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Biomedical subjects

E C Crowne

Publications and source records attributed to E C Crowne.

At least 19 recordsLinked to original sources

Characterisation of morbidity in a UK, hospital based, obesity clinic.

AIM: To identify clinical features which predict those most at risk of co-morbidities within an obesity clinic. METHODS: Children attending an obesity clinic had fasting glucose, insulin, and lipids measured prior to a standard oral glucose tolerance test (OGTT). History and examination established birth weight, family history of type 2 diabetes/obesity, pubertal status, and presence of acanthosis nigricans. Central and total fat mass was estimated by bio-impedance. RESULTS: Of the 126 children evaluated, 10.3% (n = 13) had impaired glucose tolerance (IGT); the majority (n = 11) of these would not have been identified on fasting glucose alone. Those with IGT were more likely to have a parental history of type 2 diabetes (relative risk 3.5). IGT was not associated with acanthosis nigricans. Twenty five per cent (n = 19) of those evaluated (n = 75) had evidence of the "metabolic syndrome" (MS). HDL cholesterol and triglyceride levels were related to insulin sensitivity (HOMA-R); HDL cholesterol was also related to birth weight SDS. We observed a trend for those with MS to have a lower birth weight SDS. The severity of obesity did not influence the likelihood of IGT or MS. CONCLUSIONS: Significant numbers of obese children have associated co-morbidities. Analysis of fasting blood glucose samples alone is not satisfactory to adequately evaluate glucose homoeostasis. The overall level of obesity does not predict co-morbidities. Special attention should be given to those with parental diabetes and a history of low birth weight who are more likely to have IGT and abnormal lipid profiles respectively.

Adolescent↗

Physical activity patterns in nonobese and obese children assessed using minute-by-minute accelerometry.

OBJECTIVE: To determine the levels and patterns of physical activity in a sample of obese (> or =99th percentile body mass index (BMI)) and nonobese (<99th percentile BMI) children. DESIGN: Cross-sectional study. SETTING: Children were recruited from schools in Bristol and from the childhood obesity clinic, Bristol Royal Hospital for Children. Children were instructed in the use of the accelerometer either while at school or in the clinic, and wore the instrument while carrying out their normal daily activities for 7 days. PARTICIPANTS: A total of 133 children (mean age 10.5+/-0.8 y). In all 11 (16.9%) of the 65 girls and 14 (20.6%) of the 68 boys were classified as obese (above the 99th percentile for BMI and corresponding to projected adult BMI of 30). MAIN OUTCOME MEASURES: Objectively measured physical activity volume, intensity and pattern. RESULTS: Obese children were significantly less physically active overall than their nonobese counterparts (31,844+/-13,200 vs 41,844+/-10,430 counts/h; 95% confidence interval 4407 to 15592; P=0.001). Similarly the obese children spent less time in physical activity of moderate or greater intensity than the nonobese children (9.9+/-3.9 vs 12.9+/-4.2 min/h; 95% confidence interval 1.15 to 4.80; P=0.002). Hourly patterns of activity indicated a tendency in obese children to be less active than nonobese children at times when activity was more likely to be determined by free choice, particularly outside of school time. CONCLUSIONS: Obese children demonstrated patterns of physical activity that may have contributed to and are likely to sustain their obesity. Minute-by-minute accelerometry is a valuable tool to investigate physical activity patterns in obese children. It can identify periods when intervention to increase activity may be most appropriate and provide an evidence base for specific exercise prescription in primary and secondary care.

Body Mass Index↗

The importance of testing for adrenoleucodystrophy in males with idiopathic Addison's disease.

X linked adrenoleucodystrophy (X-ALD) is considered to be a rare cause of Addison's disease, although several small series suggest a high incidence in young Addisonian males. A survey in the south west of England identified 12 male patients diagnosed with Addison's disease in the period 1987-99. In 10 of these (83%) X-ALD was the underlying cause; the other two were of autoimmune aetiology. Five boys had developed Addison's disease subsequent to the diagnosis of X-ALD. Of the remaining five, in three boys the diagnosis of X-ALD was considerably delayed (by six months to two years from that of Addison's disease) and in two it was only made as a result of this survey. We also identified a patient who presented with Addison's disease at the age of 5 years but was only diagnosed as having X-ALD at the age of 34 years; in the interim his diagnosis of adrenomyeloneuropathy had been missed. Our experience highlights the absolute necessity of measuring very long chain fatty acids in all males with idiopathic Addison's disease.

Addison Disease↗

Type 2 diabetes in obese white children.

We report four white adolescents aged 13 to 15 years (three females, one male) from the south and west region of England who presented with type 2 diabetes mellitus associated with significant obesity (body mass index more than +3SDS) in the past two years. Although these are the first reported obese, white cases from the UK to present with diabetes, we believe this clinical scenario will become more prevalent given the epidemic of childhood obesity in this country.

Adolescent↗

Pancreatic dysfunction in severe obesity.

AIMS: To investigate pancreatic function in children attending an obesity clinic. METHODS: Thirty six children (of which 34 were white) with severe obesity of prepubertal onset (body mass index more than +2 SDS) were reviewed clinically and dysmorphologically, with assessment of pancreatic function. RESULTS: Eight had dysmorphic features and 13 had learning difficulties. Four of 17 prepubertal children had hyperinsulinaemia and seven had hyperproinsulinaemia. All 19 pubertal children had hyperinsulinaemia, 14 had hyperproinsulinaemia, and one had type II diabetes. CONCLUSIONS: Metabolic abnormalities predictive of type II diabetes occur in severely obese white children.

Adolescent↗

The role of IGF-binding proteins in mediating the effects of recombinant human IGF-I on insulin requirements in type 1 diabetes mellitus.

To determine the role of IGF-binding proteins in mediating the direct effects of recombinant human IGF-I on insulin requirements in type 1(insulin-dependent) diabetes mellitus, overnight changes in IGF-I, IGF-II, and IGF-binding protein-1, -2, and -3, collected under euglycemic conditions, were compared in nine subjects after double blind, randomized, sc administration of recombinant human IGF-I (40 microg/kg) or placebo at 1800 h. On both nights a somatostatin analog infusion (300 ng/kg x h) suppressed endogenous GH production, and three timed discrete GH pulses (total, 0.029 IU/kg x night) ensured identical GH levels. After recombinant human IGF-I administration, IGF-I levels and the IGF-I/IGF-binding protein-3 ratio increased [mean +/- SEM:IGF-I, 401 +/- 22 ng/ml; placebo, 256 +/- 20 ng/ml (P = 0.0002); IGF-I, 0.108 +/- 0.006; placebo, 0.074 +/- 0.004 (P = 0.0003), respectively], and insulin requirements decreased (IGF-I, 0.12 +/- 0.03; placebo, 0.23 +/- 0.03 U/kg x min; P = 0.008). The normal within-individual inverse relationships between insulin and IGF-binding protein-1 levels were observed (lag time 2 h: r = -0.34; P < 0.01). Yet despite reduced free insulin levels (8.5 +/- 1.5; placebo, 12.2 +/- 1.2 mU/liter; P = 0.03), IGF-binding protein-1 levels were reduced after recombinant human IGF-I administration (53.7 +/- 6.8; placebo, 82.2 +/- 11.8 ng/ml; P = 0.008). The largest reductions in free insulin levels after recombinant human IGF-I and thus putative improvement in insulin sensitivity occurred in subjects with the smallest increase in the plasma IGF-I/IGF-binding protein-3 ratio (r = 0.7; P = 0.03). Taken together, these data are consistent with the hypothesis that transcapillary movement of IGF-I (perhaps mediated by IGF-binding protein-1), out of the circulation facilitates altered insulin sensitivity. These data have important implications for risk-benefit assessment of recombinant human IGF-I therapy in type 1 diabetes mellitus.

Adolescent↗

Growth hormone hypersecretion in a girl with neurofibromatosis type 1 and an optic nerve glioma: resolution following chemotherapy.

Growth hormone hypersecretion is extremely rare in childhood. We report a girl with neurofibromatosis type 1, an extensive optic nerve glioma and growth hormone hypersecretion. She was treated with chemotherapy to prevent further extension of her sight-threatening tumour. Three years after chemotherapy her growth hormone hypersecretion has resolved although she has gone on to develop precocious puberty.

Age Determination by Skeleton↗

Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes.

OBJECTIVE: To examine counterregulatory responses during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 29 prepubertal patients with type 1 diabetes underwent two overnight profiles. Data were analyzed from 16 children (median [range] 8.7 [5.9-12.9] years of age) with a night of hypoglycemia and a nonhypoglycemic night. Children hypoglycemic (< 3.5 mmol/l) on night 1 were given 25% extra carbohydrate as uncooked cornstarch with their usual evening snack on night 2 to avoid hypoglycemia. Glucose, growth hormone, and cortisol were measured every 15 min, catecholamines every 30 min, and glucagon, pancreatic polypeptide, insulin, and ketones every 60 min. A group of 15 healthy control subjects, aged 9.5 (5.6-12.1) years, underwent one overnight profile. RESULTS: Median duration of hypoglycemia was 225 (30-630) min, and glucose nadir was 2.0 (1.2-3.3) mmol/l. Insulin levels were not different on the two nights (P = 0.9, analysis of variance), but children with diabetes had higher insulin levels than normal control subjects between 2300 and 0300, maximal at 0200 (mean +/- SEM 57.4 +/- 5.7 vs. 31.6 +/- 5.0 pmol/l, P = 0.002). Peak epinephrine was higher on the night of hypoglycemia (0.98 [0.52-2.09] nmol/l) versus nonhypoglycemia (0.32 [0.21-0.62] nmol/l), P = 0.001, but norepinephrine (1.29 [1.07-2.64] vs. 1.26 [1.04-1.88] nmol/l, P = 0.5), glucagon (93 [64.2-125.6] vs. 100.5 [54.6-158] ng/l, P = 0.6), pancreatic polypeptide (410.2 [191-643.2] vs. 270.8 [158.2-777.8] ng/l, P = 0.5), and cortisol (513 [300-679] vs. 475 [235-739] nmol/l, P = 0.6) were not different. Glucose threshold for epinephrine release was very low, 1.9 +/- 0.2 mmol/l. There was a short-lived rise in growth hormone from 75-105 min after onset of hypoglycemia, maximal at 90 min (7.8 +/- 1.2 vs. 3.5 +/- 0.9 ng/ml, P = 0.02). CONCLUSIONS: The prolonged nature of nocturnal hypoglycemic episodes may be explained in part by defective counterregulation. The risk of nocturnal hypoglycemia needs to be reduced before intensification of insulin therapy can be contemplated in this age-group.

Blood Glucose↗

Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus.

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.

Adolescent↗

Effect of low dose oxandrolone and testosterone treatment on the pituitary-testicular and GH axes in boys with constitutional delay of growth and puberty.

OBJECTIVE: To investigate the effect of low dose oxandrolone and testosterone on the pituitary-testicular and GH-IGF-I axes. DESIGN: Prospective double-blind placebo-controlled trial. PATIENTS: Sixteen boys with constitutional delay of growth and puberty (CDGP) with testicular volumes 4-6 ml were randomized to 3 months treatment: Group 1 (n = 5), daily placebo: Group 2 (n = 5), 2.5 mg oxandrolone daily or Group 3 (n = 6), 50 mg testosterone monthly intramuscular injections with assessment (growth, pubertal development and overnight hormone profiles) at 0, 3, 6 and 12 months. MAIN OUTCOME MEASURES: LH and GH profiles (15-minute samples) were analysed by peak detection (Pulsar), Fourier transformation and autocorrelation. Testosterone levels were measured hourly and insulin, SHBG, IGF-I, and IGFBP-3 levels at 0800 h. Statistical analysis was by multivariate analysis of variance for repeated measures. RESULTS: LH and testosterone parameters increased significantly with time in all 16 (LH AUC, P < 0.001; peak amplitude, P = 0.02; number of peaks, P = 0.02; testosterone AUC, P = 0.02; morning testosterone, P = 0.002). In Group 2, however, LH and testosterone parameters decreased at 3 months followed by a rebound increase at 6 and 12 months. SHBG levels were markedly reduced at 3 months (P = 0.006) and a wider range of dominant GH frequencies was present although GH AUC was not increased until 6 months, with an increase in GH pulse frequency but not amplitude. IGF-I levels were increased at both 3 and 12 months. In Group 3, pituitary-testicular suppression was not apparent, but GH levels increased with an increase in GH amplitude at 3 and 12 months. CONCLUSION: Oxandrolone transiently suppressed the pituitary-testicular axis and altered GH pulsatility. Testosterone increased GH via amplitude modulation.

Adolescent↗

Insulin-like growth factors (IGFs) and IGF-I treatment in the adolescent with insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) during adolescence is associated with complex derangements of the growth hormone (GH)/insulin-like growth factor (IGF) axis. Despite GH hypersecretion, IGF-I levels and IGF bioactivity are reduced. The diabetogenic effects of GH are well established, and GH hypersecretion has been implicated in the deterioration in glycemic control during adolescence and in the development of microangiopathy. Insulin deficiency or reduced portal delivery of insulin plays a central role in the development of these abnormalities, and although continuous subcutaneous insulin delivery may improve plasma IGF-I levels, it does not necessarily suppress GH levels. Recombinant IGF-I has been proposed as an adjunct to conventional insulin therapy, as restoring circulating IGF-I levels might lead to GH suppression. Placebo-controlled studies have shown a consistent reduction in GH secretion and related improvements in insulin sensitivity following a single subcutaneous IGF-I injection (40 micrograms/kg). Repeated daily subcutaneous IGF-I administration for 1 month resulted in a sustained increase in IGF-I levels, as well as a reduction in GH secretion and insulin requirements. There was no increase in hypoglycemia or other adverse effects. Recombinant IGF-I used in conjunction with insulin may therefore provide an additional approach to the management of IDDM during adolescence, allowing correction of abnormalities in the GH/IGF axis and leading to improved control and, hence, reduced risk of long-term complications. However, this hypothesis needs to be rigorously tested in long-term placebo-controlled studies.

Adolescent↗

Degree of activation of the pituitary-testicular axis in early pubertal boys with constitutional delay of growth and puberty determines the growth response to treatment with testosterone or oxandrolone.

Early pubertal boys (testicular volume, 4-6 mL) with constitutionally delayed growth and puberty were randomized to 3 months of treatment after a baseline 12-h overnight hormone profile: group 1 (n = 5), daily placebo; group 2 (n = 5), 2.5 mg oxandrolone daily; or group 3 (n = 6), 50-mg testosterone monthly im injections. LH and GH profiles (15-min samples) were analyzed by peak detection (Pulsar), Fourier transformation, and autocorrelation. FSH and testosterone levels were measured hourly, and insulin, sex hormone-binding globulin, insulin-like growth factor-I, and insulin-like growth factor-binding protein-3 levels were determined at 0800 h. Multiple regression was used to analyze the response to treatment (growth) with respect to baseline features. Endocrine variability was marked. Profiles ranged from unreactive to well established LH pulsatility and adult testosterone levels. The areas under the curve (AUC) for LH, FSH, and testosterone ranged 10-fold (4.4-46.3 IU/L.h), 8-fold (7.9-63.4 IU/L.h), and 45-fold (3.6-161.7 nmol/L.h), respectively. The growth response was individually varied, but significantly increased 0-6 months in the active treatment groups. Age, testicular volume, and LH AUC interacted significantly (r2 = 0.95; P < 0.05). Allowance for these produced a highly significant treatment effect (P = 0.006). Age, testicular volume, LH AUC, and testosterone AUC, but not treatment, significantly increased growth by 0-12 months (r2 = 0.88; P < 0.05). We demonstrate a spectrum of activation of the reproductive axis despite tight clinical staging. This, and not GH status at treatment commencement, influenced the growth response.

Adolescent↗

Adrenocorticotrophin and cortisol secretion in children after low dose cranial irradiation.

OBJECTIVE: We investigated the effect of low dose cranial irradiation (18-24 Gy) on spontaneous ACTH and cortisol secretion in children. DESIGN: We analysed 24-hour plasma ACTH and cortisol profiles sampled at 20-minute intervals. PATIENTS: Twenty long-term survivors of acute lymphoblastic leukaemia were studied and results compared with those in 14 normal children. MEASUREMENTS: ACTH and cortisol profiles were analysed by Fourier transformation and spectral analysis of stationarized data, autocorrelation and coherency analysis. RESULTS: The normal circadian rhythms of ACTH and cortisol were preserved in the children after cranial irradiation. The median 0900 h and midnight values were 1.50(0.8-6.4)pmol/l and 1.0(0.6-3.7)pmol/l respectively for ACTH and 282(48-1913)nmol/l and 57.5(44-637)nmol/l respectively for cortisol, and were not significantly different from those in the normal group. Fourier transformation revealed dominant periodicities for ACTH at 0.7-1.1 h, equivalent to 22-34 ACTH secretory bursts per 24 hours, and for cortisol at 0.7-1.1 h and 2-4.8 h. Similar results were found in the normal group. Coherency analysis indicated a significant shared periodicity of 0.7-1.2 h in nine children, corresponding to 20-34 related secretory bursts in 24 hours for ACTH and cortisol. After pooling the coherency spectra in the cranially irradiated group, comparison with the pooled data from the normal group revealed no significant difference between the two groups in the relationship between the two hormones. CONCLUSION: No significant disruption of spontaneous ACTH or cortisol secretion, either in the amount or pattern of hormones secreted, was found in children after low dose cranial irradiation (18-24 Gy).

Adolescent↗

Irradiation-induced growth failure.

GH deficiency, skeletal disproportion and early or precocious puberty may complicate irradiation to the head or axial skeleton in childhood. Certain cohorts of children are at particular risk, including those irradiated for brain tumours and various haematological malignancies. Both GH deficiency and impaired spinal growth may result in short stature, whereas the occurrence of early puberty in association with GH deficiency reduces the time available for GH therapy. The age of the child at irradiation is critical in that, in younger children, the central nervous system is more radiosensitive, the severity of the subsequent skeletal disproportion is greatest and the onset of puberty earliest. It is the very young craniospinally-irradiated child who is most at risk of extreme short stature.

Age Factors↗

A novel variant of growth hormone (GH) insufficiency following low dose cranial irradiation.

OBJECTIVE: We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on physiological growth hormone secretion. DESIGN: We performed an analysis of 24-hour serum GH profiles using 20-minute sampling. PATIENTS: Forty-four children were studied, of whom 21 were long-term survivors of acute lymphoblastic leukaemia and 23 were normal children. They were further subdivided into prepubertal, pubertal and post-pubertal groups. MEASUREMENTS: GH profiles were analysed by autocorrelation, Fourier transformation and spectral analysis of stationarized data, and peak detection using the Pulsar peak detection program. RESULTS In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups (62 (11-124) and 137 (142-158) IU/I/h respectively, (P less than 0.01)). There was also a change in the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post-pubertal groups but sharply focused in the pubertal group. In the cranially irradiated children there was no significant increase in AUC between the prepubertal (62(13-110) IU/I/h) and pubertal groups (92 (14-163) IU/I/h). The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranially irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. CONCLUSIONS: A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty.

Adolescent↗

Relationship between urinary and serum growth hormone and pubertal status.

Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty.

Adolescent↗

Final height in girls with untreated constitutional delay in growth and puberty.

During a 10-year period, 23 girls compared to 118 boys presented with constitutional delay in growth and puberty. Of these girls, 15 were followed to final height to determine the outcome of the untreated condition in terms of both growth and psychological well-being. At presentation chronological age was 13.2 (1.7) years [mean (S.D.)], bone age delay 2.7 (0.9) years, standing height standard deviation score (SDS) -3.4 (0.9), and predicted adult height (PAH) SDS -1.3 (0.7) (Tanner-Whitehouse II method). Final height SDS was -1.5 (0.8) measured at 18.9 (2.6) years of age. Mean age at menarche was 15.6 (0.9) years. There was no significant difference between final adult height (FH) and PAH but there was a significant difference between FH and target height (P less than 0.001). Psychological questionnaires revealed no significant difference in self-esteem, marital or employment status between the patient and control groups. There was no significant correlation between self-esteem and FH but 80% felt their growth delay had affected success either at school, work or socially. Of the patients, 50% would have preferred treatment to advance their growth spurt. This study demonstrates that girls with constitutional delay in growth and puberty reached their PAH, although this was lower than the midparental heights. The girls also experienced significant distress due to delayed growth and puberty and treatment to advance growth should be considered more frequently.

Adolescent↗