sodium-ethylxanthate and Acromegaly

Data on bone mineral density (BMD) in acromegaly are conflicting as most previous studies collectively evaluated eugonadal and hypogonadal patients of both sexes, with or without active disease. We have evaluated BMD in 152 acromegalic patients of both sexes with varying disease activity and gonadal status.. Cross-sectional, retrospective.. We studied 152 acromegalic patients (99 women aged 26-72 years, and 53 men aged 21-75 years), 107 with active and 45 with controlled disease. Eighty-five patients had normal gonadal status and 67 were hypogonadal.. In all patients we measured serum GH levels by immunoenzimometric assay, and serum IGF-I levels by radioimmunoassay. BMD was assessed at spine L2-L4 (LS) and at femoral neck (FN) by dual energy X-ray absorptiometry; results are expressed as Z-values.. We evaluated the effect of GH excess on bone at different sites in relation to gonadal status, disease activity and gender. At LS, in respect to the reference population, BMD (mean +/- SE) values were higher in eugonadal patients (active: 0.71 +/- 0.29, P < 0.02; controlled: 0.65 +/- 0.28, P < 0.05) and lower in hypogonadal ones (active: -0.64 +/- 0.35, 0.1 < P < 0.05; controlled: -1.05 +/- 0.36, P < 0.01), regardless of disease activity. On the contrary, at FN, BMD was higher than in the reference population, both in eugonadal (1.01 +/- 0.22, P < 0.001) and hypogonadal (0.63 +/- 0.17, P < 0.001) patients only in subjects with active disease, but not in those in which the disease was controlled (eugonadal: 0.31 +/- 0.23, P = ns; hypogonadal 0.04 +/- 0.28, P = ns). We did not observe any difference in BMD values according to gender both at LS (males vs. females -0.02 +/- 0.30 vs. 0.01 +/- 0.24, P = ns) or at FN (0.77 +/- 0.19 vs. 0.63 +/- 0.15, P = ns).. The anabolic effect of GH excess on bone in acromegalic patients is: (i) gender-independent; (ii) evident at the spine only in eugonadal regardless of disease activity; (iii) evident at femoral neck only in the presence of active disease regardless of gonadal status.

Topics: Absorptiometry, Photon; Acromegaly; Acute Disease; Adult; Aged; Bone Density; Cross-Sectional Studies; Female; Femur Neck; Growth Hormone; Humans; Hypogonadism; Insulin-Like Growth Factor I; Male; Middle Aged; Retrospective Studies; Sex; Spine

To investigate the effect of gender on the response of GH to short-acting octreotide in patients with acromegaly, and on the GH and IGF-1 levels during long-term treatment with a slow-release formulation of octreotide.. Twenty-one men (mean age 54 years; range 26-78) and 15 women (mean age 54 years; range 22-74) with acromegaly were treated with subcutaneous injections of 100 microg short-acting octreotide twice daily. Serum samples for GH were taken before start of treatment, in the morning prior to the injection, and 1, 3, 5 and 7 h after the injection. Thirteen men (mean age 56 years; range 34-78) and 12 women (mean age 64 years; range 28-81) with acromegaly were switched from ongoing treatment with short-acting octreotide to injections of the slow-release formulation. A 4-h GH-profile and morning IGF-1 were taken at start and after 3, 9, 15 and 21 months of treatment.. Subcutaneous injections of 100 microg octreotide reduced the mean level of GH during a 7-h period to a similar extent in men and women compared to the GH levels prior to the injections. During long-term treatment with similar doses of the depot formulation of octreotide, the mean IGF-1 level remained significantly higher in the men than in the women, whereas there were no differences in the mean GH levels between the two groups.. The responses to short- and long-acting octreotide illustrate an effect of gender, due to different sensitivity to GH in the periphery. Furthermore, the results show that in the treatment of acromegaly, men will need higher doses of octreotide than women to normalize IGF-1.

Topics: Acromegaly; Adult; Aged; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Administration Schedule; Female; Follow-Up Studies; Growth Hormone; Humans; Injections, Intramuscular; Injections, Subcutaneous; Insulin-Like Growth Factor I; Male; Middle Aged; Octreotide; Retrospective Studies; Sex

In patients with acromegaly serum IGF-I is increasingly used as a marker of disease activity. As a result, the relationship between serum GH and IGF-I is of profound interest. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and women with GH deficiency require 30-50% more exogenous GH to maintain the same serum IGF-I as GH-deficient men. In a selected cohort of patients with active acromegaly, studied off medical therapy using a single fasting serum GH and IGF-I measurement, we have reported previously that, for a given GH level, women have significantly lower circulating IGF-I.. To evaluate the influence of age and gender on the relationship between serum GH and IGF-I in an unselected cohort of patients with acromegaly independent of disease control and medical therapy.. Sixty (34 male) unselected patients with acromegaly (median age 51 years (range 24-81 years) attending a colonoscopy screening programme were studied. Forty-five had previously received pituitary radiotherapy. Patients had varying degrees of disease control and received medical therapy where appropriate. Mean serum GH was calculated from an eight-point day profile (n = 45) and values obtained during a 75-g oral glucose tolerance test (n = 15). Serum IGF-I, IGFBP-3 and acid-labile subunit were measured and the dependency of these factors on covariates such as log10 mean serum GH, sex, age and prior radiotherapy was assessed using regression techniques.. The median calculated GH value was 4.7 mU/l (range 1-104). A significant linear association was observed between serum IGF-I and log10 mean serum GH for the cohort (R = 0.5, P < 0.0001). After simultaneous adjustment of the above covariates a significant difference in the relationship between mean serum GH and IGF-I was observed for males and females. On average, women had serum IGF-I levels 11.44 nmol/l lower than men with the same mean serum GH (P = 0.03, 95% CI 1.33-21.4 nmol/l). Age significantly influenced the relationship and for a given serum GH, IGF-I was estimated to fall by 0.37 nmol/l per year (P = 0.04, 95% CI 0.015-0.72).. In keeping with previous observations of relative GH resistance in normal and GH-deficient females we have observed lower serum IGF-I levels for equivalent mean serum GH levels in females patients with acromegaly. This gender-dependent difference is independent of disease activity and the use of concomitant medical therapy. Additionally, we have demonstrated that for a given serum GH level, age significantly influences IGF-I concentrations in patients with acromegaly. These data have important implications for the use of serum IGF-I and GH as markers of disease activity in acromegaly.

Topics: Acromegaly; Adult; Age Factors; Aged; Aged, 80 and over; Aging; Biomarkers; Case-Control Studies; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Regression Analysis; Sex; Sex Factors