The measurement of urinary gonadotropins for assessment and management of pubertal disorder.

OBJECTIVE: Measurement of urinary LH (uLH) and FSH (uFSH) may facilitate non-invasive pubertal assessment but there is a need for further validation by studying children and adolescents with disorders of puberty. DESIGN: 65 cases (Male: 25) with a median age of 12 years (2.9-18.1) supplied at least one non-timed urine sample for uLH and uFSH measurement by immunoassay and corrected for creatinine excretion. 25 cases were receiving GnRH-agonist (GnRH-a) at the time of sample collection. In 41 cases, urine samples were collected prior to a LHRH test and in 12 cases matched serum samples for basal LH (sLH) and FSH (sFSH) were also available. RESULTS: There was a significant correlation between sLH and uLH:uCr (r=0.82; p-value <0.001) and sFSH and uFSH:uCr (r=0.93; p-value <0.001). Based on receiver operator characteristics analysis, a uLH:uCr value of 0.05 IU/mmol as a cut-off would detect a LH peak >5U I/L with a sensitivity of 86% and a specificity of 72% with a positive predictive value of 93%. In pubertal boys (6) and girls (22) with a sLH peak >5UI/L, median uLH:uCr was 0.27 IU/mmol (0.27-0.28) and 0.17 IU/mmol (0.09-0.43), respectively. The median uFSH:uCr was 0.51 IU/mmol (0.41-0.60) for boys and 1.1 IU/mmol (0.21-2.44) for girls. In the 25 cases on GnRH-a, the median uLH:uCr for boys and girls was 0.02 IU/mmol (0.01-0.02) and 0.02 IU/mmol (0.004-0.07), respectively, and the median uFSH:uCr was 0.07 IU/mmol (0.05-0.09) and 0.27 IU/mmol (0.09-0.54), respectively. CONCLUSION: Urinary gonadotrophins reflect serum gonadotrophin concentration and may represent a reliable non-invasive method of assessing pubertal progress.

Elevated phthalates' exposure in children with constitutional delay of growth and puberty.

BACKGROUND: Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone. METHODS: In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The serum testosterone level was determined by radioimmunoassay. RESULTS: Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: ß = -45.7, p = 0.017; MEP: ß = -31.6, p = 0.022; total phthalates: ß = -24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%). CONCLUSIONS: In this case-control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level.

Metabolic studies in primary tubular hypomagnesaemia-hypokalaemia.

13 1/2 year old boy with short stature and pubertal delay had infrequent episodes of tetany. Biochemical determinations demonstrated low plasma and high urinary magnesium and potassium levels, hypocalciuria, slightly increased plasma bicarbonate, slightly reduced fractional distal reabsorption of chloride and sodium, high plasma renin activity and high urinary excretion of prostaglandins (E2, F2 alpha). The other parameters of renal functions were normal. Endocrine evaluation of short stature and pubertal delay was normal. Intracellular magnesium and potassium levels in lymphocytes and erythrocytes were within normal limits. Cyclooxygenase blockade with Indomethacin 2.5 mg/kg daily during 4 weeks normalized urinary excretion of prostaglandins and corrected in part low plasma and high urinary potassium levels, but had no effect on magnesium, calcium, sodium and chloride handling. These data raise the possibility that tubular hypomagnesaemia-hypokalaemia could be solely explained by a low renal threshold for magnesium.

The effect of long-term opiate antagonist administration to pubertal boys.

To test further the hypothesis that opiatergic pathways controlling gonadotropin production may be functional during early to mid adolescence, nine pubertal boys with bone ages ranging from 10 to 15 were given the long-acting opiate antagonist, naltrexone, for up to 4 weeks. Urinary gonadotropin measurements were assessed before, during, and after drug administration. In three early to mid-pubertal boys who received naltrexone for 3 to 4 weeks, LRH testing was also performed. No evidence of a stimulatory FSH or LH response to naltrexone was found in any of the patients evaluated. The data do not support the operation of an opiate-mediated mechanism in the control of pubertal onset in man.

[Value of the assay of urinary gonadotropins in pediatric endocrinology]. / Intérêt du dosage des gonadotrophines urinaires en endocrinologie pédiatrique.

An assay for urinary gonadotropins (UG) performed after acetone extraction is presented. This dosage was performed either on a sample of the 24 assay urine, or on the fractionated 12 hr/12 hr urines (night/day) in normal children whose ages ranged from 2 to 20 years and in children presenting with various endocrine diseases (on about 2,000 urine samples). Normal values were established according to sex and stage of puberty. In boys, the lack of overlap between values of LH (UI/24 hr) observed in stage I (prepubescent, 9-13 yrs) and those observed in stage II represents an obvious biological marker of the onset of puberty. The night/day ratio of LH also increases close to puberty, reflecting the onset of the well-known night secretion of LH, at the time of the first stages of puberty. In girls, the preferential increase in FSH is the best criterion for the onset of puberty. In children with endocrine diseases, assay for UG/24 hr is a valuable parameter of the gonadotropic function allowing 1. to separate delayed puberty from hypogonadotropic hypogonadism; 2. to confirm a diagnosis of precocious puberty and 3. to control a treatment with LHRH analogous.

Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency.

Twenty three boys with delayed adolescence (age 15.7 +/- 2.0, bone age 12.4 +/- 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirty seven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 +/- 8 micrograms/m2/12 h) and 13 with an insufficient (191 +/- 16 micrograms/m2/12 h) THS response. Values in the second and third sample were higher, indicating a delayed response. In 12 tests (group B), the results were normal (1016 +/- 143 micrograms/M2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age. The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.

Decreased LH response to the second of consecutive day luteinizing hormone releasing hormone (LHRH) in fusions among patients with constitutional delay of puberty: a phenomenon of pubertal maturation?

Consecutive day LHRH stimulation by continuous infusion has been used to evaluate pituitary reserve. Different responses on the 2 days were not present among non-pubertal hypopituitary patients, pubertal growth hormone deficient patients or adult males. However, patients with constitutionally delayed puberty demonstrated a greater serum LH response on day 1 than day 2. Urinary LH responses suggest a similar but not statistically significant pattern. This response may be a normal phenomenon of puberty or may represent part of the reason for constitutionally delayed puberty.

[Applications of the urocytogram in primary-secondary amenorrhea in adolescents]. / Applications de l'urocytogramme dans les aménorrhées primo-secondaires chez les adolescentes.

In the urinary sediment, the cellular material mainly originates from cells of the bladdertrigone. These cells are submitted to hormonal stimulation and their study constitutes the base of a cytological method called "urocytogram". The urinary sediment was examined in thirty-five young girls with backward puberty. The repeated examinations contribute to differential diagnosis and help in etiologic diagnosis. Whenever it is necessary to investigate adolescent's sex hormones, an urocytogram, a simple and painless method, is indicated.