The study finds that the incidence of pituitary Cushing is still rare but increased over the past 30 years. Its current incidence is estimated to be 2.0 cases/million/year. However it is unknown if this increase is real or due to improved physician awareness and biochemical testing.
Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.
Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987-2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.
Of 1317 patients identified:
534 (41%) had confirmed CD.
156 (12%) patients had other forms of CS,
41 (3%) had probable but unconfirmed CD, and
334 (25%) had diagnoses unrelated to CS.
The mean annual incidence between 1987-2013 of confirmed CD was 1.6 cases/million.
1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was
1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases/million, respectively.
During the last time period the incidence was higher than during the first and second time periods (P < 0.05).
The incidence of CD in Sweden (1.6 cases/million) is in agreement with most previous reports.
A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed.
Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered.
This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
More from the publication:
Cushing’s disease (CD) is a rare disorder with an estimated annual incidence between 1.2-2.4 cases/million. Studies on the incidence of CD are, however, few and usually limited by the small number of patients included. Similarly, epidemiological studies on comorbidity and mortality are often based on small patient cohorts and/or short follow-up time. Largest epidemiological study on mortality in patients with CD published so far included 320 patients in remission. Patients from four countries were included and the median follow-up time was 11.8 years. In a recent meta-analysis, data from eight studies were pooled, resulting in a total of 700 patients. Thus, knowledge on epidemiology and outcome in Cushing’s syndrome (CS), including CD, is still limited.
This study illustrates the importance of validating diagnosis in patients with presumed CD from large health care registries such as national registries. Of 1317 patients identified in the Swedish Patient Register, approximately half had endogenous CS, of whom 534 had CD.
Although CD has been known as a clinical entity for >100 years, epidemiological studies evaluating incidence are surprisingly few and most often based on small numbers of patients.
The LARGEST study published to date on incidence was based on 188 patients diagnosed with CD between 1960 and 2005 in New Zealand. The incidence in these studies varies between 1.2-1.8 cases/million/year with the exception of the study by Etxabe and Vazquez who reported an incidence of 2.4 cases per million/year.
Our result of 1.6 cases per million is therefore in agreement with most previous reports. In a recent study from the USA, an unexpectedly high incidence rate of 6.2–7.6 cases/million/year was reported. That study was based on information from an insurance database where CD was defined as a CS diagnosis (as for ICD-9) plus the diagnosis of pituitary adenoma and/or hypophysectomy. There may be several reasons for this surprisingly high incidence, but most importantly, the medical records of the patients were not reviewed. It is therefore likely that the incidence was overestimated as indicated in our study.
We noticed a higher mean incidence between 2005-2013 compared to 1987–2004. Whether this reflects a truly increased incidence of the disease or simply an increased awareness, earlier recognition, and earlier diagnosis cannot be answered.
The main strength of this study is the large number of patients where the diagnosis of CD was thoroughly evaluated. In fact, this is the largest study on incidence in patients with CD published so far. Another strength is the use of a national registry with almost 100% coverage of all patient visits in Sweden. There are, however, some limitations that need to be acknowledged. Medical records for 10% of the patients could not be retrieved despite vigorous efforts. Most of the files that were missing belonged to patients who had received the diagnosis more than 20 years previously. Also, the retrospective evaluation of the diagnosis of CD may have limitations. Although it can be considered a limitation that 41 patients had possible but unconfirmed CD, and were therefore not included in the incidence analysis, it can also be considered a strength that only patients with a confirmed diagnosis were included.
In conclusion, this nationwide study demonstrates the importance of validation of the diagnosis when using registries for epidemiological research in rare diseases such as CD. A correct diagnosis of CD was verified in less than half of the patients. Thus, the results from previous and future epidemiological studies using ICD coding for inclusion of patients with CD, as well as other rare and complex diseases, should be questioned.