Relationship of physical exercise and ageing to growth hormone production.

OBJECTIVE: The normal decline in physiological function with ageing is associated with a decrease in bioavailable growth hormone. Growth hormone has been shown to alter body composition and increase fat-free mass in older men. Increased physical fitness is accompanied by an increase in 24-h growth hormone release. The purpose of this study was to examine the effect of exercise on declining growth hormone concentrations with increasing age. DESIGN AND PATIENTS: The growth hormone production of 10 male subjects running over 40 miles per week was compared to 10 healthy age-matched sedentary males (controls 57.7 +/- 2.8 vs. runners 60.5 +/- 3.4 years). All subjects underwent a basal assessment including a two-hour serum growth hormone profile followed by estimation of maximal exercise capacity on a cycle ergometer with growth hormone estimations at peak exercise activity and every five minutes whilst cycling at 40% of maximal exercise capacity. RESULTS: Maximal exercise capacity confirmed the lifestyles of the two groups (VO2 max controls 22.36 +/-6.05 vs. runners 34.91 +/- 13.13 l/min/kg, P = 0.01). The runners had lower body-mass indices than controls (BMI 22. 3 +/- 1.5 vs. 25.5 +/- 2.0 kg/m2, P = 0.002). Peak growth hormone level during a two-hour resting profile was higher in the runners (median (range) controls 2.10 (0.20-12.20) vs. runners 5.25 (0.80-21. 00) mU/l, P = 0.03) as was the average growth hormone level during the two hour profile (mean growth hormone per 2 h median (range): controls 0.54 (0.03-4.88) vs. runners 2.17 (0.25-7.45) mU/l, P = 0. 04). Growth hormone production at maximal exercise capacity was similar. Sex hormone binding globulin and testosterone were significantly higher in the runners. CONCLUSIONS: The results suggest that regular intensive exercise in older male subjects is associated with higher growth hormone and testosterone levels and that exercise may have a role in counteracting the normal decline in growth hormone with ageing.

Urinary growth hormone following exercise to assess growth hormone production in adults.

OBJECTIVE: The insulin stress test (IST) is the most commonly used test to assess the GH reserve in children and adults. It is a time-consuming, expensive and potentially dangerous test. We investigated whether measurement of urinary growth hormone excretion following exercise would prove on reliable method to diagnose adult GH deficiency. DESIGN: Healthy volunteers underwent a standard IST to confirm GH secretion. Using a standardized exercise protocol on a treadmill, the urinary excretion of GH was measured. Three patients confirmed as GH deficient by an IST were exercised during the same exercise protocol and their urinary excretion of GH was measured. PATIENTS: Ten healthy volunteers and three patients with hypopituitarism were evaluated. MEASUREMENTS: A standard IST was performed on both healthy volunteers and patients, with measurements of plasma GH and plasma cortisol. Urinary growth hormone and urinary GH/creatinine (GH/CR) ratios were measured before and after IST. On a separate visit, healthy volunteers and patients were exercised on the treadmill with measurements of plasma GH and cortisol. Urinary GH and GH/CR ratios were measured before and after exercise. RESULTS: There was at least a two-fold increase in urinary GH and GH/CR ratios following exercise in all healthy adults. By contrast, patients with GH deficiency showed no rise in urinary GH or urinary GH/CR ratios following exercise. CONCLUSIONS: Measurements of urinary GH following exercise can distinguish between GH-deficient adults and healthy volunteers. Urinary GH excretion can be measured over a timed interval following exercise or can be expressed as the GH/CR ratio. This can be measured on a single sample following exercise and can be used to diagnose GH deficiency. The exercise test employed for this study is arduous. We are therefore performing further studies with a less strenuous exercise protocol with a view to designing a 'patient-friendly' exercise test for GH deficiency in adults.

Concentrations of free thyroxin and albumin in serum in severe nonthyroidal illness: assay artefacts and physiological influences.

Free thyroxin (FT4) estimates by two immunoassays were compared with the concentrations of albumin in serum of apparently euthyroid subjects who either were (n = 99) or were not (n = 327) suffering from severe nonthyroidal illness (sNTI). In neither group was FT4 significantly correlated with albumin (P greater than 0.05), according to a "labeled antibody" radioassay (Amerlex-MAB). On amalgamating both groups, correlation with albumin was positive and significant (P less than 0.001). In the group with sNTI, both FT4 and albumin concentrations were decreased (mean FT4 to 77% and mean albumin to 61% of the respective reference means). For an analog radioimmunoassay (Amerlex-M), FT4 in all groups was significantly (P less than 0.001) correlated with albumin. Correlation coefficients were greater than with Amerlex-MAB for both sNTI and euthyroid groups, as well as for the joint panel. Mean FT4 in sNTI was only 44% of the reference mean. Lower radio-tracer "analog" values in sNTI are exaggerated by additional technical artefacts resulting from tracer binding to albumin.

The incidence of occult thyroid disease associated with thyroid antibodies identified on routine autoantibody screening.

The presence of thyroid microsomal and/or thyroglobulin antibodies has been recorded over a 2 year period of 15 000 consecutive autoimmune profile request. Where there had been no initial clinical suspicion of thyroid diseases, 332 requests showed positive thyroid antibodies, and of these 63 (19%) had abnormal in vitro thyroid function tests (TFT). No differences were observed between the abnormal and normal groups with respect to the presence of different autoantibodies or to the age and sex distributions. Of these subjects with clinically unsuspected hypothyroidism but with abnormal TFTs, 29% were commenced on thyroxine therapy and experienced a symptomatic improvement, 25% remain well on no therapy and 9% continue on no treatment but with symptoms possibly attributable to hypothyroidism. 3% became clinically hypothyroid during a follow-up period of 2 years. 5% died of unrelated causes and there was inadequate follow-up information on the remainder. This study provides further confirmation that when thyroid antibodies, and in particular thyroid microsomal antibody, are found unexpectedly, a significant proportion of patients will have biochemical evidence of hypothyroidism and may benefit from appropriate treatment.

A method of assessing serum triiodothyronine concentrations that is independent of subject's age and variations in concentrations of binding proteins in serum.

Pairs of values for serum triiodothyronine and serum triiodothyronine binding capacity were represented as maps of points for euthyroid populations (including subjects who were pregnant or were receiving estrogens) in the age groups 18-50, 51-64, 65-79, and greater than 80 years (504 subjects) and thyrotoxic populations in the same age groups (207 subjects). For each age group the two populations were effectively separated bythe technique. Statistical analysis by the method of principal components justified the combination of all the age-related maps into a single map, allowing the assessment of serum triiodothyronine regardless of age or concentration of binding proteins in serum. The overlap of the combined populations was less than 1%. The method proposed is superior to a calculation of free triiodothyronine index in several respects.