Increased number of retinal vessels in acromegaly.

OBJECTIVE: Excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as in acromegaly, is associated with increased risk of diabetes, but whether retinal vessels are altered is unknown. The aim of this study was to evaluate retinal vessel morphology in patients with acromegaly at diagnosis and after treatment and to describe the prevalence of diabetic retinopathy in patients with long-standing acromegaly and diabetes. DESIGN: Two independent observational studies, one being prospective and the other retrospective and cross-sectional. METHODS: Retinal vessel morphology of 26 patients with acromegaly was examined at diagnosis and 1 year after treatment and compared to 13 healthy controls. Cross-sectional evaluation of 39 patients with long-standing acromegaly and diabetes was performed. Fundus photographs were digitally analyzed for vessel morphology. RESULTS: Patients with acromegaly had a median (interquartile range) of 34.3 (30.0-39.0) vessel branching points compared to 27.0 (24.0-29.0) for healthy controls (P < 0.001). Tortuosity of arterioles and venules remained unchanged. Vessel morphology did not change significantly after treatment. Patients with acromegaly and diabetes for a median of 14 years also had a high number of branching points (34.2 (32.5-35.6)), but the prevalence of diabetic retinopathy was not higher than expected in diabetic patients without acromegaly. CONCLUSIONS: Patients with acromegaly have an increased number of vascular branching points in the retina without an alteration of macroscopic vessel morphology. This is consistent with an angiogenic effect of GH/IGF-1 in humans. The prevalence of diabetic retinopathy was not increased in patients with acromegaly and diabetes.

Muscle strength in patients with acromegaly at diagnosis and during long-term follow-up.

OBJECTIVE: Patients with acromegaly have decreased body fat (BF) and increased extracellular water (ECW) and muscle mass. Although there is a lack of systematic studies on muscle function, it is believed that patients with acromegaly may suffer from proximal muscle weakness despite their increased muscle mass. We studied body composition and muscle function in untreated acromegaly and after biochemical remission. DESIGN: Prospective observational study. METHODS: Patients with acromegaly underwent measurements of muscle strength (dynamometers) and body composition (four-compartment model) at diagnosis (n = 48), 1 year after surgery (n = 29) and after long-term follow-up (median 11 years) (n = 24). Results were compared to healthy subjects. RESULTS: Untreated patients had increased body cell mass (113 ± 9% of predicted) and ECW (110 ± 20%) and decreased BF (67 ± 7.6%). At one-year follow-up, serum concentration of IGF-I was reduced and body composition had normalized. At baseline, isometric muscle strength in knee flexors and extensors was normal and concentric strength was modestly increased whereas grip strength and endurance was reduced. After one year, muscle strength was normal in both patients with still active disease and patients in remission. At long-term follow-up, all patients were in remission. Most muscle function tests remained normal, but isometric flexion and the fatigue index were increased to 153 ± 42% and 139 ± 28% of predicted values, respectively. CONCLUSIONS: Patients with untreated acromegaly had increased body cell mass and normal or modestly increased proximal muscle strength, whereas their grip strength was reduced. After biochemical improvement and remission, body composition was normalized, hand grip strength was increased, whereas proximal muscle fatigue increased.

Discontinuing long-term GH replacement therapy--a randomized, placebo-controlled crossover trial in adult GH deficiency.

CONTEXT: Adult GH deficiency (GHD) is associated with impaired quality of life (QoL) and increased cardiovascular risk. Continued long-term efficacy in terms of QoL and cardiovascular risk factors has been indicated in open surveillance studies. OBJECTIVES: The aim was to study the impact of discontinuation of long-term GH replacement on QoL, body composition, and metabolism. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled 4-month crossover trial in a referral center. PATIENTS: Sixty adult hypopituitary patients with GHD and more than 3 yr of continuous GH replacement therapy (mean treatment duration, 10 yr) participated in the study. INTERVENTION: Patients received GH or placebo. MAIN OUTCOME MEASUREMENTS: We measured QoL using validated questionnaires; body composition using computer tomography, dual-energy x-ray absorptiometry, and bioelectrical impedance spectroscopy; and insulin sensitivity using the short insulin tolerance test. RESULTS: Mean serum IGF-I decreased from 168 ± 52 to 98 ± 47 µg/liter during the placebo period (P < 0.001). Two QoL domains (emotional reactions and positive well-being) in the Nottingham Health Profile and Psychological General Well-Being questionnaires deteriorated during placebo, compared with GH treatment (P < 0.05). Waist circumference and sc and visceral fat mass increased, and extracellular water and muscle area decreased during the placebo period (all P < 0.05). C-reactive protein and total-, low-density lipoprotein-, and high-density lipoprotein-cholesterol increased, and insulin sensitivity improved during placebo, compared to GH treatment (P < 0.05). CONCLUSION: After more than 3 yr of GH replacement therapy, a 4-month period of placebo treatment caused self-perceived deterioration in QoL and increased abdominal fat accumulation. Moreover, markers of systemic inflammation and lipid status deteriorated, whereas insulin sensitivity improved. Long-term continuous GH replacement is needed to maintain therapeutic effects of GH on QoL and cardiovascular risk factors.

Baseline characteristics and the effects of two years of growth hormone (GH) replacement therapy in adults with GH deficiency previously treated for acromegaly.

CONTEXT: The effects of GH replacement in GH-deficient (GHD) adults previously treated for acromegaly are not well known. OBJECTIVE, DESIGN, AND PATIENTS: In this single-center, open-labeled, prospective study, 10 consecutive GHD adults with cured acromegaly (A group) and 10 matched GHD adults with previous nonfunctioning hypopituitary disease (NF group) were included. Comparisons were made at baseline and in the responses in body composition, muscle strength, bone mass, and metabolic indices during 2 yr of GH replacement. RESULTS: At baseline, upper leg local muscle endurance and serum low-density lipoprotein-cholesterol concentration were more impaired in the A group. The A group contained three patients with hypertension, one with diabetes mellitus type 2, and one with hyperlipidemia. The NF group had only one patient with hypertension. There were no significant between-group differences in the responses to the GH therapy. Body composition and serum lipid pattern improved in both groups without any deterioration of glucose homeostasis. At study end, no difference remained between the two groups in any variable. During the 2-yr treatment, one patient had a myocardial infarction and two had cerebral infarctions in the A group, whereas no vascular event occurred in the NF group. CONCLUSIONS: GHD patients with previous acromegaly have an impaired cardiovascular risk profile and decreased local muscle endurance as compared with other GHD patients. Two-year GH replacement eliminated these differences, but vascular events occurred more frequently in the A group. Therefore, GHD patients with cured acromegaly will benefit from GH replacement, but careful monitoring of cardiovascular status is needed.