Luteinizing Hormone-releasing Hormone Stimulation Research Articles

Insulin-like Growth Factor 1, but Not Insulin-Like Growth Factor-Binding Protein 3, Predicts Central Precocious Puberty in Girls 6–8 Years Old: A Retrospective Study

Background: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP. Objective: The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6–8 years. Methods: The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted. Results: Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75–2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters. Conclusions: In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures.

Insulin Growth Factor 1 Predicts Central Precocious Puberty in Girls 6 to 8 Years-Old: A Retrospective Study

Background: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum LH ≥ 0.3 IU/L or luteinizing hormone-releasing hormone (LHRH)-stimulated LH ≥ 5 IU/L. Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP. Objective: To assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6 to 8 years old. Methods: The study was a single-center retrospective study. Girls with confirmed CPP (n=44) and isolated premature adrenarche/thelarche (PA/PT, n=16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted. Results: Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p<0.05). IGF-1 SDS correlated positively with basal and peak LH (p<0.05). IGF-1 SDS (1.75-2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters. Conclusions: In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years-old when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more invasive procedures.

Gray Matter Differences Between Premature Pubertal Girls With and Without the Reactivation of the Hypothalamic-Pituitary-Gonadal Axis.

The onset of puberty and related hormones exerts significant effects on brain morphometric and psychosocial development. The biological mechanisms underlying how the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and puberty-related hormonal maturation sculpts human brain architecture remain elusive. To address this question, 105 premature pubertal girls (age 8–11 years) without menstruation underwent brain structural scanning on a 3T MR system, and the luteinizing hormone releasing hormone (LHRH) stimulation test was used to identify the reactivation of the HPG axis. Among the 105 girls, 63 were positive for HPG axis reactivation (HPG+), while the others showed negative (HPG-). Cortical thickness was calculated and compared between the two groups after adjusting for age. The brain regions showing inter-group differences were then extracted and correlated with the peak value of serum hormone after the LHRH stimulation test in entire sample. Compared to HPG- girls, HPG+ girls showed reduced cortical thickness mainly in the the right precuneus, right inferior temporal gyrus, and right superior frontal gyrus, while increased cortical thickness primarily in the left superior parietal lobe and right inferior parietal lobe. Linear-regression analysis revealed negative correlations between the cortical thickness of the right inferior parietal lobe with the peak value of FSH and the right precuneus with LH and E. These findings provide evidence to support the notion that the reactivation of HPG axis and changes of hormones during the early phase of hormonal maturation exert influences on the development of gray matter.

Methylphenidate and Central Precocious Puberty: A Probable Side Effect among Seven Children with the Attention Deficit Hyperactivity Disorder.

Methylphenidate (MPH) is the most preferred drug for treatment of the attention deficit hyperactivity disorder (ADHD). Here, we aimed to discuss the possible effects and mechanisms of MPH on precocious puberty (PP) via a case series with seven children who had normal body mass index. In this case series we evaluated seven children with ADHD, who had received MPH for at least 6 months (0.5 mg/kg/dose three times a day, maximum 60 mg) and admitted to Department of Pediatric Endocrinology with PP symptoms. The mean age was 8.16 years. Basal hormonal levels (luteinizing hormone [LH], follicle stimulating hormone, and estrogen/testosterone) were within normal range. Results of LH-releasing hormone stimulation tests demonstrated central pubertal responses. Glutamine, dopamine and noradrenaline are most important excitatory neurotransmitters that have a role at the beginning of puberty. The effect of MPH, cumulating dopamine and noradrenaline in the synaptic gap could be associated with the acceleration of puberty with the excitatory effect of dopamine’s gonadotropin-releasing hormone (GnRH) release, excitatory effect of noradrenaline’s GnRH release and the disappearance of GnRH receptor expression suppressor effect on prolactin disinhibitory effect.

Advanced bone age as an indicator facilitates the diagnosis of precocious puberty

ObjectiveDiagnosis of central precocious puberty has always been challenging in clinicalpractice. As an important method in the diagnosis of central precocious puberty, luteinizinghormone‐releasing hormone stimulation test is complex and time‐consuming. In many cases, clinical traits are inconsistent with luteinizing hormone‐releasing hormone stimulation testresults, therefore not reliable for diagnosis. In this study, the authors intended to find an indi‐cator that predicts the results of the luteinizing hormone‐releasing hormone stimulation testamong subjects with early pubertal signs. MethodsCases of 382 girls with early breast development before 8 years old and luteinizinghormone-releasing hormone stimulation test before 9 years old were included and underwentfollow-up tests. Patients with peak luteinizing hormone level ≥5 IU/L were considered positivein the luteinizing hormone-releasing hormone stimulation test. Anthropometric data, body massindex, bone age evaluation, blood hormones levels of luteinizing hormone, estradiol, follicle-stimulating hormone, and uterine and ovarian volumes were analyzed. ResultsSubjects with positive results in the initial test demonstrated early bone maturation, accelerated growth, and elevated basal blood luteinizing hormone, estradiol, and follicle-stimulating hormone levels, when compared with subjects with negative results in the initialtest. Subjects with positive results in the follow-up test presented a more advanced bone ageand more accelerated linear growth, when compared with subjects with negative results in thefollow-up test. ConclusionsAccording to the statistical analysis, advanced bone age is the most effectivepredictor of the result of luteinizing hormone-releasing hormone stimulation test.

Advanced bone age as an indicator facilitates the diagnosis of precocious puberty

ObjectiveDiagnosis of central precocious puberty has always been challenging in clinical practice. As an important method in the diagnosis of central precocious puberty, luteinizing hormone-releasing hormone stimulation test is complex and time-consuming. In many cases, clinical traits are inconsistent with luteinizing hormone-releasing hormone stimulation test results, therefore not reliable for diagnosis. In this study, the authors intended to find an indicator that predicts the results of the luteinizing hormone-releasing hormone stimulation test among subjects with early pubertal signs. MethodsCases of 382 girls with early breast development before 8 years old and luteinizing hormone-releasing hormone stimulation test before 9 years old were included and underwent follow-up tests. Patients with peak luteinizing hormone level ≥5IU/L were considered positive in the luteinizing hormone-releasing hormone stimulation test. Anthropometric data, body mass index, bone age evaluation, blood hormones levels of luteinizing hormone, estradiol, follicle-stimulating hormone, and uterine and ovarian volumes were analyzed. ResultsSubjects with positive results in the initial test demonstrated early bone maturation, accelerated growth, and elevated basal blood luteinizing hormone, estradiol, and follicle-stimulating hormone levels, when compared with subjects with negative results in the initial test. Subjects with positive results in the follow-up test presented a more advanced bone age and more accelerated linear growth, when compared with subjects with negative results in the follow-up test. ConclusionsAccording to the statistical analysis, advanced bone age is the most effective predictor of the result of luteinizing hormone-releasing hormone stimulation test.

Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis

To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. Cross-sectional study with retrospective analysis. University pediatric hospital. Fifteen prepubertal subjects (median age 9.0years, range 6.9-11.9years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1y, range 6.9-11.6years). None. We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects.

Clinical features of 9 patients with X-linked adrenal hypoplasia congenita caused by DAX1/NR0B1 gene mutations

To study the clinical features of 9 patients with X-linked adrenal hypoplasia congenita (AHC) by gene sequencing so as to provide diagnostic rationales. The patients were 9 cases of X-linked AHC treated at our hospital from July 2007 to June 2009. The clinical manifestations were analyzed. The blood biochemistry tests and the hormone examinations including luteinizing hormone-releasing hormone (LHRH) stimulation tests and human chorionic gonadotropin (HCG) stimulation tests were conducted to evaluate the functions of gonads. And CT scans of adrenal glands and gene tests of DAX1/NR0B1 were performed. Nine AHC patients from 8 families were studied. All patients had DAX1/NR0B1 gene mutations. The main clinical features were: (1) some patients (3 families) had a family history of X-linked recessive inheritance; (2) the ages of onset were all below 10 years old (from 2 month after birth to 9 years old) and ages of being treated at our hospital were from 15 to 34 years old; (3) all patients had adrenocortical hypofunctions, but clinical situations were different, most of them had pigmentation (n = 9), nausea and vomiting (n = 8), hypotension (n = 6), Addisonian crisis (n = 4). Others were debility, hypoglycemia and cold susceptibility. Laboratory tests indicated that all patients had hyponatremia at the onset and higher blood adrenocorticotropic hormone level, lower blood 17-hydroxyprogesterone level compared to normal controls; (4) none of the patients had puberty and there was no responses to LHRH stimulation tests, 3 of them had normal responses to HCG stimulation tests; (5) small bilateral adrenal glands were displayed on CT scans. The main clinical features of X-linked AHC are adrenocortical hypofunction and hypogonadotropic hypogonadism. But the phenotypes vary greatly in different patients. So male children with adrenal cortical hypofunction should be suspected of X-linked AHC and DAX1/NR0B1 gene tests should be performed. The sexual development of the patients also should be followed up.

Effects of Galanin and Leptin on Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone Release from the Pituitary

Background: A number of peptides regulate luteinizing hormone (LH) release. In some cases, these peptides exert an effect at the pituitary, to directly regulate LH release and/or to modulate the effects of gonadotropin-releasing hormone (GnRH). A link between nutrition and reproductive function is well established. In this study we investigated the effects of two peptides associated with appetite control, galanin and leptin, on the regulation of LH release from the pituitary. Methods: Using perifused anterior pituitary tissue from freely fed rats, we investigated the effect of galanin on basal LH release and GnRH-stimulated LH release from pituitaries in a high-estrogen (proestrus) and a low-estrogen (metestrus) environment. In addition, we examined the effect of galanin on LH release following GnRH self-priming. The effect of inhibiting protein synthesis, with cycloheximide, was also studied under these conditions. Finally, the effects of leptin alone and on a galanin-modulated LH response were investigated. Results: There was no detectable effect of leptin, either alone or in conjunction with galanin. We observed that galanin enhanced GnRH stimulation of LH secretion, an effect that was dependent on protein synthesis and on an estrogenized environment. In addition, importantly, galanin also enhanced the LH response in GnRH self-primed pulses. Conclusion: Our results provide further details on the effect of galanin on the LH surge, particularly the effect on the response to pulsatile GnRH and the effect of protein production, and thereby indicate a means by which appetite- and nutrition-related peptides may act on the ovulatory cycle at the pituitary.

Case 1: The long and short of it

A 13-and-a-half-year-old girl presented to the family physician with poor growth. She was first noticed to be short at around 10 years of age (height less than the third percentile). The problem had recently become more noticeable when the mother saw the younger sister overtake the patient in growth. The weight gain was also inadequate and she fell from the third percentile to less than the third percentile. The patient had no other symptoms. Specifically, there was no abdominal pain, nausea, vomiting, constipation, diarrhea, fever, rash or arthralgia. The patient’s appetite, energy level and sleep pattern were normal. The patient’s history was generally unremarkable. Her general development had been normal. She had not started menstruating. The family history was negative for any gastrointestinal diseases. The older sister had a goiter. The mother also had problems with her thyroid gland. Both parents and other family members were of average height. Physical examination revealed a well-looking, noticeably short adolescent. Her height was 135 cm (well below the third percentile for age) and her weight was 33.8 kg (less than the third percentile). Her vital signs were normal. There was no pallor, digital clubbing or thyromegaly. Pubertal development was early Tanner stage III breast development. There was no axillary or pubic hair. The rest of the examination was unremarkable. A laboratory investigation revealed a normal complete blood count (hemoglobin 134 g/L). Serum electrolytes, calcium, glucose, urea, creatinine, liver enzymes, ferritin, immunoglobulins, albumin, thyroid-stimulating hormone and free thyroxine were all normal. A paediatric endocrinology referral had been done. Several investigations, including growth hormone tests, an adrenocorticotropic hormone stimulation test and a luteinizing hormone-releasing hormone stimulation test, were all normal. A diagnostic test was performed.

Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates ovarian growth

Ovarian enlargement is a constant feature of syndromes of extreme insulin resistance. The objective of this study is to show the role of insulin on ovarian growth in the presence of low gonadotropin levels. Seven young patients with syndromes of extreme insulin resistance (five with lipodystrophy, one with Type B syndrome and one with Rabson-Mendenhall syndrome) were studied. Baseline LH concentrations and luteinizing hormone releasing hormone (LHRH) tests were performed. Total testosterone, insulin and C-peptide values were measured. Pelvic ultrasounds were performed. Four patients were prepubertal (age range 7-10 years old) and had prepubertal gonadotropin levels, and 2 of the 4 who were tested did not respond to LHRH (NIH 10 and RM-PAL). Three patients were Tanner stage 4 (age range 13-17 years old) and had low gonadotropins that did not respond to LHRH stimulation test. All seven patients had marked hyperinsulinaemia and 6 of 7 had at least one enlarged ovary. Testosterone values were increased in 4 of 7 patients. This represents the first example of the pathologic role of insulin to stimulate ovarian growth with low circulating gonadotropins. Thus, while ovarian growth and steroidogenesis are normally stimulated by gonadotropins at puberty, hyperinsulinaemia stimulates pathologic growth of the ovary and an androgenic steroid profile that is active at all ages. We suggest that these patients constitute a model to separate the effect of insulin from gonadotropin in stimulating ovarian growth and/or steroidogenesis.

The pleiotropic expression of the myotonic dystrophy protein kinase gene illustrates the complex relationships between genetic, biological and clinical covariates of male aging

Aging is a complex process modulated by multiple interactions between environmental and genetic factors. Myotonic dystrophy (DM 1) is an autosomal dominant disorder caused by an unstable (CTG)n repeat expansion in the DM1 protein kinase (DMPK) gene. The affected male patients' life expectancy at birth (53.2 years) is more than two decades below that observed in most occidental populations. The DMPK gene expression is pleiotropic and includes the premature expression of several agerelated signs, symptoms and metabolic disturbances including hormonal dysfunctions, progressive decrease in muscular mass, presenile cataracts, alopecia, reduced alertness, insulin resistance, dyslipidemia, erectile dysfunction and hypogonadism. The aim of this study was to analyze the relationship between aging covariates and the severity of DM1 expression in 136 DM1 male subjects. DM1 clinical expression was assessed on a validated neuromuscular disability rating scale and was correlated with plasma total testosterone (rs = -0.31, p < 0.001), luteinizing hormone (LH) (rs = 0.52, p < 0.001) and follicle stimulating hormone (FSH) (rs = 0.54, p < 0.001) levels. Following LH releasing hormone stimulation, FSH and LH concentrations increased as a function of DM1 severity (p < 0.05). Muscular disability in DM1 was also positively associated with fasting plasma insulin and triglyceride concentrations (p < 0.05). The association of plasma apolipoprotein B and low-density lipoprotein cholesterol levels with DM1 was not linear across their distribution and tended to reflect cell membrane damage progression. These results suggest that DM1, a simple M endelian trait, can represent a valuable model to illustrate the complex relationships between variables associated with male aging.

Clinical study of varicocele: statistical analysis and the results of long-term follow-up.

The results of clinical examinations of varicocele and the clinical outcome of varicocelectomy conducted at Tsukuba University Hospital, Tsukuba City, Japan were analyzed. The subjects of the present study were sixty-four infertile male patients with varicocele who visited our hospital from 1991 to 1999. A physical examination, semen analysis and hormonal evaluation were performed for each patient. Patients selected their preferred type of treatment (varicocelectomy or conservative treatment) after providing their informed consent. The age of the patients was 34.1 +/- 5.1(mean +/- standard deviation [s.d.]) years, and the infertile duration was 4.2 +/- 3.0 (mean +/- s.d.) years. Fifty-one cases were left-sided; 13 were bilateral. Mean sperm density ( yen 106/mL) was 37.2 for Grade I, 21.3 for Grade II and 9.4 for Grade III. Sperm density was significantly lower in the higher-graded patients (P = 0.008). Varicocelectomy was performed in 31 cases; the postoperative/preoperative ratio of sperm density was significantly higher in the higher-graded varicocele (P = 0.04), and the peak/base ratio of follicle-stimulating hormone (FSH) after luteinizing hormone-releasing hormone (LH-RH) stimulation was significantly decreased after varicocelectomy (P = 0.007). The pregnancy rate in the partners of the varicocelectomized group (60%) was significantly higher than in the conservatively treated group (28%) P = 0.04; the mean follow-up duration was 76.2 months. These results show that varicocele should influence spermatogenesis, therefore altered spermatogenesis could be effectively treated by varicocelectomy, and varicocelectomy should induce a higher probability of pregnancy.

The pleiotropic expression of the myotonic dystrophy protein kinase gene illustrates the complex relationships between genetic, biological and clinical covariates of male aging

Aging is a complex process modulated by multiple interactions between environmental and genetic factors. Myotonic dystrophy (DM 1) is an autosomal dominant disorder caused by an unstable (CTG)nrepeat expansion in the DM1 protein kinase (DMPK) gene. The affected male patients' life expectancy at birth (53.2 years) is more than two decades below that observed in most occidental populations. TheDMPK gene expression is pleiotropic and includes the premature expression of several agerelated signs, symptoms and metabolic disturbances including hormonal dysfunctions, progressive decrease in muscularmass, presenile cataracts, alopecia, reduced alertness, insulin resistance, dyslipidemia, erectile dysfunction and hypogonadism. The aim of this study was to analyze the relationship between aging covariatesand the severity of DM1 expression in 136 DM1 male subjects. DM1 clinical expression was assessed on a validated neuromuscular disability rating scale and was correlated with plasma total testosterone (rs = -0.31, p < 0.001), luteinizing hormone (LH) (rs = 0.52, p < 0.001) and follicle stimulating hormone (FSH) (rs = 0.54, p < 0.001) levels. Following LH releasinghormone stimulation, FSH and LH concentrations increased as a function of DM1 severity (p < 0.05). Muscular disability in DM1 was also positively associated with fasting plasma insulin and triglycerideconcentrations (p < 0.05). The association of plasma apolipoprotein B and low-density lipoprotein cholesterol levels with DM1 was not linear across their distribution and tended to reflect cell membranedamage progression. These results suggest that DM1, a simple M endelian trait, can represent a valuable model to illustrate the complex relationships between variables associated with male aging.

Insulin-like growth factor I enhances gonadotropin-releasing hormone-stimulated luteinizing hormone release from bovine anterior pituitary cells

The role of insulin-like growth factor I (IGF-I) in the release of luteinizing hormone (LH) is unclear in ruminants. In the present study, the effects of IGF-I on the release of LH stimulated by gonadotropin-releasing hormone (GnRH) were examined in primary cultures of bovine anterior pituitary (AP) cells, and the interaction between estradiol-17β (E 2) and IGF-I was characterized. GnRH(100 nM)-stimulated LH release from the cultured cells was increased ( P<0.05) 12, 24 and 36 h after addition of IGF-I (250 ng/ml), with a maximum at 12 h (48.4 ng/ml media versus 35.4 ng/ml media in controls). IGF-I at concentrations of 25, 250 and 500 ng/ml increased the release by 18.7, 24.2 and 28.9%, respectively ( P<0.05), when compared with controls (37.2 ng/ml media). E 2 (10 nM), IGF-I (250 ng/ml) and combined treatment of E 2 plus IGF-I also induced significant increases in LH release ( P<0.05). The amounts of LH release after treatment with E 2 alone was 37.3% greater than with IGF-I alone (39.0 ng/ml media versus 28.4 ng/ml media) ( P<0.05). When E 2 and IGF-I were added together (45.6 ng/ml media), the release of LH was significantly greater than with either E 2 alone or IGF-I alone ( P<0.05). E 2 (10 nM) significantly ( P<0.05) increased the amount of GnRH bound to the cells by 51.6% when compared with controls, however, IGF-I (250 ng/ml) failed to increase GnRH binding. These results show that IGF-I enhances GnRH-stimulated LH release without changing the number of GnRH receptors in cattle, and IGF-I interacts with E 2 to increase the response to GnRH.

Effects of Long-Term Erythropoietin Therapy on the Hypothalamo–Pituitary–Testicular Axis in Male Capd Patients

Gonadal dysfunction has been recognized for a long time in uremic male patients. The present study assesses the hypothalamo-pituitary-testicular axis and growth hormone status in male continuous ambulatory peritoneal dialysis (CAPD) patients, before and after recombinant human erythropoietin (rHuEPO) therapy. Single-center prospective study. Ten anemic male patients with chronic renal insufficiency, and 11 healthy volunteers with normal renal function, matched for age, were included in the study. All patients were on CAPD therapy and none had received rHuEPO treatment previously. Blood samples were collected between 0800 and 0900 hr from all patients for the determination of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and growth hormone (GH) levels. A luteinizing hormone-releasing hormone (LH-RH) stimulation test was carried out using LH-RH 100 microg intravenous as a bolus injection. Blood for FSH, LH, and GH determinations was drawn every 30 minutes during the 3-hour test period. Human chorionic gonadotropin (hCG) test was performed after 48 hours. After estimations of basal serum total and free testosterone levels, 2000 IU hCG was administered intramuscularly and repeated 48 hours later. Total and free testosterone levels were measured in blood samples collected before and 48 hours after two injections of hCG. After improvement in anemia with exogenous rHuEPO, LH-RH and hCG tests were repeated. Baseline FSH concentrations before and after rHuEPO treatment were slightly higher in CAPD patients than in healthy volunteers (p = 0.85 and p = 0.70, respectively). Areas-under-the-curve (AUCs) for FSH secretion before and after rHuEPO treatment were also slightly higher in patients than in healthy volunteers (p = 1.00 and p = 0.75, respectively). The pretreatment basal LH levels in patients were significantly higher than in controls (p < 0.001). After the improvement in anemia with rHuEPO, serum LH levels declined significantly (p < 0.05). The AUCs for LH secretion before and after rHuEPO treatment were significantly higher in patients than in controls (p < 0.05). All patients had elevated basal levels of GH with paradoxical response to LH-RH. Baseline GH levels in patients were significantly higher than those in healthy subjects (p < 0.001) before rHuEPO treatment. After treatment with rHuEPO, basal GH levels declined but did not normalize, and baseline levels of free testosterone increased significantly (p < 0.05). Anemic uremic male patients on CAPD have normal levels of testosterone with normal response to hCG administration, elevated basal levels of GH, and elevated basal levels of LH, with exaggerated response to LH-RH administration. Improvement in anemia with rHuEPO reduced the basal levels of LH and GH, but exaggerated the LH response; paradoxical GH response to LH-RH administration persisted. These results indicate a defect at the level of the hypothalamus and pituitary gland in uremic male patients undergoing CAPD, and that the improvement in anemia with rHuEPO partially restores some of these endocrine abnormalities.

The combined pituitary function test in children: an evaluation of the clinical usefulness of TRH and LHRH stimulation tests through a retrospective analysis of one hundred and twenty six cases.

The combined pituitary function test is routinely used in the endocrine investigation of short children. The TRH and luteinising hormone-releasing hormone (LHRH) response tests have been shown to be of minimal value in adults. We have evaluated the clinical utility of these tests in the context of combined pituitary function testing in children. A retrospective analysis of basal hormone measurements and pituitary stimulation tests in relation to clinical assessment of pituitary function. One hundred and twenty-six children, 82 boys and 44 girls, aged 2-17 years, who had undergone pituitary function testing were studied. The TSH response to TRH stimulation correlated directly with basal plasma TSH but not basal plasma total T4. In patients with an impaired response to stimulation, basal TSH concentrations were <2.0 mIU/l and significantly lower than in patients with a normal response (P < 0.0001). An impaired response to TRH stimulation had a positive predictive value of 0.43 and a negative predictive value of 0.90 for the diagnosis of hypopituitarism. A basal TSH concentration of <2.0 mIU/l had a positive predictive value of 0.22 and a negative predictive value of 0.92. A low basal T4 (normal range 60-140 nmol/l) in combination with an inappropriately low or normal basal TSH was always associated with a diagnosis of hypopituitarism. The responses of plasma LH and FSH to LHRH stimulation correlated directly with basal plasma LH and FSH concentrations. Basal gonadotrophin concentrations, basal sex hormone concentrations or response to LHRH stimulation could not distinguish patients with constitutional delay of growth and puberty from those with hypopituitarism. There was no apparent relationship between either basal gonadotrophin concentrations or response to LHRH stimulation and clinical assessment of pituitary function. In patients ≥13 years with constitutional delay of growth and puberty the median and interquartile ranges of basal LH and FSH were 1.4 IU/l (0.7-3.6) and 2.6 IU/l (2.2-5.2) respectively. The three hypopituitary patients in this study with chronological age ≥13 years had undetectable concentrations of both gonadotrophins. The response of LH and FSH to LHRH stimulation was significantly lower in patients ≥13 years with clinical hypopituitarism than in those with intact pituitary function (P <0.02). TRH and LHRH tests in children with short stature appear to have little value over and above the baseline hormone measurements. An abnormal response to hormone stimulation is not diagnostic of hypothalamic-pituitary disease. We have demonstrated that neither TRH nor LHRH stimulation tests should be routinely used in the investigation of children with short stature.

In vitro pituitary responsiveness to LHRH in young and old female rats. Influence of melatonin

The effect of aging and melatonin on in vitro pituitary responsiveness to luteinizing hormone-releasing hormone (LHRH) was studied. Young cyclic (3-months-old) control (cyclic-control, N=15), and melatonin (MEL) treated for 2 months (150 μg/100 g BW) (cyclic-MEL, N=15), old acyclic (23-months-old) control (acyclic-control, N=13), and MEL-treated (acyclic-MEL, N=18) rats were used. The hormones analyzed were luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). The results showed a different influence of the reproductive status as well as of melatonin on the basal secretion rate of both gonadotropins, i.e. LH and FSH. Only the basal FSH release was significantly reduced in cyclic-MEL and acyclic-controls compared to cyclic-controls. The hemipitutary FSH content raised to values similar to those observed for FSH secretion and only the cyclic-MEL group showed significantly higher FSH pituitary content than for release. LHRH addition to the incubation medium resulted in increased LH release for both cyclic and acyclic rats, but FSH release was only stimulated in acyclic rats. Melatonin treatment blunted this response in both cases. In addition, melatonin treatment inhibited prolactin release in acyclic-MEL group after LHRH stimulation but not the basal levels. Pituitary LH and prolactin contents, were significantly higher than the pituitary LH and prolactin levels released from all groups studied, and were not affected by reproductive senescence nor by exogenous melatonin. These data indicate that aging influences more the secretory than the biosynthetic processes. Melatonin influences is endocrine status-dependent, being inhibitory when pituitary hormones reach their higher values.

Rubinstein-Taybi syndrome: A girl with a history of neuroblastoma and premature thelarche

A 7-year-old girl with Rubinstein-Taybi syndrome (RTS) who had a history of neuroblastoma and premature thelarche is reported. The neuroblastoma was detected at age 6 months on a nation-wide neuroblastoma screening program, surgically removed, and took a favorable clinical course with minimal therapy. She developed isolated breasts at age 6 years, had normal plasma levels of estradiol, follicular-stimulating hormone (FSH), and luteinizing hormone (LH), and showed a FSH-predominant pattern on the LH-releasing hormone stimulation test. In view of these findings, she was diagnosed to have premature thelarche. Premature thelarche may not be uncommon in girls with RTS.

Assessment of the gonadotrophin-gonadal axis in androgen insensitivity syndrome.

To study the value of measuring serum luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT) in androgen insensitivity syndrome (AIS). Retrospective study of patients on a nationwide register of AIS. Sixty one cases of AIS with androgen receptor (AR) dysfunction (abnormalities of the AR gene and/or abnormal AR binding) were divided into three age groups: infants, < 1 year old; children, 1-13 years old; and postpubertal, > 13 years old. Age, dose of human chorionic gonadotrophin (hCG) stimulation, pre-hCG and post-hCG serum testosterone values, serum DHT values, and serum LH and FSH values before and after LH releasing hormone (LHRH) stimulation. In 23 of 30 infants testosterone was within age related reference ranges; six were above this range. The median testosterone rise following variable dosage of hCG was 9.5 times the basal value. The increment was not related to the hCG dose, age, or basal concentration of testosterone. The median basal and stimulated testosterone:DHT ratios were 2.5 and 6.1, respectively. The median increment in DHT was 2.2-fold. Seventeen of 18 FSH and 11 of 19 LH measurements were within age related ranges in infants; in seven patients LH values were above the range. LHRH stimulation performed in 39 patients showed an exaggerated LH in all age groups. The FSH response was not exaggerated in children. Although a positive hCG test excludes biosynthetic defects of testosterone, an inadequate response does not exclude AIS. Basal LH and testosterone may not be raised during early infancy. An LHRH stimulation test might be useful for evaluating cases of suspected AIS presenting in mid-childhood.