Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition

Abstract

Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease.

Familial Cerebral Cavernous Malformations

“…A recent study found small focal calcifications (SFCs) in the adrenal glands identified on computed tomography scans to be common in FCCM patients. 57 These SFCs were found to be more common in the left adrenal gland, and FCCM patients with SFCs had significantly more brain lesions than did those without SFCs ( P <0.001). It is suggested that these SFCs might be a clinically silent manifestation of disease and can be used as an imaging biomarker in FCCM patients.…”

“…It is suggested that these SFCs might be a clinically silent manifestation of disease and can be used as an imaging biomarker in FCCM patients. 57…”

Vertebral Intraosseous Vascular Malformations in a Familial Cerebral Cavernous Malformation Population: Prevalence, Histologic Features, and Associations With CNS Disease

“…Cavernous malformations in the brain are usually multiple, sometimes numbering in the hundreds. Vascular lesions in the retina in approximately 5% and in the skin in 20% of patients have also been reported [1][2][3], as have small adrenal calcifications [4]. The question of skeletal involvement is complicated by the common occurrence of intraosseous vascular malformations, commonly referred to as vertebral hemangiomas, in the general population, prompting us to include a matched control group.…”

“…This disorder, which is characterized primarily by formation and growth of cavernous malformations within the brain and spinal cord, is recognized as a multisystem neurocutaneous disorder. Vascular lesions can be found in the retina, adrenal glands, and skin of patients with FCCM [1][2][3][4]. Scattered reports exist of intraosseous vascular malformations, commonly referred to as vertebral hemangiomas, in these patients, with a presumed shared cause of the intraosseous and CNS lesions.…”

Cutaneous findings of familial cerebral cavernous malformation syndrome due to the common Hispanic mutation

“…The majority of cavernous malformations in FCCM are found in the central nervous system (CNS), where they are prone to thrombosis, growth, and hemorrhage (Tomlinson et al, ). Extraneural cavernomas, which occur more frequently with the inherited variant of the disease, have been noted in the retina, liver, adrenal glands, and skin (Campione et al, ; Haghighi, Fathi, Shahbazi, Motahari, & Friedman, ; Sirvente, Enjolras, Wassef, Tournier‐Lasserve, & Labauge, ; Strickland et al, ; Toll & Parera, ). Some cutaneous cavernomas have been shown share similar histology and identical gene mutations to their CCM counterparts (Eerola, Parera, & Gimenez‐Arnau, ).…”