Prolonged diagnostic delay in acromegaly is associated with increased morbidity and mortality

Abstract

Context Clinical features of acromegaly develop insidiously. Its diagnosis may therefore be delayed. Objective Our aim was to study diagnostic delay and its impact on morbidity and mortality in a nationwide cohort of patients with acromegaly. Design Adult patients diagnosed with acromegaly between 2001 and 2013 were identified in the Swedish National Patient Registry. Diagnostic codes for predefined comorbidities associated with acromegaly were recorded between 1987 and 2013. Diagnostic delay was calculated as the time between the first registered comorbidity and the diagnosis of acromegaly. Results A total of 603 patients (280 men, 323 women) with acromegaly were included. Mean (s.d.) diagnostic delay was 5.5 (6.2) years (median (minimum, maximum) 3.3 (0.0–25.9)) Diagnostic delay was 1–<5 years in 23% patients; 5–<10 years in 17%; and ≥10 years in 24%. No delay was recorded in 36% of patients. Overall, mean (s.d.) number of comorbidities was 4.1 (2.5) and was higher in patients with longer diagnostic delay (P < 0.0001). Overall, observed number of deaths was 61 (expected 42.2), resulting in a standardized mortality ratio (SMR) of 1.45 (95% CI: 1.11–1.86). Increased mortality was only found in patients with the longest diagnostic delay (1.76, 95% CI: 1.12–2.65). In the other groups, no statistically significant increase in mortality was recorded, with the numerically lowest SMR observed in patients without diagnostic delay (1.18; 95% CI: 0.68–1.92). Conclusions The diagnosis of acromegaly is delayed in most patients. Prolonged diagnostic delay is associated with increased morbidity and mortality.

Patient Characteristics, Diagnostic Delays, Treatment Patterns, Treatment Outcomes, Comorbidities, and Treatment Costs of Acromegaly in China: A Nationwide Study

“…In the present study, females accounted for 58.8% of all patients, significantly larger than the percentage of males. The female sex was correlated with a diagnostic delay and more comorbidities at follow-up, consistent with previous results (8,19,27,29). The average age of patients was 39 years, approximately 10 years younger than the patients from Sweden, France, Denmark and the United States but close to those from Korea and Bulgaria (14,15,23,(30)(31)(32).…”

“…GH over-secretion leads to increased serum insulin-like growth factor 1 (IGF-1), and both hormones result in a series of acromegaly-associated symptoms, i.e., facial appearance changes; overgrowth of hands and feet; headache; visual field defects; and comorbidities affecting the cardiovascular system, respiratory system, musculoskeletal organs, endocrine/metabolic system, etc (3-7). Since the above clinical features of acromegaly develop insidiously, the diagnosis of this condition is therefore often delayed, and prolonged diagnostic delays are associated with reduced quality of life (QoL) and elevated morbidity and mortality in patients with acromegaly (7)(8)(9). The main therapeutic goals include normalization of the circulating levels of GH and IGF-1, removal of pituitary tumors without damaging the adjacent structures, amelioration of symptoms and comorbidities, and restoration of normal life expectancy and QoL (3,4,10).…”

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

“…However, this age difference seemed to narrow as a function of calendar year 7 . In contrast to the meta‐analysis, studies from Denmark, 1 Sweden, 37 Iceland 3,33 and Finland 19,38 did not record an age‐related sex difference at diagnosis. The underlying explanation for this discrepancy is unclear but could involve a difference in the sex‐dependent diagnostic delay.…”

“…Females were older at the time of diagnosis and exhibited a longer diagnostic delay 7,11,17,35–37 according to the meta‐analysis. However, this age difference seemed to narrow as a function of calendar year 7 .…”

Results from ACROCOVID: an international survey on the care of acromegaly during the COVID-19 era

“…However, the true prevalence of clinically significant pituitary tumors seems to be higher [9]. As a result of the non-specific nature of some of the presenting symptoms, and the frequently subtle progression of clinical features, diagnosis is often delayed [10][11][12]. Treatment typically requires a multidisciplinary team of health care professionals including endocrinologists, neurosurgeons, and specialized endocrine nurses [13,14], and access to these professionals could potentially be severely limited under COVID-19 pandemic conditions [15,16].…”