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Biomedical subjects

E Cacciari

Publications and source records attributed to E Cacciari.

At least 55 records · Page 3Linked to original sources
PubMed1996

Islet cell surface antibodies are more common in patients and relatives in areas and during seasons with high incidence of insulin-dependent diabetes mellitus.

Although existence of islet cell antibodies (ICA) is regarded as secondary to beta cell death, islet cell surface antibodies (ICSA) might play a role in the disease process. We have collected information from nine European clinics to determine whether ICSA are more common in diabetic children or their relatives in geographical areas or time periods of high incidence of insulin-dependent diabetes mellitus (IDDM). In Finland and Sweden ("North group") with a high incidence of IDDM during childhood, 36% of the patients were positive or weakly positive for ICSA at diagnosis compared with 24% in France (p = 0.1), 11% in Berlin-Vienna (p < 0.01), and 14% in Italy (p < 0.01). This difference was seen in all age groups but was most pronounced in the youngest (0-4 y). This geographical difference was also seen among family members of whom 46% were positive or weakly positive in the North group, 25% in France (p < 0.001), 21% in Berlin-Vienna (p < 0.001), and 16% in Italy (p < 0.001). Of several analyzed antibodies (ICA, gastric parietal cell, thyroglobulin, and thyroid microsomal), only ICSA showed simultaneous positivity in all family members (r = 0.32, p < 0.01). ICSA were most common in family members of patients with short (< 8 d) duration of symptoms (p < 0.05) and showed a similar seasonality, both in patients and relatives, as the incidence of IDDM. We conclude that the geographical difference in incidence of childhood IDDM in Europe may be associated to similar geographical differences in occurrence of ICSA both in newly diagnosed diabetic children and in their relatives. Simultaneous existence of ICSA in both patients and family members and a similar seasonality for ICSA and incidence of IDDM suggest that ICSA may reflect an ongoing disease process.

Autoantibodies↗
PubMed1996

Congenital adrenal hyperplasia: neonatal mass screening compared with clinical diagnosis only in the Emilia-Romagna region of Italy, 1980-1995.

OBJECTIVE: Comparative study of the incidence of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (21ase-def CAH) and clinical findings of affected infants diagnosed via newborn screening versus case survey only in the Emilia-Romagna region of Italy. METHODS: Neonatal mass screening (from March 1980 to September 1983-Period A, and from March 1991 to August 1995-Period C) and case survey study (from 1980 to June 1995; case survey alone from October 1983 to February 1991--Period B) were performed by the Regional Referral Center for Neonatal Screening for Endocrine-Metabolic Disease with a laboratory (Central Laboratory, S. Orsola Hospital, Bologna) and clinical (First Pediatric Clinic, University of Bologna, S. Orsola Hospital, Bologna) component. A population-based sample of 420 960 newborns consecutively born in the Emilia-Romagna region from March 1980 to August 1995 were studied. Spot 17-OH-progesterone (nmol/L blood) was tested by the radioimmunoassay method after sample extraction during Period A and by fluoroimmunometric time resolved method without sample extraction during Period C. Serum 17-OH-progesterone (ng/dL or nmol/L) was tested by the radioimmunoassay method (Diagnostic Product Corporation Kit, Los Angeles, CA). The case survey was performed by means of a questionnaire sent to all regional centers dealing with pediatrics, neonatology, endocrinology, and pediatric surgery. RESULTS: Thirteen classic 21ase-def CAH were diagnosed by means of neonatal screening (combined A and C periods). One true and one questionable false-negative cases were identified. The incidence of classical 21-hydroxylase deficiency for the white population was 1:15 518 (95% confidence limits 1:9249-1:28 400) by neonatal screening plus case survey, 1:18 105 (95% confidence limits 1:10 365-1:35 041) by neonatal screening alone and 1:25 462 (95% confidence limits 1:12 925-1:59 043) by case survey alone. The sensitivity and specificity of screening for classic CAH were 83% and 99.8% for Period A and 90% and 99.2% for Period C, respectively. The percentage of salt-wasting forms and the male/female ratio were higher during the neonatal screening period than during the case survey only. Sixty-one percent of classic CAH patients benefited from a prompt diagnosis. Nonclassical 21ase-def CAH cases detected via screening and case survey were also reported. CONCLUSIONS: Even in a region with adequate neonatal services, clinical diagnosis alone of classic CAH might be delayed or misinterpreted and salt-wasting crises could cause neonatal deaths. CAH screening is thus an effective tool for diagnosing affected male infants without a family history of CAH and for preventing salt loss. However, to achieve maximal benefit from screening, quick procedures are necessary for notification of positive results and beginning prompt treatment. The possibility of false-negative cases indicates that clinical observation should never be abandoned, even with ongoing screening programs.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Response to growth hormone therapy in patients with growth hormone deficiency who at birth were small or appropriate in size for gestational age.

OBJECTIVE: To determine long-term growth response to growth hormone (GH) therapy in patients with isolated GH deficiency who had been small for gestational age and in those who had been appropriate in size for gestational age. DESIGN: Longitudinal, case-control study. SETTING: Pediatric clinic, endocrinology center, University of Bologna, Italy. PATIENTS: Sixteen GH-deficient children, small for gestational age with unknown cause, and 16 GH-deficient children, appropriate in size for gestational age, who were matched for chronologic age, bone age, pubertal stage, and target height at the beginning of treatment and were treated for 36 months. INTERVENTION: Recombinant human GH given subcutaneously at a dose of 20 IU/m2 per week in six doses per week for 36 months. MEASUREMENTS: Growth hormone levels (fluoroimmunoenzymatic method), levels of insulin-like growth factor I (radioimmunoassay), and complete 36-months auxologic follow-up. RESULTS: Patients who were small for gestational age had a modest improvement in height for chronologic age but no increase in predicted final height. Patients who were appropriate in size for gestational age had significantly better improvement in both measurements (multivariate analysis of variance: F = 6.3 (p < 0.001) and F = 3.8 (p < 0.05), respectively). Catch-up growth was similar during the first year of therapy for the two groups, after which the linear growth velocity decreased more rapidly in the small-for-gestational-age patients (multivariate analysis of variance: F = 4.9 (p < 0.05)). CONCLUSIONS: The constitutional component of the statural deficiency of small-for-gestational-age children seemed to prevail over hormonal deficiency during treatment with GH. Further follow-up to final height is necessary to evaluate these different responses.

Case-Control Studies↗
PubMed1995

Follow-up of antibodies to growth hormone in 210 growth hormone-deficient children treated with different commercial preparations.

The aim of the study was to evaluate the immunogenicity of different commercial recombinant-growth hormone preparations. The presence of antibodies to growth hormone was tested in 210 growth hormone-deficient children at 6-month intervals during treatment for 6-66 months. The patients were treated with three preparations (groups A, B and C of 70 cases each) having the authentic growth hormone sequence. Groups A and B received hormone synthesized by the recombinant DNA technique in E. coli, while the group C preparation was produced in a mammalian cell line. The preparations showed poor immunogenicity and antibodies were found as follows: 1.4% in patients of group A (1 case: binding capacity 0.2 mg/l and Ka 3.5 10(7) l M-1), 2.8% in patients of group B (2 cases; case 1 binding capacity 0.7 mg/l and Ka 1.5 10(7) l M-1; case 2 binding capacity 0.04 mg/l and Ka of 1.8 10(8) and 6.5 10(6) l M-1), and 8.5% in group C (6 cases; binding capacity from 0.4 to less than 0.02 mg/l, Ka from 1.6 10(7) to 3.8 10(8) l M-1). Only two patients of group C presented the antibodies in two subsequent examinations; in the other patients the positivity was found once. In all patients positive samples were found at intervals of 6-24 months after the start of therapy. In all antibody-positive patients growth velocity presented no decrease at the time of antibody detection and was never different to that of negative patients. We conclude that the three commercial preparations examined showed poor immunogenicity without clinical relevance.

Adolescent↗
PubMed1995

Primary empty sella: differences and similarities between children and adults.

To identify possible differences between empty sella in children and adults we studied 43 subjects (age 13.6 +/- 5.4 years, range 4.1-27 years) with hypothalamic-pituitary disorders and empty sella at magnetic resonance imaging. Pituitary function, presence of non-endocrine symptoms, perinatal history, sellar volume, pituitary height, midline or intrasellar anatomical abnormalities were evaluated. Twenty subjects had isolated growth hormone deficiency, 17 multiple pituitary hormone deficiency and 6 puberty disorders (3 precocious puberty, 2 idiopathic delayed puberty, 1 Kallmann syndrome). The group with multiple pituitary hormone deficiency had a higher percentage of subjects with complete empty sella, i.e. pituitary height < 2 mm (p = 0.016), or intrasellar anatomical abnormalities (p = 0.0002) than the other groups. The subjects with puberty disorders had a mean sellar volume higher than the other groups (p < 0.05). Apart from pituitary dysfunction, symptoms of the empty sella syndrome were infrequent (9.3% of cases) in our subjects. The age of our subjects, the frequent association between empty sella and pituitary dwarfism and the non-enlarged sellae suggest a different aetiology, perhaps congenital, for empty sella in our subjects. As in adults, empty sella may be associated with both pituitary hypo- and hyperfunction.

Adolescent↗
PubMed1995

An 8-year follow-up of anti-insulin antibodies in diabetic children: relation to insulin autoantibodies, HLA type, beta-cell function, clinical course and type of insulin therapy.

In 105 children and adolescents with IDDM, insulin antibodies were detected as a percentage of radiolabelled insulin both at onset of disease and during the first 8 years of treatment. At diagnosis, 29 patients (27%) were insulin autoantibody positive (IAA+). An inverse relationship was found between IAA levels and age at diagnosis. No significant correlation was seen between IAA positivity and HLA antigens, while there was a negative correlation between IAA and C-peptide levels in the second year of the disease. The percentage of insulin antibody (IA) positive patients increased after insulin administration, with a maximum peak between the first and second year of the disease. The IA response to insulin therapy was similar in IAA+ and IAA- patients, while it was greater in younger children. No relationship was found between IA levels and haemoglobin A1c values, daily insulin requirement, HLA and early complications. No difference in either percentage of positivity or IA levels was seen in patients treated continually for the first 5 years of the disease with monocomponent porcine insulin or human insulin. A negative correlation was found between IA and C-peptide levels in the first and second years of the disease. In conclusion, we have shown that, even after many years of disease, neither IAA nor IA, induced in equal measures by current human insulin preparations, have significant effects on the clinical course of the disease.

Adolescent↗
PubMed1995

Frequency, clinical and laboratory features of thyroiditis in girls with Turner's syndrome. The Italian Study Group for Turner's Syndrome.

A total of 478 patients, mean age 15.5 (3.6-25.3) years, suffering from Turner's syndrome, were studied in order to determine the frequency of autoimmune thyroiditis, which is defined as the presence of antithyroid antibodies (AT-Ab) and typical ultrasound findings. We found 106 (22.2%) patients positive for AT-Ab and of those 49 (10%) also had positive ultrasound findings, and were therefore considered to be affected by thyroiditis. This frequency is significantly higher (p < 0.001) than that seen in the normal population. Goitre was detected on clinical examination in only 16 (33%) and by ultrasound in 19 (39%) patients. Hormonal evaluation showed that 17 patients were euthyroid, 27 had compensated hypothyroidism, 2 were hypothyroid and 3 were in a hyperthyroid phase. Clinical signs or symptoms of hypothyroidism were absent in all hypothyroid patients. In patients with thyroiditis, neither a higher frequency of malformations and autoimmune diseases nor a correlation with karyotype, oestrogens or growth hormone therapy was found.

Adolescent↗
PubMed1995

Role of magnetic resonance imaging in hypothalamic-pituitary disorders.

Improvement of MRI diagnostic accuracy in the study of the hypothalamic-pituitary region provides precise anatomic details. In pituitary dwarfism, MRI reveals severe sella/pituitary gland and stalk hypoplasia with or without posterior pituitary ectopia, and empty sella, and this more frequently in patients with multiple pituitary hormone deficiency. Two main hypotheses have been proposed to explain these findings: traumatic stalk transection during breech delivery, and abnormal embryonic development of the pituitary gland. The association between neuroradiological findings and type/severity of endocrine alteration has not yet been clarified. In diabetes insipidus, MRI findings are normal picture, posterior lobe not visible, and thickened stalk (as expression of preclinical/initial histocytosis). Patients with central precocious puberty or hypogonadotropic hypogonadism rarely show morphologic abnormalities (hamartoma of the tuber cinereum, partially empty sella). So far, MRI permits one to identify morphologic pictures in diseases previously considered 'idiopathic'.

Humans↗
PubMed1995

Swyer-James syndrome: bronchoalveolar lavage findings in two patients.

Swyer-James syndrome (SJS) is a rare constrictive bronchiolitis that appears to be the result of acute bronchiolitis in infancy or early childhood. In the present study the cytological and immunophenotypical profile of bronchoalveolar lavage (BAL) was studied in two patients with SJS who showed a different spectrum of clinical outcome. The total BAL yield was markedly increased in the patient with chronic cough and acute episodes of dyspnoea but not in the patient with decreased exercise tolerance and longer duration of disease. In the two patients, the differential cell counts in percentage were characterized by a significant increase of neutrophils and a slight increase of lymphocytes. The analysis of lymphocyte subsets showed a significant increase of CD8+ cells (T-suppressor-cytotoxic) in both cases, resulting in a decreased CD4/CD8 ratio. In addition, an increase of cells bearing a B-phenotype (CD19+ cells) was noted in the fluid recovered from the patient with chronic cough and acute episodes of dyspnoea. In conclusion, our data suggest that SJS is an active process with inflammatory characteristics. Further studies are needed to explain the mechanism leading to the expansion in situ of immunocompetent cells.

Adolescent↗
PubMed1994

Long-term follow-up and final height in girls with central precocious puberty treated with luteinizing hormone-releasing hormone analogue nasal spray.

OBJECTIVE: To evaluate clinical, hormonal, and auxologic features in a group of girls with central precocious puberty during and after long-term treatment with luteinizing hormone-releasing hormone analogue nasal spray. DESIGN: Clinical survey, before-after trial. SETTING: Pediatric Clinic, Endocrinological Center, University of Bologna (Italy). PATIENTS: Forty-one girls with central precocious puberty were treated for 28 months (range, 12 to 60 months); 25 of them discontinued therapy at a mean chronological age of 10.0 +/- 0.9 years and were followed up for 25 months (range, 6 to 50 months). Twelve patients achieved adult height. INTERVENTION: Buserelin acetate (D-Ser [TBU] LHRH A1-9EA) nasal spray; 1800 micrograms/d subdivided into six intranasal administrations of 300 micrograms each. MEASUREMENTS/MAIN RESULTS: Basal follicle-stimulating hormone, peak gonadotropin values (fluoro-immunoenzymatic method, Eurogenetics, Tessenderlo, Belgium; sensitivity was 0.5 IU/L for luteinizing hormone and 1 IU/L for follicle-stimulating hormone), and estradiol (radioimmunoassay method, DPC Kit, Los Angeles, Calif; sensitivity was 11.01 pmol/L) were significantly suppressed (P < .0001) as of the third month of treatment and increased significantly (P < .01) to pretreatment levels 6 months after discontinuation of therapy. Uterine and mean ovarian volumes, which were stable throughout treatment, appeared significantly higher (P < .05) than before treatment at only 6 months after stopping therapy. In patients with more advanced bone age (according to Greulich and Pyle) at onset of treatment, we observed a more significant improvement of SD score for height (Tanner). Mean adult height in our patients was 159.5 +/- 6.1 cm, and the variables that were significantly associated with final height were height age/bone age ratio at onset and target height (according to Tanner). CONCLUSIONS: Long-term buserelin treatment administered nasally is effective because of completeness of inhibition, quick reversibility after treatment is stopped, and lack of side effects. Its auxologic results are different depending on bone age advancement at onset, which represents a predictor of "therapeutic success." Further follow-up would be useful.

Administration, Intranasal↗
PubMed1994

Indications for a more aggressive disease process in newly diagnosed insulin-dependent diabetic children in northern than in southern Europe.

Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3-4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden ('North') and Pittsburgh were younger (< 10 years old) at diagnosis compared with those in the other clinics in Europe (P < 0.05 versus P < 0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (< 8 days; P < 0.001) and higher blood glucose (> 20 mmol/l; P < 0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%; P < 0.01) or in France (70%; P < 0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (< 0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.

Adolescent↗
PubMed1994

Longitudinal growth and final height in long-term survivors of childhood leukaemia.

Survival of children with acute lymphoblastic leukaemia (ALL) has increased considerably in recent years and data on the spontaneous growth and final height of these children are conflicting. Therefore, we analysed the longitudinal growth and final height in 52 survivors (33 females, 19 males) of childhood ALL. These children were diagnosed and treated in a single institution, all remained in first remission and were submitted to cranial irradiation with either 2400 or 1800 cGy. None of the patients received testicular or spinal irradiation. Median age at diagnosis was 4.2 (range 1.3-9.6) years in the first group (2400 cGy) and 3.9 (0.8-10.5) years in the second (1800 cGy). Standing height was measured at diagnosis, at the end of treatment (median 3.1 years after diagnosis), 6, 12, 24 months after the end of treatment, and finally at the completion of growth. In girls a significant decrease of mean height standard deviation score (SDS) during treatment and a catch up in growth after the end of therapy was followed by a second period of reduced growth. Mean final height SDS was significantly lower than the value at diagnosis in both groups of girls, but only in males treated with 2400 cGy. Mean overall loss in height SDS from diagnosis to final height was higher in females (-1.24) than in males (-0.40) (P = 0.009). Females < or = 4 years of age at diagnosis showed a higher loss in final height than females > 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset↗
PubMed1994

Molecular study of human growth hormone gene cluster in three families with isolated growth hormone deficiency and similar phenotype.

The growth hormone (GH) gene (hGH-N) cluster was analysed using polymerase chain reaction, Southern and polymorphism analysis in five patients (including two pairs of siblings) with extreme short stature and absence of GH secretion. Patients 1 and 2 (siblings) were homozygous for a large deletion removing four genes of the cluster: hGH-N, hCS-L, hCS-A and hGH-V. Both siblings produced high anti-GH antibody levels in response to exogenous GH therapy, followed by growth arrest a few months after starting replacement therapy. In patient 3 we detected a heterozygous deletion which involved three genes of the cluster (hCS-A, hGH-V, hCS-B) and left an intact hGH-N gene. Direct sequencing of hGH-N specific amplified fragments excluded the presence of any point mutations in exons and splicing regions. In patients 4 and 5 (sisters) our study did not demonstrate any gene deletions. Analysis of polymorphic restriction patterns in this family demonstrated that both sisters inherited the same alleles from the father but different alleles from the mother, suggesting that the defect was not linked to the hGH-N gene. These results confirm the difficulty of clinical identification of subjects with hGH-N deletion and underline the importance of DNA analysis in patients with absence of GH secretion and extreme growth retardation.

Adolescent↗
PubMed1994

Adrenocortical tumors in children: a report of 12 cases.

Adrenocortical tumors in children are extremely rare, accounting only for 0.3-0.4% of all neoplasms in this age. Most frequently they secrete hormones, resulting in virilization, Cushing's syndrome or feminization, while the non-functioning ones are unusual. The authors describe 12 cases observed in 13 years (1976-1989), with a mean age of 5 years. 9 cases showed virilization, 4 presented with Cushing's syndrome and in 5 patients an abdominal mass was palpable. One case was affected by Beckwith-Wiedemann's syndrome. I.V. urography was performed in 8 patients, arteriography in 4 and since 1982 all patients were submitted to abdominal sonography and CT scan or MR imaging. Urinary 17-ketosteroids, 17-hydroxycorticoids and serum testosterone and cortisol were tested in all children. Dexamethasone suppression test was performed in 7. All patients were treated with surgery which seems to be the most suitable treatment, while the real effectiveness of treatment by drug therapy with suppressors of steroidogenesis is not confirmed in children. Histopathological examination showed typical features of adenoma in 5 cases, of adenocarcinoma in 4, while three cases revealed border line forms classified as "atypical adenomas". At the moment 10 patients are alive with a follow-up ranging from 18 months to 14 years, while 2 children with adenocarcinoma are dead.

Adenocarcinoma↗
PubMed1994

Spontaneous growth and pubertal development in Turner's syndrome with different karyotypes.

We studied spontaneous growth and pubertal development in 205 girls with Turner's syndrome, aged 1 month to 28.16 years, according to different karyotypes: 45,X (52%), X-mosaicism (12%), X-structural abnormalities (36%). Data on height, weight, height velocity, bone age and pubertal development were collected yearly in a mixed longitudinal and cross-sectional mode. Pelvic ultrasonography was performed in 133 patients, 46 of whom had contact breast thermography. Standards for height and height velocity (1-20 years) showed no differences when compared with other studies. Some differences were found when these data were subdivided by karyotype. In fact, X-mosaicism subjects had a pubertal growth spurt between 8 and 12 years of age. The spurt observed in this group cannot be justified by the more frequent presence of residual ovarian activity alone. It also appears in patients without ovaries and confirms the influence of a genetic factor on the X-chromosome. In spite of this spurt, the greatest final height was reached by 45,X subjects. X-mosaicism girls had more frequent spontaneous breast development linked to a higher percentage of visible ovaries. In this group the age of the first pubertal signs was similar to that of normal subjects and occurred much earlier than in the other groups.

Adolescent↗
PubMed1994

Empty sella in children and adolescents with possible hypothalamic-pituitary disorders.

Several computed tomographic scan studies have described empty sellae in children with hypothalamic-pituitary disorders. Magnetic resonance imaging, however, is a more precise technique for visualizing the intrasellar content, such as the stalk and pituitary lobes. Using magnetic resonance imaging, we studied 339 children and adolescents (mean age +/- SD, 12.7 +/- 4.5 yr) with possible hypothalamic-pituitary disorders to ascertain the frequency of primary empty sella and examine its relationships with other intrasellar abnormalities, pituitary function, and adverse perinatal events. One hundred and ninety-three patients had isolated GH deficiency, 43 had multiple pituitary hormone deficiency, 10 had diabetes insipidus, 17 had hypogonadotropic hypogonadism, 5 had idiopathic delayed puberty, 47 had precocious puberty, and 24 had other hypothalamic pituitary disorders of hyperfunction. One tenth (10.9%) of the patients (37 cases) had empty sella, with a marked variation of incidences among the disorders listed above. A statistically higher frequency of subjects with empty sellae was found only in patients with multiple pituitary hormone deficiency. Patients with and without empty sellae were not different in regard to age or sex. The incidence of empty sella in the various groups of patients was as follows: isolated GH deficiency, 8.8% (17 cases); multiple pituitary hormone deficiency, 34.9% (15 cases); hypogonadotropic hypogonadism, 5.9% (1 case); idiopathic delayed puberty, 40% (2 cases); and precocious puberty, 4.2% (2 cases). No patients with isolated diabetes insipidus or other hypothalamic-pituitary disorders had empty sellae. In the patients with empty sellae, abnormalities of the stalk or posterior lobe were found in 1 patient with isolated GH deficiency (5.9%), 13 patients with multiple pituitary hormone deficiency (86.7%), and no patients with puberty disorders. Likewise, adverse perinatal events were found only in 1 patient with isolated GH deficiency and 9 patients with multiple pituitary hormone deficiency. These findings suggest that empty sella is not rare in children and adolescents evaluated for hypothalamic-pituitary disorders, particularly if there is multiple pituitary hormone deficiency. Empty sella can be found regardless of abnormalities of the stalk and posterior lobe, and adverse perinatal events do not seem to be the primary etiological factor. Empty sella is usually associated with pituitary hypofunction, but it can be found in patients with hyperfunction of the hypothalamic-pituitary-gonadal axis.

Adolescent↗