Precocious Sexual Development Research Articles

Endocrine Effect of Some Mycotoxins on Humans: A Clinical Review of the Ways to Mitigate the Action of Mycotoxins.

Fungi such as Aspergillus spp. and Fusarium spp., which are commonly found in the environment, pose a serious global health problem. This study aims to present the results of epidemiological studies, including clinical cases, on the relationship between human exposure to some mycotoxins, especially zearalenone and aflatoxin, and the occurrence of reproductive disorders. In addition, examples of methods to reduce human exposure to mycotoxins are presented. In March 2023, various databases (PubMed, Google Scholar, EMBASE and Web of Science) were systematically searched using Google Chrome to identify studies evaluating the association between exposure to mycotoxins and the occurrence of complications related to impaired fertility or cancer incidence. The analysed data indicate that exposure to the evaluated mycotoxins is widespread and correlates strongly with precocious puberty, reduced fertility and increased cancer incidence in women and men worldwide. There is evidence to suggest that exposure to the Aspergillus mycotoxin aflatoxin (AF) during pregnancy can impair intrauterine foetal growth, promote neonatal jaundice and cause perinatal death and preterm birth. In contrast, exposure to the Fusarium mycotoxin zearalenone (ZEA) leads to precocious sexual development, infertility, the development of malformations and the development of breast cancer. Unfortunately, the development of methods (biological, chemical or physical) to completely eliminate exposure to mycotoxins has limited practical application. The threat to human health from mycotoxins is real and further research is needed to improve our knowledge and specific public health interventions.

OR08-6 A Novel Nonsense Mutation in Delta-Like Non-Canonical Notch Ligand 1 Gene (DLK1) in a French Girl With Central Precocious Puberty

Abstract Background Central precocious puberty (CPP) results from early reactivation of the hypothalamic-pituitary-gonadal (HPG) axis. Four monogenic causes of CPP have been described (KISS, KISS1R MKRN3 and DLK1). Rare loss-of-function mutations of DLK1, a maternally imprinted gene located on chromosome 14q32.2, were identified in families with CPP. Both inherited or de novo DLK1 mutations were described in these affected families. Objective To investigate genetic abnormalities in the DLK1 in a French cohort of patients with idiopathic CPP. Patients: Genomic DNA was obtained from 122 patients (99 girls and 23 boys) with sporadic or familial CPP. Automatic sequencing of the coding regions of DLK1 gene (5 exons, using Sanger method) was performed in all cases, including 91 familial and 31 sporadic cases. Results A pathogenic heterozygous variant in the DLK1 gene (c.372C>A p.Cys124Ter (rs749564412) was identified in a girl with sporadic CPP associated with overweight. This nonsense mutation was considered rare (gnomAD total population 1/251,082) and it was located in the third EGF-like repeat domain in the extracellular region. The affected girl had progressive breast development at 4.5 years and accelerated growth velocity. She had breast development Tanner stage 4 at 5.5 years and bone age (BA) was 6 yr. Her height was 114.5 cm and BMI 18.16 (BMI Z-score = 2.48). Basal LH and FSH was 0.6 IU/L and 5.7 IU/L, respectively. GnRH-stimulated LH and FSH peaks were 14 IU/L and 18 IU/L, respectively, with LH: FSH ratio of 0.77. Other hormonal results were normal (estradiol: 11 pg/mL; ACTH: 11 pg/mL; IGF-1: 235 ng/mL; cortisol: 77 ng/mL). Brain MRI was normal. Pelvic ultrasound revealed uterus length: 49 mm, mucosal thickness of 4 mm, ovaries 20 and 25 mm with follicles less than 10 mm. She was treated with a depot GnRH analog (triptorelin). The DLK1 variant was inherited from her asymptomatic father who had a height of 181 cm. Familial history of CPP history was denied. Conclusion DLK1 loss-of-function are rare genetic cause of familial or sporadic CPP. Novel genetic findings in this factor reinforce its role in the physiopathology of the premature HPG axis reactivation and precocious sexual development in humans. Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.

Преждевременное половое развитие у девочек: возможности лабораторной диагностики

Важность своевременного выявления причин преждевременного полового развития обусловлена прежде всего возможным наличием опухолевого процесса, а также теми состояниями, которые сопровождают ускоренный пубертат. Ключевую роль в диагностике и контроле эффективности лечения преждевременного полового развития играют лабораторные методы исследования.

Identification of differentially expressed genes associated with precocious puberty by suppression subtractive hybridization in goat pituitary tissues

The aim of this study was to identify genes related to precocious puberty expressed in the pituitary of goats at different growth stages by suppression subtractive hybridization (SSH). The pituitary glands from Jining Gray (JG) goats (early puberty) and Liaoning Cashmere (LC) goats (late puberty) at 30, 90, and 180 days were used in this study. To identify differentially expressed genes (DEGs) in the pituitary glands, mRNA was extracted from these tissues, and SSH libraries were constructed and divided into the following groups: juvenile group (30-JG vs. 30-LC, API), puberty group (90-JG vs. 180-LC, BPI), and control group (90-JG vs. 90-LC, EPI). A total of 60, 49, and 58 DEGs were annotated by 222 Gene Ontology (GO) terms and 75 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of the DEGs were significantly enriched in GO terms related to ‘structural constituent of ribosome’, ‘translation’ and ‘GTP binding’, and numerous DEGs were also significantly enriched in KEGG terms related to the Jak-STAT signaling and oocyte meiosis pathways. Candidate genes associated with precocious puberty and sexual development were screened from the SSH libraries. These genes were analyzed to determine if they were expressed in the pituitary tissues of the goats at different growth stages and to identify genes that may influence the hypothalamic-pituitary-gonadal (HPG) axis. In this study, we found precocious puberty-related genes (such as PRLP0, EIF5A, and YWHAH) that may be interesting from an evolutionary perspective and that could be investigated for use in future goat breeding programs. Our results provide a valuable dataset that will facilitate further research into the reproductive biology of goats.

A high plane of nutrition during early life alters the hypothalamic transcriptome of heifer calves

The aim was to examine the effect of rapid body weight gain during early calfhood consistent with earlier sexual development on the transcriptional profile of the hypothalamus. Angus X Holstein–Friesian heifer calves (19 ± 5 days of age) were offered a high (HI, n = 14) or moderate (MOD, n = 15) plane of nutrition from 3 to 21 weeks of age to achieve a growth rate of 1.2 kg/d and 0.5 kg/d, respectively. Following euthanasia at 21 weeks, the arcuate nucleus (ARC) region was separated from the remainder of the hypothalamus and both were subjected to RNA-Seq. HI calves exhibited altered expression of 80 and 39 transcripts in the ARC and the remaining hypothalamus, respectively (P < 0.05) including downregulation of AGRP and NPY and upregulation of POMC, previously implicated in precocious sexual development. Stress-signaling pathways were amongst the most highly dysregulated. Organ morphology, reproductive system development and function, and developmental disorder were amongst the networks derived from differentially expressed genes (DEGs) in the ARC. Gene co-expression analysis revealed DEGs within the ARC (POMC, CBLN2, CHGA) and hypothalamus (PENK) as hub genes. In conclusion, enhanced nutrition during early calfhood alters the biochemical regulation of the hypothalamus consistent with advanced sexual development in the prepubertal heifer.

Individual and joint association of adulthood experiences and parental or teacher smoking with adolescent cigarette smoking.

INTRODUCTIONOne limitation of the minimum legal age (MLA) law, the primary strategy for curbing youth smoking, is the rite-of-passage effect. Adulthood experiences and the behavior of surrounding adults help build ‘adult identity’ among adolescents. We examined the individual association of adulthood experience and joint association with significant adults who smoke with adolescent cigarette smoking.METHODSA nationally representative cross-sectional sample of 138542 South Korean adolescents aged 12–18 years (mean: 15 years) from the 2014 and 2015 Korea Youth Risk Behavior Survey was used. Adulthood markers used were tall stature, precocious sexual development, independent living, and job experience. Parents and teachers were considered significant adults. Logistic regression analyses and relative risk due to interaction (RERI) calculations were conducted.RESULTSTall stature (OR=1.19; 95% CI: 1.08–1.31), precocious sexual development (OR=1.51; 95% CI: 1.36–1.69), independent living (OR=1.24; 95% CI: 1.08– 1.43), and job experience (OR=4.38; 95% CI: 4.14–4.64) were associated with cigarette smoking among study participants. Statistically significant additive interactions were found for parental smoking and job experience (RERI=0.41; 95% CI: 0.06–0.76), teacher smoking and precocious development (RERI=0.71; 95% CI: 0.28–1.15), teacher smoking and independent living (RERI=0.68; 95% CI: 0.11–1.24), teacher smoking, and job experience (RERI=2.12; 95% CI: 1.66– 2.58).CONCLUSIONSThe association between adulthood experience and adolescent cigarette smoking suggests the rite-of-passage effect, which may be strengthened by the MLA law. Raising the MLA to an age much higher than the normative age of adulthood initiation is required. Additionally, targeted intervention for adolescents with both adulthood experience and exposure close to adult smoking are required to curb youth smoking.

SUN-LB052 Sexual Precocity in a Male Toddler Caused by Inadvertent Prolonged Exposure to Exogenous Testosterone

Background: Unintentional exposure to cutaneous androgen products leading to virilization has previously been described in children, however, continues to be an overlooked cause of precocious sexual development. Clinical Case: A 16-month-old boy presented for a second opinion consultation regarding sexual precocity. Parents noticed enlargement of his penis and appearance of sparse pubic hair at about 4 months of age, prompting referral to an endocrinologist by 10 months. A comprehensive evaluation was performed. The bone age was advanced at 13-15 months and his total testosterone was 243 ng/dL (normal < 20 ng/dL). An ACTH stimulation test was negative for disorders of steroid biosynthesis. Ultrasound examination showed normal testes and no evidence of adrenal or hepatic masses. A Lupron stimulation test, performed at 14 months of age, showed a peak LH of 1.41 mIU/mL (normal < 5 mIU/mL) and peak total testosterone of 21 ng/dL (reference range ≤ 5 ng/dL). The patient was diagnosed with familial gonadotropin-independent male-limited sexual precocity, a rare condition caused by activating mutations of the LHCGR (luteinizing hormone/choriogonadotropin receptor) gene. Treatment with bicalutamide and anastrozole was prescribed. Owing to parental concern about side effects of the prescribed medications, they did not start the recommended treatment and sought a second opinion. On exam, his length was > 99th percentile for age, stretched penile length 7.5 cm (mean ± standard deviation for this age: 4.82 ± 0.44 cm), mid-shaft diameter 2 cm, and testes 2 mL bilaterally. The scrotum was thin and pendulous and there were a few pubic hairs at the base of the penis. His total testosterone was < 10 ng/dL, LH < 0.1 mIU/mL, and hCG < 0.1 mIU/mL (all normal). Ultrasound of the testes was normal. After the visit, a more thorough history was obtained from the mother. She remembered that the child’s maternal grandfather, who provided direct care to the patient in the first year of life while she attended school, used transdermal testosterone gel daily for treatment of hypogonadism. Since the grandfather’s absence after the patient’s first birthday, the child has not had any further progression of his secondary sex characteristics. On follow-up visit at 17 months of age, patient’s exam was stable. Genetic testing for mutations of the LHCGR gene was negative. Conclusion: Exogenous exposure to transdermal androgens should be kept high on the differential diagnosis for children presenting with evidence of peripheral sexual precocity as it can save patients unnecessary and costly work-up and intervention. Physicians should also be aware of their own anchoring biases, especially when evaluating patients for a second opinion of rare diagnoses. Lastly, adult endocrinologists should be mindful in counseling patients prescribed topical testosterone agents about the risk of cutaneous exposure to female partners and children. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

ХГЧ-секретирующая герминома эпифиза – причина гонадотропин-независимого преждевременного полового развития: описание клинического случая и обзор литературы

ХГЧ-секретирующая герминома эпифиза – причина гонадотропин-независимого преждевременного полового развития: описание клинического случая и обзор литературы

Central Precocious Puberty Caused by a Heterozygous Deletion in the MKRN3 Promoter Region

Context: Loss-of-function mutations in the coding region of MKRN3, a maternally imprinted gene at chromosome 15q11.2, are a common cause of familial central precocious puberty (CPP). Whether MKRN3 alterations in regulatory regions can cause CPP has not been explored to date. We aimed to investigate potential pathogenic variants in the promoter region of MKRN3 in patients with idiopathic CPP. Patients/Methods: A cohort of 110 patients with idiopathic CPP was studied. Family history of precocious sexual development was present in 25%. Mutations in the coding region of MKRN3 were excluded in all patients. Genomic DNA was extracted from peripheral blood leukocytes, and 1,100 nucleotides (nt) of the 5′-regulatory region of MKRN3 were amplified and sequenced. Luciferase assays were performed in GT1–7 cells transiently transfected with plasmids containing mutated and wild-type MKRN3 promoter. Results: We identified a rare heterozygous 4-nt deletion (c.-150_-147delTCAG; –38 to –41 nt upstream to the transcription start site) in the proximal promoter region of MKRN3 in a girl with CPP. In silico analysis predicted that this deletion would lead to the loss of a binding site for a downstream res­ponsive element antagonist modulator (DREAM), a potential transcription factor for MKRN3 and GNRH1 expression. Luciferase assays demonstrated a significant reduction of MKRN3 promoter activity in transfected cells with a c.-150_- 147delTCAG construct plasmid in both homozygous and heterozygous states when compared with cells transfected with the corresponding wild-type MKRN3 promoter region. Conclusion: A rare genetic alteration in the regulatory region of MKRN3 causes CPP.

HCG-secreting hepatoblastoma

We describe a case of precocious sexual development in a 4-year-old boy, which was caused by HCG-secreting hepatoblastoma. The precocious sexual development manifested two months after starting polychemotherapy for hepatoblastoma, which presented as the emergence and rapid progression of pubic hair, low voice, and acceleration of the growth rate and bone age. The size of the testicles remained at the prepubertal level. We, together with oncologists, developed a therapeutic tactics: surgical removal of the tumor after the fourth course of polychemotherapy. Antiandrogenic drugs were not used because of their hepatotoxicity and inefficacy in this clinical situation.

Clinical spectrum of premature sexual developments in a tertiary care center of South India

Background: The clinical spectrum of precocious sexual development and its etiology are varied and we need to know our own data regarding this. The objective of the study was to study the clinical spectrum of premature sexual developments and the usefulness of imaging modalities in understanding the ongoing insult. Methods: Female child of less than 8 years of age and male child of less than 9 years of age with development of secondary sexual characteristics were registered and analyzed. After through clinical examination the children were subjected to investigations, which included radiological and hormonal. Results: Majority of cases 54% (14 cases) had symptoms before 2 years of age. Premature thelarche was seen in 58% and the majority 71% was less than 2 years of age. 17% of the female children with sexual precocity had true precocious puberty. Hypothyroidism as a cause of true precocious puberty is 8%. Heterosexual precocious puberty was seen in 16%. Among male children peripheral cause of isosexual precocious puberty was seen in two cases. Congenital adrenal hyperplasia as a cause of sexual precocity among both sexes was seen in 15%. All four children (100%) with true precocious puberty showed uterine length of > 3.5 cm and 93% of the children with isolated premature thelarche showed a uterine length of < 3.5 cm. Conclusions: Sexual precocity is most common among female children. Isolated premature thelarche is the most common type of sexual precocity. Ultrasound visualized uterine length helps in the differentiation of isosexual precocious puberty and isolated premature.

Medical Resource Use and Costs Related to Central Precocious Puberty: A Retrospective Cohort Study

To evaluate the economic burden of central precocious puberty (CPP) by examining direct health care resource utilization and costs. Administrative claims from the Medstat MarketScan Commercial Claims database were analyzed, and 2 cohorts of children ≤ 12 years of age were identified. The CPP cohort included patients newly diagnosed with precocious sexual development and puberty (International Classification of Diseases, Ninth Revision, Clinical Modification code 259.1x) between January 1, 2004, and June 30, 2006 (date of the initial diagnosis of CPP was designated as the "index date") who used gonadotropin-releasing hormone agonists during the 12 months after diagnosis. Each patient with CPP was matched with 4 control patients without CPP on the basis of age, sex, geographic region, and type of health insurance plan. Resource utilization and costs during the 12 months before and the 12 months after the index date were examined. A total of 172 patients with CPP and 688 control patients were identified after matching. Approximately 62% of patients were 7 to 9 years of age, and 87% were female. The patients with CPP had higher annual health care costs than did the control patients during the 12-month pre-index ($10,968 versus $783; P<.001) and the 12-month post-index ($21,071 versus $849; P<.001) periods, primarily attributable to outpatient and pharmacy costs. For the patients with CPP, annual health care costs increased by $10,103 after diagnosis. On average, annual CPP-related costs were $10,605. Monthly total health care costs for the patients with CPP increased sharply during the first month after diagnosis and remained high throughout the post-index period. In this study, health care resource use and costs among patients with CPP were substantial before and after the initial diagnosis of CPP.

Clinical characters of childhood adrenocortical tumors

Objective To analyze the clinical characters of childhood adrenocortical tumors, and to enhance the knowledge of diagnosis of this disease. Methods A retrospective analysis of clinical characters,laboratory tests,and imaging findings in 31 cases of childhood adrenocortical tumors was carried out. Results 16 cases of adenoma and 15 cases of carcinoma were included. The average age was (4.49±3.51) years old, and 67.7% of the patients were younger than 5 years old. The ratio of male to female was 1.0: 1.4. 12 patients presented only precocious sexual development, 4 patients presented only Cushing syndrome, 10 patients showed sexual precocity combined with Cushing syndrome, and 5 patients did not have any endocrine abnormalities. Raised testosterone level in 92.3% of these patients was the most common finding in laboratory tests. Only 12.5% of ultrasound images and 20.8% of CT images were consistent with pathologic diagnosis. Conclusions The clinical manifestations of adrenocortical tumors in childhood are precocious sexual development, Cushing's syndrome, or nonfunctional. The common laboratory findings are elevation of sex hormone and disorder of cortisol circadian rhythm. Precocious sexual development and elevation of androgens are more common in childhood adrenocortical tumor than those in adults. Imaging usually cannot give proper diagnosis. Final diagnosis should be established by clinical features, laboratory tests, imaging, and pathologic results. Key words: Adrenal glands; Cortical tumors; Childhood

Clinical and genetic heterogeneity of congenital adrenal hypoplasia due to NR0B1 gene mutations

X-linked adrenal hypoplasia congenita (AHC) is a rare disorder caused by mutations or complete deletion of the NR0B1 gene that encodes the DAX-1 protein, an orphan member of the nuclear receptor superfamily. AHC is characterized by adrenal insufficiency in infancy and early childhood. Later, hypogonadotropic hypogonadism (HH) manifests as pubertal failure. We evaluated the clinical, endocrine and molecular characteristics of 12 AHC patients from 5 families diagnosed between 1984 and 2007 in Israel. Most of the boys (10/12) presented with signs of adrenal insufficiency such as salt wasting and failure to thrive during the neonatal period. Aldosterone deficiency usually preceded cortisol deficiency requiring early mineralocorticoid therapy. Serum cortisol levels in the first weeks of life varied from very low to high levels (<2.76 to >1776 nmol/l). Five boys showed signs of precocious sexual development during infancy and childhood, including enlargement of the penis and testes. In four patients the initial diagnoses were erroneous. Molecular analysis of the NR0B1 gene identified point mutations in six patients including a novel splice site mutation in one patient and his family (IVS1-1G-->C). Contiguous gene deletion was found in six patients from two families who manifested impaired mental development. In X-linked AHC caused by different molecular defects in NR0B1 gene, the clinical spectrum of the disease is quite variable and precocious sexual development is a prominent feature. Genetic testing is indicated in boys presenting with salt-wasting with or without cortisol deficiency if congenital adrenal hyperplasia has been ruled out.

COMMENTARY: Transfer of Topical Testosterone Preparations to Children or Spouses

T gel (1%) products have been approved by government regulation agencies for use in men with testosterone deficiency syndrome since 2000 and 2003 [1,2]. Efficacy studies have shown topical testosterone preparations to improve such outcomes as sexual function, libido, mood, muscle mass, muscle strength, and energy [3–7]. Topical 1% testosterone gel is also associated with eugonadal testosterone values, unlike the peaks and troughs related to intramuscular testosterone enanthate or cypionate injections [1,2]. Topical 1% testosterone gel is further associated with fewer reactions at the application site compared to testosterone patch therapy [1,2]. As a result of the benefits of topical testosterone gel over intramuscular and patch testosterone alternatives, topical gel products have become a widely utilized therapeutic option for men with testosterone deficiency syndrome, especially those with hypogonadism and sexual health concerns. On May 6, 2009, however, the Food and Drug Administration (FDA) notified health care professionals that prescription testosterone gel products will be required to include a boxed warning on product labels after the FDA received a number of reports of adverse events in children and spouses. To date, reports concerning drug transfer to children and spouses have been primarily published in endocrinology and pediatric journals, with only two reports in The Journal of Sexual Medicine published in 2005 [8,9]. Patients with sexual health complaints frequently have low levels of testosterone, and as a result, sexual medicine health care providers are large prescribers of topical testosterone replacement products [10–16], including approved testosterone gels and non-approved testosterone creams, ointments, and sprays. It is important that sexual medicine health care providers be familiar with the issues of hyperandrogenism in women and virilization in young children secondary to drug transfer from topical testosterone preparations. The case of a 2-year-old boy who came into skin contact with testosterone gel presents some of the negative implications associated with exposure to topical testosterone [17]. The boy was taken to his pediatrician because of pubic hair growth. It was discovered that this pubic hair growth was not accompanied by testicular enlargement, acne, or body odor. Further investigation revealed that the pubic hair growth had been present for 4 months, and neither parent had a history of precocious sexual development. However, it was discovered that the child’s father had been using testosterone cream for the previous 12 months to treat his testosterone deficiency syndrome. The child’s father applied the cream to his forearms nightly, but did not usually have contact with his son until the following morning. When the father ceased use of the testosterone cream, the boy demonstrated no progression of puberty [17]. Similar results were found among other exposed children. An 18-month-old girl was taken to her doctor following pubic hair growth and clitoromegaly [18]. Her stepfather applied testosterone cream to his thighs and then allowed the child to sit on his lap. When the girl was examined, it was revealed that her bone age was 3 years, while her chronological age was 18 months. Her serum testosterone level wasmeasured at 390 ng/dLwhen the desired measurement for children is less than 2649

Undetectable levels of serum FSH immunoactivity and bioactivity in girls with sexual precocity due to ovarian cysts.

Clinical presentation and endocrine investigations in five girls with precocious sexual development due to ovarian cysts are presented. These girls had pubertal oestradiol and suppressed gonadotrophin responsiveness to LHRH stimulation. FSH bioactivity as measured by the rat aromatase assay was undetectable in basal and LHRH-stimulated serum samples but our results cannot exclude the possibility of the presence of a species-specific follicle stimulating factor in these patients. IM injection of depot medroxyprogesterone acetate controlled pubertal development in two children.

Larval Hysterothylacium sp. (Nematoda, Anisakidae) and trematode metacercariae from the amphipod Paracorophium excavatum (Corphiidae) in New Zealand

AbstractPreviously undescribed fourth-stage larvae of anisakid nematodes were found in the haemocoel of the amphipod Paracorophium excavatum (Thomson, 1884) (Corophiidae) in New Zealand. Morphological examination by light microscopy showed that the worms belonged to a species of Hysterothylacium Ward et Magath, 1917, based on several characters including the presence of interlabia, the location of the excretory pore posterior to the nerve ring, and the characteristics of the intestinal caecum and ventricular appendix. Interestingly, several male specimens showed precocious sexual development. This is the first record of fourth larval stage and precocious adult male specimens of Hysterothylacium in an invertebrate host, as well as the first record of anisakid larvae in New Zealand crustaceans. In addition, metacercariae of two trematode species, Coitocaecum parvum and Microphallus sp., are recorded for the first time from the amphipod P. excavatum.

Klinefelter syndrome and mediastinal germ cell tumors

Precocious puberty is not a typical manifestation of patients with Klinefelter syndrome (KS). However, there is an increased incidence of mediastinal germ cell tumors (M-GCT) in KS, whereas the discussion of a generally higher tumor risk in this condition is still controversial. A rare subgroup of KS patients consists of prepubertal children with precocious puberty due to human chorionic gonadotropin (hCG)-producing M-GCTs. We present clinical data on a boy with KS and sexual precocity, and summarize the published data on 12 boys with KS out of 54 cases of KS and M-GCT. an 8.5-year-old boy presented with signs of precocious puberty. Laboratory analyses (suppressed gonadotropins, elevated testosterone) and thoracic CT demonstrated a beta-human chorionic gonadotropin (beta-hCG) and alpha(1)-feto protein (alpha-FP) secreting mediastinal tumor. Histological analysis showed a mixed germ cell tumor comprising choriocarcinoma (CH), embryonal carcinoma (EC), mature teratoma (MT), and yolk sac tumor (YS). He was successfully treated by surgery and adjuvant chemotherapy. Epianalysis of published cases: all KS patients (n = 12), age 4-9 years, presented with precocious sexual development (PP), whereas the older ones showed thorax-associated symptoms, mainly chest pain, dyspnea, and cough. The histological distribution was also age-dependent with mixed germ cell tumors predominantly in younger patients. Thus, M-GCTs are strongly associated with precocious puberty in young boys with KS. Therefore, a karyotype analysis should be included in the clinical work-up of boys with precocious puberty and M-GCT. There is still no convincing explanation for the association of M-GCTs and KS.

Precocious sexual development due to an interstitial-cell tumour of the testis.

Precocious sexual development due to an interstitial-cell tumour of the testis.

Genetic covariation in production traits of sub-adult black bream Acanthopagrus butcheri after grow-out

Predicting the suitability and reliability of traits associated with juvenile growth as indirect selection criteria for choosing future broodstock requires accurate and repeatable estimates of genetic (co)variation for growth traits at different ages. We compared juvenile wet weight of black bream Acanthopagrus butcheri (Munro) at 6 months of age with wet weight, dressed weight, fillet yield and gonad weight in tagged individuals at 18 months of age, following 12 months of farm grow-out. Fish survival and tag retention was high, and there was significant among-family variation for all traits. The phenotypic correlations among wet weight, dressed weight and fillet yield at 18 months of age were very high (0.93-0.97) and similar to their genetic correlations (0.96). Importantly, the phenotypic correlations between wet weight at 6 months and wet weight, dressed weight and fillet yield at 18 months were high (0.63-0.65), and so too were their genetic correlations (0.66-0.73), indicating the potential for using wet weight in the hatchery as a selection criterion for improved weight and meat yield of fish at harvest. Gonad weight shared little or no phenotypic or genetic correlation with these other traits, suggesting that selection for faster growing fish will not affect fecundity or sexual maturation rate. It appears, however, that cultured black bream do become sexually mature more rapidly than wild fish, as 78% of all fish harvested in this study had developing or mature gonads, whereas less than 50% of fish in wild populations are reproductively mature by the same age. Precocious sexual development may lead to uncontrolled spawning in grow-out ponds and a potential loss of selection gains.