PubMed Health⌕ Search

Biomedical subjects

J P Span

Publications and source records attributed to J P Span.

6 recordsLinked to original sources
PubMed2001

Gender differences in rhGH-induced changes in body composition in GH-deficient adults.

In GH-deficient adults, rhGH has pronounced effects on total body water, fat free mass, and fat mass. Recently, we observed a gender difference in IGF-I responsivity to rhGH that was sex steroid dependent. The aim of the present study was to assess the effect of rhGH therapy on body composition parameters with due attention to the gender differences in biological responsiveness to rhGH. Forty-four women [36.9 +/- 11.9 yr (mean +/- SD)] and 33 men (37.2 +/- 13.8 yr) with GH deficiency were studied every 6 months during 2 yr. The treatment goal was to achieve IGF-I levels within the age-adjusted normal range. Total body water, fat free mass, and fat mass were measured by bioimpedantiometry. To reach the treatment goal, the daily rhGH dose (IU/kg/d) had to be significantly higher in women than in men at all time intervals. During rhGH therapy, total body water and fat free mass increased significantly in both men and women (P < or = 0.01 by ANOVA), but changes were more pronounced in men. Fat mass decreased during rhGH treatment and reached its nadir at 6 months, which was more pronounced in men than in women (P = 0.02 by ANOVA). After the initial decrease, fat mass increased again and reached baseline values after 2 yr of treatment. In both men and women, the total body water and fat free mass increases were closely related to the IGF-I increments (P < 0.001 by Pearson's correlation test). The decrease in fat mass correlated significantly with the increase in IGF-I in men (r = -0.89, P < 0.001), not in women. Confirming our earlier data, IGF-I responsivity to rhGH was significantly higher in men than in women at all time intervals (P < 0.01 by ANOVA). Total body water and fat free mass responsivities were also higher in men than in women (P < 0.01 by ANOVA). In conclusion, gender differences in IGF-I responsivities to rhGH are accompanied by gender differences in the extent of body composition changes to rhGH. Probably because of these gender differences in IGF-I responsivity, the increases of total body water and fat free mass to rhGH replacement were greater in men than in women. Remarkably, however, in men, only total body water and fat free mass responses relative to changes in IGF-I increased during the 2 yr of rhGH therapy (P = 0.02 and 0.01, respectively, by ANOVA). In our opinion, this phenomenon might be explained by the increasing target organ sensitivity to IGF-I over time.

Adult↗
PubMed2000

Gender difference in insulin-like growth factor I response to growth hormone (GH) treatment in GH-deficient adults: role of sex hormone replacement.

GH production in healthy women is about thrice that in men. Yet insulin-like growth factor I (IGF-I) levels are similar, suggesting a lower responsivity to GH in women. In untreated GH-deficient adults, basal IGF-I levels are reportedly lower in females than in males, and the therapeutic recombinant human GH (rhGH) dose required to achieve optimal IGF-I levels is higher in the former, suggesting a pivotal role of estrogens on rhGH requirement in GH-deficient patients. We, therefore, analyzed our 2-yr data on the effect of rhGH on serum IGF-I in 77 GH-deficient patients (33 men, mean +/- SD age, 37.2 +/- 13.8 yr; 44 women, mean +/- SD age, 36.9 +/- 11.9 yr) with due attention to gender differences and to the effects of sex hormone replacement. Of the 44 women, 33 had estrogen substitution. Of the 33 men, 23 were on androgen replacement. Patients (11 premenopausal women and 10 men) not on hormonal replacement were eugonadal. Basal IGF-I levels in untreated GH-deficient women were significantly lower than in men (8.8 +/- 0.7 nmol/L vs. 12.2 +/- 0.9 nmol/L; P < 0.01), despite similar basal GH levels. The daily rhGH dose per kg body weight required to normalize IGF-I in women was higher than in men, the difference being statistically significant at all time points (P < 0.05-0.01). The IGF-I increase (delta) per IU GH/day x kg over the 24-month period was about twice higher in men than in women. Also calculated on a weight basis, rhGH responsivity (rhGH responsivity = (deltaIGF1(nmol/L)/dose (IU/day/kg)) was higher in men than in women at all time intervals (P < 0.05-0.01). Estrogen replacement in women significantly increased rhGH requirement. The rhGH dose per kg body weight required in estrogen-substituted women was significantly higher than in nonestrogen-substituted women (P < 0.01 at t = 18 and 24 months, respectively). In women on estrogen substitution, rhGH responsivity plateaued from 6 months on, whereas in eugonadal women without estrogen substitution the responsivity for rhGH increased over time. In men, the reverse was true; rhGH responsivity increased over time in men on androgen substitution, but plateaued in men without androgen substitution. The mechanisms underlying this gender difference are not known. Differential influences of estrogens and androgens on the expression of the GH receptor gene and IGF-I messenger RNA may be operative. The present study confirms short-term data published in the literature on a sex difference in rhGH dose requirement in GH-deficient patients. It furthers extends the data by demonstrating that this sex difference in GH responsivity persists and changes during the 24 months of the study. Moreover, it shows that estrogen replacement blunts the IGF-I response to rhGH in women, whereas in men with androgen substitution the responsivity increases over time, thus bearing a risk of undertreatment in women and overtreatment in men.

Adult↗
PubMed1999

Plasma IGF-I is a useful marker of growth hormone deficiency in adults.

Diagnosing growth hormone deficiency in adults is difficult. Provocation tests are most commonly used for the diagnosis with the insulin-induced hypoglycemia test nowadays considered as the "gold standard". The role of IGF-I concentrations in diagnosing growth hormone deficiency in adults is under discussion. In 58 adult patients with proven growth hormone deficiency, the sensitivity and specificity of IGF-I concentrations in relation to growth hormone deficiency were evaluated. Reference values of plasma IGF-I were obtained from 53 healthy volunteers. Using a calculated cut-off concentration of 15 nmol/l we were able to demonstrate that IGF-I concentration is a reliable screening method for growth hormone deficiency. Using this cut-off point in a patient population younger than 40 years of age, sensitivity was 90% and specificity 89%. For patients exceeding the age of 40 years, sensitivity, specificity and positive predictive value were rather low, but the negative predictive value was as high as 90%, indicating that for patients over 40 years IGF-I concentrations above 15 nmol/l exclude growth hormone deficiency. In summary, under the age of 40 years measuring plasma IGF-I provides an useful tool to diagnose growth hormone deficiency, whereas above 40 plasma IGF-I values exceeding 15 nmol/l virtually exclude growth hormone deficiency.

Adult↗
PubMed1996

Number and percentage of NK-cells are decreased in growth hormone-deficient adults.

Snell-Bagg mice and Ames dwarf mice repeatedly show severe immunodeficiencies, affecting mostly the thymus- dependent lymphocyte system, probably caused by growth hormone deficiency. In growth hormone-deficient children contradictory data on the immune status have been reported. We investigated indices of cellular immunity in 22 adult patients with proven growth hormone deficiency in comparison to those in 100 health volunteers. Cellular immunity was assessed using total leukocyte count, percentage lymphocytes, and percentage and absolute numbers of CD3, CD4, CD8, CD19, and CD3-CD56+ (NK)-cells. Comparison revealed statistically significantly lower percentage and absolute number of NK-cells (P < 0.001). Except for a trend toward an increased CD4/CD8 ratio, no statistically significant differences for B- and T-lymphocytes could be observed. No correlation between the percentage and absolute number of NK-cells, on one hand, and the duration of growth hormone deficiency or prolactin level, on the other hand, could be demonstrated. In all these respects men did not differ from women. So, in growth hormone-deficient adults the percentage and absolute number of NK-cells are decreased.

Adolescent↗
PubMedDate not supplied

Polyglucosan bodies in brain tissue: a systematic study.

The relation between age, sex and presence of polyglucosan bodies in the brain has been systematically studied in 64 patients who did not suffer from neurological brain disorders and in 2 cases with Lafora's disease. In the normal brain the number of polyglucosan bodies is related to increasing age. Under the age of 40, polyglucosan bodies can be found sporadically in cases without a neurological disorder, but in the cases of Lafora's disease their number is uncomparatively higher. A sex relation has not been found.

Adolescent↗