Bengt-Åke Bengtsson

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.

Growth hormone-deficient adults are insulin-resistant

Patients with growth hormone deficiency (GHD) have traditionally been described as having increased insulin sensitivity with a tendency toward fasting hypoglycemia, at least in children. In other studies, impaired glucose tolerance has been found. To evaluate basal insulin sensitivity, a hyperinsulinemic, normoglycemic clamp was performed with an insulin rate of 40 mU/m2/min after an overnight fast. Fifteen patients (four women and 11 men aged 20 to 62 years) with GHD for at least 1 year were compared with 15 healthy controls matched for sex, age, and body mass index (BMI). Thirteen patients had complete pituitary deficiency and were being treated with conventional hormone replacement therapy. Two men had isolated GHD since childhood. Four men were being treated with bromocriptin. There were no significant differences between fasting blood glucose (4.4 +/- 0.1 v 4.7 +/- 0.2 [mean +/- SEM] mmol/L) or fasting plasma insulin (9.5 +/- 1.4 v 8.8 +/- 1.1 mU/L) in patients and controls, respectively. Fasting free fatty acid (FFA) levels were lower in patients (444 +/- 35 v 796 +/- 94 mumol/L, P < .01). Blood glucose levels during the clamp were similar (4.6 +/- 0.1 v 4.9 +/- 0.1 mmol/L), as were insulin levels (81 +/- 4 v 93 +/- 4 mU/L). A decrease in glucose infusion rate (GIR) was seen during the clamp in GHD subjects (3.9 +/- 0.5 v 9.9 +/- 0.7 mg/kg body weight/min) as compared with controls (P = .001). Even if corrections were made for body fat, there was a significant difference (GIR corrected per lean body mass, 5.8 +/- 0.8 v 13.9 +/- 0.9 mg/kg lean body mass/min, P < .001). The results suggest that adults with GHD are insulin-resistant. Despite this finding, normal fasting plasma insulin levels were seen.

GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety.

Long‐term experience of growth hormone (GH) replacement therapy in a large population of hypopituitary adults with GH deficiency (GHD) is limited, and safety surveillance is clearly essential. KIMS, the Pharmacia & Upjohn International Metabolic Database, is a long‐term, open, outcomes research programme of hypopituitary adult patients with GHD who are treated in a conventional clinical setting.

The Influence of Growth Hormone Deficiency, Growth Hormone Replacement Therapy, and Other Aspects of Hypopituitarism on Fracture Rate and Bone Mineral Density

To assess the influence of factors affecting fracture risk and bone density in adult hypopituitary patients with growth hormone deficiency (GHD), data from a large‐scale pharmacoepidemiological survey (the Pharmacia & Upjohn International Metabolic Database [KIMS]) were analyzed and compared with data from a control population (the European Vertebral Osteoporosis Study [EVOS]). The KIMS group consisted of 2084 patients (1112 men and 972 women) with various types of pituitary disease and EVOS consisted of 1176 individuals (581 men and 595 women). Fracture and bone mineral density (BMD) data were available from 2024 patients from the KIMS group and 392 patients from EVOS. The prevalence of fractures in patients with hypopituitarism was 2.66 times that in the non‐GH‐deficient EVOS population. Adult‐onset hypopituitarism with GHD was associated with a higher fracture risk than childhood‐onset disease, and patients with isolated GHD had a similar prevalence of fractures to those with multiple pituitary hormone deficiencies. Hormonal replacement therapy with L‐thyroxine, glucocorticoids, and sex steroids did not affect the risk of fracture in KIMS patients. In addition, fracture rates in KIMS were independent of body mass index (BMI) and the country of origin. However, smoking was associated with a higher fracture rate in this group. In summary, this is the first large‐scale analysis to support the hypothesis of an increased fracture risk in adult patients with hypopituitarism and GHD. This increased risk appears to be attributable to GHD alone, rather than to other pituitary hormone deficiencies or to their replacement therapy.

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.

Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency.

In a double-blind, cross-over, placebo-controlled trial, the effect of 26 weeks of replacement therapy with recombinant human growth hormone (rhGH) on insulin sensitivity and glucose metabolism in nine patients with adult-onset growth hormone deficiency was studied with a euglycemic clamp. Glucose production and utilization were studied with D-(3-3H)-glucose infusions. Comparisons were made with placebo treatment for 6 and 26 weeks, respectively. GH therapy for 6 weeks increased fasting plasma concentrations of glucose and insulin. However, after 26 weeks of GH treatment, no significant changes in glucose or insulin concentrations were recorded. GH treatment induced a marked change in insulin action evident after 6 weeks of therapy as shown by lower glucose infusion rates (GIRs) during the clamp compared with placebo treatment (2.6 +/- 0.4 v 4.1 +/- 0.7 mg.kg-1.min-1). This change in insulin action was due to a decreased insulin effect on glucose utilization. After 26 weeks of GH therapy, there was no significant difference in GIRs. During placebo treatment, insulin sensitivity and insulin, glucose, and nonesterified fatty acid (NEFA) concentrations were unchanged compared with concentrations measured before the study. Thus GH replacement therapy induces a change in insulin action in GH-deficient individuals. Whether this change represents a decrease in insulin action (ie, insulin resistance) or a restoration of action to normal is presently unclear, since a healthy control group was not included in the study. During long-term treatment, the present study suggests that the change in insulin action can be reversed, probably secondarily to changes in body composition.

Treatment of Growth Hormone-Deficient Adults with Recombinant Human Growth Hormone Increases the Concentration of Growth Hormone in the Cerebrospinal Fluid and Affects Neurotransmitters

In a double-blind, placebo-controlled trial, the effects of recombinant human growth hormone were studied on cerebrospinal fluid concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), monoamine metabolites, neuropeptides and endogenous opioid peptides. Twenty patients, 10 patients in each of 2 groups, with adult-onset, growth hormone deficiency were treated for 1 month with recombinant human growth hormone (0.25 U/kg/week) or placebo. All the patients received the appropriate thyroid, adrenal and gonadal hormone replacement. In cerebrospinal fluid, the mean concentration of growth hormone increased from 13.3 +/- 4.4 to 149.3 +/- 22.2 muU/l (p = 0.002), during recombinant human growth hormone treatment. The cerebrospinal fluid IGF-I concentration increased from 0.67 +/- 0.04 to 0.99 +/- 0.10 micrograms/l (p = 0.005) and the IGFBP-3 concentration rose from 13.4 +/- 1.25 to 17.5 +/- 1.83 micrograms/l (p = 0.002). The dopamine metabolite homovanillic acid decreased from 282.1 +/- 36.0 to 234.3 +/- 26.5 nmol/l (p = 0.02) and the vasoactive intestinal peptide decreased from 4.1 +/- 0.6 to 3.7 +/- 0.4 pmol/l (p = 0.03). Cerebrospinal fluid immunoreactive beta-endorphin increased from 24.4 +/- 1.8 to 29.9 +/- 2.1 pmol/l (p = 0.002). There were no significant changes compared to baseline in the cerebrospinal fluid concentrations of enkephalins, dynorphin A, the norepinephrine metabolite 3-methoxy-4-hydroxyphenyl-ethyleneglycol, the serotonin metabolite 5-hydroxyindoleacetic acid, gamma-aminobutyric acid, somatostatin or corticotropin-releasing factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular and renal effects of growth hormone

OBJECTIVE With the advent of recombinant human GH (rhGH), it has become possible in controlled clinical studies to explore the effects of GH replacement in adults with GH deficiency. The objective of this study was to determine cardiovascular and renal effects of GH replacement in adults with GH deficiency.

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.