A paradigm shift in the monitoring of patients with acromegaly: last available growth hormone may overestimate risk

TY - JOUR

T1 - A paradigm shift in the monitoring of patients with acromegaly

T2 - last available growth hormone may overestimate risk

AU - Sherlock, Mark

AU - Reulen, Raoul C

AU - Aragon-Alonso, Aurora

AU - Ayuk, John

AU - Clayton, Richard N

AU - Sheppard, Michael C

AU - Hawkins, Michael M

AU - Bates, Andrew S

AU - Stewart, Paul M

PY - 2014/2

Y1 - 2014/2

N2 - CONTEXT: Acromegaly is associated with reduced life expectancy, which has been reported to be normalized if treatment is successful in controlling GH/IGF-I levels.OBJECTIVE: Most previous studies have invariably used the last available GH/IGF-I, which may be biased as it only assesses exposure at a single point in time. We compared the last available GH/IGF-I analysis to a "time-dependent" and cumulative method, during follow-up to assess risk of mortality in the West Midlands Acromegaly study (n = 501).RESULTS: Using the last available GH, there was a statistically significant increase in mortality comparing groups as low as GH ≤ 1 μg/L vs >1 μg/L (relative risks [RR] 1.8, P = .03). This was not the case when using the "time-dependent method," where only comparisons of GH values of GH ≤5 μg/L vs >5 μg/L were suggestive of being associated with an increased risk of mortality (RR = 1.5, P = .08). When the time-dependent GH method of analysis was used, the RR of mortality at each level was lower and the associated P value was less significant. Irrespective of using the last available or time-dependent method, when IGF-I was divided into levels according to quartile or arbitrary cutoffs, there was no significant increase in mortality with higher levels.CONCLUSIONS: This study emphasizes the potential bias of using the latest available GH/IGF-I levels to predict mortality. Our study again highlights the limitations of IGF-I in predicting mortality.

AB - CONTEXT: Acromegaly is associated with reduced life expectancy, which has been reported to be normalized if treatment is successful in controlling GH/IGF-I levels.OBJECTIVE: Most previous studies have invariably used the last available GH/IGF-I, which may be biased as it only assesses exposure at a single point in time. We compared the last available GH/IGF-I analysis to a "time-dependent" and cumulative method, during follow-up to assess risk of mortality in the West Midlands Acromegaly study (n = 501).RESULTS: Using the last available GH, there was a statistically significant increase in mortality comparing groups as low as GH ≤ 1 μg/L vs >1 μg/L (relative risks [RR] 1.8, P = .03). This was not the case when using the "time-dependent method," where only comparisons of GH values of GH ≤5 μg/L vs >5 μg/L were suggestive of being associated with an increased risk of mortality (RR = 1.5, P = .08). When the time-dependent GH method of analysis was used, the RR of mortality at each level was lower and the associated P value was less significant. Irrespective of using the last available or time-dependent method, when IGF-I was divided into levels according to quartile or arbitrary cutoffs, there was no significant increase in mortality with higher levels.CONCLUSIONS: This study emphasizes the potential bias of using the latest available GH/IGF-I levels to predict mortality. Our study again highlights the limitations of IGF-I in predicting mortality.

KW - Acromegaly

KW - Adult

KW - Aged

KW - Combined Modality Therapy

KW - Female

KW - Human Growth Hormone

KW - Humans

KW - Insulin-Like Growth Factor I

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Treatment Outcome

U2 - 10.1210/jc.2013-2450

DO - 10.1210/jc.2013-2450

M3 - Article

C2 - 24243636

VL - 99

SP - 478

EP - 485

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -