Endocrine Status in Patients with Optic Nerve Hypoplasia: Relationship to Midline Central Nervous System Abnormalities and Appearance of the Hypothalamic-Pituitary Axis on Magnetic Resonance Imaging

Abstract

We here: 1) describe the phenotypic spectrum, including magnetic resonance imaging (MRI) appearances of the pituitary stalk and anterior and posterior pituitary [H-P (hypothalamic-pituitary) axis], in children with optic nerve hypoplasia (ONH) with or without an abnormal septum pellucidum (SP); and 2) define endocrine dysfunction according to the MRI findings. Medical records of 55 children with ONH who had been assessed by ophthalmology and endocrine services were reviewed. All had MRI of the brain and H-P axis. Forty-nine percent of the ONH patients had an abnormal SP on MRI, and 64% had a H-P axis abnormality. Twenty-seven patients (49%) had endocrine dysfunction, and 23 of these had H-P axis abnormality. The frequency of endocrinopathy was higher in patients with an abnormal SP (56%) than a normal SP (39%). Patients were divided into four groups based on SP and H-P axis appearance: 1) both normal; 2) abnormal SP and normal H-P axis; 3) normal SP and abnormal H-P axis; and 4) both abnormal. The frequency of multiple pituitary hormone deficiency was highest (56%) in group 4, lower (35%) in group 3, and even lower (22%) in group 2. Precocious puberty was most common in group 2. None of the patients in group 1 had endocrine dysfunction. Thus, SP and H-P axis appearances on MRI can be used to predict the likely spectrum of endocrinopathy.

A Patient with Septo-Optic Dysplasia Accompanying with Central Precocious Puberty

“…Cerebellar hypoplasia, schizencephaly, aplasia of the fornix, encephalocele, and cortical dysplasia were also reported in SOD patients [1][2][3]. In addition, neurological symptoms are frequently observed, including mental retardation, epilepsy, and communicative or behavioral difficulties [1].…”

“…Diagnosis of SOD is made based on the presence of 2 or more features of the classic triad: (i) optic nerve hypoplasia, (ii) hypopituitarism, ranging from isolated to multiple hormone deficiency, and (iii) midline brain defects (1). However, SOD is heterogeneous and may accompany other brain anomalies and developmental delay [1,2]. Regarding pubertal disturbance, patients with SOD usually show gonadotropin deficiency as a manifestation of hypopituitarism; however, it has been reported that several patients showed central precocious puberty [3].…”

“…This is presumably related to SOD. The most common hormone deficiency is GH alone or in combination with deficiencies in other pituitary hormones [1][2][3][4]. Secondary adrenal insufficiency due to ACTH deficiency has also been reported in SOD patients.…”

Update: Interim Guidance for the Evaluation and Management of Infants with Possible Congenital Zika Virus Infection — United States, August 2016

“…Infants with abnormal brain development can be at risk for hypothalamic dysfunction leading to pituitary insufficiency, and early manifestations of endocrine dysfunction might not be detected by routine newborn screening (28). Thyroid screening, including measurement of thyroid stimulation hormone (TSH) and thyroxine (either free T4 or both total T4 and estimated free T4) should be performed at age 2 weeks and again at age 3 months.…”

Vascular Cerebral Anomalies Associated with Septo-Optic Dysplasia

“…However only 30% of cases present the complete triad 2 and almost 40% of SOD patients may present with normal endocrinology 3 . We describe MRI and CT findings in a patient with SOD characterized by vascular abnormalities, emphasizing the correlation between SOD and a vascular disruption that may occur during embryologic development.…”