Efficacy and safety of growth hormone treatment in adults with growth hormone deficiency: a systematic review of studies on morbidity

Abstract

SummaryDue to the positive effects demonstrated in randomized clinical trials on cardiovascular surrogate markers and bone metabolism, a positive effect of growth hormone (GH) treatment on clinically relevant end-points seems feasible. In this review, we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency (GHD) with emphasis on morbidity: fatal and nonfatal cardiovascular disease (CVD) and stroke, fractures, fatal and nonfatal malignancies and recurrences, and diabetes mellitus. A positive effect of GH treatment on CVD and fracture risk could be concluded, but study design limitations have to be considered. Stroke and secondary brain tumours remained more prevalent. However, other contributing factors have to be taken into account. Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment. All fatal and nonfatal malignancies were not more prevalent in GH-treated adults compared to the general population. However, follow-up time is still relatively short. The studies on diabetes are difficult to interpret, and more evidence is awaited. In clinical practice, a more individualized assessment seems appropriate, taking into consideration the underlying diagnosis of GHD, other treatment regimens, metabolic profile and the additional beneficial effects of GH set against the possible risks. Large and thoroughly conducted observational studies are needed and seem the only feasible way to inform the ongoing debate on health care costs, drug safety and clinical outcomes.

Tumor Recurrence or Regrowth in Adults With Nonfunctioning Pituitary Adenomas Using GH Replacement Therapy

“…In another study, the occurrence of secondary intracranial tumors did not differ between irradiated and nonirradiated NFPA patients (1.1 vs 0.6%), but the risk of cerebrovascular events was increased in irradiated men (31). Overall, as discussed in a recent review, fatal and nonfatal malignancies do not appear to be more prevalent in GHtreated adults compared to the general population, and also not in previously irradiated patients (11,18). Nevertheless, potential side effects of pituitary irradiation should be carefully balanced against benefits.…”

“…However, several aspects that may widely vary between studies, such as treatment-related factors (eg, surgical technique, extent of surgery, radiotherapy), study population, tumor characteristics, and follow-up duration have to be taken into account when comparing different studies. So far, only a few studies in the literature have explored the possible effect of GH-RT on tumor progression in NFPA patients specifically (11,17,19,20). Buchfelder et al (20) compared operated NFPA patients who were either treated with GH-RT or not in a retrospective case-control study of 55 matched pairs.…”

Prevalence of diabetes among children treated with growth hormone in Israel

“…A total of 12 people were found to have been diagnosed with diabetes after cessation of GH treatment (≥17 years). There is evidence that adults with untreated GH deficiency can develop reduced insulin sensitivity as a result of an increase in abdominal fat; however, GH treatment may also increase the risk of developing diabetes as GH can cause insulin resistance .…”

Growth Hormone Replacement Therapy in Adult Growth Hormone Deficiency and Risk of Cancer: A Meta-Analysis

“…rates of general population, standardized by country, gender, and age [30]. Bunderen et al played a review to discuss the long-term efficacy and safety of GH treatment in AGHD patients with emphasis on morbidity [31]. In a subgroup of the review, the risk of regrowth and recurrences of pituitary tumors were not increasing in AGHD patients treated with GH compared with untreated AGHD patients, while secondary brain tumors remained more prevalent.…”