Acromegaly has a significant adverse effect on well-being and survival. The predominant determinant of outcome is the final serum GH level following treatment.
Objective: Formal studies of acromegaly have found increased mortality associated with the disorder, although reduction of serum levels of GH and IGF-I by treatment appears to improve survival. A metaanalysis of mortality studies in acromegaly has thus been performed to assess the effect of lowering serum GH and IGF-I on survival. Design and methods: Medline was searched for studies under 'acromegaly', 'mortality' and 'cause of death ' (1965-2008), and abstracts of recent meetings of the US Endocrine Society were hand searched. Studies were restricted to those presenting mortality data according to serum GH and IGF-I at last follow-up, and with mortality expressed as a standardized mortality ratio (SMR). Results: Patients with random serum GH !2.5 mg/l following treatment, mostly measured by standard RIA, had mortality close to expected levels (SMR 1.1, 95% confidence interval (CI) 0.9-1.4) compared with an SMR of 1.9 (95% CI 1.5-2.4) for those with final GH O2.5 mg/l. Similarly, a normal serum IGF-I for age and sex at last follow-up after treatment was associated with an SMR of 1.1 (95% CI 0.9-1.4) compared with an SMR of 2.5 (95% CI 1.6-4.0) for those with continued IGF-I elevation. There was a significant trend for reduced mortality in series reporting frequent use of somatostatin analogues and in studies reporting high (O70%) rates of biochemical remission after treatment. Conclusions: Clinicians treating acromegalic patients should aim for random serum GH !2.5 mg/l measured by RIA (probably !1 mg/l measured by modern sensitive immunoassay) and normal serum IGF-I values, to restore the elevated mortality of the condition to normal levels.
European Journal of Endocrinology 159 89-95
A prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250 mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6 mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no long-term clinical benefit in patients with advanced prostatic carcinoma compared to goserelin acetate alone.
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