This study was designed to investigate the annual incidence and prevalence of acromegaly, which further compared the occurrence of complications by treatment modality in Koreans from January 2013 to December 2017. Survival rate analysis was also conducted between treatment and non-treatment groups. From 2013 to 2017, the annual incidence of acromegaly in Korea was 4.2 cases per million per year, not much different from the 3.57 cases per million reported in a previous study conducted during 2010–2013 15. This was also similar to the annual occurrence rate of 2–11 cases per million people per year from a systematical review 6. There were no significant differences in the development of diabetes accrding to treatment modalities. However, hypertension showed significantly lower incidence in the medical treatment group. Over a period of 6 years since diagnosis, patients treated for acromegaly had a significantly higher survival rate than the untreated patients.
A cardiovascular disease is one of the main causes of death for acromegaly 7, and it is known that the prevalence of diabetes and hypertension is higher than that in the general population 16,17, but no studies have analyzed the occurrence of comorbidities in acromegaly patients in Korea. This study is the first report to evaluate the risk of diabetes and hypertension according to treatment modality in Korean patients with acromegaly. Patients with acromegaly are more likely to have concurrent hypertension; 1.9 times higher than that in the general population. This could be due to the direct anti-natriuretic effects of exess GH 18. Several animal studies have suggested that increased GH causes overactivation of the renin-angiotensin-aldosterone-system 19. Hyperinsulinemia also causes hyperactivity of the renin-angiotensin-aldosterone system, which promotes renal sodium reabsorption and thus increases plasma volume 20. It is also known that elevated insulin and GH levels contribute to hypertension by activation of the sympathetic nervous system 21. To indirectly estimate the therapeutic effects of acromegaly, we divided the acromegaly-treated patients into three groups: 1) medical, 2) surgical, and 3) medical plus surgical treatment group. The incidence of diabetes in the treatment group showed no significant difference when compared to the non-therapeutic group. We also investigated the incidence rate of hypertension after newly diagnosed acromegaly. This was similar to a previous study that showed significantly reduced development of hypertension after five years of medical treatment 22.
As for diabetes, there was no significant difference between the treated and non-treated groups. This was unexpected and inconsistent with previous studies showing the improvement of glucose metabolism regardless of the outcome of surgical treatment 23. The study conducted by Kinoshita et al. on patients with acromegaly in Japan demonstrated that glucose metabolism did not normalize even after acromegaly treatment due to impaired beta cell function. In addition, Shekhawat et al. showed no significant difference between pre- and postoperative beta cell function in acromegaly patients with diabetes, and this was due to increased glucose-dependent insulinotropic polypeptide resistance and reduced beta cell function due to hyperglucagonemia. Similar to Japanese, Koreans are known to have reduced insulin secretion and compensatory insulin responses before the onset of diabetes 24; thus, decreased beta-cell function may fail to recover and lead to diabetes development even after treatment of acromegaly.
In our study, the treatment group had significant survival benefits compared to the non-treatment group. A previously reported survival analysis on acromegaly patients in New Zealand showed that the life expectancy was the same as that of the general population when the GH level was less than 1 g/L after treatment9. A Finnish study, instead, showed that the life expectancies were the same as that of the general population if the GH levels remained below 2.5 g/L after treatment10. Along with these results, our analysis confirmes and emphazises the importance of effective treatment to normalize GH secretion and prevent metabolic complications in patients with acromegaly, which could further assure the survival benefit. To our best knowledge, this is the first study to report the results of survival analysis in Korean patients with acromegaly.
In this study, patients with acromegaly were defined according to the operational definition based on both the claims data codes and the BEP codes in the HIRA database. This operational definition was considered to be appropriate because the incidence and prevalence of acromegaly were observed to be similar to those of previous studies. However, due to the inevitable nature of health insurance claims data, some disease codes of patients with acromegaly might have been omitted, which could have led to an underestimation of data. Because the HIRA database did not include individual test results such as IGF-1 or GH levels, the degree of severity could not be ascertained. To compare the complications among treatment modalities, the incidence of hypertension and diabetes was analyzed for five years in patients newly diagnosed with acromegaly during 2011–2012; however, this might not have been a sufficient period for the development of complications.