ACTH Deficiency, Higher Doses of Hydrocortisone Replacement, and Radiotherapy Are Independent Predictors of Mortality in Patients with Acromegaly

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@article{632b8d74b19c405589c2a90ae9b0690f,
title = "ACTH Deficiency, Higher Doses of Hydrocortisone Replacement, and Radiotherapy Are Independent Predictors of Mortality in Patients with Acromegaly",
abstract = "Context: A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR. Methods: Using the West Midlands Acromegaly database (n = 501; 275 female), we assessed the influence of prior radiotherapy and hypopituitarism (and replacement therapy) on mortality in patients with acromegaly. Median duration of follow-up was 14.0 yr (interquartile range, 7.9-21 yr). Results: All-cause mortality was elevated [SMR, 1.7 (1.4, 2.0); P <0.001]. On external analysis, prior radiotherapy, ACTH, and gonadotropin deficiency were associated with an elevated SMR [radiotherapy SMR, 2.1 (1.7-2.6); P = 0.006; ACTH deficiency SMR, 2.5 (1.9-3.2); P <0.0005; and gonadotropin deficiency SMR, 2.1 (1.6-2.7); P = 0.037]. On internal analysis, the relative risk (RR) of mortality was increased in the radiotherapy [RR, 1.8 (1.2-2.8); P = 0.008] and ACTH-deficiency groups [RR, 1.7 (1.2-2.5); P = 0.004], but not in the gonadotropin-or TSH-deficiency groups. In the ACTH-deficient group, increased replacement doses of hydrocortisone greater than 25 mg/d were associated with increased mortality compared to lower doses. Conclusions: Radiotherapy and ACTH deficiency are significantly associated with increased mortality in patients with acromegaly. In ACTH-deficient patients, a daily dose of more than 25 mg hydrocortisone is associated with increased mortality compared to lower doses. These results have important implications for the treatment of patients with acromegaly and also raise issues as to the optimum hydrocortisone treatment regimens for ACTH-deficient patients. (J Clin Endocrinol Metab 94: 4216-4223, 2009)",
keywords = "second primary neoplasm, radiation, childhood cancer, thyroid cancer",
author = "Mark Sherlock and Raoul Reulen and {Aragon Alonso}, Aurora and John Ayuk and RN Clayton and Michael Sheppard and Michael Hawkins and Andrew Bates and Paul Stewart",
year = "2009",
month = nov,
day = "1",
doi = "10.1210/jc.2009-1097",
language = "English",
volume = "94",
pages = "4216--4223",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Endocrine Society",
number = "11",

}

RIS

TY - JOUR

T1 - ACTH Deficiency, Higher Doses of Hydrocortisone Replacement, and Radiotherapy Are Independent Predictors of Mortality in Patients with Acromegaly

AU - Sherlock, Mark

AU - Reulen, Raoul

AU - Aragon Alonso, Aurora

AU - Ayuk, John

AU - Clayton, RN

AU - Sheppard, Michael

AU - Hawkins, Michael

AU - Bates, Andrew

AU - Stewart, Paul

PY - 2009/11/1

Y1 - 2009/11/1

N2 - Context: A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR. Methods: Using the West Midlands Acromegaly database (n = 501; 275 female), we assessed the influence of prior radiotherapy and hypopituitarism (and replacement therapy) on mortality in patients with acromegaly. Median duration of follow-up was 14.0 yr (interquartile range, 7.9-21 yr). Results: All-cause mortality was elevated [SMR, 1.7 (1.4, 2.0); P <0.001]. On external analysis, prior radiotherapy, ACTH, and gonadotropin deficiency were associated with an elevated SMR [radiotherapy SMR, 2.1 (1.7-2.6); P = 0.006; ACTH deficiency SMR, 2.5 (1.9-3.2); P <0.0005; and gonadotropin deficiency SMR, 2.1 (1.6-2.7); P = 0.037]. On internal analysis, the relative risk (RR) of mortality was increased in the radiotherapy [RR, 1.8 (1.2-2.8); P = 0.008] and ACTH-deficiency groups [RR, 1.7 (1.2-2.5); P = 0.004], but not in the gonadotropin-or TSH-deficiency groups. In the ACTH-deficient group, increased replacement doses of hydrocortisone greater than 25 mg/d were associated with increased mortality compared to lower doses. Conclusions: Radiotherapy and ACTH deficiency are significantly associated with increased mortality in patients with acromegaly. In ACTH-deficient patients, a daily dose of more than 25 mg hydrocortisone is associated with increased mortality compared to lower doses. These results have important implications for the treatment of patients with acromegaly and also raise issues as to the optimum hydrocortisone treatment regimens for ACTH-deficient patients. (J Clin Endocrinol Metab 94: 4216-4223, 2009)

AB - Context: A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR. Methods: Using the West Midlands Acromegaly database (n = 501; 275 female), we assessed the influence of prior radiotherapy and hypopituitarism (and replacement therapy) on mortality in patients with acromegaly. Median duration of follow-up was 14.0 yr (interquartile range, 7.9-21 yr). Results: All-cause mortality was elevated [SMR, 1.7 (1.4, 2.0); P <0.001]. On external analysis, prior radiotherapy, ACTH, and gonadotropin deficiency were associated with an elevated SMR [radiotherapy SMR, 2.1 (1.7-2.6); P = 0.006; ACTH deficiency SMR, 2.5 (1.9-3.2); P <0.0005; and gonadotropin deficiency SMR, 2.1 (1.6-2.7); P = 0.037]. On internal analysis, the relative risk (RR) of mortality was increased in the radiotherapy [RR, 1.8 (1.2-2.8); P = 0.008] and ACTH-deficiency groups [RR, 1.7 (1.2-2.5); P = 0.004], but not in the gonadotropin-or TSH-deficiency groups. In the ACTH-deficient group, increased replacement doses of hydrocortisone greater than 25 mg/d were associated with increased mortality compared to lower doses. Conclusions: Radiotherapy and ACTH deficiency are significantly associated with increased mortality in patients with acromegaly. In ACTH-deficient patients, a daily dose of more than 25 mg hydrocortisone is associated with increased mortality compared to lower doses. These results have important implications for the treatment of patients with acromegaly and also raise issues as to the optimum hydrocortisone treatment regimens for ACTH-deficient patients. (J Clin Endocrinol Metab 94: 4216-4223, 2009)

KW - second primary neoplasm

KW - radiation

KW - childhood cancer

KW - thyroid cancer

U2 - 10.1210/jc.2009-1097

DO - 10.1210/jc.2009-1097

M3 - Article

C2 - 19808848

VL - 94

SP - 4216

EP - 4223

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -