Underlying disease risk among patients with fatigue: a population-based cohort study in primary care

Presenting to primary care with fatigue is associated with a wide range of conditions, including cancer, although their relative likelihood is unknown.

To quantify associations between new-onset fatigue presentation and subsequent diagnosis of various diseases, including cancer.

A cohort study of patients presenting in English primary care with new-onset fatigue during 2007-2017 (the fatigue group) compared with patients who presented without fatigue (the non-fatigue group), using Clinical Practice Research Datalink data linked to hospital episodes and national cancer registration data.

The excess short-term incidence of 237 diseases in patients who presented with fatigue compared with those who did not present with fatigue is described. Disease-specific 12-month risk by sex was modelled and the age-adjusted risk calculated.

The study included 304 914 people in the fatigue group and 423 671 in the non-fatigue group. In total, 127 of 237 diseases studied were more common in men who presented with fatigue than in men who did not, and 151 were more common in women who presented with fatigue. Diseases that were most strongly associated with fatigue included: depression; respiratory tract infections; insomnia and sleep disturbances; and hypo/hyperthyroidism (women only). By age 80 years, cancer was the third most common disease and had the fourth highest absolute excess risk in men who presented with fatigue (fatigue group: 7.01%, 95% confidence interval [CI] = 6.54 to 7.51; non-fatigue group: 3.36%, 95% CI = 3.08 to 3.67; absolute excess risk 3.65%). In women, cancer remained relatively infrequent; by age 80 years it had the thirteenth highest excess risk in patients who presented with fatigue.

This study ranked the likelihood of possible diagnoses in patients who presented with fatigue, to inform diagnostic guidelines and doctors' decisions. Age-specific findings support recommendations to prioritise cancer investigation in older men (aged ≥70 years) with fatigue, but not in women at any age, based solely on the presence of fatigue.