Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients

ABSTRACT Objective To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. Subjects and methods We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. Results Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). Conclusions Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency.

Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients.

OBJECTIVE: To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. SUBJECTS AND METHODS: We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. RESULTS: Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). CONCLUSIONS: Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency.

Decreased 6-Sulfatoxymelatonin Excretion in Male GH-Deficient Children and Adolescents.

AIM: To evaluate melatonin secretion in a group of untreated and treated male growth hormone (GH)-deficient children and adolescents. METHODS: We studied 44 male subjects: 8 untreated GH-deficient patients (GHDnt), 16 treated GH-deficient patients (GHDt) and 20 healthy children and adolescents as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24-hour samples), nocturnal (18.00-8.00 h) and diurnal samples (8.00-18.00 h). Levels of 6-SM were expressed as micrograms excreted per time interval and x0394; values (difference between nighttime and daytime values). RESULTS: Significant differences were observed among the 3 groups of pediatric subjects studied for total 6-SM (p < 0.0001), nocturnal 6-SM (p < 0.0001) and x0394; values (p < 0.0001). Subsequent analysis showed significantly higher levels for total 6-SM, nocturnal 6-SM and nighttime-daytime x0394; in the CG versus the GHDnt (p < 0.01) and in the CG versus the GHDt group (p < 0.01). No significant correlations were found between 6-SM excretion and insulin-like growth factor-1 values in the children and adolescents studied. CONCLUSIONS: GH-deficient patients showed lower levels of 6-SM. Our findings provide a different insight to a further understanding of some chronobiological disorders involved in GH deficiency in children.

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome.

BACKGROUND: It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients. METHODS: This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n = 93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n = 34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined. RESULTS: Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm. CONCLUSIONS: The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.

Confirmation of neonatal screening: reference intervals and evaluation of methodological changes in TSH measurement.

Neonatal reference values for serum thyrotropin are scarce and comprise only small numbers of patients. During 2006, changes were made in IMMULITE kits for TSH measurement. To validate methodological changes, 80 serum samples from patients were evaluated and to establish reference intervals, 334 neonates and infants were analyzed (divided into 4 groups). Group 1 (G1) (48-72 h of life) (n=153), group 2A (G2A) (7-10 days of life) (n=65), group 2B (G2B) (11-14 days of life) (n=35), group 3 (G3) (28-40 days of life) (n=81). Current kits overestimate TSH results by 26 to 37%; TSH (mIU/L) reference intervals (percentile 2.5-97.5) were G1 (1.1-12.7), G2A (1.8-9.8), G2B (1.1-7.1) (p < 0.03 vs. G2A), G3 (1.2-6.9). We suggest that during the second week of life, reference values should be divided into an early stage and a late stage, at least, for there to be an adequate interpretation of borderline measurements in newborn thyroid screening.

Gender-related differences in urinary 6-sulfatoxymelatonin levels in obese pubertal individuals.

The objective of this study was to measure the urinary excretion of the main melatonin metabolite 6-sulfatoxymelatonin in obese and normal weight (wt) boys and girls. The study included 94 subjects, aged 4-15.7 yr (50 obese and 44 normal wt; 48 boys) classified as: mid-childhood (4-7.99 yr), late-childhood (8-12 yr) and pubertal (10.1-15.7 yr, Tanner II-IV). Normal wt subjects were children with a body mass index (BMI) between the 25th and 75th percentiles, and the group of obese subjects included children whose BMI was above the 97th percentile. A 24-hr urine sample was collected during two intervals: (i) 18:00-08:00 hr, and (ii) 08:00-18:00 hr. Analysis of urinary 6-sulfatoxymelatonin levels was performed by radioimmunoassay. Excretion of 6-sulfatoxymelatonin was expressed as: (i) total amount excreted (microg); (ii) mug excreted per time interval, nocturnal or diurnal; and (iii) the difference between nocturnal and diurnal samples (microg, estimated amplitude). A factorial analysis of variance indicated that nocturnal 6-sulfatoxymelatonin excretion and amplitude were significantly higher in the obese individuals. A significant interaction 'BMI x age' was detected, i.e. the effect of BMI was significant in the pubertal group only. Total, nocturnal and diurnal 6-sulfatoxymelatonin excretion was significantly higher in girls. The increase in 6-sulfatoxymelatonin excretion found in obesity occurred only in boys and at the pubertal age. To what extent this increase in melatonin production contributes to a delayed puberty in some pubertal obese males remains to be established.

Tumoral versus non-tumoral hyperprolactinemia in children and adolescents: possible usefulness of the domperidone test.

UNLABELLED: The aim of this study was to evaluate the usefulness of the domperidone test for the difficult diagnosis between functional and tumoral hyperprolactinemia. We evaluated 36 patients, aged 5-18 years, 14 (12 F, 2 M) with hyperprolactinemia (non-tumoral: 10; pituitary adenoma: 4) and 22 individuals as a control group (prepubertal: 5 F, 8 M; pubertal: 4 F, 5 M). Basal prolactin (PRL) (IRMA-DPC), T4 and TSH and PRL 30 min post-domperidone (0.2 mg/kg b. wt i.v.) were measured. Non-tumoral hyperprolactinemic females showed basal PRL: 45 (29-80) (median and range) ng/ml; post-domperidone: 208 (116-290) ng/ml; delta PRL (PRL 30' - PRL 0'): 167 (77-252) ng/ml; and PRL ratio (PRL 30'/PRL 0'): 3.9 (2.3-7.6). Females with pituitary adenoma showed basal PRL: 129 (125-660) ng/ml; post-domperidone: 202 (150-535) ng/ml; delta PRL: 73 (25-135) ng/ml; and ratio: 1.2 (0.8-1.6). Two males, one with a non-tumoral hyperprolactinemia and the other one with a pituitary adenoma, presented, respectively, PRL 0':45, 160; PRL 30':130, 173; delta: 85, 13; ratio: 2.9, 1.1. All non-tumoral patients showed a PRL ratio (30'/0') > 2.3, while no patient with pituitary adenoma had a ratio > 1.6. CONCLUSIONS: PRL response to domperidone allowed us to characterize hyperprolactinemias, although the presence of a blunted response should be confirmed in a larger number of patients with tumors with 'low' PRL levels (dependence on etiology or basal PRL level?).