Endocrine Abstracts

Background: Acromegaly is characterised by growth hormone (GH) and insulin-like growth factor (IGF-1) hypersecretion. The disease is associated with increased cardiovascular, cerebrovascular and metabolic co-morbidities, resulting in excess mortality. A target GH <1 μg/l and normalised IGF-1 values correlate with mortality risk reduction. However, there is lack of consensus over which biomarker, GH or IGF-1, better predicts increased morbidity and/ or mortality.

Objective: To investigate the relationship between surrogates of vascular risk and disease activity and assess the impact on cardiovascular/cerebrovascular outcomes.

Methods: Medical records of 109 patients, identified from our local Acromegaly Registry over past 15 years, were retrospectively examined (56% male, age at diagnosis 42.6±14.0 years, 1612 person-years from diagnosis).

Results: Fifty-four patients (50%) were in biochemical remission; 35 (32%) had discordant IGF-1/GH results and 20 (18%) had elevated IGF-1 and GH>1 μg/l at last biochemical assessment of disease status. Prevalence of vascular risk factors: Hypertension – 46 patients (42%); insulin resistance (IR) – 29 patients (27%); dyslipidaemia – 32 patients (29%). Nearly half (30/61) of patients with recently documented weight were obese (BMI>30 kg/m²). The rates of hypertension (16/35, 46% vs 10/20, 50%) and IR (8/35, 23% vs 11/20, 55%) were higher in the discordant and uncontrolled groups. The presence of IR was predicted by a higher BMI (coeff=0.438, P=0.006) and older age at diagnosis (coeff=2.03, P=0.016). Longer duration of active disease also positively correlated with IR (coeff=0.947, P=0.001), although GH/IGF-1 measurements displayed no association. No significant correlation was demonstrated between age, gender and disease activity with hypertension, dyslipidaemia nor obesity. Sixteen patients (15%) had a history of cardiovascular /cerebrovascular disease (CVD/CVA), with the majority arising in the discordant GH/IGF-1 group (8/16, 50%), although no significant correlation was identified with disease activity. Dyslipidaemia was a positive predictive factor of CVD/CVA (coeff=0.42, P=0.018) whilst the other vascular risk factors were independent. A higher GH level at last biochemical assessment was also associated with a higher cardiovascular risk (coeff=0.599, P=0.010). No association was found between CVA and radiation therapy.

Conclusion: Patients with acromegaly have an unfavourable metabolic profile, in particular dyslipidaemia and insulin resistance which increase cardiovascular risk. In our cohort, high ambient GH level was a reliable biomarker for development of adverse cardiovascular events. In cases of GH/IGF-1 dichotomy, we recommend adjuvant medical treatment, especially in high GH discordance, to lower GH excess.