Sex differences in acromegaly at diagnosis: A nationwide cohort study and meta‐analysis of the literature

Abstract

Objective Data on sex differences in acromegaly at the time of diagnosis vary considerably between studies. Design A nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta‐analysis on sex differences in active acromegaly (40 studies) were performed. Method Sex‐dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin‐like growth factor 1 (IGF‐I) and growth hormone (GH) concentrations were estimated. Results The cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF‐ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma size differed between males and females. In the meta‐analysis, the weighted percentage female was 53.3% (CI95% 51.5–55.2) with considerable heterogeneity (I2 = 85%) among the studies. The mean age difference at diagnosis between genders was 3.1 years (CI95% 1.9–4.4), and the diagnostic delay was longer in females by 0.9 years (CI95% −0.4 to 2.1). Serum IGF‐I levels were significantly lower in female patients, whereas nadir GH, and pituitary adenoma size were comparable. Conclusion There are only a minor sex differences in the epidemiology of acromegaly at the time of diagnosis except that female patients are slightly older and exhibit lower IGF‐I concentrations and a longer diagnostic delay.

The Biochemical Diagnosis of Acromegaly

“…Female patients have more prolonged diagnostic delays compared to males [6]. While over the years there have been improvements in the diagnostic procedures for acromegaly, including the availability of serum IGF-1 measurement and more sensitive GH assays, the diagnostic delay and the age at diagnosis have not changed, and that is mostly secondary to the insidious onset of the clinical features, overlap of the signs and symptoms with other common conditions, and lack of disease awareness among other medical specialists [5,7].…”

Gender and age differences among patients with acromegaly

“…However, in some studies, a balanced sex distribution or male predominance has also been observed [10,14,21,22]. In recently published data from a Denmark-based nationwide cohort study including all incident cases of acromegaly from 1978 to 2010, a balanced sex distribution and comparable age at the time of diagnosis were identified [10]. However, in that study, sex distribution was associated with the calendar year, when the acromegaly was confirmed (from initial female predominance to more even sex balance).…”

“…This phenomenon is observed in autoimmune diseases as well as in pituitary tumorigenesis. Some studies suggest the role of estrogens as a potential trigger, especially in prolactinomas [10,[18][19][20]. In most studies of acromegaly patients, females are slightly more frequently affected than males (1.24:1) [2,3].…”

“…In most studies of acromegaly patients, females are slightly more frequently affected than males (1.24:1) [2,3]. However, in some studies, a balanced sex distribution or male predominance has also been observed [10,14,21,22]. In recently published data from a Denmark-based nationwide cohort study including all incident cases of acromegaly from 1978 to 2010, a balanced sex distribution and comparable age at the time of diagnosis were identified [10].…”

“…Some diseases show sexual dimorphism, and in this study, we investigate if sex is associated with the course of acromegaly. Some studies suggest that estrogens and androgens may have an impact on the GH-IGF-1 axis [8][9][10]. An age-related phenotype of acromegaly has been also observed [11][12][13][14].…”