1999 American Urological Association Gallup Survey: changes in physician practice patterns, treatment of incontinence and bladder cancer, and impact of managed care.

PURPOSE: The Health Policy Survey and Research Committee of the American Urological Association and the Gallup Organization have performed a yearly survey of American urologists since 1992 to assess practice patterns. The results of the 1999 survey are presented. MATERIALS AND METHODS: A random sample of 503 urologists was interviewed in February and March 1999. Major content areas were physician practice patterns, the impact of managed care, and the treatment of pediatric patients, prostate cancer and benign prostatic hyperplasia, female incontinence and bladder cancer. RESULTS: The average urologist is 46.8 years old, certified by the American Board of Urology, sees 78 patients and performs 3.1 major surgical procedures weekly, refers moderate and complex pediatric procedures to specialists, and receives 40.6% of practice income from managed care. CONCLUSIONS: In an era when large group practices seem to be the norm remarkably 32% of urologists remain in solo practice. There has been a shift in where urologists spend their time, that is more in the office and less in the operating room. Minor and major open surgical procedures increased from 12.4 weekly to 16.4 and 2.9 to 3.1 in 1995 and 1999, respectively. Most urologists are comfortable treating straightforward pediatric problems such as cryptorchidism but refer more complex problems to pediatric urologists. Managed care represents an ever increasing proportion of urologist practice income, while office expenses continue to increase.

1998 American Urological Association Gallup Survey: changes in physician practice patterns, treatment of ureteral stones and impact of managed care.

PURPOSE: The American Urological Association first commissioned the Gallup Organization to conduct a study to assess urologist practice patterns in 1992. We present the results of the seventh consecutive Gallup Survey performed for the Association. MATERIALS AND METHODS: A random sample of 537 American urologists who completed urological residency and practiced at least 20 hours weekly in 1997 were interviewed by telephone in March 1998. Major topic areas included general demographics, practice patterns, treatment of ureteral stones and experience with managed care. RESULTS: Demographic trends indicated a significant decrease in average urologist age from 49.4 years in 1992 to 46.8 in 1998. Of the urologists 99% reported that they treat ureteral stones. Managed care had an increasingly larger role in most practices, particularly in the western United States, where 73% of urologists reported that they contract with a Medicare health maintenance organization. CONCLUSIONS: The average age of practicing urologists significantly decreased, which may be due to an increasing number of urologists retiring at an earlier age, although this finding is not clear. Nearly all urologists treated ureteral stones with considerable consistency. Finally, managed care appeared to have a major impact on most urologists throughout the United States.

1997 American Urological Association Gallup survey: Changes in diagnosis and management of prostate cancer and benign prostatic hyperplasia, and other practice trends from 1994 to 1997.

PURPOSE: The American Urological Association first commissioned the Gallup Organization to conduct a study to assess urologist practice patterns in 1992. We present the results of the 1997 survey, the sixth consecutive Gallup survey performed for the Association. MATERIALS AND METHODS: A random sample of 502 American urologists who had completed urological residency and practiced at least 20 hours weekly in 1996 was interviewed by telephone in February and March 1997. RESULTS: Emerging trends showed significant changes since 1994 in how urologists diagnosed and treated prostate cancer. The survey revealed a significant change in the tests routinely ordered to stage newly diagnosed prostate cancer and for diagnostic evaluation of patients with benign prostatic hyperplasia. CONCLUSIONS: Urologists are becoming more cost conscious and effective in ordering pretreatment testing. Urologists are becoming more oriented toward medical treatment for the management of benign prostatic hyperplasia, and less laser surgery is being performed.

Subspecialization, recruitment and retirement trends of American urologists.

PURPOSE: Trends of urology workforce, subspecialization, recruitment practices, retirement planning, practice characteristics and managed care impacts in the United States were assessed. MATERIALS AND METHODS: In February 1996 the executive interviewing branch of The Gallup Organization selected randomly and interviewed by telephone 507 practicing urologists in the United States who had provided urological patient care for more than 20 hours per week, practiced in 1995 and completed a urological residency program. RESULTS: Several important issues emerged. Urologists think we may be training too many urologists, subspecialty board certification would be a divisive issue to urology as a whole and 90% of urologists have an active retirement plan, although 23% are not funding the plan fully. CONCLUSIONS: The American Urological Association Gallup Poll, as refined by the Health Policy Survey and Research Committee, continues to be a unique and valuable tool in assessing practice patterns, gathering demographic data and measuring opinions of the American urologist. This information will help us chart our way to the twenty-first century.

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. III. The neuroendocrine growth hormone axis during late prepuberty.

Cross-sectional studies demonstrating that physiological GH secretion varies widely among normally and slowly growing children as well as adults have created uncertainty over the definition of normal GH secretion. Furthermore, recent data indicate that the pattern of GH released under identical physiological conditions may be unique for each individual, and suggest that normality may be an individually defined condition. To investigate and develop further this concept and to avoid the confounding effects of fluctuating gonadal steroid hormone levels, we chose as a model normally growing prepubertal boys and performed a longitudinal assessment of spontaneous GH release characteristics (36 24-h GH secretion studies in 9 boys over 9-19 months). Assessment of serum GH pulse characteristics was accomplished using the Cluster pulse detection algorithm. Characteristics of underlying pituitary GH secretory events were estimated by multiple parameter deconvolution analysis. Approximate entropy was used to quantify the serial regularity or orderliness of GH release over 24 h. Among the group data, mean 24-h GH concentrations spanned a range of more than 4-fold (1.6-7.0 micrograms/L). The intersubject coefficient of variation (CV) was 41%. In contrast, values from individuals exhibited much less variability, not only for mean 24-h GH level (CV = 25 +/- 4%; P = < 0.02), but also for all assessed component GH pulse properties (P < 0.01) vs. intersubject values). Similarly, the estimated daily GH production rate, the calculated GH half-lives, and all parameters of GH secretory events varied much less for intraindividual compared to interindividual values. The sizes of the serum GH pulses gave rise to the greatest differences in overall serum GH level among individuals, as demonstrated by the large within-subject CV (50%). The most constant pulse characteristic among subjects was that of 24-h GH pulse frequency (intersubject CV = 30%). Approximate entropy estimates disclosed high within-subject consistency (mean CV = 15%). Several aspects of GH secretion and serum concentrations varied inversely with the subject's mean age-adjusted body mass index, including the 24-h GH production rate (r = -0.67; P < 0.05), the GH secretory burst amplitude (r = -0.73; P = 0.026), the mean serum GH pulse amplitude (r = -0.79; P = 0.011), and the sum of the GH pulse amplitudes (r = -0.66; P = 0.05). By contrast, no consistent pattern of increase or decrease in serum GH concentrations with advancing age was detectable during the prepubertal period. These data suggest that during prepuberty, 1) individual boys regulate daily GH secretion within relatively confined limits characteristic for that individual, much narrower than the range present in the larger population; 2) differences in mean 24-h GH levels among normally growing prepubertal boys arise primarily from differences in GH pulse size; 3) differences in body composition, as indicated by the body mass index, may influence the GH secretion range characteristic of each individual; and 4) there is no consistent change in mean 24-h GH concentrations or the orderliness (approximate entropy) of the GH release process ever time during late prepuberty as the onset of puberty approaches.

Practice trends of American urologists in the treatment of impotence, incontinence and infertility.

PURPOSE: Trends of urologist practice patterns in evaluating and treating impotence, incontinence and infertility in the United States were assessed. MATERIALS AND METHODS: In July 1995 the executive interviewing branch of the Gallup Organization selected randomly and interviewed by telephone 533 practicing urologists in the United States who had provided urological patient care for more than 20 hours per week, practiced in 1994 and completed a urological residency program. RESULTS: Treatment of male sexual dysfunction and female urinary incontinence comprises a significant portion of the professional activity of United States urologists. However, evaluation and management of male infertility occupy a small portion of the average urological work load. While more than half of United States urologist office clinical laboratories were inspected in 1994, only 2% failed evaluation due to major deficiencies. CONCLUSIONS: Male sexual dysfunction and female urinary incontinence are major areas of urological practice in the United States but male infertility is not. Few United States urologist clinical laboratories failed inspection because of major deficiencies.

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. II. Estrogen levels as determined by an ultrasensitive bioassay.

A limited number of reports of estrogen levels in prepubertal and early pubertal boys have been published because previous estrogen assays have lacked adequate sensitivity to quantitate circulating estrogen concentrations. Development of a new ultrasensitive assay has permitted measurement of estrogen levels in 23 normally growing boys progressing through puberty. Concentrations were measured at approximately 4-month intervals over a 5- to 8-yr period. The levels increased with maturation in all and correlated directly with chronological age, bone age, weight, height, pubertal stage, and testosterone and insulin-like growth factor-I levels. Of these factors, the level of testosterone had the greatest influence on the estrogen concentration. The time from peak growth velocity also significantly correlated with estrogen level. The estrogen level correlated positively with growth velocity before the time of peak growth velocity and negatively after peak growth velocity. The estrogen levels first increased significantly an average of 3 yr after pubertal onset and reached a peak by 5 yr after pubertal onset. Peak growth velocity was attained an average of 3 yr after pubertal onset. The greatest increase in the rate of rise of the estrogen level was an 11-fold rise during the year in which puberty began. The next most significant increase was a 4.8-fold rise 3 yr after pubertal onset. With respect to pubertal stage, the greatest absolute change occurred from stage 4 to stage 5 and the greatest fold change occurred from stage 1 to stage 2. The estrogen level did not significantly correlate with the 24-h GH level. In conclusion, circulating estrogen levels are very low in all boys prepubertally and rise steadily during adolescent development. The estrogen level is closely related to testosterone concentration and to the time of peak growth velocity. These findings are consistent with the hypothesis that estrogen at low levels augments skeletal growth and maturation in boys (as well as girls). They are also consistent with the hypothesis that continued exposure to estrogen leads to epiphyseal fusion. Further studies are required to define the separate and combined roles of estrogen, GH, and testosterone, as well as other factors, on growth and sexual development at puberty.

A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency--a clinical research center study.

Familial isolated GH deficiency type II (IGHD-II) is an autosomal dominant disorder that has been previously shown in some patients to be caused by heterogeneous GH gene defects that affect GH messenger RNA (mRNA) splicing. We report here our finding of multiple G-->A transitions of the first base of the donor splice site of IVS 3 (+ 1G-->A) in IGHD II subjects from three nonrelated kindreds from Sweden, North America, and South Africa. This + 1G-->A substitution creates an NlaIII site that was used to demonstrate that all affected individuals in all three families were heterozygous for the mutation. To determine the effect of this mutation on GH mRNA processing, HeLa cells were transfected with expression plasmids containing normal or mutant + 1G-->A alleles, and complementary DNAs from the resulting GH mRNAs were sequenced. The mutation was found to destroy the GH IVS 3 donor splice site, causing skipping of exon 3 and loss of the codons for amino acids 32-71 of the mature GH peptide from the mutant GH mRNA. Our finding of exon 3 skipping in transcripts of the + 1G-->A mutant allele is identical to our previous report of a different sixth base transition (+6T-->C) mutation of the IVS 3 donor splice site that also causes IGHD II. Microsatellite analysis of an affected subjects' DNA from each of the three nonrelated kindreds indicates that the + 1G-->A mutation arose independently in each family. Finding that neither grandparent has the mutation in the first family suggests that it arose de novo in that family. Our data indicate that 1) + 1G-->A IVS 3 mutations perturb GH mRNA splicing and cause IGHD II; and 2) these mutations can present as de novo GHD cases.

The use--and misuse--of growth hormone.

Recombinant growth hormone is an effective treatment for many children with short stature, but certainly not for all of them. The approach outlined here will help you make the right choices.

Fluctuations in visual neglect after stroke?

Clinical experience suggests that the visual neglect in stroke patients fluctuates over short periods of time. This fluctuation has been variously attributed to fatigue, time of day, previous activities, patient learning and compensation. Such fluctuations have clinical implications for the assessment and rehabilitation of visual neglect but do date no formal study has evaluated the extent of such fluctuation over the course of a day. Twenty-two patients with an acute stroke and 19 patients with convalescent stroke were examined for visual neglect twice on the same day using the Visual Neglect Recovery Index (VNRI), a valid and sensitive measure of the severity of neglect, which could be used to select acute patients for trials of treatment of neglect. The inter-test reliability was extremely high. In contrast to past clinical accounts most patients failed to show significant fluctuation. Although preliminary, this finding suggests that a single assessment of visual neglect, using the VNRI, could help select patients for treatment trials.

Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy.

Short-term administration of human growth hormone to children with idiopathic short stature can improve mean growth rate and predicted adult height. It is yet unknown whether therapy would alter pubertal development or affect final height. Three-year treatment results in a group of children with idiopathic short stature are reported. For year 1 of the study, 121 prepubertal children were randomly selected to receive somatotropin, 0.3 mg/kg per week, administered subcutaneously three times weekly (n = 63), or to be nontreatment control subjects (n = 58). After 1 year, all subjects were again randomly selected to receive either three-times-weekly or daily dosing at the same total dose. For the 92 subjects who completed 36 months of treatment, mean growth rate increased from a mean of 4.6 cm/yr before treatment to a mean of 8.0 cm/yr in the first year of treatment. Daily dosing resulted in a significantly faster mean growth rate (9.0 cm/yr) than three-times-weekly dosing (7.8 cm/yr) (p = 0.0005). Mean growth rates were 7.6 and 7.2 cm/yr during years 2 and 3, respectively, and did not differ by dosing group. Mean standardized height for all subjects improved from -2.7 to -1.6 after 3 years. When the growth rate was standardized for bone age, however, subjects who remained prepubertal had a significantly greater gain in mean height SD score than subjects who became pubertal during that 3-year period (p < 0.02). Mean standardized Bayley-Pinneau predicted adult height SD score increased from -2.7 to -1.6 and was independent of the timing of pubertal onset, but for individuals this score was more variable. Year-1 growth response, expressed as growth rate or change in height SD score, was the best predictor of growth in subsequent years. Responses to therapy could not be reliably predicted from baseline anthropometric variables, plasma insulin-like growth factor I SD score, growth hormone levels. Final height assessment will be needed to determine the ultimate benefit of therapy.

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. I. Serum growth hormone-binding protein.

Previous studies have provided compelling evidence that GH secretion increases transiently during midpuberty in normally growing children. Although it is likely that the increase in GH production serves a primary role in generating the pubertal growth spurt, such a conclusion necessarily assumes that other essential "down-stream" components of the GH axis responsible for mediating the effects of GH remain unchanged. To investigate this concept, we assessed longitudinally another important component of the endogenous GH axis, the serum GH-binding protein (GHBP)/receptor system, in a cohort of 11 normal boys as they matured through normal puberty. At 4-month intervals over 4.0-5.1 yr, 24-h serum GH concentration profiles and serum GHBP activity were evaluated. Serum GHBP levels varied over a more than 12-fold range (40-504 pmol/L) among all subjects. However, the values for individual subjects consistently varied within more narrow limits. The coefficient of variation for values from all subjects was 51% compared to the mean intrasubject coefficient of variation of only 30% (P < 0.05). Although the highest GHBP level (all subjects) was 12.6-fold greater than the lowest, the mean intrasubject range was only 3.1 +/- 0.5-fold (P < 0.05). The overall mean serum GHBP level correlated directly with the overall mean body mass index (r = 0.69; P = 0.018), but correlated inversely with the mean 24-h GH concentration (r = -0.61; P < 0.05). There was no significant increase in the GHBP level during puberty. However, because mean 24-h GH concentrations did increase during midpuberty, the data suggest that an increase in the relative amounts of free vs. bound GH develops during the period of the pubertal growth spurt. These data indicate that serum GHBP levels are regulated in individual children within much more narrow limits than those present in the larger population and do not undergo the dramatic changes during puberty typical of GH secretion and linear growth velocity. As a consequence, alterations may develop in the relative amounts of free vs. bound GH present in serum during the midpubertal years compared to those present during either the prepubertal or postpubertal periods. The majority of the known age-related increase in serum GHBP levels probably occurs before the period of active pubertal development. These findings strengthen further the concept that the midpubertal changes in GH secretion serve a primary role in generating the growth spurt.(ABSTRACT TRUNCATED AT 400 WORDS)

Altered growth hormone secretory dynamics in prepubertal males with constitutional delay of growth.

We have used the technique of deconvolution analysis to determine if abnormalities in growth hormone (GH) secretion or metabolic clearance underlie the observed alterations in circulating hormone concentrations in a group of seven prepubertal males with constitutional delay of growth (SHORT-DBA). The results were compared with data obtained from 13 healthy, short prepubertal males (SHORT) and 11 healthy prepubertal male subjects of normal stature (NORMAL). Although the mean 12-h overnight GH production rates were invariant among the groups (8.0 +/- 1.0 versus 7.3 +/- 0.7 versus 6.7 +/- 1.2 micrograms/L, NORMAL versus SHORT versus SHORT-DBA for all comparisons), different secretory mechanisms were operative. The secretory burst half-duration (time interval of the secretory event at half-maximal amplitude) of the SHORT-DBA subjects (26 +/- 1 min) was greater (p = 0.02) than that of the SHORT group (20 +/- 1 min); values for both the SHORT and SHORT-DBA subjects were indistinguishable from that of NORMAL controls (22 +/- 2). Both the mass of GH released per secretory episode and the maximal rate of hormone secretion were less (p < or = 0.02 and the p < 0.01, respectively) for the SHORT-DBA subjects [16 +/- 2 micrograms/unit of body distribution volume (Lv) and 0.6 +/- 0.1 microgram/Lv/min, respectively] compared with those of the NORMAL (26 +/- 2 micrograms/L, and 1.1 +/- 0.1 micrograms/Lv/min, respectively) and SHORT (28 +/- 4 micrograms/Lv and 1.3 +/- 0.2 micrograms/Lv/min, respectively) groups; values for the latter two groups were indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS)

The Gospel Oak project 1987-1990: provision and use of community services.

This longitudinal survey of elderly people examines morbidity and service usage. 705 elderly people who lived in their own homes were interviewed as part of the Gospel Oak project in 1987/88, and in 1990, 524 (74.3%) were re-interviewed--90 (12.8%) had died, 51 (7.2%) had moved and 40 (5.7%) refused a follow-up interview. The results indicate that 60% of residents (1987/88 and 1990) had been in contact with community services within the month before the survey. Respondents with depression were mostly in contact with the health service, those with dementia were in contact with social services. Long-term activity-limited people had high contact with both services, although this finding was less likely among newly activity-limited people. Multiple service-users from the first survey were likely to be either dead, or high service-users in 1990. Low service-users tended to continue to be low service-users. New users were generally living alone, aged around 70 years and had been relatively healthy previously. Respondents who stopped using services were generally younger, mostly women, and possibly depressed. People who had never been service-users, were generally younger and healthier. Information on community services performance is inadequate to ensure targeted, efficient services, and this survey gives detailed information to help planning and resource allocation.

Ovulation and menstrual function of adolescent girls with central precocious puberty after therapy with gonadotropin-releasing hormone agonists.

Chronic GmRH agonist (GnRHa) administration has been shown to suppress pituitary-gonadal function in children with central precocious puberty (CPP), but long term data after the reactivation of gonadarche posttherapy are not yet available. This study evaluated the menstrual function of 46 girls with CPP who had been treated for at least 2 yr with GnRHa (deslorelin or histrelin, sc, daily) and were up to 7 yr posttreatment, including 21 postmenarcheal girls who collected weekly overnight urine samples for 12 consecutive weeks to assess rates of ovulation by urinary pregnanediol-3 beta-glucuronide measurements. Menarche occurred at age 12.1 +/- 1.0 yr (mean +/- SD), on the average 1.2 +/- 0.8 yr posttherapy (range, 0.1-4.3 yr). Menstrual cycle lengths became increasingly regular, with cycles of 25- to 35-day duration reported by 41% of the girls in the first year postmenarche and 65% of the girls studied 3 or more years postmenarche. Ovulation was demonstrated in 50% of the girls studied within 1 yr of menarche and in 90% of the girls studied 2 yr or more postmenarche, including 5 girls who reported pregnancies. The development of regular ovulatory menstrual function in these girls with CPP is in accord with previously documented patterns in normal adolescents. While these data provide further evidence supporting the safety of long term GnRHa therapy, continued studies will be necessary to characterize fully the reproductive function in CPP patients through adolescence and adulthood.

Psychosocial short stature: a syndrome with many variables.

PSS is at least two syndromes of significant frequency, which often go unrecognized. It occurs in all socioeconomic groups. It is variable in its presentation and often masquerades in its subtle forms as other pathological causes of short stature such as GHD, CDGP, malabsorption and failure to thrive. It is an entity about which we understand little in respect to biochemical pathophysiology, and one which offers a challenge to both clinicians and basic scientists.

Properties of spontaneous growth hormone secretory bursts and half-life of endogenous growth hormone in boys with idiopathic short stature. Genentech Collaborative Group.

We analyzed endogenous GH secretory dynamics and MCRs by a novel quantitative deconvolution technique in 20 boys with idiopathic short stature (ISS) and 35 boys of normal stature in Tanner stage I of puberty. We tested the null hypotheses that 1) ISS is not associated with any alterations in the frequency, mass, amplitude, or duration of spontaneous GH secretory bursts and/or the 24-h GH production rate; and 2) the half-life of endogenous GH is not altered in ISS. The boys with ISS had a mean (+/- SEM) bone age of 8.0 +/- 0.42 yr and a chronological age of 10 +/- 0.50 yr. The latter was similar to the chronological (and bone) age of the normal boys of 9.8 +/- 0.23 (and 9.3 +/- 0.34) yr. Mean height SD scores were significantly lower in ISS boys, viz. -2.7 +/- 0.15 in ISS vs. +0.34 +/- 0.13 in normal boys (P less than 0.001). Plasma insulin-like growth factor-I concentrations were similar in the two groups, as were (24-h) mean serum GH concentrations, viz. 3.5 +/- 0.29 micrograms/L in ISS and 4.1 +/- 0.49 micrograms/L in normal boys (P = NS). Deconvolution analysis revealed that the mean number of GH secretory events per 24 h was similar in normal and ISS boys, viz. 9.6 +/- 0.76 (normal) vs. 8.4 +/- 0.55 (ISS), and that there was no significant difference in mean GH interburst intervals. The amplitude, mass, and duration of computer-resolved GH secretory bursts also did not differ in normal and ISS boys. The half-lives of endogenous GH were estimated to be 16 +/- 0.77 min in the ISS and 18 +/- 0.93 min in the control boys (P = NS). The calculated daily GH secretion rate per unit distribution volume was not significantly reduced in ISS, i.e. 194 +/- 19 micrograms/L.day in ISS vs. 177 +/- 19 micrograms/L.day in control boys. Moreover, daily GH secretion rates corrected for body mass index (weight/height2) in the twp groups were not significantly different. In summary, the present cohort of boys with ISS manifested no significant alterations in GH secretory burst frequency, duration, mass, or amplitude or in the half-life of endogenous GH compared to normal boys in Tanner stage I of pubertal development. Indeed, whether daily GH secretion rates are expressed per unit distribution volume or per unit body mass index, groups of boys with ISS and normal height controls secrete similar total amounts of GH. We conclude that the overall dynamics of GH secretion and clearance in boys with ISS considered as a whole cannot be distinguished readily from physiological patterns observed in prepubertal boys of normal height.

Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: relationship to age, pubertal status, and body mass.

Mean plasma GH concentrations increase in normal boys during mid- to late-puberty. To investigate the nature of the pituitary secretory events and/or altered metabolic clearance responsible for these serum GH concentration changes, we performed multiple-parameter deconvolution analysis of 46 24-h serum GH concentration-time series obtained from normal boys at various stages of puberty and young adulthood. The subjects ranged in chronological age from 7-27 yr. The height and weight of each subject were between the 5th and 95th percentile for age. The calculated daily mass of GH secreted was greatest (P less than 0.001) in late pubertal boys (mean +/- SE, 1810 +/- 250 micrograms/24 h) and was triple the value in prepubertal boys (610 +/- 65 micrograms/24 h). When the values were normalized and expressed as mass of GH secreted per unit (m2) body surface area or per L distribution volume, GH secretion in late pubertal boys was still significantly greater than that in any other group (P less than 0.05). These values for late pubertal boys were nearly double the corresponding values for prepubertal boys (1160 +/- 160 vs. 600 +/- 58 micrograms GH/m2.24 h and 440 +/- 63 vs. 270 +/- 25 micrograms GH/L vol.24 h, respectively). When the effect of clearance mechanics on serum GH concentrations was removed mathematically, the primary change in predicted GH secretory burst parameters during pubertal development was an increase in GH mass released per burst resulting from an increase in the maximal rate of GH secretion attained within the bursts. These changes in the amplitude of GH release events were specific, in that they were largely independent of any accompanying alterations in duration or frequency of the GH secretory bursts or in serum GH half-life. Correlation analysis revealed that the 24-h GH secretion rate varied inversely with the subjects' body mass index SD score (r = -0.65; P less than 0.01), suggesting that differences in body mass, even within the normal range, contribute to the wide variability in daily GH secretion rates among normally growing children. The plasma insulin-like growth factor-I concentrations of all subjects correlated positively with the calculated 24-h GH secretion rate (r = 0.51; P less than 0.001). In summary, the primary neuroendocrine alteration responsible for the augmented serum GH concentrations characterizing mid- to late-puberty in boys is an increased mass of GH released per pituitary secretory episode resulting from an increased maximal rate of GH secretion within each burst.(ABSTRACT TRUNCATED AT 400 WORDS)