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AACE Clinical Case Reports 2019Prader-Willi syndrome (PWS) is a rare genetic neuroendocrine disorder characterized by hypotonia, obesity, short stature, and mental retardation. Incomplete or delayed...
OBJECTIVE
Prader-Willi syndrome (PWS) is a rare genetic neuroendocrine disorder characterized by hypotonia, obesity, short stature, and mental retardation. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty is rarely seen.
METHODS
This study reports the clinical, biochemical, and histologic findings in 2 boys with PWS who developed central precocious puberty.
RESULTS
Both boys were started on growth hormone therapy during the first years of life according to the PWS indication. They had both bilateral cryptorchidism at birth and had orchidopexy in early childhood. Retrospective histologic analysis of testicular biopsies demonstrated largely normal tissue architecture and germ cell maturation, but severely decreased number of prespermatogonia in one of the patients. Both boys had premature adrenarche around the age of 6. Precocious puberty was diagnosed in both boys with enlargement of testicular volume (>3 mL), signs of virilization and a pubertal response to a gonadotropin-releasing hormone (GnRH) test and they were both treated with GnRH analog.
CONCLUSION
The cases described here displayed typical characteristics for PWS, a considerable heterogeneity of the hypothalamic-pituitary function, as well as testicular histology. Central precocious puberty is extremely rare in PWS boys, but growth hormone treatment may play a role in the pubertal timing.
PubMed: 31967069
DOI: 10.4158/ACCR-2019-0245 -
Clinical Endocrinology Feb 2020Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities... (Review)
Review
Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.
Topics: Adrenal Gland Diseases; Age of Onset; Body Height; Child; Child Development; Endocrinology; Growth Disorders; Humans; Pediatrics; Practice Guidelines as Topic; Prevalence
PubMed: 31747461
DOI: 10.1111/cen.14131 -
BMC Pediatrics Nov 2019Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no...
BACKGROUND
Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no concordance results have been obtained, especially for boys in puberty. Moreover, the sample sizes of previous studies were small, and were not representative.
METHODS
We conducted a cross-sectional survey including 1148 boys aged 6-14 years, they were divided into overweight/obesity (OW/OB) group and normal weight (NW) group. Puberty status was assessed according to Tanner scale and testicular volume. Serum levels of pregnenolone, 17-OH progesterone, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione were detected by LC-MS. Serum free testosterone and sex hormone-binding globulin (SHBG) levels were measured by chemiluminescence immunoassay.
RESULTS
The 17-OH progesterone, DHEA, androstenedione and free testosterone levels of OW/OB boys at prepubertal stage or at the age 6 = < 10 years group were higher than those of the NW boys (all the P values were < 0.01). Furthermore, androstenedione and free testosterone levels were lower in OW/OB boys at late puberty, and the trend continued at the post pubertal stage for FT (P < 0.01-0.05). DHEA, androstenedione, and FT levels persisted to be higher at the 10~ < 12 years in OW/OB boys but not for 17-OH progesterone. FT level was lower in the OW/OB group at the 12~ < 15 years group. The SHBG levels in the OW/OB boys were lower than those in the NW ones at the 6~12 years group, and prepubertal to early pubertal stage.
CONCLUSIONS
Premature adrenarche is more likely in OW/OB boys. More attention should be given to the lower androgen levels of OW/OB boys at late pubertal and post pubertal stages.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Cortex Hormones; Age Factors; Androstenedione; Child; Corticosterone; Cross-Sectional Studies; Dehydroepiandrosterone; Humans; Male; Organ Size; Overweight; Pediatric Obesity; Pregnenolone; Puberty; Puberty, Precocious; Sex Hormone-Binding Globulin; Testis; Testosterone
PubMed: 31690265
DOI: 10.1186/s12887-019-1755-5 -
Journal of the Endocrine Society Oct 2019Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown.
CONTEXT
Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown.
OBJECTIVE
To study cardiometabolic profile in adult women with previous PA.
DESIGN AND PARTICIPANTS
Thirty women with PA and 41 control subjects were followed from prepuberty to young adulthood.
MAIN OUTCOME MEASURES
Prevalence of the metabolic syndrome (MetS) and clinical and biochemical cardiovascular risk factors.
RESULTS
There were no differences in the prevalence of MetS or in any parameters indicating dyslipidemia, hypertension, hepatosteatosis, atherosclerosis, or low-grade inflammation between the study groups. However, prevalence of insulin resistance (IR; = 0.014) and acanthosis nigricans ( = 0.010) was higher in the PA group. Neither fasting glucose nor insulin concentrations differed between the study groups, but HbA1c [adjusted for body mass index (BMI) = 0.011] and Homeostatic Model Assessment of Insulin Resistance ( = 0.044; BMI-adjusted = nonsignificant) were higher in the PA group. Although BMI and fat percentage were comparable between the study groups, the PA group had higher central fat mass than the control group. In the whole study population, MetS and IR were associated with greater adult fat mass, but no prepubertal factors predicting later IR were found.
CONCLUSION
PA does not seem to be associated with MetS, dyslipidemia, hypertension, atherosclerosis, or low-grade inflammation in young adult women. However, some women with PA may be at an increased risk of unfavorable glucose metabolism, which is associated with increased central adiposity at adult age rather than determined by prepubertal factors.
PubMed: 31528825
DOI: 10.1210/js.2019-00193 -
Journal of Pediatric Endocrinology &... Nov 2019Background Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action associated with levels of dehydroepiandrosterone sulfate (DHEAS)...
Background Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action associated with levels of dehydroepiandrosterone sulfate (DHEAS) ≥40 μg/dL, before age 8 years in girls and 9 years in boys, without breast or testicular enlargement. The aim of this study was to characterize a population of prepubertal Caucasian children with PA and to compare them with regard to gender and body mass index (BMI) (normal BMI vs. overweight/obesity). Methods We performed a cross-sectional study of Portuguese Caucasian prepubertal children followed, due to PA, in pediatric endocrinology clinics of a university hospital. Results Eighty-two girls and 15 boys were included (mean age at evaluation: 7.4 ± 1.3 years). The mean birth weight was 2990 ± 689 g; only two children were small for gestational age. Girls presented premature pubarche at a younger age (median [interquartile range (IQR)] 6 (5-6) years vs. 7 (7-8) years in boys; p < 0.001). No gender differences were found for gestational age, birth weight, maternal age at menarche, anthropometry, bone age advancement or androgen levels. The majority of the subjects were overweight or obese (59%). Overweight/obese PA children were taller and had a more advanced bone age than normal-BMI PA children. Overweight/obese children presented higher levels of DHEAS and androstenedione. Bone age advancement and DHEAS were correlated (r = 0.449; p = 0.05). Conclusions We found no evidence of reduced fetal growth. Girls presented premature pubarche at a younger age. No major gender differences in androgen levels were found in prepuberty. Obese and overweight PA children tend to be taller, have a more advanced bone age and higher levels of androgens than normal-BMI PA children.
Topics: Adrenal Gland Diseases; Body Mass Index; Child; Child, Preschool; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Female; Follow-Up Studies; Humans; Male; Obesity; Overweight; Prognosis; Puberty, Precocious
PubMed: 31472065
DOI: 10.1515/jpem-2019-0185 -
Journal of Clinical Research in... Jun 2020Loss-of-function mutations of are an X-linked cause of central hypothyroidism (CeH) and hypoprolactinemia. A boy who is now 15.2 years old presented at the age of 7.69...
Loss-of-function mutations of are an X-linked cause of central hypothyroidism (CeH) and hypoprolactinemia. A boy who is now 15.2 years old presented at the age of 7.69 years for evaluation of obesity. Previous thyroid function evaluation suggested CeH [FT4 0.6 ng/mL, thyroid-stimulating hormone (TSH) 2.2 mIU/L] but his physician took no action. At presentation he was clinically and biochemically euthyroid, prepubertal and obese. Serum prolactin (PRL) was undetectable. Biochemistry was normal except for mild hypercholesterolemia, total cholesterol 198 mg/dL. Subsequently FT4 and TSH levels fluctuated between 0.72-0.95 ng/dL (normal 0.8-2.0) and 1.94-5.77 mIU/L (normal 0.3-5.0), respectively. Sequencing of gene revealed a novel genetic change c.3805C>T in exon 19; substitution of amino acid Arginine at position 1269 with a premature «stop» codon resulting in an altered protein product. The patient additionally presented delayed adrenarche, low height velocity that resolved spontaneously and normal pubertal onset associated with increased FSH levels. At 14 years-of-age, while the patient was at Tanner stage 4, PRL levels became detectable, rising gradually to 2.3 ng/mL at last examination. Thyroxine replacement therapy resulted in decrease in total cholesterol 103 mg/dL. A high index of suspicion for the disorder is needed since several measurements of thyroid function may be required for CeH to be disclosed. The patient’s normal FT4 levels and normal intelligence would have resulted in a missed diagnosis if the serum PRL levels had not been measured. This case highlights the importance of measuring PRL in a boy with low normal FT4 and normal TSH levels.
Topics: Adolescent; Humans; Hypothyroidism; Immunoglobulins; Male; Membrane Proteins; Prolactin
PubMed: 31448769
DOI: 10.4274/jcrpe.galenos.2019.2019.0085