Sex Differences in Acromegaly at Diagnosis

A Nationwide Cohort Study and Meta-Analysis of the Literature

Jakob Dal; Benedikte G. Skov; Marianne Andersen; Ulla Feldt-Rasmussen; Claus L. Feltoft; Jesper Karmisholt; Eigil H. Nielsen; Olaf M. Dekkers; Jens Otto L. Jørgensen


Clin Endocrinol. 2021;94(4):625-635. 

In This Article

Abstract and Introduction


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 (R 2 = 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 (I 2 = 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.


Acromegaly is a rare disorder caused by chronic hypersecretion of growth hormone (GH) from a pituitary adenoma. Recent data from population-based studies suggest a prevalence of 85–137 cases per million inhabitants and an annual incidence of approximately four cases per million person years.[1–5] The natural history of GH-secreting pituitary adenomas is subject to inter-individual variation with distinct clinical, radiological and histopathological subtypes.[6,7] The onset of acromegaly is insidious and a diagnostic delay of 5–10 years is common,[8] although this period may have shortened within recent years.[7,9]

As opposed to other hormone-secreting pituitary tumours where a female preponderance is present, it is less clear if the incidence and prevalence of acromegaly differ between men and women.[10] Two recent reviews conclude that acromegaly is more prevalent in women but the gender distribution differs considerably between cohorts.[11,12] Female predominance has indeed been reported,[13–17] and females are often older at the time of diagnosis.[13,16–18] Most of the observations on sex differences derive from registries reporting a low disease prevalence, which could indicate underdiagnosis of a subgroup of patients including older males with mild acromegaly.[13–17] A more even gender distribution has been reported in recent population-based surveys with overall higher disease prevalence.[1,3,19,20]

Serum insulin-like growth factor I (IGF-I) concentrations at the time of diagnosis are lower in females,[21,22] but it is less clear whether GH concentrations and pituitary tumour size also display a gender difference.[22,23] Such data are relevant for understanding the natural history of the condition and for providing gender-based reference values, where appropriate.[24]

The inconclusive data on gender differences in acromegaly highlight the need for population-based studies with complete coverage and follow-up. We therefore conducted a population-based cohort study in Denmark and a meta-analysis of the literature to examine sex differences in active acromegaly.