Pubertal Patients Research Articles

Fecal continence in patients having undergone posterior sagittal anorectoplasty procedure for a high anorectal malformation improves at adolescence, as constipation disappears

Background/Purpose: Constipation is a major complication in patients who have undergone posterior sagittal anorectoplasty (PSARP) operation for a high anorectal malformation. Overflow incontinence is the main cause of fecal soiling in these patients. The aim of this study was to outline the natural history of constipation in patients with high anorectal malformations and relate this to the functional outcome at the end of the patient's growth period. Methods: The study group consisted of 22 pubertal or postpubertal patients (median age 15; range, 13 to 25) with high or intermediate anorectal malformations repaired by PSARP procedure. The patients have been followed-up since birth. Constipation was defined as a need to use medical treatment or diet to ensure bowel emptying. Continence was classified as follows: grade 1, no soiling in any circumstances; grade 2, staining less than once a week, no fecal accidents; grade 3, staining more than once a week, no fecal accidents; grade 4, daily soiling or accidents, need for regular enemas, or the antegrade colonic enema procedure. All patients underwent anorectal manometry and magnetic resonance imaging of the spine and spinal cord. Results: At the time of the study 2 (9%) of the 22 study group patients had constipation, but 15 (68%) had been constipated before puberty. Eleven patients (50%) were fully continent (grade 1) without constipation. Six of those had a history of constipation associated soiling. Three patients (14%) had occasional staining (grade 2) and no constipation. Two of them had been constipated with significant soiling before the onset of puberty. In the 5 (22%) patients with frequent staining (grade 3) the degree of soiling had decreased after the disappearance of constipation. Two of the 3 patients with poor outcome (grade 4) require regular enemas for recalcitrant constipation. Spinal cord anomalies were detected in 4 and abnormal sacrum in 15 patients. Of the anorectal manometric parameters, only the force of voluntary sphincter squeeze correlated with the functional result. Conclusion: In the majority of patients who underwent PSARP procedure for high anorectal malformation, constipation disappears at adolescence, and this is associated with improved fecal continence outcome. J Pediatr Surg 36:1218-1221. Copyright © 2001 by W.B. Saunders Company.

Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: Alterations in Cortisol Pharmacokinetics at Puberty

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, treatment with glucocorticoid and mineralocorticoid substitution is not always satisfactory. Suboptimal control is often observed in pubertal patients, despite adequate replacement doses and adherence to treatment. We investigated whether the pubertal process is associated with alterations in cortisol pharmacokinetics resulting in a loss of control of the hypothalamic-pituitary-adrenal axis. We determined the pharmacokinetics of hydrocortisone administered iv as a bolus. A dose of 15 mg/m2 body surface area was given to 14 prepubertal (median age, 9.4 yr; range, 6.1–10.8 yr), 20 pubertal (median, 13.5 yr; range, 10.6–16.8 yr), and 6 postpubertal (median, 18.2 yr; range, 17.2–20.3 yr) patients with salt-wasting CAH. All patients were on standard replacement therapy with hydrocortisone and 9α-fludrocortisone. Serum total cortisol concentrations were measured at 10-min intervals for 6 h following iv hydrocortisone bolus and analyzed using a solid-phase RIA. The serum total cortisol clearance curve was monoexponential. Mean clearance was significantly higher in the pubertal group (mean, 427.0 mL/min; sd, 133.4) compared with the prepubertal (mean, 248.7 mL/min; sd, 100.6) and postpubertal (mean, 292.4 mL/min; sd, 106.3) (one-way ANOVA, F = 9.8, P < 0.001) groups. This effect persisted after adjustment for body mass index. The mean volume of distribution was also significantly higher in the pubertal (mean, 49.5 L; sd, 12.2) than the prepubertal (mean, 27.1 L; sd, 8.4) patients but not in the postpubertal (mean, 40.8 L; sd, 16) (ANOVA, F = 15.2, P < 0.001) patients. The significance remained after correction for body mass index. There was no significant difference in mean half-life of total cortisol in prepubertal (mean, 80.2 min; sd, 19.4), pubertal (mean, 84.4 min; sd, 24.9), and postpubertal (mean, 96.7 min; sd, 9.9) patients. Similar differences between groups were observed when the pharmacokinetic parameters of free cortisol were examined. In addition, the half-life of free cortisol was significantly shorter in females compared with males (P = 0.04). These data suggest that puberty is associated with alterations in cortisol pharmacokinetics resulting in increased clearance and volume of distribution with no change in half-life. These alterations probably reflect changes in the endocrine milieu at puberty and may have implications for therapy of CAH and other conditions requiring cortisol substitution in the adolescent years.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: alterations in cortisol pharmacokinetics at puberty.

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, treatment with glucocorticoid and mineralocorticoid substitution is not always satisfactory. Suboptimal control is often observed in pubertal patients, despite adequate replacement doses and adherence to treatment. We investigated whether the pubertal process is associated with alterations in cortisol pharmacokinetics resulting in a loss of control of the hypothalamic-pituitary-adrenal axis. We determined the pharmacokinetics of hydrocortisone administered iv as a bolus. A dose of 15 mg/m(2) body surface area was given to 14 prepubertal (median age, 9.4 yr; range, 6.1--10.8 yr), 20 pubertal (median, 13.5 yr; range, 10.6--16.8 yr), and 6 postpubertal (median, 18.2 yr; range, 17.2--20.3 yr) patients with salt-wasting CAH. All patients were on standard replacement therapy with hydrocortisone and 9 alpha-fludrocortisone. Serum total cortisol concentrations were measured at 10-min intervals for 6 h following iv hydrocortisone bolus and analyzed using a solid-phase RIA. The serum total cortisol clearance curve was monoexponential. Mean clearance was significantly higher in the pubertal group (mean, 427.0 mL/min; SD, 133.4) compared with the prepubertal (mean, 248.7 mL/min; SD, 100.6) and postpubertal (mean, 292.4 mL/min; SD, 106.3) (one-way ANOVA, F = 9.8, P < 0.001) groups. This effect persisted after adjustment for body mass index. The mean volume of distribution was also significantly higher in the pubertal (mean, 49.5 L; SD, 12.2) than the prepubertal (mean, 27.1 L; SD, 8.4) patients but not in the postpubertal (mean, 40.8 L; SD, 16) (ANOVA, F = 15.2, P < 0.001) patients. The significance remained after correction for body mass index. There was no significant difference in mean half-life of total cortisol in prepubertal (mean, 80.2 min; SD, 19.4), pubertal (mean, 84.4 min; SD, 24.9), and postpubertal (mean, 96.7 min; SD, 9.9) patients. Similar differences between groups were observed when the pharmacokinetic parameters of free cortisol were examined. In addition, the half-life of free cortisol was significantly shorter in females compared with males (P = 0.04). These data suggest that puberty is associated with alterations in cortisol pharmacokinetics resulting in increased clearance and volume of distribution with no change in half-life. These alterations probably reflect changes in the endocrine milieu at puberty and may have implications for therapy of CAH and other conditions requiring cortisol substitution in the adolescent years.

Evidence of a Restrictive Spirometric Pattern in Older Thalassemic Patients

Background: Lung impairment represents one of the complications of thalassemia major whose clinical picture can remain in subclinical form all life long. Few works have been published and the results are contradictory. Objectives: The aim of this study was to determine the spirometric pattern, the age of onset in thalassemic boys and girls, and to investigate the association with the onset of endocrinological complications. Methods: We studied 48 patients, divided into three groups according to pubertal stages, in order to better distinguish the periods of life in which different endocrinological complications usually appear. Group A: (n = 14; 8 F, 6 M; age 10.8 ± 1.7 years): prepubertal patients; group B (n = 21; 10 F, 11 M; age 15.7 ± 1.1 years): pubertal patients; and group C (n = 13; 9 F, 4 M; age 19.0 ± 1.4 years): postpubertal patients. Pulmonary function tests (PFTs) and diffusing capacity for carbon monoxide (D_CO), corrected for both Hb values (D_CO*) and alveolar volume (K_CO), were performed 2 days after blood transfusion and were considered pathologic when they fell below 80% of the predicted value. Results: All patients in group A showed normal PFTs, D_CO* and K_CO values, as well as normal endocrinological assessment. By contrast, all those in group C showed a restrictive spirometric pattern with reduced D_CO* (63 ± 8%), elevated K_CO values (120 ± 14%), a variable degree of hypoxia (P_O2 82 ± 9%), and high serum ferritin levels. Only 2 patients showed a radiological picture of interstitial fibrosis. Furthermore, 9 patients had hypogonadism and 3 hypothyroidism. In group B, only 3 patients showed a restrictive pattern and 1 of them reduced D_CO* values, and 2 out of 3 patients had hypogonadism. Considering all patients on the whole, D_CO* was negatively correlated with both serum ferritin (r = –0.58; p < 0.05) and age (r = –0.57; p < 0.05). Conclusions: The presence of a restrictive pattern in 16 older patients associated with both high serum ferritin levels and endocrinological complications in a lot of them was the main feature in this study. Iron overload might be the main factor determining lung impairment, even though a more accurate evaluation is necessary. Possible pathological mechanisms and the role of the genotype are discussed.

Glicemic control in prepubertal and pubertal patients with diabetes type 1 - a one year ambulatory follow-up

OBJECTIVE: To evaluate glycemic control in type 1 diabetes mellitus patients followed in 1998. PATIENTS AND METHODS: We studied 38 patients [22 males; age = 10.4 -/+ 4.1 years; 12 (31.6%) prepubertal, 26 (68.4%) pubertal], with diabetes duration of 3.7-/+3.4 years and age of diagnosis of 7.2 -/+ 4.7 years. HbA1c was determined using high-performance liquid chromatography (L-9100 Merck Hitachi, reference value =2.6 to 6.2%). RESULTS: HbA1c was 8.04 -/+ 2.4%, without association with gender and puberty. In the 27 patients with at least two HbA1c determinations, the level of glycemic control changed in 8 (29.6%) and remained the same in 19 (70.4%). From these, glycemic control was poor in 3 (11.1%) and good in 16 (59.3%). Among the patients with good glycemic control, HbA1c was always within reference values in 4 (25%); 7 (43.75%) had at least one HbA1c measurement within these limits; and in 5 (31.25%), all HbA1c measurements were above the upper limit of the reference range. There was no association between the last glycemic control evaluation and the number of HbA1c determinations. The intraindividual coefficient of variation of HbA1c in the group that had at least three HbA1c determinations (n = 19) was 11.2 -/+ 5.6% (P = 0.0000). CONCLUSION: In our study, although most patients presented satisfactory glycemic control during the follow-up period, only 4 patients (14.8%) maintained normal values of HbA1c. The variability of HbA1c must be evaluated when considering the interrelation between glycemic control and evolution to microvascular complications in diabetis.

Effect of calcium and vitamin D supplementation on bone mineral density of celiac children

We were interested in detecting the changes in bone mineral density (BMD) in prepuberal and puberal celiac children after 24 months of supplementation with 1000 mg of calcium and 400 U of vitamin D daily. 19 celiac children (16 females, and 3 males, age 6 to 15 years) with good compliance to the gluten free diet for at least two years, paired with 19 healthly children of the same age and sex were studied. Celiac patients had mean calcium intakes of 739 mg per day, that increased to 1444 mg per day after nutritional supplementation, with 84 and 74% of compliance during the first and second years of supplementation. Celiac patients did not show significant changes in stature and nutritional status during supplementation. The whole group of celiac subjects showed a significant increase in z score of WB-BMD and FN-BMD from the start and until 24 months of supplementation, compared to the controls (WB-BMD: −0.24±0.40 and −0.80±0.59 vs 0.49±0.62 and 0.62±0.83. FN-BMD:−0.41±0.96 and 0.04±1.12 vs 0.58±1.29 and 0.36±1.15 respectively) Total group and pubertal celiac patients showed a significantly greater variation (delta z score) of hip BMD (FN-BMD 0.53 ± 0.85 p <0.025 and 0.47 ± 0.72 p<0.001) than controls (−0.21 ± 0.66 and −0.39 ± 0.49 respectively). Despite this increase in BMD, after 24 months of supplementation celiac patients still had significantly lower values than the controls (WB −0.08 ± 0.59 p<0.05, FN 0.04 ± 1.12 p <0.03). Although calcium and vitamin D supplementation for 24 months had beneficial effects on the bone mass of celiac patients in whole body (WB) and femoral neck (FN) measurements, these did not reach the BMD of controls.

Prevalence of abnormal urinary albumin excretion in adolescents and children with insulin dependent diabetes: the MIDAC study

OBJECTIVETo examine the prevalence of microalbuminuria, defined as an albumin to creatinine ratio (UAC) equal to or greater than 2 mg/mmol in at least two of three early morning urine...

Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with Type 1 diabetes mellitus: relation to glycaemic control and microvascular complications.

To evaluate serum levels of vascular endothelial growth factor (VEGF) in a large group of children, adolescents and young adults with Type 1 diabetes mellitus to investigate whether increased VEGF concentrations are associated with long-term glycaemic control and microvascular complications. The study involved 196 patients with Type 1 diabetes mellitus (age range 2-24 years, onset of diabetes before the age of 12 years, duration of disease longer than 2 years), without clinical and laboratory signs of microvascular complications; they were divided into three groups (group 1 - n = 37, age < 6 years; group 2 - n = 71, age 6-12 years; group 3 - n = 88, age > 12 years). Fifty-three adolescents and young adults (age 16.1-29.7) with different grades of diabetic retinopathy and microalbuminuria were also selected (group 4). A total of 223 healthy controls were matched for age and sex with each group of patients with diabetes mellitus. VEGF serum levels were significantly increased in pre-school and pre-pubertal children with diabetes as well as in pubertal patients compared to controls. VEGF concentrations were markedly increased in adolescents and young adults with microvascular complications compared with both healthy controls and diabetic patients without retinopathy or nephropathy. Multivariate analysis showed that elevation of VEGF in serum was an independent correlate of complications. One-year mean HbA1c values were significantly correlated with VEGF concentrations (r = 0.372; P < 0.01). Children with HbA1c levels greater than 10% had significantly higher VEGF concentrations when compared with matched patients whose HbA1c levels were lower than 10%. In poorly controlled diabetic children (HbA1c > 10%), long-term (2 years) improvement of glycaemic control (aiming at HbA1c < 7%) resulted in a significant reduction of VEGF levels. VEGF serum concentrations are increased in prepubertal and pubertal children with diabetes. Glycaemic control influences VEGF serum levels. Severity of microvascular complications is associated with marked increase of VEGF concentrations in the serum of these patients.

Hamartoma in a pubertal patient with complete androgen insensitivity syndrome and R(831)X mutation of the androgen receptor gene

Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder. Individuals with CAIS ordinarily have normal breast development, pubertal feminization, bilateral testes, female external genitalia, a blind-ended vagina, and no müllerian derivatives. The actual frequency of malignant gonadal tumors among this group has been estimated to be no more than 5%; the risk of gonadal malignancy in CAIS is considered low in women before 25 years of age (1). Benign tumors such as hamartomas, Sertoli cell adenomas, and, rarely, Leydig cell tumors have been reported in association with CAIS (1).

Growth over 10 years following a 1-year trial of growth hormone therapy.

The growth of short children with chronic renal failure (CRF) and renal transplants was assessed over 10 years following entry into a 1-year trial of recombinant human growth hormone (rhGH) therapy. Patients were divided into three groups: 6 prepubertal patients with CRF (group 1), mean (range) age at start of trial 7.7 (5.0-10.4) years; 6 prepubertal patients with renal transplants (group 2), age 11.9 (9.5-14.6) years; and 6 pubertal patients with renal transplants (group 3), age 15.6 (14.1-18.3) years. In group 1, the mean (range) height standard deviation score (Ht SDS) increased from -2.9 (-3.7 to -2.2) to -1.9 (-2.9 to -0.5) over 4.0 (0.3-9.1) years of rhGH (P=0.04), and was -1.6 (-2.9 to -0.4) after 10 years of follow-up (NS). In group 2 Ht SDS increased from -3.3 (-4.5 to -1.9) to -2.9 (-5.4 to -0.5) over 2.7 (1.0-6.0) years and was -3.0 (-6.3 to -0.1) at final height (NS). In group 3 Ht SDS increased from -3.4 (-4.3 to -2.6) to -3.0 (-3.4 to -2.2) over 1.4 (0.2-2.3) years (NS) and was -2.5 (-3.0 to -1.9) at final height (P=0.03 from stopping rhGH to final height). Final height was attained in 13 patients, in whom Ht SDS increased from -3.2 (-4.3 to -1.9) to -2.6 (-3.9 to -0.5) on rhGH (P=0.004) and to -2.2 (-4.4 to -0.1) after stopping treatment (P=0.04). Four patients died, 2 have chronic hepatitis C, and 1 has had surgery for parathyroid adenomata. In conclusion, the majority of patients had an improvement in Ht SDS while on rhGH, which was maintained after stopping treatment.

Gray-scale and power doppler sonographic appearances of acute inflammatory diseases of the scrotum.

We describe the spectrum of gray-scale and power Doppler sonographic appearances in inflammatory scrotal diseases. Twenty-five patients ranging in age from 3 to 69 years underwent gray-scale and power Doppler sonography with multifrequency transducers of 7-9 MHz or 10-13 MHz. In addition, color Doppler and power Doppler findings were compared in 7 cases. In all 5 prepubertal patients, power Doppler imaging demonstrated hyperemia associated with epididymitis and, in some cases, orchitis. Among the 20 pubertal and adult patients, power Doppler imaging revealed increased vascularity associated with spermatic cord involvement, epididymitis, orchiepididymitis, or orchitis. Enlargement and heterogeneity of the epididymis and/or testis were seen in 11 patients, with vas efferens ectasia in 3 patients. Abscess formation and testicular infarction were easily depicted by power Doppler imaging. In 5 cases total, hyperemia was the only sonographic finding of inflammation. In the comparison between color and power Doppler imaging, a subjective increase in the number and length of vessels was seen with power Doppler imaging. Power Doppler imaging is an easy and fast Doppler modality for evaluating inflammatory conditions of the scrotum and proved especially useful in cases with no gray-scale sonographic anomalies, in prepubertal patients, and in patients with abscesses or ischemic lesions.

Height, Bone Mineral Density and Bone Markers in Congenital Adrenal Hyperplasia

Aim: To evaluate height, bone growth, areal bone mineral density (aBMD), volumetric bone mineral density (vBMD) and markers of bone turnover in a group of patients affected by congenital adrenal hyperplasia (CAH). Patients: There were 50 patients (23 males, 27 females), aged 1–28 years, affected by CAH due to 21-hydroxylase deficiency: 27 with the salt-wasting (SW); 14 with the simple virilizing (SV), and 9 with the nonclassical (NC) forms. Methods: Bone morphometry was evaluated with the metacarpal index (MI) and lumbar aBMD and vBMD (L2–L4) by dual energy X-ray absorptiometry. Serum osteocalcin was used as a marker of bone formation, while urinary cross-linked N-telopeptides of type-I collagen and free deoxypyridinoline levels were evaluated as indexes of bone resorption. Results: The height standard deviation score (SDS) was –0.41 ± 1.4 in SW patients, –0.01 ± 1.9 in SV patients, and –0.01 ± 2.3 in NC patients. There was no significant difference among groups and against zero. The MI SDS was also not different between groups and against zero.aBMD was significantly lower in the pubertal patients compared with normal values, but only when patients with the SW and SV forms were considered together (p < 0.05). vBMD was significantly reduced in all patients with the classical form. Bone markers were not different in patients and controls. Conclusion: Our study shows that normal height can be attained in CAH patients; however, an impairment in bone growth and mineralization may be found in adolescents and young adults affected by the classical form.

Low serum inhibin B concentrations in male survivors of childhood malignancy

The aim of this study was to assess the value of serum inhibin B in detecting male gonadal dysfunction in childhood cancer survivors. 27 male postpubertal (Tanner's pubertal stage G5 or P6) and 12 pubertal (≥G2) patients were drawn from the endocrine follow-up protocol of childhood cancer patients at the Paediatric Clinic of Turku University Hospital, Turku, Finland. The average time (mean±S.D.) between the diagnosis and this study was 11.7±4.5 years in the postpubertal and 7.0±3.9 years in the pubertal group. Serum samples for the determination of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, testosterone, and inhibin A and B dimers were collected. The demographic factors, pubertal stage and testicular size of the patient were measured at the same routine outpatient visit. Serum inhibin concentrations were correlated to testicular volume and gonadotrophin concentrations. Strong correlations were observed between testicular size ( r=0.80, P<0.001) or FSH ( r=−0.58, P=0.002) and inhibin B concentration in the postpubertal group. Inhibin A was not detectable (<2 pg/ml). Testicular volume measurement was accurately documented in 21 postpubertal subjects. Patients with small testicles (<10 ml) had inhibin B concentrations under 42 pg/ml and those whose testicular size was over 13 ml had inhibin B concentrations exceeding 100 pg/ml. In all 12 pubertal survivors, serum inhibin B levels were ≥94 pg/ml, except in one case of testicular cancer where inhibin B was 8.1 pg/ml and the FSH concentration was elevated. Inhibin B seems to be an indicator of male gonadal function in postpubertal childhood cancer survivors and could be used in the estimation of gonadal function of male survivors earlier than testicular volume or semen analyses would be routinely possible. However, the correct cut-off level of serum inhibin B, as well as the details of inhibin B physiology during puberty, remain to be determined before semen analysis can be replaced by the measurement of inhibin B.

Pelvic ultrasonography in Turner syndrome: standards for uterine and ovarian volume.

The purpose of this study was to investigate uterine and ovarian size according to age and pubertal stage in patients with Turner syndrome. Ultrasonographic evaluation of the uterus and the ovaries was performed in 93 patients with Turner syndrome, aged 12 days to 17.85 years. The data were compared with those of 190 healthy controls. One or both ovaries were detected in 41 of 93 patients (44%). Within the prepubertal group, mean uterine volume and mean ovarian volume of the patients with Turner syndrome were significantly (P<0.001) lower than those of controls (0.5+/-0.2 ml versus 1.0+/-0.3 ml; 0.3+/-0.3 ml versus 0.6+/-0.4 ml, respectively). In prepubertal girls, no significant relationship was found between age and uterine size or ovarian size. Both uterine volume and ovarian volume of 19 women with spontaneous puberty increased during breast development, although mean uterine volume and mean ovarian volume were significantly (P<0.01) lower than those of pubertal control patients.

Phychosocial Impact of GH and LHRH Analogue Treatment in Pubertal Patients with Growth Hormone Deficiency (GHD)

Phychosocial Impact of GH and LHRH Analogue Treatment in Pubertal Patients with Growth Hormone Deficiency (GHD)

Demonstration of estrogen receptor-beta immunoreactivity in human growth plate cartilage.

Estrogens affect longitudinal bone growth through their action on endochondral bone formation. Two estrogen receptors are known, the classical estrogen receptor-alpha (ER alpha), newly demonstrated in human growth plate cartilage, and a recently cloned estrogen receptor-beta (ER beta). The present study aimed to localize a possible expression of ER beta protein in human growth plates. Tissue samples were obtained from tibial and femoral growth plates in four female pubertal patients undergoing epiphyseal surgery. Immunohistochemistry, using two different ER beta-specific antibodies, demonstrated positive staining for ER beta in hypertrophic epiphyseal chondrocytes from all patients. No staining was noted in resting or proliferative chondrocytes. These data suggest that in addition to ER alpha, human epiphyseal chondrocytes also express ER beta. The physiological role of ER beta in the regulation of longitudinal bone growth in humans remains to be elucidated.

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 μg/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/m 2/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/m 2 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.

Residual beta-cell function and spontaneous clinical remission in type 1 diabetes mellitus: the role of puberty.

To investigate the role of puberty on spontaneous clinical remission and on secretion of residual C-peptide during the first year of type 1 diabetes mellitus, we studied 77 pre-pubertal, 39 pubertal and 41 post-pubertal type 1 diabetic patients. Spontaneous partial clinical remission (HbA1c within the normal range and insulin dose less than 0.3 U x kg(-1) body weight x day(-1) lasting for at least 10 days) decreased with duration of diabetes: months 3 vs 6 vs 12, respectively 13 vs 7 vs 4% (P<0.025). Remission was higher in post-pubertal than pubertal and prepubertal patients: month 6 respectively 20 vs 5 vs 1% (P<0.001). Secretion of C-peptide was significantly lower in pre-pubertal than the other two groups of patients. Basal and stimulated C-peptide secretion were higher in patients in clinical remission than in those who were not: basal value 0.4 (0.26-0.53) vs 0.28 (0.14-0.4) nmol/l (P<0.05); stimulated value 0.63 (0.5-0.95) vs 0.56 (0.31-0.74) nmol/l (P<0.05). Spontaneous remission is less frequent in children and adolescent patients than in adult post-pubertal patients, but different mechanisms may be involved. Low residual insulin secretion seems implicated in children meanwhile low insulin sensitivity could be more important in pubertal patients.

Does the long-term clinical course of type I diabetes mellitus differ in patients with prepubertal and pubertal onset? Results of the Berlin Retinopathy Study.

The objective of the present study was to investigate potential differences at presentation of type I diabetes and during its long-term clinical course in children and adolescents with prepubertal and pubertal manifestation. Clinical, immunological and biochemical characteristics at diabetes onset of 453 patients (320 prepubertal, 133 pubertal; median age at manifestation 7.1 years (0.7-13.9) and 13.1 years (9.2-17.6), respectively) were evaluated. Glycaemic control and exogenous insulin requirements were followed prospectively, with a median follow up of 9.4 years. At the onset of the disease no differences concerning the degree of metabolic decompensation, impairment of somatic health, and islet cell antibody status could be detected between the groups, except for a smaller body weight loss in pubertal patients (P=0.011). The duration of partial remission (insulin requirements <0.5 IU/kg body weight/day) was unrelated to age or pubertal status at onset. It was found to be longer in boys than in girls in the total cohort (median duration: 279 vs 215 days, P = 0.0071). Despite an absence of differences during the early course of the disease, glycaemic control was better, and daily insulin doses were significantly lower in patients with pubertal onset, after 6 years of diabetes. Adolescents with a pubertal onset of type I diabetes have a more benign long-term course of the disease demonstrating better glycaemic control and lower insulin requirements, although the presentation of the disease at onset and its course during the first 6 years are not different from those of children with a prepubertal manifestation of diabetes.

Impaired androgen production in female adolescents and young adults after total body irradiation prior to BMT in childhood.

Pubertal development and androgen production were evaluated 1-10 years after bone marrow transplantation (BMT) in 15 females aged 14-23 (mean 17) years. Before BMT, these patients had received combination chemotherapy for hematologic malignancy, and all had had a transplant program including total body irradiation (TBI). Of the nine patients who were pre-menarcheal at BMT, two had subsequently experienced spontaneous menarche at 11.5 and 13.3 years of age. Six were post-menarcheal, but became amenorrheic after BMT. Menstruation subsequently started spontaneously in one of them 6 years after BMT. At the time of the study, three patients were early to mid-pubertal and 12 late pubertal or post-pubertal. Twelve patients were receiving sex steroid substitution therapy. Serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) were determined. Androgen levels of late pubertal and post-pubertal transplanted patients were compared with 19 post-menarcheal patients aged 14-21 (mean 17) years who had been treated for hematologic malignancy with conventional chemotherapy. Testosterone levels of 52 healthy post-menarcheal females aged 14-29 (mean 19) years were measured as controls. Androgen levels of the BMT patients were lower than those of the conventionally treated patients. Differences in testosterone, androstenedione and DHEA levels were significant. Three spontaneously menstruating BMT patients had normal androgen levels. Testosterone levels of the conventionally treated patients and healthy controls were similar. Subnormal androgen production might be one factor behind the problems in pubertal development and sex life experienced by females after BMT. The use of these hormone levels for follow-up purposes and the potential value of androgen replacement therapy in females after TBI merit further study.