Pituitary Gland Duplication Syndrome: An International Imaging Analysis

Duplication of the pituitary gland is a rare developmental anomaly. Multiple associated craniofacial malformations have previously been reported with the largest series to date consisting of 5 patients. In this multi-institutional series of 10 patients, we present a detailed review of the imaging features and discuss a possible overarching pathogenesis that would explain most of the detected malformations.

Inclusion criteria for this retrospective imaging review were the presence of a pituitary stalk and gland duplication and the characteristic appearance of the hypothalamic ventral midline. In addition to the clinical presentation, we recorded the imaging findings of 10 patients (9 girls) through onsite and online reviews. Genetic analysis was available for 6 patients.

The duplicated pituitary stalk and gland showed normal imaging appearances in all patients. Mammillary bodies were clearly identified lateral to the characteristic prominence of the hypothalamic ventral midline. Strands of tissue extending to the anterior dura ("limited ventral myeloschisis") were noted at the medulla oblongata in 10, and at the cervical spinal cord in 7 patients. The medulla oblongata showed a "butterfly" appearance on axial images in 9 patients. Ten patients had cervical segmentation anomalies ("zipperlike"), 9 had anterior-posterior brainstem patterning defects (small pons, elongated medulla), and corpus callosum measurements were abnormal in all patients. Three patients each presented with diencephalic-mesencephalic junction abnormalities and 4 with an anterior mesencephalic "cap." An oropharyngeal teratoma was present in 4 patients. Genetics was normal in 3 of the 6 patients studied; the remainder were found to have mutations in EFNB1 and a gene variant of GIT1, 2 copies of 7 and 8 exon of SMN1 gene, and 2.126 megabase duplication at bands q11.1 and q11.2 of 1 chromosome 15, respectively.

Duplication of the pituitary gland presents as well-defined craniofacial and cervical spine malformation phenotype. Axial mesoderm duplication generating an excess of Sonic Hedgehog may be the primary embryologic driver leading to this condition.