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Excess mortality falling, pituitary surgery increasing for acromegaly

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March 5, 2018

Daniel Olsson
Daniel S. Olsson

Excess mortality for adults diagnosed with acromegaly has markedly declined in past 3 decades, with researchers also observing an increase in the use of pituitary surgery and a decrease in the prevalence of hypopituitarism as more patients are prescribed pharmacotherapy, according to findings from a nationwide analysis conducted in Sweden.

Daniel S. Olsson, MSc, MD, PhD, professor at the Sahlgrenska Academy Institute of Medicine at the University of Gothenburg, Sweden, and colleagues analyzed data from 1,089 patients with an acromegaly diagnosis due to a pituitary tumor between 1987 and 2013, identified through the Swedish National Patient Register (mean age at diagnosis, 52 years). Researchers followed patients from first diagnosis of acromegaly until death or December 2013 (mean follow-up time, 11.8 years), linking mortality and pharmacotherapy data from the Swedish Cause of Death Register and the Prescribed Drug Register, and calculated standardized mortality ratios (SMRs) using the observed number of deaths among patients with acromegaly and the expected number of deaths in the overall Swedish population. The cohort was stratified into three groups by year of diagnosis to assess whether mortality has changed over time: 1987-1995, 1996-2004 and 2005-2013.

Within the cohort, 700 patients (64%) underwent pituitary surgery, 144 patients (13%) underwent radiotherapy and 361 (33%) underwent neither, with 370 (34%) patients diagnosed with hypopituitarism and 41 (4%) diagnosed with diabetes insipidus.

During the study period, 232 patients died compared with the expected number of 83, for an SMR of 2.79 (95% CI, 2.43-3.15). SMR was similar between sexes.

The greatest number of deaths occurred from circulatory diseases (n = 93) and malignant neoplasms (n = 49), according to researchers, with SMRs of 2.95 and 1.76, respectively. Researchers also observed an increased SMR for death from infectious diseases (SMR = 7.91; 95% CI, 1.58-14.24), and an increased SMR for death by ischemic heart disease for women only (SMR = 2.85; 95% CI, 1.63-4.07).

In analysis by treatment type, researchers found, in patients diagnosed since 2005, SMR was lowest for patients treated with surgery alone (SMR = 0.45; 95% CI, 0-1.08), followed by patients treated with pharmacotherapy and surgery (SMR = 0.98; 95% CI, 0-2.35) and patients treated with pharmacotherapy alone (SMR = 2.03; 05% CI, 0.62-3.44). The frequency of pituitary surgery increased across the three periods, from 58% to 63% to 72%, respectively (P < .001). Additionally, the prevalence of hypopituitarism declined during the three periods, from 41% between 1987 and 1995 to 23% between 2005 and 2013 (P < .001). Mortality also decreased over time, falling from 3.45 (95% CI, 2.87-4.02) between 1987 and 1995 to 1.86 (95% CI, 1.04-2.67) between 2005 and 2013 (P = .015).

“Although mortality in acromegaly was still increased compared to that for the general population, it showed that the excess mortality has significantly declined during recent decades,” the researchers wrote. “Also, noteworthy changes were recorded in treatment patterns, with an increasing use of pituitary surgery over time; concurrently, a decreasing prevalence of hypopituitarism was observed.”

The researchers noted that the lowest SMR of 0.45 was recorded for patients treated with surgery only vs. an SMR of 0.98 for those treated with pharmacotherapy and surgery, but the data do not allow conclusions on the optimal treatment pattern because the number of events were too few and patients treated with different therapeutic strategies have different degrees of tumor burden and severity. – by Regina Schaffer

Disclosures: Olsson reports he has served as a consultant for Ipsen, Pfizer and Sandoz. Please see the study for the other authors’ relevant financial disclosures.

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Lisa Nachtigill

The study is important in that it offers information on mortality rate associated with acromegaly, stratified by era, from a large Swedish National Registry with comprehensive, age-adjusted mortality data compared with the general Swedish population. The finding that mortality associated with acromegaly is decreasing over time is reassuring. This study suggests that as the prevalence of surgical therapy, alone or along with medical therapy, increases, so does survival in this disease. The subset analysis of gender interestingly shows sex-specific differences: Women with acromegaly have a significantly increased risk of dying from ischemic cardiovascular disease compared with the general female population of Sweden, while more men with acromegaly died of malignancies than expected in the general male population. However, limitations include lack of information on detailed clinical characteristics of the patients (such as tumor size, biochemical control and comorbidities) and the absence of specific information on medical therapies prior to 2005.

Given these limitations and the nature of registry-based, retrospective study design, all of which the authors recognize, a direct cause or reasons for the decrease in standardized mortality rate over time cannot be definitively determined. Another limitation to consider is that the diagnosis of acromegaly was based on coding in the registry without correlation with medical records definitively confirming acromegaly. However, this study is encouraging in that it reveals that survival outcome for acromegaly has improved in recent years compared with decades ago. Future studies examining the relationship between specific medical therapies, degree of biochemical control, and survival will be useful for reevaluating management strategies and treatment goals in acromegaly: How good or perfectly normal does control of growth hormone and IGF1 need to be to reduce standardized mortality ratio to that expected in general population?

Lisa B. Nachtigall, MD

Clinical Co-Director, Neuroendocrine and Pituitary Clinical Center
Massachusetts General Hospital
Associate Professor, Department of Medicine
Harvard Medical School

Disclosure: Nachtigall reports that she has served as a consultant for Ipsen and has received funds from Chiasma and Ipsen.