-
Annals of Pediatric Endocrinology &... Sep 2022Congenital hypogonadotropic hypogonadism (CHH) is characterized by complete or partial failure of pubertal development because of inadequate secretion of gonadotropic...
Congenital hypogonadotropic hypogonadism (CHH) is characterized by complete or partial failure of pubertal development because of inadequate secretion of gonadotropic hormones. CHH consists of hypogonadotropic hypogonadism with anosmia or hyposmia, Kallmann syndrome, and the normosmic variation normosmic idiopathic hypogonadotropic hypogonadism. CHH is one of the few treatable diseases of male infertility, although men with primary testicular dysfunction have irreversibly diminished spermatogenic capacity. The approach to CHH treatment is determined by goals such as developing virilization or inducing fertility. This review focuses on the current knowledge of therapeutic modalities for inducing puberty and fertility in men with CHH.
PubMed: 36203268
DOI: 10.6065/apem.2244208.104 -
Journal of Endocrinological... Jan 2009Children with perinatal HIV infection may present with clinical features of endocrine dysfunction such as growth failure and pubertal delay. Pediatric care providers and... (Review)
Review
Children with perinatal HIV infection may present with clinical features of endocrine dysfunction such as growth failure and pubertal delay. Pediatric care providers and pediatric endocrinologists should implement appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in these children. Growth and pubertal delay can be exacerbated by a variety of treatable infectious, endocrine, nutritional, and immunological disorders. Timely diagnosis and appropriate treatment of these conditions may lead to improvement or even normalization of growth and puberty. HIV-infected children with advanced disease should undergo periodic growth evaluation, including GH levels, IGF-I, IGF binding protein 3 and androgens, in order to identify subclinical endocrine dysfunction. However, little is known about the association between HIV infection and endocrine dysfunction in children. Highly active antiretroviral therapy may also be associated with endocrine dysfunction with consequences on growth and puberty. Growth retardation and pubertal delay are always seen in children with advanced HIV infection and are often related to the proinflammatory milieu found in advanced AIDS. Growth and pubertal impairment are markers of advanced disease and require proper evaluation. A dysregulation of the hypothalamic-pituitary axis, toxic or allergic drug reactions may play a role in growth and pubertal delay of HIV-infected children. These dysfunctions require careful monitoring, in order to assess metabolic alterations that may be important in regulation of growth among HIV infected children. Better understanding of the mechanisms leading to impairment of growth and puberty in children with perinatal HIV-1 infection might lead to appropriate treatment when required.
Topics: Abdominal Fat; Anti-HIV Agents; Child; Child Development; Female; Growth Disorders; Growth Hormone; Growth Hormone-Releasing Hormone; HIV Infections; Humans; Hypothalamo-Hypophyseal System; Male; Puberty; Puberty, Delayed
PubMed: 19337023
DOI: 10.1007/BF03345686 -
Frontiers in Endocrinology 2023Impaired testosterone secretion is a frequent following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical...
INTRODUCTION
Impaired testosterone secretion is a frequent following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.
METHODS
Monocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 years after HSCT and showing, upon enrollment, clinical and biochemical signs consistent with pubertal onset and progression were included. Clinical and biochemical data collected every 6-12 months were recorded.
RESULTS
Of 130 patients enrolled, 56% were prepubertal, while 44% were peri-/postpubertal upon HSCT. Overall, 44% showed spontaneous progression into puberty and normal gonadal profile, while the remaining experienced pubertal arrest (1%), isolated increase of FSH (19%), compensated (23%) or overt (13%) hypergonadotropic hypogonadism. Post-pubertal testicular volume (TV) was statistically smaller among patients still pre-pubertal upon HSCT ( 0.049), whereas no differences were recorded in adult testosterone levels. LH and testosterone levels showed a specular trend between 20 and 30 years, as a progressive decrease in sexual steroids was associated with a compensatory increase of the luteinizing hormone. A variable degree of gonadal dysfunction was reported in 85%, 51%, 32% and 0% of patients following total body irradiation- (TBI), busulfan-, cyclophosphamide- and treosulfan-based regimens, respectively. TBI and busulfan cohorts were associated with the lowest probability of gonadal event-free course (<0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan ( 0.024). Chemo-only regimens were associated with statistically larger TV (0.001), higher testosterone ( 0.008) and lower gonadotropin levels (0.001) than TBI. Accordingly, the latter was associated with a 2-fold increase in the risk of gonadal failure compared to busulfan (OR 2.34, CI 1.08-8.40), whereas being pre-pubertal upon HSCT was associated with a reduced risk (OR 0.15, CI 0.08-0.30).
CONCLUSIONS
a) patients pre-pubertal upon HSCT showed a reduced risk of testicular endocrine dysfunction, despite smaller adult TV; b) patients showed downwards trend in testosterone levels after full pubertal attainment, despite a compensatory increase in LH; c) treosulfan was associated to a statistically lower occurrence of hypogonadism than busulfan, with a trend towards larger TV, higher testosterone levels and lower gonadotropins.
Topics: Adult; Child; Humans; Male; Busulfan; Leydig Cells; Retrospective Studies; Hypogonadism; Hematopoietic Stem Cell Transplantation; Testosterone
PubMed: 38152128
DOI: 10.3389/fendo.2023.1292683 -
Best Practice & Research. Clinical... Mar 2002Chemotherapy and irradiation to the hypothalamic-pituitary-gonadal axis given for childhood cancer carry with them a risk of endocrine late effects. These treatment... (Review)
Review
Chemotherapy and irradiation to the hypothalamic-pituitary-gonadal axis given for childhood cancer carry with them a risk of endocrine late effects. These treatment modalities are part of the treatment of common oncological diseases in childhood such as acute lymphoblastic leukaemia, brain tumours, Hodgkins lymphoma and solid tumours outside the central nervous system. Cranial irradiation of a prepubertal child can induce early or even precocious puberty, particularly in girls. Hypogonadotrophic hypogonadism may develop at a later stage. Irradiation of the gonads, as e.g. part of total body irradiation before bone marrow transplantation, will most likely cause gonadal failure and late, incomplete or absent puberty in girls. Many boys will experience a normal pubertal development except for small testes. Alkylating agents given for a variety of childhood cancers, are gonadotoxic. After high doses of these drugs, girls are at great risk of developing ovarian failure, whereas boys will usually go through puberty normally. Many children receive a combination of several treatment modalities, which complicates the prediction of pubertal development. Control and management of children with cancer at risk of having a disturbance of puberty is difficult and requires detailed knowledge of endocrinology as well as oncology. This chapter reviews the common treatments for the most frequent childhood cancers, the known effects of the therapy on pubertal development and provides outlines of control and management.
Topics: Adolescent; Antineoplastic Agents; Bone Marrow Transplantation; Child; Female; Humans; Male; Neoplasms; Puberty; Puberty, Delayed; Radiotherapy
PubMed: 11987901
DOI: 10.1053/beem.2002.0183 -
Journal of Pediatric Surgery Jun 2022Pediatric intestinal failure (PIF) affects nutrition, metabolism, and endocrine development, but its downstream impact on puberty is unknown.
BACKGROUND
Pediatric intestinal failure (PIF) affects nutrition, metabolism, and endocrine development, but its downstream impact on puberty is unknown.
METHODS
A retrospective review was performed of patients age >8 years with PIF managed at an intestinal rehabilitation program. Outcomes of interest were peak height velocity (PHV), age at PHV, and age at pubertal onset (Tanner stage 2). Outcomes were stratified by sex and compared to established norms.
RESULTS
Of 110 patients with PIF, 54.5% were male. Compared to the CDC 50th percentile, PHV in PIF patients was similar for females (8.09±2.36 vs. 7.37 cm/yr;p = 0.23) but significantly higher for males (9.27±2.56 vs. 7.91 cm/yr;p = 0.038). Age at PHV in PIF patients was significantly younger for both males (12.31±2.14 vs. 13.38 years;p = 0.049) and females (10.70±1.06 vs. 11.71 years;p = 0.001). PIF patients reached pubertal onset earlier than published norms; this was significant for males (12.41±1.80 vs. 13.44 years;p = 0.014), but not for females (10.45±1.81 vs. -11.15 years;p = 0.13). The mean height-for-age Z-score was -1.2, with 20% of patients having a Z-score less than -2.
CONCLUSIONS
Pubertal onset and growth are neither delayed nor diminished in patients with PIF. The high incidence of short stature, however, highlights the importance of optimizing prepubertal linear growth to attain full height potential.
TYPE OF STUDY
Prognosis study (Retrospective cohort study).
Topics: Body Height; Child; Female; Humans; Intestinal Failure; Male; Puberty; Retrospective Studies
PubMed: 35287963
DOI: 10.1016/j.jpedsurg.2022.01.057 -
Frontiers in Endocrinology 2022Puberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human...
BACKGROUND
Puberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex Growth Forum Database (Eu-IGFD) Registry (NCT00903110).
METHODS
The Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019.
RESULTS
This analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3-13.0) cm/year in boys and 6.8 (1.3-9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1.
CONCLUSION
Children and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.
Topics: Adolescent; Child; Clinical Studies as Topic; Female; Growth Disorders; Hearing Loss, Sensorineural; Humans; Insulin-Like Growth Factor I; Male; Recombinant Proteins; Registries
PubMed: 35250870
DOI: 10.3389/fendo.2022.812568 -
Journal of Pediatric Endocrinology &... Mar 2003Cystic fibrosis (CF) is an autosomal recessive disease characterized by respiratory and intestinal insufficiencies. It has been reported in the literature that patients... (Review)
Review
Cystic fibrosis (CF) is an autosomal recessive disease characterized by respiratory and intestinal insufficiencies. It has been reported in the literature that patients with CF show delayed growth and puberty and girls with CF achieve menarche at older age than normal females. Infertility, in both sexes, and menstrual dysfunction, in girls, are common in patients with CF. Previous data suggest that the degree of failure of growth and development is correlated with malnutrition and severity of progressing pulmonary disease. Despite improved nutrition and intensive treatment, patients with CF have delayed puberty and growth pubertal spurt. This maturational lag is accompanied by a significant delay in attaining pubertal levels of insulin-like growth factor-I (IGF-I), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex steroid hormones.
Topics: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Fatty Acids; Gonads; Humans; Hypothalamo-Hypophyseal System; Insulin; Insulin Secretion; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Nutrition Disorders; Puberty; Puberty, Delayed
PubMed: 12729402
DOI: No ID Found -
Lancet (London, England)
Topics: Adolescent; Adrenal Insufficiency; Child; Humans; Male; Puberty; Testosterone Congeners
PubMed: 74768
DOI: No ID Found -
Biochimica Et Biophysica Acta Dec 2012The purpose of this review is to summarize science-based new treatments for human reproductive failure and future developments. (Review)
Review
PURPOSE
The purpose of this review is to summarize science-based new treatments for human reproductive failure and future developments.
RESULTS
First will be discussed popular but erroneous myths of current non-science based treatments. Then will be discussed new treatments and their scientific base, including ovary and egg freezing, and transplantation to preserve fertility in young women undergoing gonadotoxic chemotherapy and radiation for cancer; new perspectives on human epididymal sperm maturation based on a comparison between ICSI (intracytoplasmic sperm injection) with testis sperm versus epididymal sperm; simplifying IVF and reducing cost by more intelligent and milder ovarian stimulation; improving pregnancy rate in older women; searching the genome to find genes which control spermatogenesis and whose deletion or mutation causes spermatogenic failure; and human spermatogenic stem cell culture to treat azoospermia, and to preserve fertility in pre-pubertal boys undergoing cancer treatment.
CONCLUSION
With stem cell biology and molecular understanding of reproductive failure, new therapies for previously untreatable infertility are currently on the near horizon. Conversely our clinical results with new therapeutic approaches are adding to our understanding of the basic science of reproduction. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.
Topics: Female; Humans; Infertility, Female; Infertility, Male; Male; Pregnancy; Reproduction; Reproductive Techniques, Assisted
PubMed: 23046814
DOI: 10.1016/j.bbadis.2012.10.004 -
Children (Basel, Switzerland) Aug 2014In the face of excellent survival rates for pediatric and adolescent cancer, preserving the opportunity to have biological children is an important component of long... (Review)
Review
In the face of excellent survival rates for pediatric and adolescent cancer, preserving the opportunity to have biological children is an important component of long term quality of life. Yet, modern chemotherapeutic regimens continue to pose a threat to fertility. The only fertility preservation methods available to pre-pubertal children of both genders is cryopreservation of gonadal tissue, a highly experimental intervention, or shielding/re-location of reproductive tissue in the setting of radiation. These techniques are available in the post pubertal population as well, but post pubertal patients also have the option for cryopreservation of gametes, a process that is much simpler in males than females. For this reason, prior to the initiation of therapy, sperm banking should be considered standard of care for males, while consideration of embryo or oocyte cryopreservation should be limited to those females at risk of developing ovarian failure. Attention to reproductive health and fertility preservation should continue after the completion of therapy. Establishing programs that streamline access to current fertility preservation techniques will assist in ensuring that all eligible patients can avail themselves of current options.
PubMed: 27417474
DOI: 10.3390/children1020166