girls between the ages of 5 and 12 years. The average estradiol level in the girls with TS (6.4 +/- 4.9 pmol/l estradiol equivalents) was significantly lower than in the normal prepubertal girls (12.7 +/- 10.8 pmol/l estradiol equivalents; p < 0.01). Girls with TS were significantly shorter, and weighed less than the normal prepubertal girls, as expected. The estradiol level was not significantly correlated with height, bone age, or degree of bone age delay. In conclusion, girls with TS have significantly lower estradiol levels than normal age-matched prepubertal girls. This report is consistent with the hypothesis that the lack of normal ovarian function in girls with TS is evident even before puberty.     

Acipimox, a nicotinic acid analog, stimulates growth hormone secretion in short healthy prepubertal children

Recent studies in adult volunteers have demonstrated that the free fatty acid reduction induced by acipimox, a nicotinic acid analog, stimulated GH secretion per se and enhanced in an additive manner the GH secretion elicited by such different stimuli as pyridostigmine, GHRH and GHRP-6. In order to evaluate whether acipimox administration stimulates GH secretion in prepubertal children, we administered a single oral dose of acipimox (100 mg for children weighing <30 kg and 200 mg for those >30 kg) to 14 healthy prepubertal children with a mean age of 8.2 +/- 1.9 years, a mean bone age of 6.2 +/- 3.0 years, growing along the 5-10th percentiles, and with normal thyroid function and IGF-I levels. Acipimox administration elicited a sustained increase in GH from a mean baseline level of 0.6 +/- 0.4 to 6.7 +/- 2.4 microg/l at the end of the test (p<0.05), with a mean GH peak of 10.5 +/- 3.5 microg/l. GH release was delayed so that peak GH levels were achieved 180 minutes after acipimox administration. In order to determine whether acipimox was capable of enhancing the GH secretion elicited by levodopa (L-Dopa), we administered either oral L-Dopa (250 mg for children weighing <30 kg and 500 mg for those >30 kg) or oral acipimox plus L-Dopa to the same children on different days. GH concentrations increased in a similar fashion following either of these tests (from a baseline level of 1.2 +/- 0.4 and 0.7 +/- 0.4 microg/l to 8.4 +/- 2.7 and 9.3 +/- 2.9 microg/l at the end of the test (p<0.001), with peak GH concentrations of 13.1 +/- 4.1 and 11.8 +/- 3.3 microg/l after L-Dopa or acipimox plus L-Dopa, respectively). Although the peak GH concentrations obtained after the combined administration of acipimox plus L-Dopa were similar to those obtained after either acipimox or L-Dopa administration, a larger number of our patients reached a GH cut-off point of >7 microg/l following combined therapy than with either stimulus alone (13/14 patients with combined therapy and 10/14 with acipimox alone). No side effects other than mild facial flushing were noted after acipimox administration. These results indicate that: 1) following the administration of a single oral dose of acipimox, significant GH secretion was elicited in healthy short prepubertal children; 2) the combined administration of acipimox plus L-Dopa did not, however, enhance the GH secretion of this group of children; 3) acipimox was well tolerated with minimal side effects; and 4) further studies in both GH sufficient and GH deficient children are necessary to evaluate acipimox's usefulness in assessing GH reserve.     

Polycystic ovary and gonadoblastoma in Turner's syndrome

Turner's syndrome (TS) is characterized by typical facial features, short stature, hypergonadotropic hypogonadism, streak gonads, infertility, hearth and kidney malformations. Typical karyotype is 45,X0; however, 6% of TS have mosaic patterns including Y chromosome or fragments of Y. This karyotype is a risk factor of developing a dysgerminoma in dysgenic gonads. Furthermore, rare cases of polycystic ovary are described in young-adult patients with TS. We describe the clinical case of a 12-year-old girl with TS treated with GH who showed a good response to treatment. She developed an ovary with histological polycystic pattern and a contralateral gonadoblastoma in the streak gonad. Laparoscopic gonadectomy was performed, with a good prognosis. Of remark is the opportunity to carry out gonadectomy in prepubertal age in girls with TS and Y chromosome material. This is a rare precocious case of polycystic ovary in TS, with different evolution in the two gonads with different histological differentiation.     

Endogenous growth hormone secretion does not correlate with growth in patients with Turner's syndrome. Italian Study Group for Turner Syndrome

We investigated in Turner's syndrome patients whether the decrease in growth hormone (GH) secretion is frequent or sporadic, whether or not reduced GH secretion contributes to insufficient growth, and whether age, spontaneous presence of telarche and/or pubarche, karyotype and weight influence GH secretion decrease. We evaluated GH reserve in 301 patients by classical stimulation tests and in 68 of these patients mean nocturnal spontaneous secretion was also measured. Spontaneous telarche and/or pubarche were present in 33% of girls aged > 9 years. In 11% of patients, weight was more than 20% above levels appropriate for height. In 36.2% of patients (low-responders), we observed a reduction of the GH reserve (peak < or = 10 micrograms/l during two stimulation tests). Moreover, we noted reduced mean nocturnal spontaneous secretion (< or = 3.3 micrograms/l) in 61.8% of patients. Karyotype and the presence/absence of spontaneous telarche and/or pubarche did not influence either GH reserve or mean nocturnal spontaneous secretion. GH secretion (both GH reserve and mean nocturnal spontaneous secretion) did not influence height, yet low-responders had a significantly higher chronological age than normal-responders. Obese Turner's girls were low-responders and showed reduced mean nocturnal spontaneous secretion more frequently than normal weight girls; body mass index was significantly higher in patients with reduced GH secretion when compared to patients with normal GH secretion. We conclude that impairment of GH secretion is frequent in Turner's syndrome patients, especially if obese; that GH secretion impairment is not related to karyotype or spontaneous telarche and/or pubarche; that GH secretion is irrelevant to growth in these, patients and, therefore, its evaluation is unnecessary.     

Cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children

Growth hormone (GH) hypersecretion is associated with an increased incidence of cardiac hypertrophy and subclinical abnormalities of left ventricular (LV) function. The unlimited availability of biosynthetic GH has led to progressively increased dosage when treating GH-deficient children, raising the question of its cardiovascular effects during long-term therapy. We compared 22 children (8 girls, 14 boys), mean age 12.1 years (range 3–17 years) with GH deficiency who were receiving chronic GH treatment (GH group) with 22 normal controls matched for sex and body size in order to evaluate: (1) LV volume, mass, and systolic function by two-dimensional guided M-mode echocardiography; (2) LV diastolic function by pulsed-wave Doppler sampling of the transmitral flow; and (3) cardiac output and systemic vascular resistance by Doppler echocardiography. All patients had been on chronic GH therapy for 13.8±7.6 months (range 5–30 months) with an average dose of 0.95±0.12 IU/kg per week (range 0.69–1.17 IU/kg per week). Blood pressure did not differ between the two groups. LV volume, mass, ejection fraction, and mean velocity of circumferential shortening did not differ significantly between the GH group and controls; nor did the peak- and end-systolic meridional stress. All patients had a normal contractile state as estimated by the relation between mean velocity of circumferential shortening and end-systolic meridional stress. The LV filling parameters did not differ between the two groups, and there was no difference in cardiac index and systemic vascular resistance. These f9ndings suggest that long-term treatment with high doses of GH in GH-deficient children and adolescents does not lead to adverse cardiac effects. Whether longer-duration therapy could cause morphofunctional alterations of the left ventricle requires further investigation.     

Is insulin-like growth factor-1 monitoring useful in assessing the response to growth hormone of growth hormone-deficient children?

OBJECTIVE: To assess the relationship between insulin-like growth factor-1 (IGF-1), the growth hormone (GH) dose utilized to treat GH-deficient children and the changes noticed in height-standard deviation score (H-SDS) and height velocity (HV). STUDY DESIGN: We studied 24 prepubertal GH-deficient patients with a mean age of 10.5 +/- 1.8 years and a mean bone age (BA) of 8.4 +/- 2.1 years. H-SDS for chronologic age (CA) and BA before therapy were -2.6 +/- 0.8 and -1.2 +/- 0.8, whereas height velocity (HV)-SDS was -1.1 +/- 1.5. Serum IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured before, after 6 and 12 months of GH, and correlated with the GH dose used. Based on the increment of IGF-1 used during treatment, patients were divided into 2 groups: G1 (>1 SDS) and G2 (<1 SDS). HV-SDS and interval height increases were analyzed. RESULTS: HV-SDS, as well as H-SDS for CA and BA during the first year of treatment, were significantly greater than before therapy. IGF-1 SDS increased significantly during the first 6 months of therapy (P <.0003), but increased no further at 12 months despite the use of a higher GH dose (0.1 vs 0.14 IU/kg/day), whereas IGFBP-3 SDS increased at both 6 and 12 months. There was no correlation between the GH dose used and IGF-1 and IGFBP-3 levels. When patients were divided according to their IGF-1 increment during therapy, a significant increase in H-SDS for BA and in HV-SDS was noted only in group 2. CONCLUSIONS: The increment in IGF-1 SDS during therapy did not correlate with the interval height increase. IGF-1 measurement may be helpful in monitoring compliance and safety, but seems to be less useful in adjusting the GH dose needed to treat prepubertal GH-deficient children.     

Growth hormone treatment of Turner syndrome patients with insufficient growth hormone response to pharmacological stimulation tests

Growth before and during treatment with biosynthetic human growth hormone (hGH) was studied in 13 patients with Turner syndrome (TS) and a growth hormone (GH) response of less than 10 g/l to two standard provocative tests. During 1 year of treatment with hGH (0.15 IU/kg per day) height velocity (mean±SD) increased significantly (P<0.001) from 3.7±1.8 cm/year to 7.6±1.5 cm/year. The auxological data in these girls before and during treatment with hGH were similar to those observed in TS patients with a normal response of GH to pharmacological stimuli. It is concluded that in girls with Turner syndrome GH testing should only be performed when height velocity is below the Turner norm. In TS patients with residual growth potential a clinically significant growth acceleration can be obtained with a higher-than-replacement dose of hGH, i.e. 0.15 IU/kg per day, regardless of GH testing.     

Effectiveness of growth hormone (GH) therapy in GH-deficient children and non-GH-deficient short children

The growth response during short-term growth hormone (GH) treatment was evaluated in eight prepubertal non-GH-deficient (non-GHD) children and compared with six prepubertal GH-deficient (GHD) patients. Standard doses of GH can improve growth rate in GHD and in some non-GHD patients. In neither group the growth response can be predicted by the acute increase in Thymidine Activity or Somatomedin-C levels. A diagnostic trial of GH treatment may be the only certain method of selecting the short non-GHD patients who may benefit from long-term GH therapy.Abbreviations GH growth hormone - GHD growth hormone deficient - Sm-C somatomedin C - TA thymidine activity     

Turner's syndrome and thyroid disease: a transverse study of pediatric patients in Brazil

An increased prevalence of autoimmune thyroid disease (AITD) has been described in Turner's syndrome (TS), but the extent of this association is still controversial. Some studies also suggest that AITD is more frequent among patients with X-isochromosome. In order to determine the prevalence of AITD among girls with TS, and to look for an association with age and karyotype, we evaluated 71 patients with a mean age of 11.4 years (range 0-19.9). 15.5% (11/71) were hypothyroid, 17 (23.9%) were positive for thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibodies, and 24 (33.8%) had thyromegaly. No abnormality was observed before 4 years, and the highest frequencies were observed after 16 years. There were no significant differences concerning thyroid findings among patients with a 45,X karyotype, mosaics, and structural rearrangements. Half of the patients (35/71) exhibited one or more abnormalities, which demonstrates the importance of careful evaluation of thyroid function in all girls with TS.     

Differences of hexarelin-induced prolactin and cortisol responses between prepubertal and early pubertal short children and lack of correlation with gonadotropin-releasing hormone-induced gonadotropin response

Hexarelin (HEX), a synthetic hexapeptide with strong GH-stimulating activity, is known to induce the release of prolactin (PRL) and cortisol (F). The responses of GH and F vary according to age and pubertal development, correlating with serum levels of sex steroids, while the release of PRL does not. We evaluated GH, PRL and F responses to HEX (2 microg/kg i.v.) in 19 children with short stature, 12 prepubertal (Tanner stage I) and 7 early pubertal (stage II), and their correlation with those of FSH and LH to GnRH and with the serum levels of testosterone (T) or estradiol (E2). At baseline, the GH, PRL, F and sex steroid serum levels did not vary in the two groups of patients. HEX induced a strong GH and a slight PRL increase in prepubertal and early pubertal children, with no differences in the extent of the response, while F secretion was not affected in either group; these responses did not correlate with those of the gonadotropins to GnRH nor with basal T or E2.     

Spontaneous growth in Chinese patients with Turner's syndrome and influence of karyotype

The pretreatment mixed cross-sectional and longitudinal height measurements of 203 patients with Turner's syndrome (TS) were analysed. Only one observation was included per year per child and a total of 858 observations formed the basis of the growth study. The mean and SD values were fitted separately by a second-degree polynomial function, giving smoothed growth curves. The spontaneous growth pattern of Chinese girls with TS runs parallel to published Caucasian TS growth curves. The mean final height of Chinese patients with TS was 142 cm compared to 147 cm and 139 cm observed in Northern European and Japanese patients, respectively. Patients with the 46, X, i(Xq) karyotype were found to be significantly shorter, whereas children with the 45, X/46, XY and 46, X, del(Xq) karyotypes were significantly taller among this group of patients. Patients with TS who were disomic for Xp are significantly taller than patients who were monosomic for Xp. Our results suggest that karyotype can have a significant effect on the growth of children with TS.     

Growth hormone secretory dynamics in subjects with normal stature

To evaluate the dynamics of growth hormone (GH) secretion in subjects with normal stature and to determine whether a correlation exists between height and the quantity of GH secreted, we determined the 24-hour GH concentration by measuring GH levels every 30 minutes in 27 boys and 19 girls of normal height, 7 to 18 years of age, of whom 24 were prepubertal and 22 in various stages of puberty. Spontaneous GH secretion had wide variations, with values ranging from less than 1.0 to 67.0 micrograms/L. In prepubertal children the highest GH levels were usually noted during sleep; in pubertal subjects the highest values were distributed almost equally between sleep and wake hours. In all subjects, GH secretion appeared to decrease before meals, followed by an increase after meals. Most indexes of GH secretion and insulin-like growth factor I levels were significantly greater in pubertal than in prepubertal subjects (p less than 0.002), and in both groups the GH concentration was significantly greater during sleep (p less than 0.005). In all groups the 24-hour GH concentration correlated significantly with the area under the GH curve, 24-hour GH pulse amplitude, and GH concentration and peak GH level during sleep and wake hours (P less than 0.0001); 24-hour GH concentrations correlated with insulin-like growth factor I levels only when the entire group of 46 subjects was considered (p less than 0.01). There were no significant correlations between 24-hour GH concentration and the subjects' age, bone age, height (SD score), weight (SD score), or body mass index. We conclude that in subjects with normal stature, mean 24-hour GH concentrations vary considerably and in the low range overlap with values reported in hypopituitarism.