-
Journal of the Endocrine Society Jul 2017Premature adrenarche (PA) has been associated with increased metabolic risk.
CONTEXT
Premature adrenarche (PA) has been associated with increased metabolic risk.
OBJECTIVE
To describe the risk of precocious thelarche (PT; <8 years), pubarche (PP; girls <8 years, boys <9 years), and gonadarche (PG; <9 years) in children with high dehydroepiandrosterone sulphate (DHEAS [HD]) vs those with normal DHEAS (ND).
SETTING AND INTERVENTION
Longitudinal Chilean cohort (n = 1052, 49.9% girls). Annual clinical examination including secondary sex characteristics by Tanner staging. Logistic regression models were adjusted by age and BMI.
MAIN OUTCOME
Assess the relationship between DHEAS and premature thelarche, gonadarche, and pubarche in both sexes.
RESULTS
At age of DHEAS determination, overweight/obesity was present in 44.3% of boys and 42.9% of girls. Incidences of any precocious event were observed in 17.2% of boys and in 25.4% of girls, presented as 8.7% of PG and 8.5% of PP in boys and as 21.3% of PT and 4.1% of PP in girls. In crude and adjusted models in boys, HD did not increase the risk of earlier pubertal events. Conversely, girls with HD had a 2.6 times greater risk of early thelarche and a three times greater risk of early pubarche compared with girls with ND concentrations.
CONCLUSION
In Chilean adolescents, precocious events of pubertal development were in line with the worldwide secular trend of earlier sexual maturation. HD was only associated with PT and PP in girls. Continuous follow-up of this cohort is a unique opportunity to prospectively address and analyze the interrelationships among HD, early growth, and adiposity as determinants of gonadarche, pubertal rate/sequence progression, and ovarian function.
PubMed: 29264531
DOI: 10.1210/js.2017-00120 -
Frontiers in Endocrinology 2017Premature adrenarche (PA) has been linked to early thelarche and menarche, but longitudinal data on growth and pubertal development after PA are insufficient.
BACKGROUND
Premature adrenarche (PA) has been linked to early thelarche and menarche, but longitudinal data on growth and pubertal development after PA are insufficient.
METHODS
Growth and pubertal development of mostly full-term and appropriate for gestational age-born 43 PA (36 girls) and 63 control children (52 girls) were analyzed prospectively. Children examined first at the mean age of 7.6 years were reexamined at the mean age of 12.0 years.
RESULTS
The PA girls but not the boys were taller and had higher body mass index (BMI) than the controls. A higher proportion of the PA than control girls had reached menarche, while the same percentage of the PA and control boys were at Tanner genital stage ≥2. The PA girls with premature pubarche (PP) were taller but not heavier and had more often reached menarche by the age of 12 years than the PA girls without PP. The PA girls with menarche had lower birth length (BL) and higher prepubertal insulin-like growth factor 1 (IGF-1) concentrations compared with non-menarcheal PA girls. In logistic regression analyses for all girls, lower BL standard deviation score, earlier maternal menarche, and higher prepubertal IGF-1 were independently associated with menarche.
CONCLUSION
At 12 years of age, the PA girls had higher BMI, advanced linear growth, and accelerated pubertal development with earlier menarche than the control girls. The PA girls with PP were taller and had earlier menarche than the PA girls without PP. Lower BL and higher prepubertal IGF-1 concentration were predictive factors for menarche by the age of 12 years.
PubMed: 29163361
DOI: 10.3389/fendo.2017.00291 -
Hormone Research in Paediatrics 2017To determine whether psychological characteristics of girls with variations of early puberty and their mothers change over time and with treatment in girls with central...
BACKGROUND
To determine whether psychological characteristics of girls with variations of early puberty and their mothers change over time and with treatment in girls with central precocious puberty (CPP).
METHODS
Girls with CPP, premature adrenarche (PA), and early normal puberty (ENP) completed psychological assessments at baseline and after 1 year along with their mothers. All girls with CPP were treated with GnRH analogs. Psychological effects of group and time were examined using 2 × 3 mixed ANOVAs.
RESULTS
Sixty-two subjects aged 7.5 ± 1.4 years (range 4.8-10.5) were enrolled, of whom 36 (15 with CPP, 8 with PA, and 13 with ENP) completed 1-year follow-up assessments. Psychological measures were normal in all girls. No significant group differences were found for any measure of girls' psychological functioning at either time point. However, across all groups there was change over time with a decrease in perceived physical competence (p < 0.001) and an increase in perceived maternal acceptance (p = 0.001).
CONCLUSION
No abnormalities in psychological functioning were found among girls with variations of early puberty, and all groups were in the normal range. Our results are largely reassuring regarding concerns of adverse psychological consequences of early puberty in girls.
Topics: Adrenarche; Anxiety; Child; Child, Preschool; Depression; Female; Follow-Up Studies; Humans; Mothers; Personality; Puberty, Precocious; Social Adjustment
PubMed: 28926827
DOI: 10.1159/000479688 -
Journal of Pediatric and Adolescent... Oct 2017The congenital adrenal hyperplasias comprise a family of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is due to... (Review)
Review
The congenital adrenal hyperplasias comprise a family of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is due to 21-hydroxylase deficiency associated with mutations in the 21-hydroxylase gene, which is located at chromosome 6p21. The clinical features associated with each disorder of adrenal steroidogenesis represent a clinical spectrum that reflect the consequences of the specific mutations. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and preservation of fertility. For adolescent and adult men, prevention and early treatment of testicular adrenal rest tumors is beneficial. In this article key aspects regarding pathophysiology, diagnosis, and treatment of congenital adrenal hyperplasia are reviewed.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adult; Child; Female; Fertility; Hirsutism; Humans; Male; Mutation; Sexual Maturation; Steroid 21-Hydroxylase
PubMed: 28450075
DOI: 10.1016/j.jpag.2017.04.001 -
Pediatric Endocrinology, Diabetes, and... 2017Polycystic ovary syndrome (PCOS) is a complex disease. Depending on the used criteria the prevalence of PCOS ranges from 6 to 20%. It is necessary to exclude diseases... (Review)
Review
Polycystic ovary syndrome (PCOS) is a complex disease. Depending on the used criteria the prevalence of PCOS ranges from 6 to 20%. It is necessary to exclude diseases leading to androgen excess. The participation of genetic and environmental factors is considered in the etiology of PCOS development. The highest rate of incidence of PCOS is assessed in girls who were born SGA and developed premature adrenarche later in life.The free androgen index (FAI) is concerned as the most sensitive marker of hyperandrogenaemia in PCOS although insulin resistance, anti-Müllerian hormone (AMH),and deficiency of vitamin D may intensify metabolic disturbances. The ultrasound criteria used in adolescent patients prefer the estimation of the ovarian volume or the ratio of ovarian stroma to total ovary, rather than the number of ovarian follicles. PCOS is connected with different metabolic disorders. Post-binding defect in signal transduction is responsible for insulin resistance. This defect results from an impaired activity of the kinase receptor. Moreover, the adipose tissue of PCOS women differs substantially from the tissue of the others according to morphology and function. The adipocytes produce lower amounts of adiponectin, which is an insulin-sensitizing agent. Dyspidemia with high triglycerides and low high density lipoprotein cholesterol concentrations is frequently noticed. Cardio-metabolic risk factors, insulin resistance, and endothelial dysfunction accompany PCOS from the very beginning. Oxidative stress plays a role as a link among systemic inflammation and dysfunction of endothelial cells and abnormal thecal cell action. The treatment efforts in PCOS depend on the patient's main problems. Modification of diet and lifestyle is the most important recommended advice to each woman independent of age and weight.
Topics: Adipose Tissue; Adult; Female; Humans; Insulin Resistance; Metabolic Diseases; Polycystic Ovary Syndrome
PubMed: 29574473
DOI: 10.18544/PEDM-23.04.0094 -
Archives of Endocrinology and Metabolism 2016Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic...
Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.
Topics: Child; DNA Methylation; Gonadotropin-Releasing Hormone; Hormone Replacement Therapy; Human Growth Hormone; Humans; Male; Prader-Willi Syndrome; Puberty, Precocious; Recombinant Proteins
PubMed: 27982202
DOI: 10.1590/2359-3997000000196 -
Anales de Pediatria (Barcelona, Spain :... Nov 2017There is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant...
BACKGROUND
There is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant presence of obesity and other metabolic disturbances. An attempt is made to study these potential associations in a cohort of girls with IPA from our hospital.
PATIENTS AND METHODS
A descriptive cross-sectional study was conducted that included girls with a diagnosis of IPA from the Paediatric Department of the Fundación Jiménez Díaz (Madrid, Spain) between January 2007 and May 2015. A record was made of family and personal history with perinatal data, as well as anthropometric data and biochemical values at the time of diagnosis.
RESULTS
Out of a total of 76 girls with IPA, 2.7% had a history of small for gestational age. When body mass index was analysed according to modified criteria of WHO 2007/Cole 2000, 11.8% were overweight, and 11.8% were obese at diagnosis. Using the criteria set by the Spanish Ministry of Health, 6.6% were overweight and 18.4% obese, with 21.2% of the girls being insulin resistance, and 13.95% having dyslipidaemia. None of them had hypertension. From a comparative analysis between normal and overweight and obesity IPA girls, the latter had significantly higher levels of triglycerides and insulin, a higher HOMA index, and lower levels of HDL cholesterol.
CONCLUSIONS
IPA girls included in the study do not have a higher prevalence of small for gestational age compared to the general population. Prevalence of overweight and obesity in girls with IPA is not higher than the prevalence in the normal population.
Topics: Adrenarche; Child; Cross-Sectional Studies; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age; Metabolic Diseases; Puberty, Precocious
PubMed: 27838354
DOI: 10.1016/j.anpedi.2016.10.004 -
IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management.The Journal of Clinical Endocrinology... Apr 2016Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal...
CONTEXT
Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations.
OBJECTIVE
We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management.
METHODS
We collected clinical and biochemical characteristics of 69 male patients (35 children, 34 adults) and 56 female IGSF1 mutation carriers (three children, 53 adults) from 30 unrelated families according to a standardized clinical protocol. At evaluation, boys were treated with levothyroxine in 89%, adult males in 44%, and females in 5% of cases.
RESULTS
Additional symptoms in male patients included small thyroid gland volume (74%), high birth weight (25%), and large head circumference (20%). In general, the timing of pubertal testicular growth was normal or even premature, in contrast to a late rise in T levels. Late adrenarche was observed in patients with prolactin deficiency, and adult dehydroepiandrosterone concentrations were decreased in 40%. Hypocortisolism was observed in 6 of 28 evaluated newborns, although cortisol concentrations were normal later. Waist circumference of male patients was increased in 60%, but blood lipids were normal. Female carriers showed low free T4 (FT4) and low-normal FT4 in 18% and 60%, respectively, delayed age at menarche in 31%, mild prolactin deficiency in 22%, increased waist circumference in 57%, and a negative correlation between FT4 concentrations and metabolic parameters.
CONCLUSION
IGSF1 deficiency represents the most common genetic cause of central hypothyroidism and is associated with multiple other characteristics. Based on these results, we provide recommendations for mutational analysis, endocrine work-up, and long-term care.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Female; Genetic Diseases, X-Linked; Humans; Hypothyroidism; Immunoglobulins; Infant; Male; Membrane Proteins; Middle Aged; Neuropsychological Tests; Practice Guidelines as Topic; Quality of Life; Syndrome; Thyroxine; Young Adult
PubMed: 26840047
DOI: 10.1210/jc.2015-3880 -
Hormone Research in Paediatrics 2015Studies that evaluate both body composition and metabolic syndrome (MeS) risk in prepubertal children with premature adrenarche (PA) are limited.
BACKGROUND
Studies that evaluate both body composition and metabolic syndrome (MeS) risk in prepubertal children with premature adrenarche (PA) are limited.
METHODS
Fifty-eight prepubertal children (aged 5-9 years, 33 female and 25 male), 30 with PA and 28 controls, were evaluated for the presence of MeS as defined by age-modified National Cholesterol Education Program Adult Treatment Panel III criteria. A subset had dual-energy X-ray absorptiometry and bone markers (n = 23/58) to evaluate the effect of hyperandrogenism on metabolic abnormalities and body composition.
RESULTS
There was no difference in the prevalence of MeS between PA and controls (p = 0.138). Children with MeS were obese with an increased waist circumference (WC) and decreased high-density lipoprotein levels. Androgens were not associated with having more than one criterion for MeS (p = 0.08) but were associated with triglycerides and WC (p = 0.029 and p = 0.041, respectively). Lean mass was greater in PA subjects (p = 0.039), and androgens correlated with bone mineral density (p = 0.029) and total body fat (p = 0.008). Subjects with a higher percent of body fat were more likely to have more than one MeS risk factor (p = 0.005).
CONCLUSIONS
MeS was seen only in obese subjects whether or not they had PA. Thus, it appears that obesity drives metabolic risk in the prepubertal population rather than PA. Our findings are important in determining how the prepubertal patient with PA should be evaluated for metabolic risk.
Topics: Adipose Tissue; Adrenarche; Age Factors; Body Composition; Child; Child, Preschool; Cholesterol; Female; Humans; Male; Metabolic Syndrome; Obesity; Puberty, Precocious; Triglycerides; Waist Circumference
PubMed: 26513727
DOI: 10.1159/000441498 -
International Journal of Pediatric... 2015Cushing Syndrome is difficult to diagnose, and the comorbidities and persistent late effects of hypercortisolemia after treatment of the primary disease are challenging...
CONTEXT
Cushing Syndrome is difficult to diagnose, and the comorbidities and persistent late effects of hypercortisolemia after treatment of the primary disease are challenging for the patient and the endocrinologist.
OBJECTIVE
To report the case of a girl with obesity and hypertension, ultimately diagnosed with Cushing syndrome due to primary pigmented nodular adrenocortical disease. In this case, the complications of hypercortisolism persisted short term despite surgical intervention.
PATIENT
A 4 year old morbidly obese African-American girl with developmental delay presented with hypertensive emergency in the ER and 18-month history of progressive weight gain. Her previous history included premature adrenarche, hypertension, seizures and a random high cortisol with suppressed ACTH. She was subsequently stabilized, and a diagnostic work-up persistently demonstrated elevated cortisol and suppressed ACTH. An abdominal MRI showed bilateral adrenal multinodular disease, consistent with multinodular hyperplasia of the adrenal glands. Based on these findings the patient underwent a bilateral adrenalectomy, which confirmed primary pigmented nodular adrenocortical disease. The patient had a complicated, protracted post-operative course requiring adjustment of therapy for persistent hypertension. Two months after surgery, she was readmitted to the Emergency Department with hyperpyrexia and hypertension and succumbed to the complications of sepsis.
CONCLUSIONS AND OUTCOME
This case highlights the significant diagnostic and therapeutic challenges in treating children with Cushing syndrome. Resolution of the source of hypercortisolemia does not imply regression of hypertension or recovery of the immune system. Although the child underwent bilateral adrenalectomy, persistent consequences of prolonged severe hypercortisolism contributed to her death two months later.
PubMed: 26322079
DOI: 10.1186/s13633-015-0014-2