Duplication of the Pituitary Gland (DPG)-Plus Syndrome Associated With Midline Anomalies and Precocious Puberty: A Case Report and Review of the Literature

Abstract

Duplication of the pituitary gland (DPG)-plus syndrome is a very rare developmental disorder with few cases described in the literature and characterized by multiple midline and central nervous system malformations. The hypothalamus and hypophysis involvement may be clinically associated with endocrine abnormalities. A 5.9-year-old female child was admitted to our Clinic for premature thelarche and acceleration of growth. DPG-plus syndrome with paired infundibula and pituitary glands was diagnosed after birth, when she appeared small for gestational age and she presented with lingual hypoplasia, cleft palate, right choanal stenosis, nasopharyngeal teratoma, and facial dysmorphisms. Neuroimaging revealed a duplication of the infundibula, the pituitary gland, and the dens of the epistropheus despite surgical removal of a rhino-pharyngeal mass performed at the age of two months. An array-CGH revealed a 2p12 deletion. At our evaluation, bone age assessment resulted advanced and initial pubertal activation was confirmed by Gonadotropin-Releasing Hormone stimulation test. Hormonal suppression treatment was started with satisfactory results. This case shows that DPG-plus syndrome must be considered in presence of midline and craniofacial malformations and endocrinological evaluations should be performed for the prompt and appropriate management of pubertal anomalies.

Duplication of the Pituitary Gland: CT, MRI and DTI Findings and Updated Review of the Literature

“…At the level of the craniocervical junction, our patient showed an absence of the anterior arch and an incomplete fusion of the posterior synchondrosis of the atlas, a broadened base of C2, a broad/duplicated odontoid process and a bony fusion of a midline ossicle (possibly the secondary ossification center/persistent ossiculum terminale) with the clivus. Similar anomalies seen with DPG can be found in the literature [12,14]. Bony vertebral anomalies are seen in 35% of patients with DPG [17].…”

“…It is attributed to the altered inductive role of the split rostral tip of the notochord on ependymal differentiation and cell migration and results in the interruption of lateral cell migration, which constitutes the hypothalamic nuclei [9]. Endocrine alterations, such as precocious puberty, hypogonadotropic hypogonadism with delayed sexual development, hypothyroidism, or hyperprolactinemia are frequent in DPG-plus syndrome and endocrinological evaluations should be performed to initiate appropriate management [14]. Endocrine anomalies could be a result of nuclear derangement and dysregulation of the hypothalamic-pituitary axis [14].…”

“…Endocrine alterations, such as precocious puberty, hypogonadotropic hypogonadism with delayed sexual development, hypothyroidism, or hyperprolactinemia are frequent in DPG-plus syndrome and endocrinological evaluations should be performed to initiate appropriate management [14]. Endocrine anomalies could be a result of nuclear derangement and dysregulation of the hypothalamic-pituitary axis [14].…”

“…Many patients with DPG-syndrome do not survive the first months of life [17]. Endocrine alterations are frequent in patients with DPG-plus syndrome and these patients may present with precocious or delayed puberty [14]. The exact pathogenesis of DPG is still unknown.…”

Severe Hyponatremia in a 46-Year-Old Female With Pituitary Stalk Duplication and Primary Empty Sella Syndrome

“…In 2007, Kandpal et al were the first to report two cases of partial duplication in adult patients [ 1 ]. Pituitary gland duplication is commonly associated with other craniofacial abnormalities such as duplication of the infundibulum, tubo-mamillary fusion, duplication of the basilar artery, agenesis/hypoplasia of the corpus callosum, hypertelorism, cleft palate, craniopharyngeal canal, oropharyngeal teratomas, and vertebral segmentation anomalies [ 2 ]. In this article, we report pituitary stalk duplication in a 46-year-old female with primary empty sella (PES).…”