Hormonal changes in thalassaemia major.

Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2-5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH exretions were normal or low and LH normal or raised.The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed.     

Longitudinal gonadal function after bone marrow transplantation for acute lymphoblastic leukemia during childhood

Total body irradiation and high-dose chemotherapy, applied as a preparatory regimen for bone marrow transplantation (BMT) in children with acute lymphoblastic leukemia (ALL), are particularly hazardous to the gonads and, in addition, can impair hypothalamo pituitary-gonadal control. Longitudinal data on pubertal development and gonadal function in these patients are limited. Twenty-one ALL patients (15 males, 6 females) who had successfully undergone allogeneic BMT before puberty (age at BMT: 3.4-12.3 yr) were followed up in University Children's Hospital, Tübingen, Germany over 2 (minimum) to 14 (maximum) years. Tanner development scores, serum testosterone and estradiol, basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were analyzed. During pubertal age, the levels of FSH and LH rose consecutively, resulting in noticeably elevated serum concentrations in 100% and 89%, respectively, of boys older than 14 years and in 75% and 75%, respectively, of girls older than 13 years. Nevertheless, pubertal development has been normal in all patients except in one boy and two girls who required substitution with sexual steroids, as timely puberty (i.e. boys < 14 years, girls < 13 years) did not start. In males with normal puberty, testosterone levels, however, were found to be low-normal. In conclusion, after BMT preceded by total body irradiation for childhood ALL, gonadal function is impaired. Even if normal pubertal development occurs, deficiencies in long-term endocrine function cannot be ruled out. In view of the high FSH levels, the prognosis for fertility is doubtful.     

Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children

The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age advancement (3.4 +/- 1.5 years) and negative height standard deviation for bone age (-2.7 +/- 1.5) than those with PPP (1.9 +/- 1.6 years and -1.3 +/- 1.3) and premature thelarche (0.4 +/- 0.4 years and -0.8 +/- 0.8). Patients with neurogenic CIPP had significantly higher levels of baseline and GnRH-stimulated levels of LH and FSH and LH:FSH ratio than those with idiopathic CIPP. Occurrence of neurogenic CIPP in seven girls with an age of onset after 6 years emphasizes the need for CNS imaging in these girls contrary to the current recommendations. The fact that 65.6% cases of idiopathic CIPP presented after the age of 6 years raises the possibility that these patients may be physiological variants of normal puberty. Pointers to neurogenic CIPP included early age of onset in girls, clinical features of CNS involvement, and elevated basal and stimulated LH levels and LH:FSH ratio.     

4岁内儿童性早熟57例

目的探讨4岁内儿童性早熟的病因、诊断要点,研究简易的促性腺激素释放激素(GnRH)激发试验的可行性。方法对57例<4岁性早熟患儿的临床资料进行回顾性分析。57例均行GnRH激发试验,对中枢性与部分中枢性组患儿的LH值进行秩和检验。结果本组男3例,女54例。外周性性早熟36例(63.1%);中枢性性早熟(CPP)4例;部分性CPP17例。CPP促黄体生成素(LH)升高为甚,50%峰值落在60~90min,部分性CPP促卵泡生成素(FSH)升高为甚,84.2%峰值落在90~120 min;CPP与部分性CPP 30、60、90、120 min LH比较有显著差异(P均<0.01)。结论<4岁儿童性早熟以女性发病为主,多为外周性性早熟。GnRH激发试验对病因分类很必需,应在0、60、120 min测LH、FSH,以明确CPP和部分性CPP。     

Hormonal profile of puberty in South Australian children II

Serum follicle stimulating hormone (FSH), luteinising hormone (LH) and oestradiol (E₂) concentrations in 117 girls aged 8 to 17.9 years were related to chronological age (CA), bone age (BA), breast development (B1–5+) and pubic hair development (PH1–5+). A progressive rise in serum LH and E₂ was noted in relation to CA, BA and pubertal development. Serum FSH levels reached a peak in mid-puberty and fell thereafter. The FSH/LH ratio decreased with advancing CA and BA. In comparing the data in girls (Part II) with that in boys (Part I) serum FSH and LH levels began to rise earlier in girls and were generally higher than levels seen in boys throughout puberty. Similarly, an earlier rise in serum E₂ in girls compared with T in boys supported the concept of an earlier activation of the female gonad.     

Increased LH and FSH secretion after cranial irradiation in boys

The effect of high-dose cranial- and craniospinal irradiation and chemotherapy on the gonadotropin-sex steroid axis was studied during different stages of puberty by measuring pulsatile secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. The patients were thirteen boys who had been treated for malignant brain tumor residing well away from the hypothalamo-pituitary region. The median time to follow-up was 9 (1–16) years. The onset of puberty was early in the patients, median 10.5 years, compared to the average age for Swedish boys, which is at median 12.4 years. There was, before puberty, no significant difference in LH and FSH secretion between patients and a control group of normal boys. In early, mid- and late stages of puberty, however, LH and FSH secretion was increased in the patients overall, whereas testosterone secretion was maintained within the normal range in spite of signs of gonadotoxocity with small testicular volumes. These results indicate that the vulnerable parts of the gonadotropin releasing hormone (GnRH)-gonadotropin (LH, FSH)-gonadal axis are the regulatory system that determines the timing of pubertal induction and the gonads. The GnRH-LH, FSH-releasing neurons appear relatively resistant to cranial irradiation as they are able to respond with supranormal LH and FSH levels for long periods of time after treatment. Med Ped Oncol 29:280–287, 1997. © 1997 Wiley-Liss, Inc.     

Growth hormone secretory dynamics in children with precocious puberty

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.     

Gonadotrophin and Growth Hormone Secretion Throughout Puberty

ABSTRACT. The secretion patterns of gonadotrophin and growth hormone (GH) were investigated in normal healthy children at different stages of pubertal development. The plasma levels of luteinizing hormone (LH) and GH were measured at 10-minute intervals from 12.00 h to 18.00 h and from 24.00 h to 06.00 h using immunoradiometric assays. The levels of follicle-stimulating hormone (FSH) and testosterone were measured hourly. In young prepubertal girls and boys LH was undetectable during the day or night. In children of pubertal chronological age, in whom secondary sexual characteristics had not appeared (stage 1 onset), LH was detectable during the night only. With the progression of puberty there was a gradual increase in the secretion of LH, resulting from increases in both the frequency and amplitude of LH pulses. There was a clear increase in the secretion of FSH during day and night from stage 2 onwards. The secretion of GH also increased with the progression of puberty, due to an increase in pulse amplitude. The increase in GH secretion did not appear to be related to the increase in LH secretion, but rather to changes in the sex steroids.     

Normal values of LH and FSH excretion in the urine of children and juveniles by the luteonosticon and FSH-nosticon test (author's transl)

The normal values of the LH and FSH excretion in 12-h-overnight-urine-samples were measured by the commercial technique for the estimation of LH (Luteonosticon) and FSH (FSH-nosticon). These methods were used to determine the hormone excretion of these hormones in healthy individuals, 94 boys (0-18 years) and 48 girls (0-16 years). Only one urine sample was assayed for each subject. There was a highly significant correlation between the plasma LH and FSH concentrations and the urinary content of the same hormones: for FSH, r = 0.8 and for LH, r = 0.6. The plasma concentrations were measured radioimmunologically immediately before the period of urine collection. Five girls with Turner's syndrome aged 12 to 17 years showed LH values (5.0-14.5 IU/12 h) at the upper end of or slightly above the normal range and pathologically high values (22.2-43.5 IU/12 h) for FSH.     

Serum prolactin, FSH and LH during puberty in girls and boys.

Serum prolactin, follicle-stimulating hormone and luteinizing hormone were determined in 200 girls and 80 boys. The boys have been examined on three occasions at one-year intervals and the girls twice at 1.5-year intervals. In girls, serum FSH rapidly increased in the youngest age groups (7.5-11.5 years), whereas in boys, the increase took place later and the first significant increase was seen between age groups 9.5 and 12.5 years. In girls, a rise in serum LH took place later than that of FSH (between 10.5 and 11.5 years), and LH peaked at 13.0-13.5 years. In boys, the timing in the changes of serum LH closely resembled that of FSH. The girls displayed a significant increase in serum prolactin between 7.5 and 8.5 years, and this was followed by a slow progressive increase. In the group of boys, serum prolactin did not show any significant changes. In girls, there was a correlation between serum LH and body weight, as well as calculated fat amount and body fat percentage early in puberty. There was no correlation between serum LH and chronological or bone age in this age group, which suggests that the correlation found is not due to age-related parallel phenomena.     

SERUM PROLACTIN, FSH AND LH DURING PUBERTY IN GIRLS AND BOYS

ABSTRACT. Serum prolactin, follicle-stimulating hormone and luteinizing hormone were determined in 200 girls and 80 boys. The boys have been examined on three occasions at one-year intervals and the girls twice at 1.5-year intervals. In girls, serum FSH rapidly increased in the youngest age groups (7.5–11.5 years), whereas in boys, the increase took place later and the first significant increase was seen between age groups 9.5 and 12.5 years. In girls, a rise in serum LH took place later than that of FSH (between 10.5 and 11.5 years), and LH peaked at 13.0–13.5 years. In boys, the timing in the changes of serum LH closely resembled that of FSH. The girls displayed a significant increase in serum prolactin between 7.5 and 8.5 years, and this was followed by a slow progressive increase. In the group of boys, serum prolactin did not show any significant changes. In girls, there was a correlation between serum LH and body weight, as well as calculated fat amount and body fat percentage early in puberty. There was no correlation between serum LH and chronological or bone age in this age group, which suggests that the correlation found is not due to age-related parallel phenomena.     

Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotropins in hypophysogonadal disorders of children and adolscents. VII. Constitutional delay of puberty in males.

Serum gonadotropins (LH and FSH) were measured by radioimmunoassay before and after intravenous injection of 0.1 mg/m2 of synthetic luteinizing hormone-releasing hormone in 20 male patients, aged 15 to 18 years, with constitutional delay of puberty. Basal plasma levels of LH and FSH were in the prepubertal range. After administration of LH-RH, the increase in LH was significantly high than in prepubertal control subjects, aged 1 to 13 years; the difference between test patients and pubertal control subjects was not significant. The increase in FSH was in the prepubertal range, significantly lower than that in pubertal control subjects. This discrepancy between LH and FSH responses to LH-RH is similar to that observed in normal boys at the late prepubertal stage and suggests that an elevation of readily releasable pituitary stores of LH correlates with the first step of pubertal onset in males, even if puberty is delayed.     

The gonadotrophins response to GnRH test is not a predictor of neurological lesion in girls with central precocious puberty

OBJECTIVES: To assess the value of gonadotrophin releasing hormone (GnRH) stimulation test in identifying intracranial abnormality in girls with central precocious puberty (CPP). PATIENTS AND METHODS: A study of 67 girls diagnosed with CPP who underwent cranial MRI scans. Patients were not receiving any therapy and there were no neurological signs or symptoms at presentation. Patients underwent evaluation of GnRH stimulation test and plasma oestradiol levels at presentation. RESULTS: Mean age at onset of puberty was 6.2 years (range 2.0 to 8.0 years). Intracranial abnormalities were present in 10 (15%) patients, while 57 girls (85%) had no abnormalities. No significant difference was shown between girls with intracranial abnormality and girls without intracranial abnormality in basal LH or FSH values, peak LH or FSH values, LH/FSH peak ratios, peak LH/basal LH ratios, peak FSH/ basal FSH ratios at presentation. CONCLUSION: GnRH stimulation test does not identify those with underlying intracranial abnormality at presentation. MRI imaging remains necessary in all cases of central precocious puberty in girls.     

Children with sickle cell disease: growth and gonadal function after hematopoietic stem cell transplantation

The aim of this study is to describe the growth, pubertal development, and gonadal function of a cohort of 30 sickle cell disease children who underwent bone marrow transplantation. They all received the standard pretransplant conditioning regimen of busulfan (14 or 16 mg/kg) and cyclophosphamide (200 mg/kg). Growth was normal both before and after transplant. Seven out of 10 girls had severe ovarian failure and requirement for estrogen replacement. Three out of 10 girls recovered some ovarian function posttransplant, with spontaneous pubertal development, menses, and 1 successful normal pregnancy. Follicle-stimulating hormone (FSH) serum levels were very high during spontaneous puberty and slowly normalized thereafter in these 3 patients. The 3 girls with ovarian function recovery differed from the 7 others by the lower busulphan dose of the conditioning regimen they received (14 rather than 16 mg/kg). All boys showed spontaneous pubertal development. However, most of them had small testis and elevated serum FSH levels, reflecting germinal epithelium damage. Testosterone level was low normal and luteinizing hormone elevated, reflecting Leydig cell insufficiency. In conclusion, 7/10 girls had complete gonadal failure and most of the boys had spontaneous puberty but germinal epithelial failure. Serum FSH levels showed important variations over time in the same patient.     

Monthly urinary LH and FSH secretory patterns in normal children and patients with sexual disorders

Urinary gonadotropin concentrations were determined by polyclonal double antibody RIA after ammonium sulfate extraction. Good correlation was observed between urinary gonadotropin/creatinine ratios in first morning voided and full 24-h urine collections. Using consecutive 30-d first morning voided urine specimens from normal children and from patients with sexual disorders, we have studied the monthly patterns of nighttime gonadotropin secretion. In normal prepubertal girls, the levels of urinary LH were low with few variations and those of urinary FSH were higher with episodic fluctuations. In early pubertal girls, the levels of urinary LH increased with striking, rhythmic fluctuations. The same changes were seen in urinary FSH. A single big surge of urinary gonadotropins was observed in postmenarcheal girls. In normal boys, the secretory patterns of urinary gonadotropins were similar to those of normal girls, but varied less. In patients with idiopathic precocious puberty, the patterns of urinary gonadotropins were similar to those of normal subjects matched for sexual stage. The measurement of 30-d first morning voided urinary gonadotropins can provide a simple and physiologic test of gonadotropin function in children.     

Comparison between spontaneous gonadotropin concentration profiles and gonadotropin response to low-dose gonadotropin-releasing hormone in prepubertal and early pubertal boys and patients with hypogonadotropic hypogonadism: assessment by using ultrasensitive, time-resolved immunofluorometric assay.

To assess whether nocturnal gonadotropin concentration profiles in children could be predicted by measurement of peak gonadotropin levels after gonadotropin-releasing hormone (GnRH) administration, we measured spontaneous gonadotropin levels every 20 min and the gonadotropin responses to low-dose GnRH using an ultrasensitive, time-resolved immunofluorometric assay in 61 boys with short stature and/or delayed puberty. Spontaneous nocturnal LH pulses were observed in 58 out of 61 patients. After GnRH administration in a dose of 25 ng/kg, all of the 61 patients had significant LH and FSH responses, and GnRH-stimulated peak LH and FSH levels were highly correlated with maximal spontaneous nocturnal LH and FSH levels, respectively (r = 0.83 for LH and r = 0.91 for FSH; p less than 0.00001). Analysis of individual subjects revealed that GnRH-stimulated peak LH levels were almost identical to maximal nocturnal LH levels in the subjects whose GnRH-stimulated peak LH levels were between 5 and 10 IU/L, whereas GnRH-stimulated peak LH levels tended to be higher than maximal nocturnal levels in the subjects whose GnRH-stimulated peak LH levels were 5 IU/L or lower. To determine if there were any parameters in the gonadotropin response to GnRH that might be useful in distinguishing early pubertal boys from prepubertal boys, we evaluated the gonadotropin response to GnRH in 44 prepubertal and 10 early pubertal normal short boys. Although maximal nocturnal LH levels did not overlap between prepubertal and pubertal groups, GnRH-stimulated LH peak levels overlapped considerably between the two groups. Even the GnRH-stimulated peak LH to peak FSH ratio overlapped between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two-year results of treatment with depot leuprolide acetate for central precocious puberty.

We report results from 2 years of therapy with the long-acting form of the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate, which was previously reported in short-term trials to be efficacious in the treatment of central precocious puberty. Thirteen girls and two boys, aged 1.9 to 9.7 years, who satisfied clinical criteria including GnRH-stimulated luteinizing hormone (LH) greater than 10 IU/L (mean radioimmunoassay LH, 29.1 +/- 5.54 IU/L), received depot leuprolide, 6 to 15 mg intramuscularly every 4 weeks. Estradiol (or testosterone), insulin-like growth factor I, and GnRH-stimulated gonadotropins were obtained at baseline, at 2 months, and at 6-month intervals with bone age determinations. Pubertal progression ceased in all patients, and menses did not occur. Mean increase in height during therapy was 5.77 +/- 2.0 cm/yr. Predicted adult height increased over baseline by 5.52 +/- 1.16 cm at 18 months. Mean estradiol values in the girls declined from 3.3 +/- 0.6 to 0.60 +/- 0.03 ng/dl, with no overlap of baseline and treatment values. The mean basal LH value was unchanged by therapy; mean basal and peak LH values for all follow-up GnRH stimulation tests were 4.05 +/- 0.57 and 4.95 +/- 0.70 IU/L, respectively. Basal and peak follicle-stimulating hormone (FSH) values were suppressed from 4.10 +/- 0.62 and 10.06 +/- 1.34 IU/L, respectively, to generally undetectable levels (< 1). Comparison with untreated control patients suggested that basal LH did not completely return to prepubertal levels, whereas FSH levels were suppressed below prepubertal levels. Estradiol, FSH, and LH levels reached their nadir by 2 months; in contrast, mean serum levels of insulin-like growth factor I progressively declined from +0.57 +/- 0.19 SD score to -0.06 +/- 0.22 SD score at 24 months. Two girls were withdrawn from the study because of reactions at injection sites, with apparent sterile abscess formation in one patient. This study provides evidence that (1) long-term treatment with depot leuprolide is characterized by immediate and sustained laboratory and clinical suppression, (2) GnRH-stimulated LH and random FSH and estradiol concentrations are useful laboratory measures of efficacy, and (3) the progressive increase in predicted adult height is temporally associated with decreased serum levels of insulin-like growth factor I and striking deceleration of bone age advancement.     

Growth of anorexic adolescents

Growth and puberty were studied in 19 children with anorexia nervosa (15 girls and 4 boys), the onset being before puberty or in its early stages. Growth retardation reached 2.04 +/- 1.39 SD, with important individual changes and for some patients a prolonged interruption of growth. Seventeen of 19 patients presented delayed puberty, and in some, hypogonadism persisted after recovery from anorexia nervosa. Endocrine investigations concerning the pituitary somatotropic (GH) and gonadotropic (FSH, LH) secretions, as well as gonadal steroids showed highly variable changes from one patient to another and even variations in the same patient from one test to another. However, no correlation could be found between the hormonal abnormalities and the degree or length of undernutrition. Some patients recovered normal endocrine function when they reached an adequate weight, others kept a lasting deficiency. The endocrine impairment in anorexia, well known in adults, is probably more severe in adolescents.     

Repeated circadian growth hormone,luteinizing hormone,and follicle-stimulating hormone in children: Influence of 9-alpha-fluorohydrocortisone

Growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in plasma of 5 children at different pubertal stages and suffering from moderate orthostatic complaints, were measured by radioimmunoassay (RIA). Parameters for secretory capacity were arginine loading and circadian hormonal patterns in hourly intervals from 8 a.m. to 8 p.m. and in half-hourly intervals from 8 p.m. to 8 a.m. before and after 6 weeks treatment with 9-alpha-fluorohydrocortisone (9-alpha-F, Astonin-H, Fa. Merck, Darmstadt, 0.1–0.2 mg/day). Plasma GH during arginine tests and in circadian levels remained unchanged, but circadian LH showed a consistent slight rise in all children.With pubertal development, magnitude and timing of GH peaks increased in boys, and rather decreased in the two girls toward late puberty. Episodic fluctuation of LH and FSH were more marked during sleep, and increased in the three boys as puberty advanced. Similar intraindividual patterns for GH and LH, but not for FSH were noted in 4 children. Timing of GH and LH peaks appeared to be correlated. An intrinsic hereditary long-term regulatory principle is discussed.Dedicated to Prof. Dr. K. H. Schäfer on the occasion of his 65th birthday.     

Pulsatile secretion of LH and FSH in prepubertal and early pubertal boys revealed by ultrasensitive time-resolved immunofluorometric assays

Pulsatile secretion of LH and FSH was examined in 10 prepubertal (aged 4.5-12.9 y) and seven early pubertal (aged 12.8-14.5 y) boys with ultrasensitive (0.019 and 0.014 IU/L) time-resolved immunofluorometric assays. Plasma LH and FSH levels were measured every 15 or 20 min for 6 h during the day and night. The lowest mean LH level in a prepubertal boy was 0.02 IU/L and in eight other prepubertal boys mean LH levels were less than 0.4 IU/L. In early pubertal boys the mean LH levels ranged from 0.3 to 6.5 IU/L. The difference in mean FSH level between prepubertal (0.61 IU/L) and early pubertal boys (1.85 IU/L) was smaller than the difference in LH level. All boys had significant LH and FSH pulses. The LH interpulse interval was 135 +/- 86 min (mean +/- SD) and 76 +/- 65 min for the prepubertal and pubertal boys, respectively (p less than 0.01). For FSH, the respective values were 150 +/- 122 and 221 +/- 157 min (p = NS). The mean LH pulse amplitudes were 11-fold greater in the early pubertal boys than in the prepubertal boys, whereas the mean FSH pulse amplitudes were similar between the two groups. The present method shows that the mean LH levels in prepubertal boys are much lower, and the increase during puberty larger, than previously reported. The increase is apparently due to increased pulse frequency and amplitude. The increase in mean FSH level is smaller and evidently not caused by an increase in pulse frequency or pulse amplitude.