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Biomedical subjects

Alan D Rogol

Publications and source records attributed to Alan D Rogol.

At least 19 recordsLinked to original sources

Persistent hypercalcemia after parathyroidectomy in an adolescent and effect of treatment with cinacalcet HCl.

BACKGROUND: Hyperparathyroidism is uncommon in adolescence and is more likely to persist after parathyroidectomy than in adults. Cinacalcet HCl is a new calcimimetic that has been used successfully for the treatment of primary and secondary hyperparathyroidism in adults, but its use in adolescents has not been reported. CASE: A 16 year-old male presented with hypercalcemia that had persisted for 1.5 years after parathyroidectomy for primary hyperparathyroidism. Parathyroid hormone (PTH) concentrations were nonsupressed despite a mean (SD) serum calcium concentration of 2.82 (0.06) mmol/L. Treatment with cinacalcet HCl was initiated and a pharmacodynamic profile was obtained for serum calcium, phosphorus, and PTH. Cinacalcet HCl normalized serum calcium. The changes in PTH were assay dependent. ISSUES: We use this case conference to review the evaluation of hypercalcemia in adolescents, examine the changes in relevant laboratory results during treatment with cinacalcet HCl, and discuss differences among assays for PTH. CONCLUSIONS: Interpretation of PTH results in patients treated with cinacalcet HCl requires consideration of the pharmacodynamic effects of the drug and the nature of the PTH assay.

Adolescent↗

Bone age and onset of puberty in normal boys.

Many conditions that delay skeletal maturation also delay the onset of puberty, whereas conditions that accelerate skeletal maturation often hasten the onset puberty, raising the possibility that skeletal maturation influences pubertal onset. To determine whether this concordance is also present in normal children, we analyzed data from 30 normal boys participating in a longitudinal study. Height, weight, and serum testosterone concentrations were assessed every 6 months and bone age (Fels method) every year. Pubertal onset was defined by serum testosterone > or =30 ng/dL. The variability in bone age at onset of puberty was not less than the variability in chronological age. In addition, there was no significant correlation between skeletal advancement and pubertal advancement (r=0.01, P=0.9). Similarly, there was not a significant correlation between pubertal advancement and height age advancement, weight age advancement, or BMI age advancement. Our findings do not support the hypothesis that skeletal maturation directly influences the age of pubertal onset in normal boys.

Adolescent↗

A workshop on pubertal hormone replacement options in the United States.

BACKGROUND: The optimal pubertal hormone replacement therapy in females and males is unclear. OBJECTIVE: To review hormone replacement options for hypogonadal teenagers and to determine the relevant attitudes and practices of pediatric endocrinologists in the United States. DESIGN/METHODS: A workshop on pubertal hormone replacement options was held during the Lawson Wilkins Pediatric Endocrine Society meeting in 2004. A questionnaire was distributed to investigate the audience's attitudes and practices in inducing puberty. RESULTS: The majority of respondents used conjugated estrogens to treat hypogonadal girls with the primary aim of treatment being attainment of maximal adult height. The majority of respondents used depot testosterone to treat hypogonadal boys with the primary aim of treatment being pubertal development and virilization. CONCLUSIONS: The use of physiological sex hormone replacement to optimize the induction of puberty in hypogonadal adolescents was recommended. The workshop revealed striking differences between US and European pediatric endocrinologists regarding their practices and attitudes regarding the induction of puberty in hypogonadal females. Detailed studies are necessary to develop more uniform guidelines.

Adolescent↗

Increases in overweight after adenotonsillectomy in overweight children with obstructive sleep-disordered breathing are associated with decreases in motor activity and hyperactivity.

OBJECTIVE: To examine the effect of adenotonsillectomy (T&A) in children with obstructive sleep-disordered breathing on growth, hyperactivity, and sleep and waking motor activity. METHODS: We studied 54 children who were aged 6 to 12 years and had adenotonsillar hypertrophy and an obstructive apnea-hypopnea index of > or =1 before and 12 months after they all received adenotonsillectomy (T&A). We measured their height, weight, percentage overweight (patient BMI - BMI at 50th percentile)/BMI at 50th percentile x 100) and obtained a hyperactivity score from parent report on a standardized behavior questionnaire scale. A subset of 21 of these children were also studied for motor activity by wrist actigraphy for 7 consecutive days and nights before and 12 months after T&A. RESULTS: After T&A, mean obstructive apnea-hypopnea index decreased from 7.6 to 0.6. Height percentile did not change, but weight percentile increased; as a consequence, percentage overweight increased from 32.0% to 36.3%. Hyperactivity scores and total daily motor activity were reduced after T&A. From linear regression, the reduction in hyperactivity scores predicted an increase in percentage overweight. Reduced motor activity was correlated with increased percentage overweight. CONCLUSIONS: An increase in percentage overweight after T&A in children with obstructive sleep-disordered breathing is correlated to decreased child hyperactivity scores and to decreased measured motor activity in the subset studied. These associations suggest that the increase in overweight may be attributable to reductions in physical activity and fidgeting energy expenditure.

Adenoidectomy↗

Pubertal alterations in growth and body composition: IX. Altered spontaneous secretion and metabolic clearance of growth hormone in overweight youth.

Deconvolution analysis was used to determine 12-hour spontaneous nocturnal growth hormone (GH) secretion and GH half-life in lean (body mass index, <85th percentile; n = 39) and overweight (body mass index, > or =85th percentile; n = 18) youth. The integrated GH concentration, GH burst mass, and half-life were lower (P < .05) in overweight than in lean youth. For each unit increase in percentage of body fat, integrated serum GH concentrations, secretory burst mass, and half-life declined by 83.6 microg/L per minute (r = -0.39, P < .01), 0.22 microg/L (r = -0.28, P < .05), and 0.2 minute (r = -0.38, P < .01), respectively. The effect of overweight on GH secretion was independent of pubertal status. Hierarchical regression models tested the hypothesis that altered GH secretion in youth is more related to total adiposity than abdominal visceral fat. When age, sex, fat-free mass, testosterone, and estradiol were held constant, the sequential addition of abdominal visceral fat did not increase R2 for any GH secretion variable. Sequential addition of percentage of body fat increased R2 (P < .05) for integrated GH concentration, total secretory rate, secretory burst mass, and pulsatile production rate. We conclude that serum GH concentrations are reduced in overweight youth primarily because of reduced GH burst mass with no change in the number of secretory events and secondarily to reduced GH half-life. Based on the model that GH-releasing hormone predominantly increases GH pulse amplitude whereas somatostatin primarily controls GH pulse frequency, these results suggest that overweight in youth diminishes GH-releasing hormone stimulation resulting in truncated GH bursts but does not alter the number of somatostatin withdrawal intervals so that GH burst frequency is conserved.

Abdomen↗

Endocrine control of body composition in infancy, childhood, and puberty.

Body composition exhibits marked variations across the early human lifetime. The precise physiological mechanisms that drive such developmental adaptations are difficult to establish. This clinical challenge reflects an array of potentially confounding factors, such as marked intersubject differences in tissue compartments; the incremental nature of longitudinal intrasubject variations in body composition; technical limitations in quantitating the unobserved mass of mineral, fat, water, and muscle ad seriatim; and the multifold contributions of genetic, dietary, environmental, hormonal, nutritional, and behavioral signals to physical and sexual maturation. From an endocrine perspective (reviewed here), gonadal sex steroids and GH/IGF-I constitute prime determinants of evolving body composition. The present critical review examines hormonal regulation of body composition in infancy, childhood, and puberty.

Adipose Tissue↗

New facets of androgen replacement therapy during childhood and adolescence.

The goals of androgen therapy for adolescents are to promote linear growth and secondary sexual characteristics, at the same time as permitting the normal accrual of muscle mass and bone mineral content. Secondary goals are mainly in the psychosocial sphere, in which pubertally delayed boys feel that they look too young, are not considered a 'peer' in their age group and have difficulty competing in athletic endeavours. These goals are irrespective of the causes of delayed pubertal development: constitutional delay of growth and puberty (CDGP), a transient but very common form of pubertal delay and, much less commonly, primary or secondary permanent hypogonadism. Not all boys with CDGP require testosterone therapy, but those that come to a referral practice are likely candidates, as the watchful waiting period has finished. Although a range of androgen preparations is available for adults (injectable, oral, implantable and cutaneous patches and gels), most are drug delivery devices that are appropriate for full adult androgen replacement. These doses are too large for the induction of puberty. Therefore, at present, the injectable form is the only one that is easily adaptable for the increasing amounts of androgen necessary for the various stages of pubertal development. All preparations deliver testosterone that is readily converted to dihydrotestosterone by 5-alpha reductase. The author's practice is to begin with injecting 50-75 mg of one of the long-acting esters (enanthate or cypionate) per month, and gradually escalate to 100-150 mg/month, before changing to twice monthly dosage. As most adolescents have delayed puberty, the therapy is needed for 6-18 months before the hypothalamic-pituitary-gonadal axis functions at the late adolescent/adult level in those with CDGP. Those with permanent hypogonadism will require lifelong therapy. Once adequate virilisation is induced, and virtually full adult height is reached, any of the therapies noted above can be used in those permanently hypogonadal, whether primarily or secondarily.

Adolescent↗

Magnesium deficiency is associated with insulin resistance in obese children.

OBJECTIVE: Magnesium deficiency has been associated with insulin resistance (IR) and increased risk for type 2 diabetes in adults. This study was designed to determine whether obese children exhibit serum or dietary magnesium deficiency and its potential association with IR. RESEARCH DESIGN AND METHODS: We studied 24 obese nondiabetic children (BMI > or =85th percentile) and 24 sex- and puberty-matched lean control subjects (BMI <85th percentile). We measured serum magnesium, indexes of insulin sensitivity, dietary magnesium intake (using a food frequency questionnaire), and body composition (by air displacement plethysmography). RESULTS: Serum magnesium was significantly lower in obese children (0.748 +/- 0.015 mmol/l, means +/- SE) compared with lean children (0.801 +/- 0.012 mmol/l) (P = 0.009). Serum magnesium was inversely correlated with fasting insulin (r(s) = -0.36 [95% CI -0.59 to -0.08]; P = 0.011) and positively correlated with quantitative insulin sensitivity check index (QUICKI) (0.35 [0.06-0.58]; P = 0.015). Dietary magnesium intake was significantly lower in obese children (obese: 0.12 +/- 0.004 vs. lean: 0.14 +/- 0.004 mg/kcal; P = 0.003). Dietary magnesium intake was inversely associated with fasting insulin (-0.43 [-0.64 to -0.16]; P = 0.002) and directly correlated with QUICKI (0.43 [0.16-0.64]; P = 0.002). CONCLUSIONS: The association between magnesium deficiency and IR is present during childhood. Serum magnesium deficiency in obese children may be secondary to decreased dietary magnesium intake. Magnesium supplementation or increased intake of magnesium-rich foods may be an important tool in the prevention of type 2 diabetes in obese children.

Adipose Tissue↗

Single-center experience with pediatric Cushing's disease.

OBJECT: Despite ongoing advances in surgical and radiotherapeutic techniques, pediatric Cushing's disease remains a diagnostic and therapeutic challenge. The authors report on the results of a single-center retrospective review of 33 pediatric patients with Cushing's disease, providing details with respect to clinical presentation, diagnostic evaluation, therapeutic course, complications, and outcomes. METHODS: There were 17 female and 16 male patients whose mean age was 13 years (range 5-19 years) in whom a diagnosis of Cushing's disease was based on clinical and biochemical criteria. Typical symptoms included weight gain (91%), prepubertal growth delay (83%), round facies (61%), hirsutism (58%), headache (45%), abdominal striae (42%), acne (33%), amenorrhea (24%), and hypertension (24%). In 67% of the cases, preoperative magnetic resonance images revealed a pituitary lesion and in 82% of the cases the imaging studies effectively predicted lateralization. Inferior petrosal sinus sampling was performed in seven patients (21%), and in all of these cases lateralization was 100% reliable. Fifty-five percent underwent selective adenomectomies and 45% underwent subtotal hypophysectomies. Complications included one case of diabetes insipidus, one of persistent hypocortisolemia necessitating prolonged glucocorticoid replacement therapy, and one minor vascular injury that did not necessitate postoperative management modification or cause sequelae. There were no surgery-related deaths and no cases of postoperative cerebrospinal fluid leakage or meningitis. During a mean follow-up period of 44 months, clinical remission was ultimately achieved in 91% of patients: 76% after transsphenoidal surgery alone and an additional 15% after adjuvant radiosurgery and/or adrenalectomy following surgical failure. Three patients (12%) experienced disease recurrence and underwent a second surgical procedure at 18, 81, and 92 months, respectively; based on clinical and biochemical criteria a second remission was achieved in all. Three patients (9%) remain with persistent disease. CONCLUSIONS: Pediatric Cushing's disease is a rare condition, often requiring a multidisciplinary diagnostic and a multimodal therapeutic approach for successful long-term remission.

Adolescent↗

Bisphosphonate treatment of pediatric bone disease.

The science of measuring bone mineral density has developed rapidly and, with it, an improved understanding of the efficacy and safety of various therapeutic interventions in adults. In contrast, the meaning and precision of such measurements in children are equivocal, and the concept of treatment for low bone density in the young patient is still largely undecided. In this report we review the present state of knowledge regarding the use of bisphosphonates during childhood to ameliorate the skeletal abnormalities associated with osteogenesis imperfecta, idiopathic juvenile osteoporosis, fibrous dysplasia of bone and cerebral palsy. Because of the paucity of long-term studies among children regarding the safety and efficacy of these drugs, it is difficult to formulate strong evidence-based recommendations for their use, except perhaps in children with osteogenesis imperfecta.

Bone Density↗

Pubertal androgen therapy in boys.

Anabolic-androgenic steroids (AAS) are necessary for normal male sexual differentiation and development and pubertal development. Androgen therapy is appropriate for boys with delayed development (constitutional delay of growth and puberty, CDGP) as well as those with primary or secondary hypogonadism. The principal goal is to restore the serum testosterone (T) level to the normal range at each stage of adolescent development and then to the normal adult range if the hypogonadism is permanent. In addition the levels of dihydrotestosterone and estradiol should also be within the normal range. One should be able to do that with a wide variety of androgen preparations-injectable, implantable, and cutaneous patches or gels. However, during the transition from prepubertal to adult it is difficult to reliably deliver the relatively small doses of T necessary for adolescent development using any of the cutaneous preparations. Androgen therapy should permit normal linear growth (including the adolescent growth spurt), adolescent sexual development, and the attainment of normal body composition including lean body mass, bone and the appropriate regional distribution of body fat as well as the psychological development appropriate for the stage of adolescent development.

Adolescent↗

Childhood obesity.

In March 2004 a group of 65 physicians and other health professionals representing nine countries on four continents convened in Israel to discuss the widespread public health crisis in childhood obesity. Their aim was to explore the available evidence and develop a consensus on the way forward. The process was rigorous, although time and resources did not permit the development of formal evidence-based guidelines. In the months before meeting, participants were allocated to seven groups covering prevalence, causes, risks, prevention, diagnosis, treatment, and psychology. Through electronic communication each group selected the key issues for their area, searched the literature, and developed a draft document. Over the 3-d meeting, these papers were debated and finalized by each group before presenting to the full group for further discussion and agreement. In developing a consensus statement, this international group has presented the evidence, developed recommendations, and provided a platform aimed toward future corrective action and ongoing debate in the international community.

Child↗

Gender and hormonal regulation of growth.

Puberty is the transitional period between childhood and adulthood when substantial growth, sexual maturation, and reproductive capacity is attained. The onset of puberty is triggered by the combined action of the somatotropic (GH-IGF-I) and gonadotropic (GnRH-LH/FSH-sex steroid) hormone axes, the latter of which stimulates the former to produce the pubertal growth spurt. Studies of GH secretion in boys and girls, in Turner's syndrome, in hypogonadal girls, and in androgen-deficient boys have revealed estrogen-dependent mechanisms controlling GH production, age-dependent response to and control of GH, and gender-dependent differences in response to GH therapy. The interplay between the somatotropic and gonadotropic hormone axes during puberty has profound implications on the treatment of adolescent patients in need of hormone replacement therapy for growth deficiency or hypogonadism.

Adolescent↗

Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection.

OBJECTIVE: To examine whether greater severity of HIV infection is associated with delayed initiation of pubertal development among perinatally HIV-infected children, and to compare sexual maturation of perinatally HIV-infected children with children in the general US population using the National Health and Nutrition Examination Survey III. METHODS: In a prospective cohort study, the authors studied 983 HIV-infected children aged 6 to 18 years, who had Tanner stage assessed on at least two occasions between 1995 and 2000. Analyses were conducted separately for girls and boys to identify factors associated with onset of puberty or adrenarche (progression beyond Tanner stage 1). RESULTS: Among children who were in Tanner stage 1 at their first assessment, 185 of 413 (45%) girls and 144 of 434 (33%) boys entered puberty during the observation period. In multivariate longitudinal regression analyses adjusted for age, race/ethnicity, time interval between study visits, and other clinical factors, girls with severe immunosuppression (CD4% <15) were significantly less likely to enter adrenarche (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.29-0.83) and puberty (OR, 0.57; 95% CI, 0.33-0.96) compared with girls who were not immunosuppressed (CD4% > or =25). For boys, those with severe immunosuppression were significantly less likely to enter adrenarche (OR, 0.52; 95% CI, 0.28-0.96) and tended to be less likely to begin puberty (OR, 0.69; 95% CI, 0.39-1.22) compared with boys who were not immunosuppressed. Qualitative comparisons suggested that HIV-infected children may experience delayed puberty and adrenarche compared with similarly aged children in the general US population. CONCLUSIONS: Immunosuppression was associated with delayed pubertal onset in perinatally HIV-infected children. Further studies of perinatally HIV-infected and uninfected children are needed to better quantify the delay in pubertal onset and to compare the pace of pubertal maturation.

Adolescent↗

Do growth hormone (GH) serial sampling, insulin-like growth factor-I (IGF-I) or auxological measurements have an advantage over GH stimulation testing in predicting the linear growth response to GH therapy?

OBJECTIVE: To compare the relative utility of GH secretion via pharmacological stimulation, overnight serial sampling, IGF-I levels and auxological variables as predictors of change in height standard deviation score (deltaHt SDS) during GH treatment. DESIGN: A multicentre observational study. PATIENTS: Prepubertal children (n = 825) with idiopathic growth failure who were subsequently treated with GH were divided into two groups, based on their maximum GH response to pharmacological stimulation testing: (1) idiopathic GH deficiency (IGHD), defined by a maximum GH response < 10 microg/l (n = 300); and (2) idiopathic short stature (ISS), with a maximum GH response > or = 10 microg/l (n = 525) (GH conversion factor: 3 IU = 1 mg). MEASUREMENTS: Overnight spontaneous GH secretion was measured in all patients. The following characteristics of spontaneous GH secretion were studied: maximum or peak GH, mean peak GH, number of GH peaks, pooled GH, mean GH, and approximate entropy of GH secretion. RESULTS: Although children with IGHD had lower indices of spontaneous GH secretion, there were no differences between IGHD and ISS groups in baseline Ht SDS, growth rate or IGF-I level. The dose and duration of GH therapy were similar. There was no statistically significant difference in the mean (+/- SD) change in Ht SDS (deltaHt SDS) in the two groups (IGHD 1.3 +/- 0.9 and ISS 1.2 +/- 0.8). Measures of spontaneous secretion, such as peak GH, mean of GH peaks, mean area under GH peaks, and mean GH, as well as IGF-I concentrations, were all statistically significantly correlated with deltaHt SDS in IGHD children (P < 0.0001). A significant correlation was also observed for pooled GH (P = 0.002) and approximate entropy (P = 0.01). Children with the most severe ISS (Ht SDS < -3.33) demonstrated a more disorganized pattern of GH secretion compared to children who were not as short (Ht SDS -2.33 to -1.64), as indicated by a higher approximate entropy (0.673 +/- 0.193 vs. 0.607 +/- 0.161, P < 0.004). This increased disorder in GH secretion was accompanied by lower IGF-I levels (104 +/- 99 microg/l vs. 137 +/- 74 microg/l, P < 0.001), even though pooled GH concentrations were indistinguishable between the two groups (2.2 +/- 1.3 microg/l vs. 2.0 +/- 1.0 microg/l). Children with IGHD demonstrated lower approximate entropy than did those with ISS (0.551 +/- 0.235 vs. 0.631 +/- 0.182, P < 0.0001). Duration of GH treatment, height deficit and genetic potential (midparental Ht SDS) were the most important variables influencing deltaHt SDS in children receiving GH therapy. Maximum stimulated GH, IGF-I and indices of spontaneous GH secretion also correlated with deltaHt SDS, but their relative importance varied among diagnostic groups. CONCLUSIONS: Patients with GH deficiency demonstrate a reduced capacity for GH secretion, while those with idiopathic short stature exhibit a more disorderly and less functional secretory pattern. Although effective in predicting a response to GH treatment in patients with severe GH deficiency, overnight serial sampling is less practical than other methods currently available. In addition, serial sampling was less useful as a predictor of growth response to exogenous GH in patients with idiopathic short stature.

Blood Specimen Collection↗

Relationship of leptin to bone mineralization in children and adolescents.

Serum leptin concentrations and bone mass are concordant in several respects. Obesity is associated with increased serum leptin concentrations and bone mineral, whereas undernutrition reduces serum leptin concentrations and bone mineral. Furthermore, both bone mineral and serum leptin concentrations increase at the initiation of puberty. However, there is a lack of empirical evidence of an independent association of serum leptin concentrations and bone mineral in youth. Thus, we used hierarchical regression to determine whether serum leptin concentrations were related to bone mineral in boys (n = 28) and girls (n = 31). Bone mineral content, density, and apparent density of the total body and body regions were measured by dual-energy x-ray absorptiometry and statistically adjusted for chronological age, fat mass, bone-free fat-free mass, and serum IGF-I and estradiol concentrations. Sequential addition of serum log((10)) leptin concentrations to the block of body size variables and the block of hormone variables did not increase R(2) for any of the total or regional bone mineral content, bone mineral density, and bone mineral apparent density variables. We conclude that serum leptin concentrations do not add to the prediction of bone mineral in youth after accounting for age, fat mass, bone-free fat-free mass, and serum IGF-I and estradiol concentrations.

Adipose Tissue↗