Cesare Terzi

Plasma Adrenocorticotropin, Cortisol, and Dehydroepiandrosterone Response to Corticotropin-Releasing Factor in Normal Children during Pubertal Development

ABSTRACT: The adrenocorticotropin (ACTH), Cortisol, and dehydroepiandrosterone responses to synthetic human corticotropin-releasing factor (CRF) were studied in 28 endocrinologically healthy children (age 1–16 yr) and in six adult volunteers (age 24–42 yr). CRF was given as an intravenous bolus (1 μg/kg body weight) between 0900 and 1000 hr. Significant increments in ACTH and Cortisol levels after CRF were observed in all subjects, with an ACTH peak value of 48.2 ± 3.4 pg/ml at 10 min (p < 0.001). The ACTH and Cortisol response patterns after CRF did not change with age or pubertal maturation and did not differ in children and in adults. In contrast, the dehydroepiandrosterone response to CRF clearly was related to the stage of pubertal development. The peak value after CRF significantly increased from puberty stage 1 to puberty stage 5 (164 ± 18 versus 779 ± 86 ng/100 ml, p < 0.001). In adults, the mean dehydroepiandrosterone peak value after CRF did not differ from that of P5 children. These results show that CRF can be given safely to children. The absence of age-dependent ACTH and Cortisol responses and a dehydroepiandrosterone response changing with pubertal maturation points to the existence of factors involved in the control of adrenal androgen production other than ACTH.

Leuteinizing hormone responses to leuprolide acetate discriminate between hypogonadotropic hypogonadism and constitutional delay of puberty

OBJECTIVE To assess if leuprolide acetate stimulation discriminates between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty (CDP) in males. DESIGN Case-control study. SETTING Patients attending an academic research environment. PATIENTS Only male patients were studied: 10 with HH (group 1, age 16.5 +/- 6.0 years), 8 prepubertal with CDP (group 2, age 14.3 +/- 1.2 years), 6 healthy prepubertal (group 3, age 9.5 +/- 3.3 years), and 8 healthy late-pubertal (group 4, age 15.1 +/- 3.1 years). INTERVENTION(S) Blood samples were obtained after an overnight fast. Leuprolide acetate was then administered SC, and blood samples were drawn at 0, 30, 60, 120, 180 minutes, and 6 and 24 hours after stimulation. MAIN OUTCOME MEASURE(S) Clinical follow-up evaluations of data and serum levels of LH, FSH, 17-hydroxyprogesterone, and testosterone. RESULT(S) Basal LH levels were similar in groups 1 through 3 and differed significantly from those in group 4. Peak serum LH levels were significantly higher in CDP compared with HH (8.9 +/- 1.4 vs. 1.4 +/- 0.2 IU/L). Baseline FSH levels were significantly higher only in pubertal boys (versus the HH group); peak levels did not differ among the groups. Basal and peak testosterone levels were significantly higher only in the control pubertal group when compared to the other groups; peak 17-hydroxyprogesterone concentrations were significantly higher in pubertal controls compared with HH and CDP. CONCLUSION(S) Peak LH responses clearly discriminate HH from CDP. Timing for blood sampling should be fixed at 0, 60, 120, 180 minutes after stimulation.

THE RATE OF CORTISOL DECREASE DURING CLONIDINE TEST INFLUENCES THE AMOUNT OF SUBSEQUENT GH RESPONSE

INTRODUCTION. Glucocorticoids enhance or suppress the Clonidine (CL) induced GH release depending to the time of administration and CL has been claimed to decrease Cortisol (F) levels in normal adults. Our purposess were 1) to establish if results in adults are relevant in a more physiological setting in children are 2) to detect circumstance in which a low GH responsivity to CL could be explaned by a peculiar pattern of HAA activation. SUBJECTS AND METHODS. 17 prepubertal subjects without GH deficit (7 females, 10 males; age 6.916 to 12.883 yrs; H-SDS: -3.065 to -0.527; BMI-SDS: -1.542 to 2.505) whose height or height growth velocity falls below the 3rd centile for age were randomly assigned to one of the following study groups: A (-15 min. GHRH, 0 min CL, n:5)8(0 min CL, CHRH 60 min., n:6) or C (0 min CL, 120 min CHRH, n:6) dosage in every group: CL 150 ug/m2 po, GHRH ug/kg iv). Blood samples were gainec 0,15,30,45,60,90,120 min after CL and 0,5,15,30,45,60,90,120 min after GHRH. F and GH were measured in every sample by RIA.RESULTS. No statistical difference in F and GH peak height between groups were detected. The F decrease rate (basal-nadir F, FD) during CL test was significantly and negatively related to GH peak (GHP) or GH Delta (GHD) (DF vs. pGH, p=0.0407, p=0.5004; CF vs. DGH, p=0.0279, r=0.5479). DISCUSSION. Adopted CL dosis had no effect on maximal GHRH-dependent F release. Otherwise our results suggest that GH responses are sensitive to the F decrease rate during CL test. This mechanism could be advocated in the explanation of discordant effects of CL treatment on growth.

EVIDENCES OF OVARIAN HYPERFUNCTION IN ADDLESCENT GIRLS WITH INSULIN DEPENDENT DIABETES MELLITUS (IDDM) AND MENSTRUAL DISORDERS

Diabetic women present an elevated incidence of mestrual disorders often associated with partial gonadotropic insufficiency with reduced LH, E2 and ovarian androgen production. Among our adolescent IDDM population 8 over 36 postmenarcheal girls (22%) complained of oligo- or amenorrhea and 4 of hirsutism also. To verify therir pituitary and ovarian functions we assessed the gonadotropine and ovarian steroid response to the administration of 500 ng s.c. of GnRHa Leuprolide acetate in 7 patients with IDDM (age 17.8±1.7 yrs) and 12 age-matched normal girls. Basal and stimulated LH, FSH, E2, DEAS, 1 and basal 17OHP and 04-A levels were similar in the two groups, regardless of elevated baseline androgens levels in few girls. 24hr-stimulated 17OHP levels were significantly higher in patients than in controls (7.8±2.2 vs. 2.8±0.3 nMol/L, P 0.0001). D4-A responses were also higher than in control although the difference was not statistically significant (9.8±1.4 vs. 6.1±0.7 nMol/L n.s.). This behaviour was similar to that of a previously studied group of 35 adolescents with hirsuitism and ovarian hyperfunction (17OHP 7.0±0.4 nMol/L, D4-A 11.2±0.9 nMol/L). These data demonstrate the presence of a high incidence of ovarian hyperfunction in adolescent diabetic girls which can underline the menstrual disorders. We need a follow-up of these patients to clarify whether they will develop a clear hyperandrogenism, as suggested by our results, or a partial gonadotropin insufficiency as other observed in older diabetic patients.

CIRCULATING POLYMORPHIC FORMS OF ACTH AND RELATED PEPTIDES: AGE—DEPENDENT NATURE OF DEXAMETHASONE SUPPRESSION IN MALE RATS

Proopiomelanocortin(POMC) through post-translational processes gives rise to a series of structural related peptides. These include MSHs, ACTHs, CLIPs, LPHs,and endorphins. In this study we have examined various molecular forms of ACTH-like immunoreactivity(ACTH-LI) present in systemic blood of male rats by chromatofocusing. To gain further insight into the physiological basis of the release of ACTH-LI peptides and its age-dependent nature, we have studied various molecular forms of ACTH-LI under dexamethasone(DX), which is expected to inhibit the release of endogenous CRF. Resolution of circulating ACTH-LI peptides utilizing chromatofocusing revealed 6 heterogenous components having isoelectric points between 4.7 and 3.29. The results demonstrated entirely different patterns of ACTH-LI peptides seen in the prepubertal group and the adult group. While the prepubertal pattern showed a relative shift to less acidic components, the adult animals had more acidic components. Under DX less acidic components in the prepubertal group were diminished and acidic components were increased. In the adults the less acidic components did not show any alterations, while the more acidic component (peak VI) was greatly enhanced. With these studies as a baseline, it convincingly demonstrates that the alterations in the ACTH-LI components with maturation are perhaps involved in the biopotency of a hormone, and inhibition of CRF by DX modulates the shift of the components from less acidic to more acidic forms.