Persistence of Diabetes and Hypertension After Multimodal Treatment of Acromegaly.

Context: Diabetes and hypertension are frequent comorbidities of acromegaly. Objective: To analyze the course of diabetes and hypertension at diagnosis and after multimodal therapy in a large cohort of patients with acromegaly. Design and Setting: Retrospective study at a tertiary care center. Patients and Methods: A total of 522 patients with acromegaly treated according to a preestablished protocol. Main Outcome Measures: Prevalence of diabetes and hypertension and its relationship with biochemical indices of acromegalic control. Results: The cohort was stratified according to disease activity upon last visit to clinic: (1) surgical remission (n = 122), (2) pharmacologically controlled (n = 92), (3) active disease (n = 148), (4) insulinlike growth factor (IGF)-1 discordance (n = 64), and (5) growth hormone (GH) discordance (n = 96). The prevalence of diabetes and hypertension at diagnosis was 30% and 37%, respectively, and did not change upon the last visit (30.6% and 38%). Both comorbidities were more prevalent at diagnosis and on the last visit than in the general population. Diabetes was less prevalent on the last visit in patients who achieved surgical remission than in those who persisted with active disease (25% vs 40%, P = 0.01). Upon multivariate analysis, diabetes was associated with an IGF-1 at diagnosis >2× upper limit of normal, with the persistence of active acromegaly, the presence of hypertension upon the last visit, with the presence of a macroadenoma, and with female sex. Conclusion: Our findings underscore the importance of an integral approach when managing these patients, focusing not only on the control of GH and IGF-1 levels but also on the timely diagnosis and the specific treatment of each comorbidity.

Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic.

CONTEXT: Acromegaly is usually due to the excessive secretion of GH by a pituitary adenoma. It is frequently accompanied by comorbidities that compromise quality of life and results in elevated mortality rates. OBJECTIVE: To evaluate mortality and morbidity in patients with acromegaly receiving multimodal care. SETTING: Tertiary care center. DESIGN, PATIENTS, AND METHODS: Retrospective evaluation of 442 patients (65.4% women; mean age, 43.5 ± 13.1 y) followed for a median of 6 years (interquartile range [IQR], 3-10). RESULTS: Twenty-two patients died during the study period (4.9%), representing a total standardized mortality ratio (SMR) of 0.72 (95% confidence interval [CI], 0.41-1.03). Standardized mortality ratios were 1.5 and 0.44 for patients whose last GH was above and below 2.5 ng/mL, respectively; 1.17 and 0.16 for those whose last GH was above and below 1 ng/mL, respectively; and 0.94 and 0.46 for those whose last IGF-1 was above and below 1.2 times the upper limit of normal (ULN), respectively. The prevalence of diabetes mellitus, hypertension, heart disease, and cancer was 30%, 35%, 8%, and 4.7%, respectively. The most common cause of death was cancer. On multivariate analysis, diabetes, heart disease, and cancer were related to a baseline GH > 10 ng/mL; the presence of cancer and the last IGF-1 were significant predictors of mortality. Survival decreased as the latest GH levels increased from < 1 ng/mL to > 5 ng/mL and as IGF-1 increased from < 1.2 to > 2 times the ULN. CONCLUSIONS: Mortality in acromegaly can be successfully reduced, provided patients are treated using a multimodal approach with careful management of comorbidities.

Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly.

CONTEXT: Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture. OBJECTIVE: Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment. SETTING: The study was conducted at a specialized clinic at a tertiary care hospital. DESIGN, PATIENTS, AND METHODS: We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR. MAIN OUTCOME MEASURES: We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics. RESULTS: Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58). CONCLUSIONS: The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy.