Thord Rosén

Serum insulin‐like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin

OBJECTIVE There Is a cllnlcal 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, llfe style factors, blood pressure, body composition, blood llplds, plasma fibrlnogen, Parathyroid hormone (PTH) and osteocalcin.

Decreased psychological well-being in adult patients with growth hormone deficiency

OBJECTIVE Besides effects on body composition, bone mineral content and lipid metabolism, GH seems to influence quality of life, according to previous studies of limited numbers of patients with GH deficiency of childhood and adult origin. In this study psychological well‐being was assessed in a large number of patients with GH deficiency of adult origin.

Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency

OBJECTIVE Growth hormone deficiency in adults with hypopituitarism has previously received little attention. Recent data, however, suggest that GH deflciency 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.

Growth hormone treatment of growth hormone-deficient adults results in a marked increase in Lp(a) and HDL cholesterol concentrations.

The effects of growth hormone treatment of adults with adult-onset pituitary insufficiency on lipoproteins and apolipoproteins were investigated. Nine patients, one women and eight men (age range, 34-58 years), who had been treated for pituitary tumors were studied. They had complete pituitary insufficiency with a duration of at least 1 year. All patients received replacement therapy with thyroid hormones, glucocorticoids, and gonadal steroids. The study had a double-blind, placebo-controlled, crossover design for active treatment with recombinant human growth hormone (0.25-0.5 units/kg per week s.c. given each evening) for 6 months. Fasting serum levels of cholesterol; triglycerides; high density lipoprotein and low density lipoprotein cholesterol; apolipoproteins A-I, B, and E; and lipoprotein (a) were measured before and after 6 and 26 weeks of treatment. Lipoprotein (a) concentrations increased markedly during treatment and were about twice as high compared with pretreatment levels. Serum cholesterol and low density lipoprotein cholesterol concentrations were decreased after 6 weeks of treatment, but levels had returned to pretreatment levels after 26 weeks. High density lipoprotein cholesterol concentrations increased during treatment and were significantly higher than pretreatment levels after 26 weeks of treatment. Serum triglyceride concentrations did not change significantly, but in two patients with marked hypertriglyceridemia, growth hormone treatment resulted in a marked decrease. Serum concentrations of apolipoproteins A-I, B, and E did not change significantly, but changes in apolipoprotein A-I and B concentrations were in parallel to those observed for high density lipoprotein cholesterol and low density lipoprotein cholesterol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

High fibrinogen and plasminogen activator inhibitor activity in growth hormone-deficient adults.

Hypopituitary patients on routine replacement therapy except growth hormone (GH) have an increased risk of death from cardiovascular diseases compared with healthy subjects. Untreated GH deficiency might explain the premature death from vascular disease. Plasminogen activator inhibitor (PAI-1) activity, fibrinogen, insulin, blood lipid, and blood pressure levels were studied in 20 GH-deficient adults (10 men, 10 women) 50 +/- 11 years old with routine hormone replacement therapy (except GH) and compared with 20 healthy control subjects matched for sex, age, and body mass index. GH-deficient subjects had a higher waist-to-hip circumference ratio (P < .001), serum triglycerides (P < .02), PAI-1 activity (13.2 +/- 10.6 versus 6.8 +/- 4.8 U/mL [P < .05]), and fibrinogen (3.2 +/- 0.7 versus 2.4 +/- 0.6 g/L [P < .001]) and lower blood glucose (P < .05) compared with control subjects. Blood pressure, insulin, and cholesterol levels were similar. The aberrations found in this study might contribute to an increased atherothrombotic propensity and play a role in the pathogenesis of cardiovascular disease.

Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults

Until now, GH treatment in GH‐deficient adults has employed dose schedules of GH based on body weight or body surface area and has ignored individual responsiveness to GH. This trial has studied the effects of an individualized GH dose adjusted to match a combination of clinical response, normalization of serum IGF‐I concentration and body composition.

Effects of 1 Year of Growth Hormone Therapy on Serum Lipoprotein Levels in Growth Hormone–Deficient Adults Influence of Gender and Apo(a) and ApoE Phenotypes

We investigated the influence of gender and apoE and apo(a) phenotypes as well as the effect of the metabolic effects of growth hormone (GH) on the effect of GH therapy on serum lipoprotein concentrations in GH-deficient (GHD) adults. Forty-four consecutive patients, 30 men and 14 women aged 46.5 (range, 19 to 76) years with GHD due mainly to pituitary tumors, were treated with recombinant human GH for 12 months. Serum concentrations of lipoproteins, insulin, thyroxine, and insulin-like growth factor-I were determined, body composition was assessed by bioelectrical impedance, and apo(a) and apoE phenotypes were analyzed. Lipoprotein(a) [Lp(a)] concentrations in the GHD subjects were compared with a gender- and apo(a) phenotype-matched control group. After 12 months of GH treatment, the total cholesterol, LDL cholesterol, and apoB concentrations decreased, the HDL cholesterol and apoE concentrations increased, and the apoA-I and triglyceride concentrations were unchanged. Before treatment, the Lp(a) concentration was similar to that in the control group. However, after 12 months of treatment, the Lp(a) concentration had increased by 44% and 101% above baseline and the control group, respectively. Men and women responded differently to GH, with a more marked increase in Lp(a) concentration and fat-free mass and a more pronounced decrease in body-fat mass in men. Apo(a) phenotypes had no major influence on the effect of GH therapy. The only significant difference between apoE phenotypes was a higher baseline Lp(a) concentration among apoE4 heterozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Surgery on Cardiovascular Risk Factors in Mild Primary Hyperparathyroidism

CONTEXT Mild primary hyperparathyroidism (pHPT) seems to have a good prognosis, and indications for active treatment (surgery) are widely discussed. The extraskeletal effects of PTH, such as insulin resistance, arterial hypertension, and cardiovascular (CV) risk, may however be reversible by operation. OBJECTIVE Our aim was to study biochemical markers of bone turnover, indices of the metabolic syndrome, and various risk markers for CV disease in patients with mild pHPT randomized to observation without surgery or operative treatment and followed for 2 yr. DESIGN/SETTING/PATIENTS A total of 116 patients (mean age, 63 +/- 8 yr; 19 men and 97 women) who on May 1, 2008, had performed the 2-yr visit in a randomized study on mild pHPT (serum calcium at baseline, 2.69 +/- 0.11 mmol/liter) and where frozen samples were available from baseline and follow-up participated in the study. RESULTS Calcium and PTH levels were normalized after surgery, and biochemical markers of bone turnover decreased by 35%, followed by a significant increase in BMD in the spine (2.7%; P < 0.01) and femoral neck (1.1%; P < 0.02) compared with the observation group. No significant differences were observed between the groups for blood pressure, markers of insulin resistance, detailed cholesterol metabolism, adipokines, or parameters of inflammation and CV surrogate markers. CONCLUSIONS We observed expected effects on biochemical markers of bone turnover and bone mass after surgical treatment of mild pHPT, with stable values in the group randomized to observation. For a variety of measures of the metabolic syndrome, adipokines, and CV risk factors, no benefit of operative treatment could be demonstrated. Neither did we observe any deleterious effects of conservative management in the 2-yr perspective.

Fracture incidence in GH-deficient patients on complete hormone replacement including GH

Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men.

Supraphysiological growth hormone: less fat more extracellular fluid but uncertain effects on muscles in healthy active young adults.

Objectives  To study the effects on body composition after 1 months administration of supraphysiological doses of growth hormone (GH) in healthy, active young adults with normal GH‐IGF‐I axis.