Mortality in acromegaly: a 20-year follow-up study.

OBJECTIVE: It is unclear whether mortality still is increased in acromegaly and whether there are gender-related differences. We dynamically assessed outcome during long-term follow-up in our nationwide cohort. PATIENTS AND METHODS: We studied standardized mortality ratios (SMRs) relative to the general population and causes of death in acromegaly (n=333) compared with age- and gender-matched controls (n=4995). RESULTS: During 20 (0-33) years follow-up, 113 (34%) patients (n=333, 52% women) and 1334 (27%) controls (n=4995) died (P=0.004). SMR (1.9, 95% CI: 1.53-2.34, P<0.001) and all-cause mortality (OR 1.6, 95% CI: 1.2-2.2, P<0.001) were increased in acromegaly. Overall distribution of causes of death (P<0.001) differed between patients and controls but not cardiovascular (34% vs 33%) or cancer deaths (27% vs 27%). In acromegaly, but not in controls, causes of deaths shifted from 44% cardiovascular and 28% cancer deaths during the first decade, to 23% cardiovascular and 35% cancer deaths during the next two decades. In acromegaly, cancer deaths were mostly attributed to pancreatic adenocarcinoma (n=5), breast (n=4), lung (n=3) and colon (n=3) carcinoma. In acromegaly, men were younger than women at diagnosis (median 44.5 vs 50 years, P<0.001) and death (67 vs 76 years, P=0.0015). Compared with controls, women (36% vs 25%, P<0.01), but not men (31% vs 28%, P=0.44), had increased mortality. CONCLUSIONS: In acromegaly, men are younger at diagnosis and death than women. Compared with controls, mortality is increased during 20 years of follow-up, especially in women. Causes of deaths shift from predominantly cardiovascular to cancer deaths.

Managing diabetes care using an integrated regional e-health approach.

A total of 175 patients with Types 1 and 2 diabetes in primary care and university hospital outpatient departments were randomized into a study group (n = 101) or usual care (n = 74). The study group used an e-health application with a diabetes management system and a home care link. Usual care did not involve e-health, i.e. the patients made regular general practitioner visits about every three months. After 12 months HbA1c decreased significantly in both groups of patients. The differences were small, but HbA1c was significantly lower in the study group than the controls. Diastolic blood pressure, fasting plasma glucose, serum total cholesterol, serum LDL-cholesterol and serum triglycerides were significantly lower in the study than in the control group. This was achieved with fewer visits by study patients to doctors and nurses. Use of e-health in diabetes care for 12 months was able to provide equivalent diabetic control to usual care, and improved cardiovascular risk factors.

Quality of life in treated patients with acromegaly.

CONTEXT: It is not known to what extent quality of life of patients treated for acromegaly is dependent on levels of GH and IGF-I attained. OBJECTIVE: The objective of this study is to examine the health-related quality of life (HRQoL) and its dependence on treatment outcome and modality in a nationwide survey of acromegalic patients. DESIGN, SETTING, AND PATIENTS: All eligible patients with acromegaly, diagnosed from January 1980 through December 1999 in Finland, were invited to a follow-up study, carried out 11.4 +/- 5.7 (mean +/- sd) yr after initial treatment. HRQoL of the patients, measured by the generic 15D instrument, was compared with that of the general population. Factors related to HRQoL were analyzed by logistic regression. MAIN OUTCOME MEASURE: HRQoL was the main outcome measure. RESULTS: Of 277 eligible patients, 231 (83.4%) participated in the follow-up study. Of them, 51.1% were in remission according to consensus criteria. The patients reported reduced HRQoL in comparison to the age- and gender-standardized general population (P < 0.001). HRQoL was related to nadir GH in oral glucose tolerance test (GHOGTT) in an inverted U-shaped fashion (overall P = 0.021). Patients with GHOGTT nadir values between 0.3-1.0 microg/liter had a better HRQoL than those with lower or higher values. A normal IGF-I (P = 0.038) and not having had radiotherapy (P = 0.004) were also associated with a better HRQoL. CONCLUSIONS: HRQoL is reduced in treated patients with acromegaly. The best HRQoL may be achieved by normalization of IGF-I and by targeting the GHOGTT nadir to levels between 0.3 and 1.0 microg/liter. Radiotherapy is associated with adverse HRQoL.

Effect of sex and assay method on serum concentrations of growth hormone in patients with acromegaly and in healthy controls.

BACKGROUND: Diagnosis and follow-up of acromegaly is based on measurements of serum growth hormone (GH) concentrations during an oral glucose tolerance test (OGTT). A nadir value <1 microg/L is commonly used to define a normal response, but some authors suggest lower cutoff values. METHODS: To compare the results and subsequent patient classification obtained with 3 GH assays, we obtained basal serum samples from 78 apparently healthy adult controls (43 women and 35 men; median age, 32.5 years) and from 71 treated (44 women and 27 men; median age, 55.2 years) and 7 untreated acromegaly patients (4 women and 3 men; median age, 54.6 years), and OGTT was performed on all patients and on 72 of the 78 controls. GH was determined by 2 immunometric assays-a double monoclonal (AutoDELFIA; Wallac) and a monopolyclonal (Immulite 2000; DPC) assay-and in a limited set of samples by an RIA (Spectria RIA; Orion). RESULTS: There was a strong correlation (r = 0.995; P < 0.001) between the 2 immunometric methods, but the results obtained with the Immulite 2000 were, on average, 1.4-fold higher than those obtained with the AutoDELFIA. At concentrations around the cutoff (1 microg/L), however, the difference was approximately 2-fold. Overall, the Orion RIA method also showed a good correlation (r = 0.951-0.959) with the other methods, but it did not measure concentrations <2 microg/L. Women had higher basal and OGTT nadir GH concentrations than men. CONCLUSION: Reference intervals should be determined separately for each method, and the need for establishing sex-specific reference values should be investigated.

A nationwide survey of mortality in acromegaly.

CONTEXT: Increased mortality in acromegaly has been confined to those with posttreatment basal GH of 2.5 microg/liter or greater, but the impact of IGF-I and pituitary radiotherapy on mortality has remained controversial. OBJECTIVE: The purpose of this nationwide survey was to examine the all-cause mortality of patients with acromegaly and evaluate the impact of treatment outcome and mode of treatment on survival. DESIGN, SETTING, AND PATIENTS: All-cause mortality of all patients with acromegaly diagnosed during January 1980 and December 1999 in the five university hospitals of Finland was followed up by the end of 2002 (12.5 +/- 5.6 yr) and compared with that of the general population by using age- and gender-adjusted standardized mortality ratios (SMRs). Logistic regression analysis was used to investigate factors related to mortality within the survey population. MAIN OUTCOME MEASURE: Mortality was the main outcome measure. RESULTS: Of the 334 patients, 56 (16.8%) had died during follow-up. SMR of the patients was 1.16 [confidence interval (CI) 0.85-1.54, not significant (NS)]. However, patients with basal serum GH concentration 2.5 microg/liter or greater (SMR 1.63, CI 1.10-2.35, P < 0.001) measured 5.2 +/- 4.4 yr after the initial treatment, and those irradiated (SMR 1.69, CI 1.05-2.58, P < 0.001) showed excess mortality. In a multivariate model, the effect of radiotherapy was of borderline significance only (P = 0.083). Posttreatment IGF-I levels, available for 72.2% of the patients, did not have impact on mortality. CONCLUSIONS: The posttreatment basal GH concentration less than 2.5 microg/liter in acromegalic patients is associated with a normal lifespan. Excess mortality is confined to poorly controlled patients and possibly those who have received conventional radiotherapy.

High dose intravenous methylprednisolone pulse therapy versus oral prednisone for thyroid-associated ophthalmopathy.

PURPOSE: To compare the effectiveness of intravenous (i.v.) methylprednisolone pulse therapy and oral prednisone when used as the initial treatment of patients with mild or moderate thyroid-associated ophthalmopathy. METHODS: Thirty-three consecutive patients with thyroid-associated ophthalmopathy in Helsinki and Turku University Hospitals were randomly assigned either i.v. methylprednisolone pulse therapy (group A, n = 18) or oral prednisone (group B, n = 15). Treatment outcomes were measured by subjective changes in the grade of diplopia and quantitatively in several ophthalmic variables at 3 and 12 months. Any decision to proceed with additional treatment at 3 months was made on clinical grounds. The study was open in respect of both the initial treatment and the need for additional therapy. RESULTS: No significant differences in the grade of diplopia, proptosis or soft tissue activity scores were noted between groups A and B from 0 to 3 months. However, group A required additional forms of therapy at 3 months less frequently than did group B (p = 0.038). CONCLUSIONS: Our data suggest that i.v. methylprednisolone pulse therapy and oral prednisone are equally effective as initial treatments for thyroid-associated ophthalmopathy where diplopia, proptosis and signs of soft tissue inflammation are concerned. When additional treatment is required, i.v. methylprednisolone pulse therapy may be more effective than oral prednisone. However, the study's limitations meant that any decision to give additional treatment after the initial therapy was made on clinical grounds.