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Hormone Research in Paediatrics 2021Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal...
BACKGROUND
Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP.
OBJECTIVE
The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6-8 years.
METHODS
The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted.
RESULTS
Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75-2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters.
CONCLUSIONS
In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures.
Topics: Child; Female; Follicle Stimulating Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Luteinizing Hormone; Puberty, Precocious; Retrospective Studies; Sensitivity and Specificity
PubMed: 34098553
DOI: 10.1159/000516361 -
The Journal of Clinical Endocrinology... Aug 2021Premature adrenarche (PA) may increase the risk for polycystic ovary syndrome (PCOS).
CONTEXT
Premature adrenarche (PA) may increase the risk for polycystic ovary syndrome (PCOS).
OBJECTIVE
To study features of PCOS in young adult women with a history of PA.
METHODS
Thirty PA and 42 control females were followed from prepuberty to young adulthood (median age 18.1 years). The main outcome measures were ovarian function, the use of contraceptives, and clinical and biochemical indicators of hyperandrogenism.
RESULTS
We found no differences in the use of hormonal contraceptives (50 vs 50%, PA vs controls, respectively; P > .999), indication for using contraceptives (P = .193), or in the history of oligo- (17 vs 26%, P = .392) and amenorrhea (0 vs 0%, P > .999). Among women not using hormonal contraceptives, those with a history of PA had a higher prevalence of hirsutism (27 vs 0%, P = .023) but not acne (87 vs 67%, P = .252). Steroid profiles were broadly comparable between the groups, but PA women had lower sex hormone-binding globulin (SHBG) concentrations (30.1 vs 62.4 nmol/L, P < .001) resulting in higher free androgen index (3.94 vs 2.14, P < .001). The difference in SHBG levels persisted through body mass index adjustment. SHBG correlated negatively with the homeostasis model assessment for insulin resistance (r -0.498, P = .003). Anti-Müllerian hormone concentrations were comparable between the groups (39.3 vs 32.1 pmol/L, P = .619).
CONCLUSION
PA was not associated with evident ovarian dysfunction in young adult women. However, women with a history of PA had decreased SHBG levels and thus, increased bioavailability of circulating androgens.
Topics: Acne Vulgaris; Adolescent; Adrenarche; Amenorrhea; Androgens; Anti-Mullerian Hormone; Body Mass Index; Case-Control Studies; Contraceptives, Oral, Hormonal; Female; Follow-Up Studies; Hirsutism; Humans; Hyperandrogenism; Insulin Resistance; Ovarian Function Tests; Polycystic Ovary Syndrome; Prevalence; Sex Hormone-Binding Globulin; Steroids; Young Adult
PubMed: 34060603
DOI: 10.1210/clinem/dgab385 -
The Tohoku Journal of Experimental... Apr 2021The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types... (Review)
Review
The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types located within the glomerulosa, fasciculata and reticularis of the adrenal cortex. Abnormal adrenal steroidogenesis leads to a variety of diseases that can cause hypertension, metabolic syndrome, infertility and premature adrenarche. The adrenal cortex can also develop steroid-producing adenomas and rarely adrenocortical carcinomas. In vitro cell culture models provide important tools to study molecular and cellular mechanisms controlling both the physiologic and pathologic conditions of the adrenal cortex. In addition, the presence of multiple steroid-metabolizing enzymes within adrenal cells makes it a model for defining possible endocrine disruptors that might block these enzymes. The regulation and dysregulation of human adrenal steroid production and cell division/tumor growth can be studied using freshly isolated cells but this requires access to human adrenal glands, which are not available to most investigators. Immortalized human adrenocortical cell lines have proven to be of considerable value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis and tumorigenesis. Current human adrenal cell lines include the original NCI-H295 and its substrains: H295A, H295R, HAC13, HAC15, HAC50 and H295RA as well as the recently established MUC-1, CU-ACC1 and CU-ACC2. The current review will discuss the use of primary cultures of fetal and adult adrenal cells as well as adrenocortical cell lines as in vitro models for the study of human adrenal physiology and pathophysiology.
Topics: Adrenal Cortex; Cell Line, Tumor; Cells, Cultured; Humans; Models, Biological
PubMed: 33840647
DOI: 10.1620/tjem.253.217 -
Journal of Research in Medical Sciences... 2020Prolactinoma is a rare tumor of childhood. Clinical presentations of prolactinoma include amenorrhea, delayed puberty, and galactorrhea. For the first time, in this...
Prolactinoma is a rare tumor of childhood. Clinical presentations of prolactinoma include amenorrhea, delayed puberty, and galactorrhea. For the first time, in this case, elevated prolactin levels were associated with unexpected premature pubarche. We describe an 8-year, 7-month-old boy with acne and gradual appearance of pubic hair, corresponding to tanner stage 2. Hormonal tests showed severe hyperprolactinemia (prolactin = 246.8 μg/L and pooled prolactin = 175 μg/L and macroprolactin = 5 μg/L) and mildly elevated level of dehdroepiandrostenedion sulfate (DHEAS) and testosterone. Magnetic resonance imaging (MRI) findings confirmed the presence of a pituitary macroprolactinoma, measuring 14 mm × 12 mm × 8 mm on the right side of the pituitary gland. Cabergoline therapy was commenced (0.5 mg/week) and after 3 months, no evidence of pubarche progression was observed. Prolactin level and tumor size markedly reduced. At the 9-month follow-up visit, a normal MRI was reported. This case highlights that even when facing premature pubarche, careful examination is mandatory, and if no obvious etiology is found for premature pubarche, clinicians should consider prolactinoma.
PubMed: 33824673
DOI: 10.4103/jrms.JRMS_118_20 -
Endocrine Reviews Nov 2021Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to... (Review)
Review
Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to adrenocorticotropin (ACTH) that are best indexed by dehydroepiandrosterone sulfate (DHEAS) rise. These changes are related to the development of the zona reticularis (ZR) and its unique gene/enzyme expression pattern of low 3ß-hydroxysteroid dehydrogenase type 2 with high cytochrome b5A, sulfotransferase 2A1, and 17ß-hydroxysteroid dehydrogenase type 5. Recently 11-ketotestosterone was identified as an important bioactive adrenarchal androgen. Birth weight, body growth, obesity, and prolactin are related to ZR development. Adrenarchal androgens normally contribute to the onset of sexual pubic hair (pubarche) and sebaceous and apocrine gland development. Premature adrenarche causes ≥90% of premature pubarche (PP). Its cause is unknown. Affected children have a significantly increased growth rate with proportionate bone age advancement that typically does not compromise growth potential. Serum DHEAS and testosterone levels increase to levels normal for early female puberty. It is associated with mildly increased risks for obesity, insulin resistance, and possibly mood disorder and polycystic ovary syndrome. Between 5% and 10% of PP is due to virilizing disorders, which are usually characterized by more rapid advancement of pubarche and compromise of adult height potential than premature adrenarche. Most cases are due to nonclassic congenital adrenal hyperplasia. Algorithms are presented for the differential diagnosis of PP. This review highlights recent advances in molecular genetic and developmental biologic understanding of ZR development and insights into adrenarche emanating from mass spectrometric steroid assays.
Topics: Adrenal Hyperplasia, Congenital; Adrenarche; Androgens; Child; Child, Preschool; Female; Humans; Polycystic Ovary Syndrome; Puberty, Precocious
PubMed: 33788946
DOI: 10.1210/endrev/bnab009 -
Reproductive Sciences (Thousand Oaks,... Mar 2022Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease affecting about 20-25% of women in reproductive age. Different mechanisms could contribute to the... (Review)
Review
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease affecting about 20-25% of women in reproductive age. Different mechanisms could contribute to the development of its typical clinical features (i.e. hirsutism, acne, oligo-amenorrhea, alopecia). Some genetic and epigenetic aspects and lifestyle changes seem to be involved in PCOS development. In this review, we shall summarize data from principal studies evaluating the impact of major genetic, epigenetic and environmental factors on the appearance of this female disorder. Literature review and analysis of the most relevant data until May 2020. Current data suggest the importance of genetics and epigenetics in the appearance of PCOS. Several genes, including those related to adrenal and ovarian steroidogenesis as well as those associated with hormonal response to gonadotrophins, androgens and insulin, have been demonstrated to be associated with PCOS. Besides, the phenomenon of methylation of genes and the presence of specific microRNA (miRNA) could take part in PCOS aetiology. Intrauterine exposure to androgens, glucocorticoids and/or some stressful conditions for foetus could contribute to the development of PCOS and other disorders observed in adolescence and later (e.g. premature adrenarche, atypical puberty, metabolic syndrome). Emerging studies report a theoretical role of endocrine disruptors, intestinal dysbiosis and Advanced Glycation End products (AGEs) in PCOS. PCOS is a polygenic and multifactorial hormonal and metabolic dysfunction. An appropriate knowledge of personal and/or family history, lifestyle and nutritional habits of PCOS patients has a great importance to early identify and manage this syndrome.
Topics: Epigenomics; Female; Humans; Life Style; Polycystic Ovary Syndrome
PubMed: 33709373
DOI: 10.1007/s43032-021-00515-4 -
The Lancet. Diabetes & Endocrinology Apr 2021Prader-Willi syndrome is a rare genetic neurodevelopmental disorder resulting from the loss of expression of maternally imprinted genes located in the paternal... (Review)
Review
Prader-Willi syndrome is a rare genetic neurodevelopmental disorder resulting from the loss of expression of maternally imprinted genes located in the paternal chromosomal region, 15q11-13. Impaired hypothalamic development and function is the cause of most of the phenotypes comprising the developmental trajectory of Prader-Willi syndrome: from anorexia at birth to excessive weight gain preceding hyperphagia, and early severe obesity with hormonal deficiencies, behavioural problems, and dysautonomia. Growth hormone deficiency, hypogonadism, hypothyroidism, premature adrenarche, corticotropin deficiency, precocious puberty, and glucose metabolism disorders are the main endocrine dysfunctions observed. Additionally, as a result of hypothalamic dysfunction, oxytocin and ghrelin systems are impaired in most patients. Standard pituitary and gonadal hormone replacement therapies are required. In this Review, we discuss Prader-Willi syndrome as a model of hypothalamic dysfunction, and provide a comprehensive description of the accumulated knowledge on genetics, pathophysiology, and treatment approaches of this rare disorder.
Topics: Animals; Endocrine System Diseases; Humans; Hypothalamus; Prader-Willi Syndrome; Proteins
PubMed: 33647242
DOI: 10.1016/S2213-8587(21)00002-4 -
Hormone Research in Paediatrics 2020Recent studies have shown 11-oxygenated androgens (11oAs) are the dominant androgens in premature adrenarche (PA). Our objective was to compare 11oAs and conventional...
INTRODUCTION
Recent studies have shown 11-oxygenated androgens (11oAs) are the dominant androgens in premature adrenarche (PA). Our objective was to compare 11oAs and conventional androgens in a well-defined cohort of children with PA or premature pubarche (PP) and correlate these androgens with metabolic markers.
METHODS
A prospective cross-sectional study was conducted at a university hospital. Fasting early morning serum steroids (including 11oAs) and metabolic biomarkers were compared and their correlations determined in children ages 3-8 years (F) or 3-9 years (M) with PA or PP (5 M and 15 F) and healthy controls (3 M and 8 F).
RESULTS
There were no differences between PA, PP, and controls or between PA and PP subgroups for sex, BMI z-score, or criteria for childhood metabolic syndrome. Dehydroepiandrosterone sulfate (DHEAS) was elevated only in the PA subgroup, as defined. 11oAs were elevated versus controls in PA and PP although no differences in 11oAs were noted between PA and PP. Within the case cohort, there was high correlation of T and A4 with 11-ketotestosterone and 11β-hydroxyandrostenedione. While lipids did not differ, median insulin and HOMA-IR were higher but not statistically different in PA and PP.
CONCLUSIONS
PA and PP differ only by DHEAS and not by 11oAs or insulin sensitivity, consistent with 11oAs - rather than DHEAS - mediating the phenotypic changes of pubarche. Case correlations suggest association of 11oAs with T and A4. These data are the first to report the early morning steroid profiles including 11oAs in a well-defined group of PA, PP, and healthy children.
Topics: Adrenal Glands; Androgens; Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Puberty, Precocious
PubMed: 33530089
DOI: 10.1159/000513236 -
Endocrinology and Metabolism Clinics of... Mar 2021The pathophysiology of symptomatic polycystic ovary syndrome (PCOS) often unfolds across puberty, but the ontogeny of PCOS is difficult to study because, in general, its... (Review)
Review
The pathophysiology of symptomatic polycystic ovary syndrome (PCOS) often unfolds across puberty, but the ontogeny of PCOS is difficult to study because, in general, its pathophysiology is well entrenched before the diagnosis can be confirmed. However, the study of high-risk groups (daughters of women with PCOS, girls with premature pubarche, and girls with obesity) can offer insight in this regard. Available data support the hypothesis that the pubertal development of PCOS involves various combinations of genetic predisposition, intrauterine programming, hyperinsulinism, and numerous other abnormalities that provoke reproductive symptoms (eg, hyperandrogenism, ovulatory dysfunction) in response to the pubertal increase in gonadotropin secretion.
Topics: Adolescent; Female; Humans; Hyperandrogenism; Obesity; Polycystic Ovary Syndrome; Puberty; Puberty, Precocious
PubMed: 33518184
DOI: 10.1016/j.ecl.2020.10.003 -
Journal of the Endocrine Society Feb 2021
PubMed: 33381669
DOI: 10.1210/jendso/bvaa166