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Background: The diagnostic value of non-invasive methods for diagnosing renal artery stenosis in patients with renal insufficiency is incompletely known., Methods: Forty-seven consecutive patients with moderately impaired renal function and a clinical suspicion of renal artery stenosis were investigated with computed tomography angiography (CTA), gadolinium-enhanced magnetic resonance angiography (MRA), contrast-enhanced Doppler ultrasound and captopril renography. The primary reference standard was stenosis reducing the vessel diameter by at least 50% on CTA, and an alternative reference standard ('morphological and functional stenosis') was defined as at least 50% diameter reduction on CTA or MRA, combined with a positive finding from ultrasound or captopril renography., Results: The frequency of positive findings, calculated on the basis of individual patients, was 70% for CTA, 60% for MRA, 53% for ultrasound and 30% for captopril renography. Counting kidneys rather than patients, corresponding frequencies were 53%, 41%, 29% and 15%, respectively. In relation to the CTA standard, the sensitivity (and specificity) at the patient level was 0.81 (0.79) for MRA, 0.70 (0.89) for ultrasound and 0.42 (1.00) for captopril renography, and at the kidney level 0.76 (0.82), 0.53 (0.81) and 0.30 (0.86), respectively. Relative to the alternative reference standard, corresponding values at the patient level were 1.00 (0.62) for CTA, 0.90 (0.69) for MRA, 0.91 (1.00) for ultrasound and 0.67 (1.00) for captopril renography, and at the kidney level 0.96 (0.76), 0.85 (0.79), 0.71 (0.97) and 0.50 (0.97), respectively., Conclusions: CTA and MRA are superior to ultrasound and captopril renography at diagnosing morphological stenosis, but ultrasound may be useful as a screening method and captopril renography for verifying renin-dependent hypertension.

Objective: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I., Design and Methods: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects., Results: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study., Conclusions: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.

Background: Our aim was to determine whether the aldosterone synthase (CYP11B2) -344 C/T polymorphism was associated with the blood pressure (BP)-lowering response to antihypertensive treatment., Methods: Patients with mild-to-moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind study to receive treatment with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan (n = 43), or the beta1-adrenergic receptor blocker atenolol (n = 43). The aldosterone synthase (CYP11B2) -344 C/T polymorphism was analyzed using solid-phase minisequencing and related to BP reduction after 3 months treatment. Serum aldosterone levels were measured., Results: After 3 months treatment the mean reductions in BP were similar for both treatment groups. When assessing the systolic BP reduction in the irbesartan group, patients with the TT variant had a more pronounced reduction (-21 +/- 19 SD mm Hg, n = 17) than both the TC (-14 +/- 18 mm Hg, n= 18) and CC (0 +/- 17 mm Hg, n = 8) genotypes (P = .04). There was no association between this polymorphism and the diastolic BP response. The -344 C/T polymorphism was not associated with the BP response to atenolol. Nor was it related to the baseline serum aldosterone level., Conclusions: The aldosterone synthase -344 C/T polymorphism was related to the BP-lowering response in hypertensive patients treated with the AT1-receptor antagonist irbesartan.

Objective: To study plasma concentrations of insulin-like growth factor-I (IGF-I) in adults with type 1 diabetes (IDDM) in comparison with a reference population, and the influence of glycaemic control, dose of insulin, and sex on the concentration of circulating IGF-I in IDDM., Design and Methods: Patients with type 1 diabetes were recruited consecutively from our outpatient diabetes unit. In all, 79 men and 55 women aged 20-60 years with a disease duration >/=6 years (range 6-51 years) took part in the study. A reference population of 80 men and 83 women aged 20-60 years was randomly obtained from the population registry. IGF-I was measured with radioimmunoassay after acid-ethanol extraction., Results: Mean +/- s. d. values of IGF-I were lower in patients with diabetes (146+/-66 microg/l) than in controls (238+/-83 microg/l, P<0.001). Those with diabetes had lower IGF-I concentrations in all age groups and the differences were highly significant in all decades except in women aged 50-59 years. IGF-I was negatively correlated with age in patients and controls. No correlation was found between IGF-I and glycaemic control measured as haemoglobin A(1c) (HbA(1c)) in the patients. IGF-I was positively associated with the dose of insulin/kg body weight in male patients independently of age, HbA(1c) and body mass index (P<0.03), but not in female patients (P=0.14)., Conclusions: Our data show that IGF-I concentrations are low in adult patients with type 1 diabetes with a disease duration >/=6 years, independently of glycaemic control. This suggests that subcutaneous insulin substitution is inadequate to normalize circulating IGF-I concentrations in patients without endogenous insulin secretion.

Population-based reference values for IGF-I and IGF-binding protein-1 (IGFBP-1) have been established. One hundred and one women and the same number of men, 20-70 years old, were randomly selected from the population registry in the community of Linköping. Participation rate was 67%. Venous blood was drawn in the fasting state. Serum IGF-I was measured by RIA after acid-ethanol extraction and IGFBP-1 was determined by ELISA. IGF-I levels did not differ between genders and the decline with age was similar in men and women (men: Y = 366-3.28 x age (years), r = -0.61, P < 0.0001; women: Y = 386-3.49 x age, r = -0.57, P < 0.0001, P = 0.4 for difference in slope). There were negative correlations between IGF-I and plasma lipids and blood pressure in both genders, but none was independent of age. Serum angiotensin-converting enzyme activity correlated positively with IGF-I in men independently from age (r = 0.21, P = 0.01). The distribution of IGFBP-1 was positively skewed and it was higher in women than in men (5.9 +/- 4.8 micrograms/l and 4.0 +/- 3.3 micrograms/l respectively; Mann-Whitney, P = 0.002). In men and in the women not taking oestrogen, IGFBP-1 correlated positively with age (Spearman rank correlation (Spearman: men: r = 0.32, P = 0.002; women: r = 0.24, P = 0.03). C-peptide correlated negatively (Spearman: men: r = -0.38, P = 0.002; women: r = -0.49, P < 0.000) and sex hormone binding globulin positively with IGFBP-1 (Spearman: men: r = 0.50, P < 0.0001; women: r = 0.55, P < 0.0001). IGF-I declined with age while IGFBP-1, which is considered to modulate the free bioactive fraction of IGF-I, increased. This suggests that IGF-I activity might be even lower in elderly subjects than is accounted for by the low total IGF-I.