Pubertal Boy Research Articles

A Perplexing Case of Pituitary Apoplexy Masquerading as Meningoencephalitis

Pituitary apoplexy (PA) is extremely rare in children and adolescents. It is a life-threatening condition usually results from sudden hemorrhage or infarction induced swelling in a pituitary adenoma. The clinical manifestations of PA include severe headaches, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Therefore, the presence of meningeal irritation may lead to misdiagnosis as a case of meningoencephalitis or spontaneous subarachnoid hemorrhage, and delay in the proper management of the disease. We report a case of 17-year-old pubertal boy who developed sudden severe headache, vomiting, slurring of speech and abnormal behaviour followed by impaired sensorium with fever. The patient who was initially diagnosed with meningoencephalitis (ME) based on clinical presentation and cerebrospinal fluid (CSF) analysis, which was consistent with bacterial meningitis. MRI of brain was performed, confirming a pituitary macroadenoma with hemorrhage and ischemic changes in both basal ganglia and pons. A complete analysis of the pituitary hormones revealed decreased cortisol and thyroid hormone level and hyperprolactinemia and he was subsequently started on placement corticosteroid and L-thyroxine therapy and cabergoline. After 14/ days of antimicrobial therapy with ceftriaxone and ampicillin, the patient improved and was discharged on hormone replacement therapy and surgical advised. Hereby, we report our case with a review of literatures. Bangladesh J Medicine July 2022; 33(1) : 85-88

Somatic Mutations of GNA11 and GNAQ in CTNNB1-Mutant Aldosterone-Producing Adenomas Increases Aldosterone and Aldosterone Synthase (CYP11B2)

Abstract Most aldosterone-producing adenomas (APA) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals suggests the existence of co-driver mutations which influence the development or phenotype of APAs. Gain-of-function mutations in both CTNNB1 and GNA11 were found by whole exome sequencing in 3 of 41 APAs from a UK/Irish cohort. Targeted sequencing for exon 3 mutations of CTNNB1 and p.Gln209 mutations of either GNA11 or closely homologous GNAQ confirmed these and 7 further double mutant APAs in this discovery cohort. The presence of GNA11/Q p.Gln209 mutations in CTNNB1 mutant APAs were replicated in 2 cohorts from France (n=14) and Sweden (n=3). In total, 16 (59%) of the 27 CTNNB1 mutant APAs investigated had a mutation at p.Gln209 of GNA11 (n=11) or GNAQ (n=5). Interestingly, CTNNB1-mutant APAs were more commonly present in women (23/27), and of these, those with GNA11/Q mutations were all women except for a pubertal boy. To also note, 9 of 10 of the UK/Irish double mutant APAs in the discovery cohort presented in puberty, pregnancy, or menopause. Mutation of p.Gln209, or homologous p.Gln in GNAS, GNA12-14, impair hydrogen bonds between G-protein α and β subunits. Transfection of H295R cells, an immortalised adrenocortical cell line heterozygous for the p.Ser45Pro mutation of CTNNB1 but wild-type for GNA11-14/Q/S, by each of the GNA11/Q mutations increased aldosterone secretion and CYP11B2 expression (encoding aldosterone synthase) by 1.93-6.1-fold and 8.0-9.8-fold respectively, compared to vector or wild-type -transfected cells. In ZG, GNA11/Q mediate the aldosterone response to angiotensin II, via stimulation of intracellular Ca2+ release by inositol trisphosphate. In the mutant-transfected cells, the stimulatory effect of angiotensin II 10 nM was retained. In order to determine whether the p.Gln209 mutations stimulate aldosterone production even in the absence of CTNNB1 activation, the transfections of H295R cells were repeated after either 24-h treatment with the CTNNB1 inhibitor, ICG-001, or silencing of CTNNB1 using the ONTARGETplus SMARTpool SiRNAs (Dharmacon). Both interventions reduced the aldosterone production relative to vehicle/control-treated cells; however neither ICG-001 nor silencing of CTNNB1 blunted the fold-increase in aldosterone secretion seen in mutant-transfected cells compared to wild-type. In summary, we report the discovery of gain-of-function mutations of the G-protein, GNA11, or its close homologue, GNAQ, in multiple APAs which majority presented during periods of high LH/HCG. To date, the mutation is always residue p.Gln209, and associated with a gain-of-function mutation of CTNNB1. These GNA11/Q p.Gln209 mutations increase aldosterone and CYP11B2 production both in the presence and in the absence of CTNNB1 activation.

A prospective study on the long-term outcome of prepubertal and pubertal boys undergoing testicular biopsy for fertility preservation prior to hematologic stem cell transplantation.

Few studies have reported the long-term outcomes of prepubertal and pubertal boys undergoing testicular biopsy for fertility preservation (FP). This prospective longitudinal study examined 21 boys (aged 1.5-14.5 years) who underwent testicular biopsy for FP prior to allogeneic (n=20) or autologous (n=1) hematological stem cell transplantation (HSCT) between 2003 and 2010. During counseling, pubertal boys were encouraged to produce a sperm sample by masturbation , while prepubertal boys were presented with surgical testicular tissue retrieval as an option for experimental FP. Clinical outcomes included postoperative complications, pubertal development, and sex-hormone levels. Survivors approaching adulthood were encouraged to provide semen samples. Twenty boys, including 14 in prepuberty and six in early puberty (Tanner stage 2-3), underwent open testicular biopsies. Two pubertal biopsies contained mature sperms, which were cryopreserved. Testicular tissue was vitrified in the remaining 18 cases. One pubertal boy (Tanner stage 4) underwent percutaneous testicular sperm aspiration and sperms obtained were cryopreserved. Postoperative complications (hematoma or infection) were rare. Overall, 14 boys survived>5 years (mean follow-up after HSCT, 7.2 years) and 11 showed advanced puberty. Semen samples were provided by five boys and obtained sperm were cryopreserved from two. Individuals at adulthood had normal testosterone levels but subnormal testicular size, high follicle stimulating hormone, and low inhibin B and anti-Müllerian hormone levels. No long-term risks were detected during continuous clinical follow-up. Experimental testicular biopsies for FP were well accepted by the patients and families, despite the absence of methods to use prepubertal tissue for fertility treatment.

SAT-224 Recurrent Co-Driver Mutation in CTNNB1-Mutant Aldosterone-producing Adenomas (APA), Causing Reversible Hypertension in Puberty, Pregnancy or Menopause

Background: Three patients with a syndrome of LH/HCG-activated primary aldosteronism in pregnancy or menopause carrying somatic CTNNB1 mutations were reported four years ago (Teo et al. NEJM 2015). This proved but half the story. Diagnosis of an APA in a 12-year old boy with severe hypertension revealed an apparently essential co-driver mutation. Methods: WES of tumour and blood was performed in the pubertal boy. Candidate genes were Sanger sequenced in other APAs from GB/Ireland, and France with known or suspected CTNNB1 mutations. LHCGR, GNRHR and CYP11B2 expression were measured in all available patients’ APAs and the adjacent adrenal gland (AAG) by RT-PCR. RNA and gDNA from the zona glomerulosa (ZG) of the proband’s AAG were collected by laser capture microdissection for Sanger sequencing of GNA11 and CTNNB1. Function of mutant genes was assessed by measurement of aldosterone production and LHCGR expression by immunofluorescence (IFC) in NCI-H295R adrenocortical cells and primary human APA cells. Results: The proband’s APA contained a p.(S45F) somatic mutation in CTNNB1, and a p.(Q209P) somatic mutation of the GTPase-activating residue (Q209) in GNA11. Mutations of Q209, to P or H, were also found in six other GB/Irish patients with previously identified mutations of CTNNB1 (S33C, G34R, T41A, S45F, or S45P). All seven patients remain normotensive 2-12 years post-adrenalectomy, including some with long-standing pre-operative hypertension. Four of the 13 French patients with CTNNB1 exon 3 mutant APAs have somatic mutation of Q209 of either GNA11 (n=3) or GNAQ. In comparison with their own AAG, the GB/Irish double mutant APAs showed an increase in expression of LHCGR, CYP11B2 and GNRHR by 32-166, 158-18980, and 1174-6642 fold, respectively. All four French double-mutants had >10 fold higher LHCGR than APAs with single mutations of CTNNB1 or other genes. Hyperplasia of ZG was observed in the ZG of the boy’s AAG but no APCC was detected. Homozygous or heterozygous Q209P mutation of GNA11 was detected in multiple ZG samples in RNA and/or gDNA but WT in CTNNB1 exon 3. H295R cells (CTNNB1 S45P) were GNA11 WT. Overexpression of GNA11 Q209 mutation increased aldosterone secretion to 465% of GNA11 WT overexpressing cells (n=6, P<0.001) and CYP11B2 expression was also increased several-fold. Smaller increases were seen in primary human adrenal cells after double-transfection by GNA11 and CTNNB1 mutants (n=3, P<0.001). This also caused membrane expression of LHCGR, visualised by IFC. Conclusions: APAs with double mutation of GNA11/GNAQ Q209 and CTNNB1 have a distinct phenotype, in which hypertension is triggered by high LH or HCG, and cured in all cases by adrenalectomy. GNA11/Q mediates the aldosterone response to ANGII, and the Q209 codon is analogous to the Q227 of GNAS, mutated in McCune Albright. Mosaicism for GNA11 may cause ZG hyperplasia.

Unilateral testicular enlargement in a teenager with Beckwith-Wiedemann syndrome: a case report

BackgroundBeckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth disorder. A major feature is lateralized overgrowth, which can variably involve a single body district up to the entire hemisome. Visceral asymmetrical involvement has been observed, commonly represented by enlargement of one kidney or adrenal gland, rather than one gonad.Case presentationWe report the case of a pubertal boy affected by BWS, who developed a progressive testicular enlargement, ipsilateral to the pre-existing external body overgrowth. Asymptomatic unilateral testis enlargement started after regular pubertal onset and worsened over time, without any associated pathological findings in a long-term follow-up. Since biopsy is not indicated in case of benign macro-orchidism, we hypothesize that this asymmetric enlargement could be an expression of visceral lateralized overgrowth in BWS.ConclusionsAt the best of our knowledge, this is the first detailed report of unilateral testicular overgrowth in BWS. We revised common causes of painless unilateral scrotal masses in the pediatric age. Considering both the overall frequency of neoplasia and the malignancies predisposition in BWS, a testicular cancer should be carefully ruled out through a close follow-up, before stating a benign condition. A normal ultrasound pattern, together with normal serum hormonal levels and negative tumor markers, make testicular neoplasms highly unlikely.

SAT-305 Hyperactive Behavioral Change during Combination Treatment of Aromatase Inhibitor and Recombinant Human Growth Hormone in Early Puberty Patient: A Case Report

Aromatase inhibitor (AI) is a drug that blocks the converstion of androgens to estrogens, originally approved by FDA as a treatment of breast cancer in postmenopausal women. In several studies, it has been proposed that AI can be used as a off-label treatment to improve the final adult height in short pubertal boys by delaying growth plate closure, because that estrogen has an important role in pubertal growth spurt by promoting the closure of epiphyses, skeletal maturation in males as well as females. AI has been also introduced to be used for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts. In recent studies, AI appears effective in increasing final adult height, however, safety concerns also remain including androgenic adverse effect and vertebral deformities. Although that we experienced that there has been no major adverse effects in AI-treated pubertal boys as reported in other studies, we would like to introduce a case of pubertal boy showing hyperactive behavioral change when co-treated with AI and rhGH for short stature and early puberty. A 10 years and 2 months-old boy visited our clinic and his initial examination revealed as follows; height was 143.7cm (81th percentile) and weight was 45.3kg (89th percentile); secondary sexual characteristics of Tanner stage III. Bone age was assessed to be 13 years by TW3 method. He was diagnosed as ADHD in previous years, but not prescribed medicine because of well-controlled behavior. We diagnosed the patient as early puberty, and combination treatment of GnRH agonist and rhGH was started. After 10 months, GnRH agonist treatment was discontinued, and after-GnRHa AI treatment was started to slow down bone age progression and improve his height. We prescribed letrozole 2.5mg once a day. After 7 months, we discontinued AI because of his aggravated hyperactivity and uncontrolled aggressive behavior which was much more severe than before. We could not rule out the possibility of testosterone-mediated side effect. At that time, his height was 170.4cm with a gain of 26.7cm (chronological age of 13 years and 3 months). The progression of bone age was successfully suppressed during the treatment. After 1 years of completion, we checked his near-final height as 173.4cm. In conclusion, testosterone levels have been thought to be linked to aggression and violent behavior in adults and postpubertal adolescents in previous studies. Therefore, clinicicans should be aware of possible behavioral change in AI-treated early pubertal boys, which can be mainly induced by hypertestosteronemia, and further studies are needed to reveal other androgenic adverse effects.

SAT-308 Obsessive and Compulsive Behavioral Change during Combination Treatment of Aromatase Inhibitor and Recombinant Human Growth Hormone in Early Puberty Patient: A Case Report

Aromatase inhibitor (AI), mostly combined with recombinant human growth hormone (rhGH), has been proposed as a effective treatment to improve the final adult height in short pubertal boys by delaying growth plate closure. However, safety concerns also remain, because of limited safety profile of AI usage in pediatric population. Several recent studies have revealed adverse effects of AI, including possible alterations in vertebral bone growth and vertebral anomalies, decreased HDL, increased hematocrit. Although that estrogens might have a role in the regulations of cognitive functions and AIs that block estrogen synthesis cross the blood-brain barrier, a recent trial suggested that AI did not impact the cognitive performance in peripubertal boys. In this report, we would like to introduce a rare case of showing obsessive and compulsive behavioral change in a early pubertal boy who was co-treated with AI and rhGH. A 13 years and 5 months-old boy visited our clinic and his initial examination revealed as follows; height was 160.5cm (45th percentile) and weight was 47.6kg (29th percentile); secondary sexual characteristics of Tanner stage IV. His pelvis x-ray showed risser stage 2, which is assessed to be about 16 years of bone age. He was otherwise healty with no other medical problems. His father's height was 170cm, his mother's height was 151cm, and his midparental height was calculated as 167cm. The patient and his parents wanted to improve his final adult height, and we commenced combination treatment of AI and rhGH after taking agreement. We prescribed letrozole 2.5mg once a day. After 2 months of the start of AI treatment, his parents compaint of his obsessive and compulsive behavioral change, which was not noticed before taking the drug. He complaint of obsessive thoughts and unwanted emotional pull that caused anxiety and distress. Also, he showed compulsive behavior of repeating reading one phrases of the same page. He was in intense stressful situation of preparing important test, however, we could not rule out the possibility of potential adverse effect of AI. Therefore, we discontinued AI. After discontinuing the drug, the symptom improved. During 3 months of combination treatment, he has achieved his height as 162.4cm with a gain of 1.9cm. The progression of bone age was successfully suppressed during the treatment. In conclusion, no significant influence on cognitive performance has been reported in previous studies, however, those studies focused on memory function. Potential effects on other behavioral change have not heen extensively evaluated. Therefore, clinicicans should be aware of possibility of compulsive behavioral change in AI-treated early pubertal boys, and further studies are needed to reveal the relationship.

Is Acute Testicular Pain and Vomiting in a Pubertal Boy Pathognomonic of Testicular Torsion?

Is Acute Testicular Pain and Vomiting in a Pubertal Boy Pathognomonic of Testicular Torsion?

Attitudes of parents of Klinefelter boys and pediatricians towards neonatal screening and fertility preservation techniques in Klinefelter syndrome.

To evaluate the attitude of parents of Klinefelter syndrome (KS) boys and pediatricians with regard to early detection of KS and fertility preservation, a specific questionnaire investigating the acceptability towards neonatal screening for KS and the use of testicular biopsy and sperm collection was designed. The responses of 49 pediatricians and 18 parents were evaluated. All parents and 67% of the pediatricians consider neonatal screening for KS to be a good option. A total of 83.3% of the parents agree on performing a testicular biopsy in their pubertal KS boy, 72.2% are in favor of banking spermatozoa after masturbation while 77.7% agree on spermatozoa banking after penile vibro-stimulation or rectal electro-stimulation under general anesthesia. Sixty-nine percent of pediatricians would counsel parents and KS adolescents in favor of early detection and cryopreservation of spermatozoa after masturbation, and 71.2% agrees on testicular biopsy to detect spermatozoa or eventually spermatogonial stem cells (SSCs) for cryopreservation in minor KS patients. The majority of KS parents and pediatricians, completing a specific designed questionnaire on fertility preservation modalities, were in favor of neonatal screening of KS. Both sperm collection and SSC collection are highly appreciated by parents and pediatricians, despite the currently experimental character of these fertility preservation strategies.

Combined treatment with GH and anastrozole in a pubertal boy with Cushing's disease and postsurgical GH deficiency

Growth failure is a characteristic manifestation of pediatric Cushing's disease. Catch-up growth is usually incomplete after cure of the disease, and final height is often compromised. Possible mechanisms for this phenomenon include postoperative persistence of GH hyposecretion and absence of retardation of bone maturation in spite of GH deficiency. This report describes the outcome in the case of a boy with Cushing's disease for whom GH replacement therapy was combined with anastrozole, an aromatase inhibitor, in order to delay skeletal maturation and extend the available time for linear growth. The case of a 14 years 4-months-old pubertal male (Tanner stage III) with GH deficiency after successful surgical treatment of Cushing's disease is presented. His height was 147.2 cm (-2.34 SDS), and his midparental target height 171.2 cm (-0.95 SDS). Bone age was 13.5 years and predicted adult height 163.2 cm (-2.2 SDS). Combined treatment was administered for 2.5 years. GH was maintained up to age 18 years. Anastrozole induced a substantial deceleration of bone age. Near-final height at 18 years was 169.5 cm (-1.07 SDS). Puberty progressed normally. Compared with population reference data, bone mineral density before GH plus anastrozole treatment was -4.07 SDS in the lumbar spine and -1.85 SDS in the femoral neck. These measures increased to -1.95 and -0.89 SDSs respectively, at 18 years, when GH was discontinued. Combined treatment with GH and aromatase inhibitors could be a therapeutic alternative to improve the stature of pubertal boys with Cushing's disease and postsurgical GH deficiency.

Continuous subcutaneous hydrocortisone infusion (CSHI) in a young adolescent with congenital adrenal hyperplasia (CAH)

Congenital adrenal hyperplasia (CAH) is an autosomal recessive enzymatic defect caused by mutations or deletions of the cytochrome P450 21-hydroxylase CYP21 gene. Oral therapy with glucocorticoids and mineralcorticoids is administered to prevent adrenal crisis and to control hyperandrogenism. During puberty this type of therapy is difficult to manage owing to physiological and hormonal changes and poor compliance. We describe a case of a pubertal boy affected by CAH, in whom continuous subcutaneous infusion of hydrocortisone led to improved metabolic control and compliance.

Idiopathic benign bilateral testicular enlargement in a pubertal boy: a case report and review of literature

We present a case of 12-year-old boy with idiopathic benign bilateral testicular enlargement. We eliminated precocious puberty, juvenile hypothyroidism, adrenal rest tumors, X-linked mental retardation, and bilateral testicular neoplasms. The clinical and laboratory features and differential diagnosis of benign bilateral testicular enlargement are discussed.

Letrozole Significantly Improves Growth Potential in a Pubertal Boy With Growth Hormone Deficiency

Clinical experience with using an aromatase inhibitor to suppress estrogen production during puberty for improvement of growth potential in adolescents with short stature is limited. This report documents treatment of such a patient with a combination of growth hormone and letrozole, a third-generation aromatase inhibitor. Our case demonstrates a favorable outcome on a short-term basis.

Androgenic Activity in Autism

Back to table of contents Previous article Next article Letter to the EditorFull AccessAndrogenic Activity in AutismSylvie Tordjman, M.D, Ph.D., Pierre Ferrari, M.D., Veronique Sulmont, M.D., Michel Duyme, Ph.D., and Pierre Roubertoux, Ph.D., Sylvie TordjmanSearch for more papers by this author, M.D, Ph.D., Pierre FerrariSearch for more papers by this author, M.D., Veronique SulmontSearch for more papers by this author, M.D., Michel DuymeSearch for more papers by this author, Ph.D., and Pierre RoubertouxSearch for more papers by this author, Ph.D., Paris, FrancePublished Online:1 Apr 2006https://doi.org/10.1176/ajp.154.11.1626-aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail TO THE EDITOR: In four of 12 prepubertal autistic children (6–10 years old) in our inpatient child psychiatry department, we have observed precocious secondary sexual characteristics (growth of pubic hair, increase of testis volume) that suggest high androgenic activity in infantile autism. In addition, there are four times more male than female autistic patients (1). These observations are consistent with Geschwind and Galaburda's theory (2): excess testosterone in the fetus may cause anomalies in the development of the left hemisphere, which in turn provoke cognitive dysfunction such as that found in subjects with autism.To test our hypothesis of a hyperandrogeny and autism association, we measured plasma testosterone and adrenal androgen in nine drug-free inpatients with DSM-IV autism and 62 normal subjects of same age, sex, weight (within 2 kg), and stage of puberty. Written informed parental consent was obtained for all subjects. The autistic group consisted of five prepubertal boys and two prepubertal girls (8–10 years old), one pubertal boy (17 years old), and one pubertal girl (13 years old). Some studies have shown a positive correlation between testosterone and aggression (3). In order to control for this variable, we divided the nine children into three groups according to their aggressive behavior exhibited during the several months before the blood drawing. Three of the children had exhibited explosive aggression against others (anger, broken objects, violence toward others). Three engaged in self-mutilations, and three demonstrated no aggression and were in a severe state of autistic withdrawal. The appearance of aggression against others was associated with having fewer of the main symptoms of autism (autistic withdrawal, stereotypies, language dysfunctions).The comparison group, chosen from a pediatric unit, consisted of 21 prepubertal boys and 19 prepubertal girls (9–10 years old), nine pubertal boys (16–17 years old), and 13 pubertal girls (12–13 years old). All blood samples were collected at 10:00 a.m. Measures of plasma testosterone concentration and adrenal androgen were made by immunoradiometry.Results showed that three of the nine autistic subjects had an abnormally high plasma testosterone concentration (over two standard deviations above the mean for the comparison subjects), with values above that of the highest in the comparison subjects. Among the autistic subjects, plasma testosterone concentration values (ng/ml) were 0.64 for a prepubertal 10-year-old boy, 8.8 for the pubertal 17-year-old boy, and 0.5 for the pubertal 13-year-old girl, whereas the appropriate comparison group means were 0.06 (SD=0.03, range=0.01–0.15), 5.51 (SD=1.27, range=0.27–7.50), and 0.12 (SD=0.09, range=0.01–0.25), respectively. These three children all showed aggression against others. Thus, high plasma testosterone concentrations were present in all autistic subjects who exhibited aggression against others. The 10-year-old boy exhibited pubic hair growth. The 13-year old girl had a level of adrenal androgen (4.40 ng/ml) that was 500% higher than the mean level of the comparison subjects (mean=0.88, SD=0.39, range=0.36–1.70). The other autistic subjects showed normal adrenal androgen levels.This is the first report of an association between abnormally high androgenic activity and aggression in subjects with autism. Although a previously reported study did not find group mean elevations in plasma testosterone in prepubertal autistic subjects (4), it appears here that in certain autistic individuals, especially those in puberty, hyperandrogeny may play a role in aggressive behaviors. Also, there appear to be distinct clinical forms of autism that are based on aggressive behaviors and are not classified in DSM-IV. Our preliminary findings suggest that abnormally high plasma testosterone concentration is associated with aggression against others and having fewer of the main autistic symptoms. Obviously, further studies are required with larger samples and longitudinal assessments.

Unilateral enlargement of the testis in childhood: Does it need exploration?

Unilateral testicular enlargement in the pubertal boy is not an indication for exploration and biopsy, if the clinical features and investigations show no evidence of malignancy. In the prepubertal boy, unilateral testicular enlargement is not necessarily an indication for exploration if there are no clinical or investigational grounds for suspicion of neoplasia. Close follow-up is essential.

LOW DOSE OXANDROL ONE THERAPY IN CONSTITUTIONALLY DELAYED GROWTH

27 boys (aged 7.6-16yrs) with delayed growth were subdivided by testicular size into prepubertal (<4mls) and pubertal (≥4mls). 13 received 2.5mg/d oxandrolone (Ox) for 3 months, and 14 acted as controls. Each group grew at a velocity below the 25th centile over the preceding 0.3-1.4yrs. The controls continued to grow poorly over the next 6 months. Ox promoted an increase in velocity in prepubertal (4.4 to 7.5cm/yr, p=0.05) and pubertal buys (4.7 to 8cm/yr, p<0.05) during therapy, maintained over the subsequent 3 months only in the pubertal group (to 9.3cm/yr). The prepubertal decelerated after treatment (to 5.4cm/yr).GH secretion (arginine, GRF and during the first 90mins of sleep) was assessed at entry and 6 months in prepubertal controls, and at entry, 3 and 6 months in treated boys. No change in peak GH response or “areas under curve” (AUC) were seen in the prepubertal groups. At 3 and 6 months, treated pubertal boys had significantly greater AUC and GH peaks during sleep than the prepubertal, associated at 6 months with increases in basal testosterone (3.7nmol/l at entry to 18.2nmol/l, p<0.01) and somatomedin-C ( 140 to 2l4ng/ml, p<0.05). These changes were not seen in the prepubertal boys.Ox does not. alter the GH status of prepubertal boys, but enhances growth probably through a direct action on cartilage. Persistent, growth acceleration in the pubertal boy is associated with increased GH and somatomedin levels.

Electroencephalogram and neuroendocrine parameters in pubertal and adolescent depressed children: A case report study

EEG sleep recordings and two provocative neuroendocrinological tests (the DST and the GH stimulation test after desipramine) were investigated in two depressed pubertal monozygotic twin boys with Major Depressive Disorder and compared with results from one normal pubertal control boy and an adolescent girl suffering from major depression. REM latency was reduced in the adolescent depressed girl but not in the pubertal depressed twin children when compared to the normal control. Sleep continuity and sleep architecture were, however, disturbed in pubertal and adolescent depression as a function of severity of the depressive state. The results of the DST showed abnormal cortisol values in the most severely depressed twin and in the depressed adolescent. GH secretion after DMI showed a clear GH response in the less depressed twin and in the normal subject while in the depressed adolescent, the GH response was blunted. The findings suggest that REM latency disturbances in our depressed patients do not appear before adolescence, while neuroendocrine dysfunction can already be present in pubertal depression.

Plasma Testosterone Response to Short-Term Human Chorionic Gonadotropin Administration in Men with Follicle-Stimulating Hormone Suppressed by Exogenous Estrogen

In order to investigate the role of FSH in Leydig cell function, six men were given four daily injections of HCG (4,000 IU) while receiving oral ethinyl estradiol. The peak testosterone levels in these subjects were contrasted to the results obtained in seven men who received HCG without additional exogenous steroid treatment. Urinary and plasma FSH was suppressed to 26% and 50%, respectively, of basal values by the estrogen treatment. Peak plasma testosterone determinations following HCG did not differ in the two groups of subjects. Additionally, an early pubertal boy had a normal HCG-induced testosterone rise while his urinary FSH was suppressed by estradiol to lower than prepubertal levels. The data indicate the short-term FSH suppression does not alter testicular responsivity to short-term HCG administration. A role for FSH in Leydig cell testosterone production in men has yet to be demonstrated.

PERIPHERAL RESISTANCE TO THYROXINE: A CAUSE OF SHORT STATURE IN A BOY WITHOUT GOITRE

A euthyroid pubertal boy was investigated for short stature and was found to have an elevated serum thyroxine and delayed bone age. In spite of high thyroxine levels, there were no clinical signs of hyperthyroidism and kinetic studies revealed a normal rate of thyroxine metabolism. Plasma TSH levels were elevated but there was no goitre. Administration of up to 900 mug of thyroxine or 225 mug of triiodothyronine led to minimal changes in urinary hydroxyproline excretion, pulse rate and body weight. These observations indicate that this boy has a target organ insensitivity to thyroid hormones. When compared with other patients with this disorder, the studies further emphasize that this condition may have a variable clinical presentation. In addition, the extent of the target organ defect may not be evident from routine clinical and laboratory observations. The possible molecular basis of the defect is discussed.

The Response of Pituitary Gonadotropes to Synthetic LRF in Children with Glucocorticoid-Treated Congenital Adrenal Hyperplasia: Lack of Effect of Intrauterine and Neonatal Androgen Excess

Previous studies have demonstrated that the secretory reserve of the pituitary gland during childhood and adolescence is characterized by an age-related increase in LH secretion and a sex dichotomy of FSH secretion evoked by LRF. To determine if prenatal and neonatal androgen excess alters hypothalamic-pituitary-gonadal function, as in the neonatally androgenized rodent, we assessed pituitary sensitivity to 100 mug synthetic LRF in 9 girls and 2 boys with glucorticoid-treated congenital virilizing adrenal hyperplasia (CAH). In the 7 prepubertal girls with CAH, plasma LH following LRF rose to 2.0 plus or minus 0.4 (SE) ng/ml (LER 960) and did not differ from normal prepubertal children (1.7 plus or minus 0.1) and was lower (P less than 0.002) than in normal pubertal children (4.9 plus or minus 0.3). The 2 pubertal girls had LH rises in the pubertal range. In the 2 boys with CAH, the one with the more advanced bone age, 11-6/12 yr, developed true precocious puberty following initiation of cortisone treatment and had a pubertal LRF-evoked LH release on 3 occasions; the more immature boy, bone age 10, had a prepubertal LH rise. In the 7 prepubertal girls with CAH, plasma FSH rose to 8.1 plus or minus 1.6 (SE) ng/ml (LER 869), which did not differ from normal prepubertal girls (5.3 plus or minus 1.9), but was significantly (P less than 0.001) greater than in normal prepubertal boys (2.9 plus or minus 0.4). In these girls with CAH, basal plasma T (27.4 plus or minus 4.0 (SE) ng/dl) and 17-OHP (2703 plus or minus 1143 (SE) ng/dl) were greater than in prepubertal children, but plasma E1 and E2 were in the normal range. The pubertal boy had plasma T, E1, and E2 levels appropriate for his degree of sexual maturation. The results suggest: (1) age-related LH secretion evoked by LRF in glucocorticoid-treated CAH is appropriate for skeletal maturation; (2) the sex dichotomy of FSH secretion following LRF is preserved in CAH despite intrauterine and variable postnatal exposure to excess androgen and continuing slightly elevated plasma T during childhood; and (3) precocious puberty may follow initiation of cortisone treatment in a child with CAH whose bone age and secretory reserve of pituitary gonadotropins are in the pubertal range.