Extreme elevation of serum angiotensin-converting enzyme (ACE) activity: always consider familial ACE hyperactivity

Abstract

Measurement of serum angiotensin-converting enzyme (ACE) activity can be helpful in the diagnosis and disease monitoring of sarcoidosis. Elevated serum ACE activity is found in 60-70% of sarcoidosis patients. Usually, the ACE activity is mildly increased (<3-fold the upper limit of the reference range) in sarcoidosis patients. Extremely elevated ACE activity is suggestive of the benign condition known as 'familial hyperactivity of ACE'. Familial hyperactivity of ACE is a relatively rare condition and can be confirmed by genetic testing. Considering a genetic cause of strongly elevated serum ACE activity is important to prevent possible overdiagnostics. Here, we highlight the factors that may complicate the interpretation of serum ACE activity measurements, and we present two cases that illustrate the importance of interdisciplinary consultation when extremely elevated serum ACE activity is measured.

The Diagnosis of Sarcoidosis

“…22 This lack of sensitivity and specificity, taken together with genetic polymorphisms in angiotensin-converting enzyme gene and the low prevalence of sarcoidosis in both the general population and in patients with nonspecific symptoms, makes SACE activity poorly suited as a screening test for sarcoidosis. 23 Tuberculin skin test and interferon-gamma release assay A tuberculin skin test should be considered as part of the workup for newly diagnosed sarcoidosis. Because almost all patients with active sarcoidosis are anergic to purified protein derivative, a positive test suggests a diagnosis other than sarcoidosis.…”

Utility of angiotensin‐converting enzyme and serum calcium levels in cutaneous sarcoidosis

“…Serum ACE level has historically been reported to correlate with the number of systemic sarcoidal granulomas, as well as potentially with disease severity 8–10 . Despite the presence of elevated ACE levels in approximately 2/3 of patients with sarcoidosis, the majority of patients with elevated ACE levels do not have sarcoidosis, and controversy remains over the utility of this measurement 11–13 . The laboratory evaluation of patients with sarcoidosis often includes measuring serum calcium and ACE levels 7,14 …”

“…[8][9][10] Despite the presence of elevated ACE levels in approximately 2/3 of patients with sarcoidosis, the majority of patients with elevated ACE levels do not have sarcoidosis, and controversy remains over the utility of this measurement. [11][12][13] The laboratory evaluation of patients with sarcoidosis often includes measuring serum calcium and ACE levels. 7,14 A subset of patients is first diagnosed with sarcoidosis via skin biopsy.…”