Prepubertal Diagnosis Research Articles

Causes, patterns and severity of androgen excess in 487 consecutively recruited pre- and post-pubertal children.

ObjectiveAndrogen excess in childhood is a common presentation and may signify sinister underlying pathology. Data describing its patterns and severity are scarce, limiting the information available for clinical decision processes. Here, we examined the differential diagnostic value of serum DHEAS, androstenedione (A4) and testosterone in childhood androgen excess.DesignRetrospective review of all children undergoing serum androgen measurement at a single center over 5 years.MethodsSerum A4 and testosterone were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased androgen underwent phenotyping by clinical notes review.ResultsIn 487 children with simultaneous DHEAS, A4 and testosterone measurements, we identified 199 with androgen excess (140 pre- and 59 post-pubertal). Premature adrenarche (PA) was the most common pre-pubertal diagnosis (61%), characterized by DHEAS excess in 85%, while A4 and testosterone were only increased in 26 and 9% respectively. PCOS was diagnosed in 40% of post-pubertal subjects, presenting equally frequent with isolated excess of DHEAS (29%) or testosterone (25%) or increases in both A4 and testosterone (25%). CAH patients (6%) predominantly had A4 excess (86%); testosterone and DHEAS were increased in 50 and 33% respectively. Concentrations increased above the two-fold upper limit of normal were mostly observed in PA for serum DHEAS (>20-fold in the single case of adrenocortical carcinoma) and in CAH for serum androstenedione.ConclusionsPatterns and severity of childhood androgen excess provide pointers to the underlying diagnosis and can be used to guide further investigations.

Prepubertal diagnosis of Klinefelter syndrome due to penoscrotal malformations: Case report and review of literature.

We report a case of 4 months old infant diagnosed as Klinefelter syndrome associated with perineal hypospadias, severe ventral chordee and complete penoscrotal transposition. A review of previous reported cases was carried out. Penoscrotal malformations at birth are very rare in Klinefelter syndrome. Awareness of the current standard indications of Karyotyping can help early detection of these cases.

Early-onset Crohn's disease is a risk factor for smaller final height.

Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Can Kallmann syndrome be occasionally diagnosed during childhood? Genetic diagnosis in a child with associated renal agenesis and mirror movements

Can Kallmann syndrome be occasionally diagnosed during childhood? Genetic diagnosis in a child with associated renal agenesis and mirror movements

Anovulation after precocious pubarche: early markers and time course in adolescence.

Adolescent girls with a history of precocious pubarche (PP) are known to be at increased risk for ovarian hyperandrogenism, an endocrinopathy related to reduced fetal growth, but the characteristics of their ovulatory function have not been fully documented. We assessed ovulatory function by weekly urinary LH and salivary progesterone measurements over 3 consecutive months in 85 adolescent girls with known weight and gestational age at birth: 49 girls had no history of PP (age, 14.7+/-1.7 yr), and 36 had a history of PP (age, 14.4+/-2.0 yr); 55 girls were in the early postmenarcheal phase (0-3 yr after menarche), and 30 were in the late postmenarcheal phase (> 3 yr after menarche). In girls with PP, the 17-hydroxyprogesterone (17-OHP) response to ACTH was determined at prepubertal diagnosis of PP, and serum androgen and gonadotropin concentrations were measured in adolescence together with insulin responses to an oral glucose load. Early postmenarche, the fraction of girls with ovulations was similar in the non-PP and PP subgroups (61% vs. 62%), as was the fraction of ovulatory cycles (25% vs. 22%). Late postmenarche, however, the fractions of ovulating girls and ovulatory cycles were strikingly higher (P < or = 0.001) in the non-PP than in the PP subgroup (91% vs. 20% and 47% vs. 12%). Within the PP subgroup, anovulatory girls were found to have a lower weight SD score at birth (mean+/-SEM) than ovulatory girls (-1.22+/-0.3 vs. -0.36+/-0.3; P = 0.03), a higher 17-OHP response to ACTH before puberty (333.1+/-31 vs. 203.8+/-26 ng/dL; P < 0.002), and, in adolescence, lower serum sex hormone-binding globulin levels and higher circulating LH, free androgen indexes, and insulin responses. In conclusion, these findings indicate that girls with PP are at increased risk for anovulation from late (not early) adolescence onward, particularly those girls with a low weight at birth and/or a high 17-OHP response to ACTH at prepubertal diagnosis of PP.

5 CONFIRMATION OF HYPOGONADOTROPIC HYPOGONADISM (HH) SUSPECTED AT PREPUBERTAL AGE

We have previously reported that prepubertal diagnosis of HH could be assumed on the basis of micropenis and cryptorchidism, olfactory disturbances, low LH response to GnRH infusion and subnormal clinical and histological response to prolonges treatment with hCG.In order to confirm the diagnosis of HH at pubertal age, 12 patients with suspicious prepubertal diagnosis of HH were studied, due to the clinical appearance, hCG test; Testosterone (T: ng/dl) basal: 31.9 ± 25.9, T post hCG: 111 ± 97.8 and with GnRH infusion (0.83 ug/min): LH (IU/L) basal: 2.8 ± 1.9, LH Max: 7.5 ± 3.9; FSH (IU/L) basal: 2.1 ± 1.9, FSH Max: 5.1 ± 2.8.In all patients the clinical diagnosis of HH was confirmed at the last control carried out at the age of 17.17 ± 2.18 years. Their height was 170.6 ± 5.62 cm, testicular volume 2.11 ± 0.93 ml and anosmia was detected in 6 out of 12. All of them required therapy with exogenous testosterone.These results demonstrate the wtilily of hormonal tests for the prepubertal diagnosis of HH in boys with micropenis and cryptorchidism.

Klinefelter's syndrome with the XXYY sex chromosome complex: With particular reference to prepubertal diagnosis

The most common chromosomal complement in Klinefelter's syndrome is 47 with the XXY sex chromosome complex. Although mental retardation may be recognized early in life, it is difficult to establish a clinical diagnosis of Klinefelter's syndrome before puberty when the small testes, gynecomastia, and other physical stigmata may become apparent. This paper describes two examples of Klinefelter's syndrome with the XXYY sex chromosome complex, in one of which skeletal abnormalities led to chromosomal studies and the prepubertal diagnosis. In addition it is suggested that dermatoglyphic studies may provide a further diagnostic aid in the early recognition of these cases.

AUTORADIOGRAPHY IN A BOY WITH XXY KARYOTYPE.

Approximately 0.2% to 0.3% of newborn male infants are sex-chromatin positive. 19,4,18 Therefore they probably represent future cases of Klinefelter's syndrome. In contrast to this high frequency of sex-chromatin positive males is the scarcity of the prepubertal diagnosis of the XXY patient. Usually children who later develop the Klinefelter's syndrome show no malformations betraying the abnormal chromosomal state. In two cases, however, the presence of hypospadias led to the finding of the XXY sex chromosome pattern at an early age. 9,10 We recently had the opportunity to study a boy with hypospadias and XXY karotype. Report of a Case A 4-year-old boy was referred in November, 1963, to The Cincinnati Children's Hospital for chromosomal analysis. He had been born in August, 1959, with a rather severe hypospadias, the opening of the urethra being at the base of the penis. He had a bifid scrotum in which both testes were felt;