Cushing’s Disease Study Shows Importance of Confirming Diagnosis

The annual incidence of Cushing’s disease in Sweden increased between 2005 and 2013 compared to earlier periods, according to nationwide data. However, this could be because of factors other than a truly higher disease frequency, including greater awareness and earlier diagnosis.

Also, the findings demonstrate the importance of confirming Cushing’s disease diagnosis in large registries, the researchers said.

The study, “The incidence of Cushing’s disease: a nationwide Swedish study,” was published in the journal Pituitary.

The small number of patients in studies of Cushing’s disease have limited appropriate analysis of its incidence. To address this gap, the scientists used the Swedish National Patient Register, aiming to  assess the annual incidence of Cushing’s and validate its diagnosis in patients with presumed disease.

“This is the largest study on incidence in patients with [Cushing’s disease] published so far,” the researchers stated.

There were 1,317 patients registered with a diagnostic code for Cushing’s syndrome or Cushing’s disease between 1987 and 2013. Their diagnosis was then validated by reviewing clinical, biochemical, and imaging data, as well as disease-related alterations in the body tissues.

This led to confirmation of diagnosis in less than half of the patients — 534 (41%). Mean age at diagnosis was 43 years, but 32 patients (6%) were younger than 18 at diagnosis; 17 were girls. The median follow-up duration was 10 years.

There were 41 patients (3%) with probable but not confirmed Cushing’s disease; 156 (12%) had other forms of Cushing’s syndrome — such as cortisol-producing adrenal adenoma, ectopic adrenocorticotrophic hormone (ACTH)-producing tumors, and cortisol-producing adrenocortical cancer  — and 334 (25%) had diagnoses unrelated to Cushing’s. Medical records for 132 patients (10%) were missing.

Among the confirmed Cushing’s disease cases, 469 (88%) had documented typical signs and symptoms of the disease, 460 (86%) had biochemical results supporting the diagnosis, 287 (54%) had a visible pituitary adenoma on imaging, and 176 (33%) had performed an inferior petrosal sinus sampling.

As for treatment strategy in confirmed Cushing’s disease, the most common option was pituitary surgery, in 381 of the 494 patients (77%) with available data. Radiation therapy was used in 57 (12%) cases, and bilateral adrenalectomy — removal of both adrenal glands — in 56 (11%). Pituitary surgery was also the primary treatment in 331 of 342 patients (97%) diagnosed in 1990 or later.

The analysis of Cushing’s disease incidence was conducted in the 390 patients diagnosed in 1987 or later. The mean annual incidence between 1987 and 2013 was 1.6 cases per million. According to the scientists, this is in line with the majority of previous reports.

In the periods of 1987–1995, 1996–2004 and 2005–2013, this incidence was 1.5, 1.4, and 2.0, respectively. This means that the annual incidence was higher between 2005-2013 than in the two other, and earlier, periods.

However, “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,” the team cautioned.

“This study illustrates the importance of validating diagnosis in patients with presumed CD from large health care registries such as national registries,” they added.