Increasing of Acromegaly Prevalence in Guayaquil, Ecuador: 2000-2019

Background: Reliable and up-to-date information on the epidemiology of acromegaly in Latin American countries remains to be lacking. Aims: This study aims to update the epidemiological data on acromegaly in Guayaquil city, Ecuador. Methods: Prospective and retrospective data of patients with acromegaly were collected from the five public health system hospitals in Guayaquil City, Ecuador, from January 2000 to December 2019. Age at diagnosis, baseline growth hormone levels, growth hormone after oral glucose overload, and serum insulin-like growth factor-1 concentrations were recorded. We determined the rate of prevalence of acromegaly using the 2010 population census information and the projected Ecuadorian population by calendar year and canton for the period from 2000 to 2019. Results: A total of 132 cases of acromegaly were reported, of which 77 are women (58 %) and 55 men (42 %) (Female-to-male ratio, 1.4:1). The overall mean age at diagnosis was 46 years (SD, 16 y). The mean age in women was determined to be 46.9 years (SD, 16.3 y), while for the men, it was 45.1 years (SD, 15.8 y). Our findings show that the prevalence of acromegaly is 49 cases per million inhabitants. Conclusions: The prevalence of acromegaly in Guayaquil, Ecuador are higher than what was previously reported and are closer to those described in the international literature.


Introduction
Acromegaly is known to be an orphan disease caused by the hypersecretion of growth hormone (GH) [1]. In order to generate reliable epidemiological data on acromegaly, large population studies are required [1]. Acromegaly has been determined to affect both men and women; it often has late diagnosis, at a mean age of have revealed that both Iceland and Malta have recorded increasing prevalence in the past 5 years (>13 cases per 100,000 inhabitants) [5,6] ; meanwhile, basing on the national registries, Sweden, Spain, and Denmark have reported a lower prevalence, with 36-39 cases per million inhabitants [3,7].
Incidence studies published before 2000 have reported a worldwide annual incidence consistently less than five cases per million inhabitants [2,8]. However, the global annual incidence reported in more recent studies is found to be much higher, ranging from 2 to 11 cases per million inhabitants [5,6,9,10].
Data from cancer registries tend to sub-report benign tumors, including pituitary adenomas. In addition, data obtained from isolated tertiary reference centers worldwide are deemed affected by selection bias and wide variations in reference patterns [8].
Studies based on national acromegaly registries can provide broader and more longitudinal snapshots of acromegaly in each country [1,2,8]. Most of these studies come from European countries and the United States [8].
There are no national acromegaly registries in Latin American countries, except for Mexico. Among the four Latin American countries in which the epidemiology of acromegaly has been studied (Mexico [11], Brazil [12], Argentina [13], and Ecuador [14]), the prevalence of this disease was determined to range from 18 to 365 cases per million inhabitants. It should be noted that the population, design of the studies, and methodology used (not based on the national population, small sample size, and cohort of pituitary tumors) differ greatly between these countries. The incidence in these countries ranges from 1.3 to 9.2 cases per million inhabitants, although with similar methodological drawbacks [13,14]. In 2016, Lopez et al [14], described the epidemiology of acromegaly in Guayaquil city, finding a prevalence of 18.7 cases per million inhabitants and an incidence of 1.3 cases per million peopleyears. In this current study, we sought to update the epidemiology of acromegaly based on the information recorded in the past 20 years.

Materials and Methods
This is a multicenter, longitudinal, prospective, and retrospective study. Data were collected from patient visits to the outpatient clinics of endocrinology departments of the five participating hospitals during the study period (2000-2019). Information such as age, sex, age at diagnosis, biochemical tests, pituitary imaging studies, were recorded. A biochemical diagnosis of acromegaly can be established when the nadir GH after a 75 g glucose load was greater than 1 ng/mL and there was also an elevated IGF-1 level for age and sex. To measure the prevalence of this disease, information

Discussion
Globally, there are differences in terms of the prevalence of acromegaly between regions and countries. In Europe, before 2000, the overall prevalence of acromegaly was less than 7 cases per 100,000 inhabitants [2,7]. More recently, in the past 5 years, its prevalence has increased to more than 13 cases per 100,000 inhabitants [5,6,9], as per the studies conducted in the populations of Iceland and Malta. This may be attributed to the improvements in the diagnostic methods, which aim to likely reduce under diagnosis.
It is also possible that the diagnosis may have improved as a result of the availability of large national databases in recent population studies [8]. Increased prevalence may also be a result of increased patient survival, owing to better surgical techniques, post-surgical follow-up, and medical treatment [8]. However, the same case was not reported in Spain, Denmark, and Sweden, which all recorded a lower prevalence of acromegaly (3.6-3.9 cases per 100,000 inhabitants) [3,7].
In Latin American countries, the prevalence of acromegaly was found to range from 18 to 365 cases per million inhabitants. Its prevalence is 18 cases per million inhabitants in Mexico [11], 365 cases per million inhabitants in Brazil [12], 140 cases per million inhabitants in Argentina [13], and 18.7 per million inhabitants in Ecuador [14] The prevalence reported in this study (48.9 cases per million inhabitants) is 2.6 times higher than that previously reported in our city [14] and is similar in range to those described  [17]. Most studies have shown a predominance of the disease in women, ranging from 51 % to 61 % [2,7]; this is in contrast to some studies reporting no differences in sex prevalence (51 % vs 49 %) [18].
In a previous study, we have described the predominance of acromegaly in women (64.5 %), with a female-to-male ratio of 1  [7,9,18,20].
In Latin America, only Mexico has a national acromegaly registry, which published its information in 2016 [11].
We should point out the following strengths and weaknesses of this present work. First, this study was conducted in the most populous city in Ecuador (24.5 % of the total population) [15] and in the five hospitals of the public health system that are considered as referral centers for patients throughout the city. We believe that this would provide us with a more realistic view of the epidemiology of acromegaly in our city. Second, hospitals and clinics in the city's private health system did not participate in this study, which could have limited the inclusion of more cases. However, in Guayaquil, more than 90 % of patients with acromegaly are treated in hospitals within the public health system, so our coverage would be almost complete. Third, the sample size of cases with acromegaly is small, making it impossible to extrapolate the results to the entire population of Ecuador.

Conclusions
With the aim to update the epidemiology of acromegaly in Guayaquil, we observed an increasing trend in prevalence rate, compared with previous reports. The sub-diagnosis and subregistration of cases that we described previously have been reduced.