Göran Lindstedt

OBJECTIVE: There is a clinical need for population based reference values for serum insulin-like growth factor I (IGF-I). We have therefore determined serum IGF-I concentrations in a random population sample from Sweden and have related the levels to age, sex, life style factors, blood pressure, body composition, blood lipids, plasma fibrinogen, parathyroid hormone (PTH) and osteocalcin. PATIENTS: Within the framework of the WHO MONICA Project in the city of Göteborg, Sweden, 197 men and 195 women aged 25-64 years were studied. RESULTS: Women aged 25-34 years had higher IGF-I concentration than men (mean 278 vs 227 micrograms/l) but in the interval 55-64 years values were lower in women than in men (158 vs 171 micrograms/l). IGF-I correlated positively with height and inversely with age, body mass index, systolic blood pressure and total cholesterol in both sexes. Negative relations between IGF-I and high density lipoprotein-cholesterol, as well as with amount of tobacco smoked, were found in men, and between IGF-I and diastolic blood pressure, triglycerides and PTH in women. When age was allowed for in multivariate analyses, most of these relations disappeared. However, among men IGF-I was positively associated with fibrinogen and negatively with age and smoking. IGF-I was negatively associated with age and coffee consumption in women. CONCLUSION: The present data can be used as reference values for IGF-I (at least in Caucasians) for the diagnosis of growth hormone disturbances and as guidelines for growth hormone substitution.

OBJECTIVE: Growth hormone deficiency in adults with hypopituitarism has previously received little attention. Recent data, however, suggest that GH deficiency might be essential for the long-term prognosis of these patients. Earlier studies have documented that GH regulates body composition; in this, body composition in adult patients with hypopituitarism including GH deficiency was studied. DESIGN: A follow-up study of patients with hypopituitarism on routine replacement therapy with L-thyroxine, cortisone acetate and sex steroids. PATIENTS: One hundred and six patients (69 males, mean age 52.5 years and 37 females, mean age 53.4 years) diagnosed as having growth hormone deficiency on the basis of low IGF-I concentration or a maximum GH-response less than 5 mU/l after an insulin/glucagon tolerance test. MEASUREMENTS: Body composition was estimated from body weight, total body water and total body potassium and the results were compared with values predicted from height, weight, age and sex, using data from a large number of healthy subjects. RESULTS: The total body water was significantly lower than that predicted from the observed body weight (P < 0.001), as was the extracellular water (P < 0.001) and the extracellular/intracellular water quotient (P < 0.001). On average, the body cell mass was similar to the predicted value, but the observed/predicted body cell mass ratio correlated positively with age at follow-up. The body cell mass was lower than predicted in subjects below the age of 50 years (P < 0.01). The body fat was higher than predicted (P < 0.001); the increases was also noted in lean subjects. The observed body weight in male subjects was 7.5 kg higher (P < 0.001) than that predicted from healthy subjects of the same body height, a difference explained by an average increase of 6.6 kg in the body fat (P < 0.001) and 1.6 kg in the body cell mass, with a simultaneous reduction of 0.7 kg in the extracellular water (NS). Male patients suffering from untreated androgen deficiency had lower body cell mass than those on androgen treatment. Female subjects weighed 3.6 kg (NS) more on average than healthy women, a difference explained by an increase in the body fat of 6.0 kg (P < 0.001) with a simultaneous decrease of 2.4 kg in the extracellular water (P < 0.001). The body cell mass was similar to that seen in the controls. CONCLUSIONS: Adult patients with growth hormone deficiency have an increased body weight compared to normals of the same age, sex and height, due to an increment of the body fat with a simultaneous reduction in the total body water.

Efficacy of different methods in screening for iron deficiency was re-examined in a randomly selected sample of 38-year-old women (n = 203) with known iron status based on absence/presence of stainable iron in bone-marrow smears. The study was made in 1968-69. Serum ferritin (SF) was determined in 1978 in frozen sera using the Ramco IRMA and, in 1992, samples were re-analysed using a RIA calibrated with the International Standard 80/602 for SF determination. The effect of storage on SF was calculated from a previously established relationship (courtesy of Dr Mark Worwood, Cardiff) between the results obtained with the Ramco assay and assays calibrated with IS 80/602. The distributions in iron replete and iron deficient women showed less overlap (diagnostic efficiency 91%) for SF than for other haematological parameters. The best discrimination was obtained at SF < 16 micrograms/l (specificity 98%; sensitivity 75%). Absence of iron stores was associated with signs of an iron deficient erythropoiesis, starting already at SF 25-40 micrograms/l. Use of multiple criteria to diagnose iron deficiency falsely reduces prevalence figures for iron deficiency.

Serum sex-hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were evaluated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM), myocardial infarction, stroke, and premature death in a prospective study of 1462 randomly selected women, aged 38-60 yr, over 12 yr of observation. In multivariate analysis, taking only age into consideration as a confounding factor, low initial concentration of SHBG was significantly correlated to the incidence of NIDDM and stroke, and high initial concentration of CBG was correlated to the incidence of NIDDM. There were also significant correlations between SHBG and CBG concentrations on one hand and possible risk factors for the end points studied, such as serum triglycerides, serum cholesterol, fasting blood glucose, body mass, body mass index, waist/hip ratio, smoking habits, and systolic blood pressure, on the other. When these possible confounders, in addition to age, were taken into consideration in multivariate analyses, only the inverse significant correlation between SHBG and NIDDM remained. The increased incidence of diabetes was confined to the lowest quintile of SHBG values, where it was 5-fold higher than in the remaining group. This incidence was further increased to 8- and 11-fold in the lowest 10 and 5% of the values, respectively. We conclude that SHBG is a uniquely strong independent risk factor for the development of NIDDM in women.