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Pediatric Endocrinology Reviews (PER) is the most respected international peer reviewed journal in Pediatric Diabetes, Nutrition Metabolism and Genetics. Hypothyriodism, Hyperthyriodism, Glycemic Management for Children with Diabetes Glucose Monitoring Adrenal Insufficiency Turner Syndrome Late Adolescence Klinefelter Syndrome Children with Short Stature and Growth Failure: Heightism Type 1 Diabetes in Children Growth Hormone Treatment for GHD Insulin-like Growth Factor-I Growth Hormone Deficiency SGA Children with Short Stature Receiving GH Treatment Hypothalamic Obesity Adolescent Gynecomastia Hematospermia in Adolescents Gain-of-Function CDKN1C Mutations Craniopharyngioma Succinate-Dehydrogenase Deficient Paragangliomas/Pheochromocytomas Adrenal Steroidogenesis: Impact on Gonadal Function Focal Congenital Hyperinsulinism (CHI)  Longevity Hormone Klotho Pediatric Congenital Hypothyroid Lysosomal Storage Diseases Juvenile NCL (CLN3 Disease) GM1 and GM2 Gangliosidoses Types A and B Niemann-Pick Disease CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis) Krabbe Disease Fucosidosis Nuclear Factor Kappa B (NF-κB) in Growth Plate Chondrogenesis Persistent Müllerian Duct Syndrome LHX4 Gene Alterations Stunted Growth 45,X/46,XY Gonadal Dysgenesis Thyroid Hemiagenesis Nutrimetabolomics and Adipocitokines Chromosomal Microarray Analysis (CMA) Chromosomal microarray, Copy Number Variant (CNV), Prenatal, Amniocentesis, Comparative genomic hybridization, SNP array, Diagnosis, Clinical Abreviations: aCGH – array-based comparative genomic hybridization, ASD – autism spectrum disorder, BAC – bacterial artificial chromosome, CHD – congenital heart disease, CMA – chromosomal microarray analysis, CNV – copy number variant, CVS – chorionic villus sampling, DD – developmental delay, DNA – deoxyribonucleic acid, FISH – fluorescent in situ hybridization, GABA - gammaaminobutyric acid, ID – intellectual disability, LOH – loss of heterozygosity, NGS – next generation sequencing, NIPT – noninvasive prenatal testing, NOS – not otherwise specified, PGD - preimplantation genetic diagnosis, SNP – single nucleotide polymorphism, VUS – variant of unclear clinical significance Central precocious puberty, Traumatic brain injury, Pathophysiology Nephrolithiasis, Nephrocalcinosis, Hypercalciuria, Hyperoxaluria, Hypouricemia, Cystinuria, Genetics 

Vol. 11 Supplement 2

February 2014

 

Embryology and Physiology of Testicular Development and Descent

Helena E Virtanen MD PhD, Jorma Toppari MD PhD, Professor

Abstract

Sexual differentiation starts with the development of bipotential gonads that further differentiate into testes or ovaries. The fetal testis secretes hormones that guide the differentiation of internal and external sex organs, whereas the fetal ovary remains rather inactive hormonally. Defects in gonadal differentiation or hormone secretion and action result in disorders of sex development (DSD). Testicular descent is a continuum that has often been described to occur in two main phases: the transabdominal phase and the inguinoscrotal phase. The first phase is according to animal studies dependent on Leydig cell-derived insulin-like peptide 3 (INSL3) that induces male-like development of the gubernaculum. This phase is rarely disrupted in man. The inguinoscrotal phase is dependent on androgens, also secreted by Leydig cells.

Ref: Ped Endocrinol. Rev. 2014:11(Suppl 2): 206-213

Key Words: testis, cryptorchidism, Sertoli cell, Leydig cell, germ cell

 

Diagnosis and Evaluation of Hypogonadism

Mark J McCabe PhD, Rodrigo E Bancalari MD, Mehul T Dattani MD

Abstract

Hypogonadism is defined as defects in gonadal response to gonadotropins or sex hormone biosynthesis. Clinical evaluation and diagnosis of patients is challenging, particularly before puberty. Basal determinations of the gonadotropins luteinizing hormone, follicle-stimulating hormone, the gonadal sex steroids testosterone and/or estrogen and markers of gonadal function including inhibin B and anti-Müllerian hormone are useful, but only at specific ages, thus necessitating combined hormonal tests with meticulous physical examination. GnRH testing can be useful, and may be used in combination with hCG testing to discriminate between isolated hypogonadotropic hypogonadism and constitutional delay of growth and puberty. Urine steroid profiles may be helpful in the diagnosis of androgen biosynthetic defects. Also increasingly important is genotypic screening for genetic or chromosomal abnormalities, together with detailed family and medical histories including antecedent substance abuse, chronic disease, and exposure to chemotherapy or radiotherapy. This chapter explores the diagnosis and evaluation of patients with hypogonadism and reviews the genetic/chromosomal factors involved in the condition.

Ref: Ped Endocrinol. Rev. 2014:11(Suppl 2): 214-229

Keywords: Primary/secondary hypogonadism, Kallmann syndrome, Klinefelter syndrome, genetics, sexual development and puberty

 

Treatment of Hypogonadism in Males

Sara Watson, MD1, John S. Fuqua, MD1, Peter A. Lee, MD, PhD2

Abstract

The treatment of adolescent males with hypogonadism using testosterone is dependent on the underlying diagnosis as well as the patient’s and family’s preferences. Those with testicular failure, always a pathologic condition, begin lifelong therapy, while short-term therapy is often begun for those who have a delayed puberty. There is a wide variety of testosterone formulations available, with differences in adverse events sometimes associated with the method of administration. The goals of treatment involve stimulating physical puberty, including achievement of virilization, a normal muscle mass and bone mineral density for age, and improvement in psychosocial wellbeing. While androgen therapy results in physical changes of puberty, the potential for fertility must be considered for those with permanent gonadotropin deficiency. In this population, therapy with gonadotropins or gonadotropin releasing hormone may be effective. For those with testicular failure, fertility may be possible but requires assisted reproductive procedures.

Ref: Ped Endocrinol. Rev. 2014:11(Suppl 2): 230-239

Key Words: diagnosis, outcomes, hypogonadotropic hypogonadism, delayed puberty, testosterone

 

Cryptorchidism: A Clinical Perspective

Claude Kollin M.D PhD and E. Martin Ritzén M.D PhD

Abstract

Incomplete descent of the testes is the most common genital anomaly in newborn boys. The prevalence varies with apparent geographical differences. The etiology of cryptorchidism is considered to be multifactorial (genetic, maternal, and environmental factors), and it occurs most often as an isolated disorder with no obvious cause. Cryptorchidism should not be left untreated, since there is an increased risk of developing testicular cancer and infertility/subfertility. However, the mode and timing of treatment, as well as the risks of subfertility and testicular cancer have long been controversial. There is increasing evidence that treatment should be performed early in life. Randomized volumetric and histological studies have shown that early treatment before the age of one year is beneficial for testicular development and future spermatogenesis compared to later treatment. It remains to be proven that this difference persists into adulthood. Due to the low efficacy rate and the possible adverse effects of hormonal treatment, surgery is preferred. The exact optimal time for orchidopexy is not known, but it should probably be before one year of age, at centers with expertise in pediatric anesthesiology and pediatric surgery/urology. The risk of testicular cancer is also reduced if orchidopexy is performed before puberty; however it remains to be proven if treatment in early infancy reduces the risk even further.

Ref: Ped Endocrinol. Rev. 2014:11(Suppl 2): 240-250

Keywords: Cryptorchidism, testis, treatment, fertility, orchidopexy, testicular cancer, review

 

Testicular Germ Cell Tumors

Leendert H.J. Looijenga

Abstract

Human germ cell tumors are of interest because of their epidemiology, clinical behavior and pathobiology. Histologically, they are subdivided into various elements, with similarities to embryogenesis. Recent insights resulted in a division of five types of human germ cell tumors. In the context of male germ cells, three are relevant; Type I: teratomas and yolk sac tumors of neonates and infants; Type II: seminomas and nonseminomas of (predominantly) adolescents and adults; and Type III: spermatocytic seminomas of the elderly. Recent studies led to significant increases in understanding of the parameters involved in the earliest pathogenetic steps of human germ cells tumors, in particularly the seminomas and nonseminomas (Type II). In case of a disturbed gonadal physiology, either due to the germ cell itself, or the micro-environment, embryonic germ cells during a specific window of sensitization can be blocked in their maturation, resulting in carcinoma in situ or gonadoblastoma, the precursors of seminomas and nonseminomas. The level of testicularization of the gonad determines the histological composition of the precursor. These insights will allow better definition of individuals at risk to develop a germ cell malignancy, with putative preventive measurements, and allow better selection of scientific approaches to elucidate the pathogenesis.

Ref: Ped Endocrinol. Rev. 2014:11(Suppl 2): 251-262

Key Words: Germ cell tumors; precursor lesion; risk stratification; animal models; genvironment

 

Macroorchidism In Childhood and Adolescence: an Update

Vincenzo De Sanctis MD1, Maria Marsella MD2, Ashraf Soliman, MD3, PhD, FRCP , Mohamed Yassin MBBS, CABM, M Sc, FACP4

Abstract

In the last 30 years, scientific literature has been enriched with studies which demonstrate the importance of evaluating testis volume to recognize certain genetic and endocrine diseases. Macroorchidism is defined as an increase of testicular volume at least twice the norm for age. In clinical practice, when macroorchidism is suspected , the testicular volume may be evaluated with the Prader orchidometer and/ or US, calculated by this formula: L x W x H x 0.71 and the resulting value should be compared with a table of percentiles for each age. Macroorchidism is a relatively uncommon sign; however, when present, it almost always has clinical relevance. Five groups of conditions are reviewed: genetic, endocrine, idiopathic and secondary to neoplasm or testicular torsions. An X-linked mental retardation syndrome must be suspected in all patients with macrorchidism, phenotypic abnormalities, and mental retardation. Furthermore, it is important to identify other males affected in the same family to confirm the X-linked transmission. In these cases, the patient must be referred to specialized cytogenetic centres for determination of fragile sites. Other possible etiologies of macroorchidism are long-standing primary hypothyroidism, adrenal remnants in congenital adrenal hyperplasia, follicle stimulating hormone (FSH)- secreting pituitary macroadenomas, local tumors, lymphomas, and aromatase deficiency. Early diagnosis is important in order to identify and reduce the incidence of X-linked mental retardation in affected families and to begin treatment in endocrinologic, tumoral and surgical disorders.

Ref: Ped Endocrinol. Rev. 2014:11(Suppl 2): 263-273

Keywords: Macroorchidism, testicular enlargement, genetic macroorchidisms, endocrine macroorchidisms, idiopathic macroorchidism, neoplasm, testicular torsion

 

Varicocele: A Dilemma in Adolescent Males

Nadine G. Haddad M.D.1, Christopher P. Houk M.D. 2, Peter A. Lee M D. Ph.D.3

Abstract

Varicoceles are the most common cause of infertility in men. Despite the high prevalence of varicoceles, only a small percentage of men with varicoceles have subfertility or infertility. In adolescents, the prevalence of varicoceles increases dramatically during puberty to reach adult prevalence rates. The development of varicoceles during puberty can impair testicular growth and function. Data on hormonal and semen parameters in adolescents with varicoceles are limited, making it harder to determine which varicoceles are associated with infertility and which may benefit from surgery. The main indications for varicocelectomy in adolescents with varicoceles include a volume differential between unaffected and affected testes or abnormality in semen analysis.

Ref: Ped Endocrinol. Rev. 2014:11(Suppl 2): 274-284

Keywords: Varicocele, adolescents, infertility, spermatogenesis, testosterone, testicular volume