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No association between long-term GH replacement, comorbidities in nonfunctioning pituitary adenoma
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Patients with growth hormone deficiency due to nonfunctioning pituitary adenoma experienced excessive morbidity due to cerebral infarction and sepsis regardless of whether they received long-term GH therapy, whereas treatment was associated with a normal incidence of type 2 diabetes, despite higher BMI and more severe hypopituitarism in treated patients, according to findings from an observational, registry-based study.
Studies examining whether there is an association have produced mixed results, the researchers wrote, and it remains unknown to what extent GH deficiency — and GH therapy —contribute to the development of type 2 diabetes and other comorbidities, including cerebral infarction, malignant tumors, myocardial infarction or fractures.
“We found long-term replacement with growth hormone to be safe in hypopituitary patients regarding comorbidities, including cardiovascular events, type 2 diabetes, fracture and malignancies,” Daniel S. Olsson, MSc, MD, PhD, professor at the Sahlgrenska Academy Institute of Medicine at the University of Gothenburg, Sweden, told Endocrine Today. “We were surprised to find that the incidence of type 2 diabetes was normal in patients receiving growth hormone but was increased in patients without this replacement. This result was found despite that fact that the replaced group had higher BMI and more severe hypopituitarism.”
Olsson and colleagues analyzed data from 426 patients treated or followed for nonfunctioning pituitary adenoma between 1997 and 2011, selected from the Swedish National Patient Register. Researchers assessed information on tumor treatment, hormone therapy, antihypertensive medication, BMI and duration of GH therapy. For patients with type 2 diabetes, researchers assessed HbA1c values, insulin treatment, oral antidiabetes therapies and lipid-lowering therapies. Researchers followed the cohort through December 2014 or until death. Patients were stratified by use of GH therapy. Researchers calculated standardized incidence ratios (SIRs) based on the observed number of comorbidities among patients with nonfunctioning pituitary adenoma vs. the expected number of comorbidities in the background population.
Within the cohort, 207 patients received GH therapy (145 men) and 219 did not (129 men). Median duration of GH therapy was 11.7 years; mean age at diagnosis was 56 years for treated patients and 65 years for untreated patients. Median follow-up time for treated and untreated patients was 12.2 years and 8.2 years, respectively.
Incidence of cerebral infarction was increased for the whole cohort regardless of GH therapy status, with an SIR of 1.39 (95% CI, 1.03-1.84), and was most evident among 97 patients who underwent radiotherapy, in which 19 cerebral infarctions occurred vs. the expected number of 9.8 (P = .011).
“The study showed an increased overall incidence of cerebral infarction in patients with [nonfunctioning pituitary adenoma] compared to the general population that was related to previous radiotherapy, but not to GH [replacement therapy],” the researchers wrote.
Incidence of myocardial infarction was similar for treated and untreated patients, with SIRs of 1.18 (95% CI, 0.73-1.8) and 1.23 (95% CI, 0.82-1.78), respectively. Incidence of receiving medical treatment for hypertension was also similar between groups.
In assessing incidence of type 2 diabetes, the researchers found that the SIR was higher among untreated patients (1.65; 95% CI, 1.06-2.46) vs. treated patients, who had an SIR similar to the background population (0.99; 95% CI, 0.55-1.63). Treated patients with type 2 diabetes had higher BMI vs. untreated patients with type 2 diabetes (P = .01), according to researchers, and glycemic status was similar among treated and untreated patients.
The incidence of sepsis requiring hospitalization was also similar between treated and untreated patients, with rates for both groups close to double that of the background population (P < .001). Incidence of malignant tumors was not increased for treated or untreated patients when compared against the background population, according to the researchers.
“Our findings regarding type 2 diabetes mellitus are to be interpreted with caution since the design of the study was retrospective and non-randomized, which of course include a potential risk of selection bias,” Olsson said. – by Regina Schaffer
For more information:
Daniel S. Olsson, MSc, MD, PhD, can be reached at Sahlgrenska Academy Institute of Medicine at the University of Gothenburg, Department of Internal Medicine and Clinical Nutrition, Grona straket 8, SE-413 45 Gothenburg, Sweden; email: daniel.olsson@gu.se.
Disclosures: The Gothenburg Growth Hormone Database is supported partly through unrestricted grants from Novo Nordisk, Pfizer and Sandoz. Olsson reports he has served as a consultant for Ipsen, Pfizer and Sandoz. Another author reports he has served as a consultant to AstraZeneca and Viropharma/Shire, and received lecture fees from Novo Nordisk, Otsuka and Pfizer.
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