J Pediatr Endocr Met 2015; aop
Ayse Pinar Cemeroglu*, Tarin Coulas and Lora Kleis
Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study Abstract Background: Septo-optic dysplasia (SOD) is a rare condition with variable clinical pictures and spectrum of findings. Objective: To analyze the spectrum of findings, frequency and age of onset of hypothalamic-pituitary dysfunctions in children with SOD. Method: A retrospective electronic medical record (EMR) chart review was done for patients with SOD seen in a tertiary care center’s pediatric endocrinology clinic between January 1, 2012, and March 31, 2014. The diagnostic criteria for SOD included presence of ≥ 2 of the following: (i) optic nerve hypoplasia, (ii) agenesis/hypoplasia of septum pellucidum and/or corpus callosum and (iii) hypothalamicpituitary dysfunction. Results: Eighty patients fitting the diagnostic criteria of SOD were included in this study. The majority of patients (96%) had optic nerve hypoplasia on magnetic resonance imaging and were diagnosed due to visual issues including nystagmus (36%) or strabismus (13.8%). Hypothalamic-pituitary dysfunction was most common (51%) when optic nerve hypoplasia was present with (36%) or without (15%) dysgenesis of septum pellucidum and/or corpus callosum compared to dysgenesis of septum pellucidum and/or corpus callosum alone (4%). Hypothalamic-pituitary dysfunction was noted in 55% of patients, and most (86%) were diagnosed ≤ 2 years of age. Central hypothyroidism and growth hormone deficiency were most common followed by secondary/tertiary adrenal insufficiency and diabetes insipidus. Conclusions: The risk of hypothalamic-pituitary dysfunction in SOD is highest ≤ 2 years of age and when both optic nerve hypoplasia and dysgenesis of septum pellucidum/ *Corresponding author: Ayse Pinar Cemeroglu, MD, Pediatric Endocrinologist, Associate Professor of Pediatrics, Michigan State University, MI, USA; and Pediatric Endocrinology, Spectrum Health Medical Group, Helen DeVos Children’s Hospital, Grand Rapids, MI, USA, Phone: +616-391-3933, Fax: +616-391-6240, E-mail: [email protected] Tarin Coulas: Michigan State University, Grand Rapids, MI, USA Lora Kleis: Helen DeVos Children’s Hospital, Spectrum Health Medical Group, Pediatric Endocrinology, Grand Rapids, MI, USA
corpus callosum are present, suggesting a need for more frequent follow-up and screening tests for hypothalamicpituitary dysfunction in these patients. Keywords: hypothalamic-pituitary dysfunction; optic nerve hypoplasia; septo-optic dysplasia. DOI 10.1515/jpem-2015-0008 Received January 8, 2015; accepted February 19, 2015
Introduction Septo-optic dysplasia (SOD), previously called de Morsier syndrome, was first described in 1949 when Reeves discovered an association between optic nerve abnormalities and absent septum pellucidum (1, 2). It was not until 1970 that Hoyt then described pituitary abnormalities associated with SOD (3). Although the signs and symptoms of SOD are quite varied, it is classically diagnosed clinically with the presence of two or more components of the triad including (i) optic nerve hypoplasia, (ii) midline brain abnormalities (such as agenesis or hypoplasia of the septum pellucidum and/or corpus callosum), and (iii) pituitary hormone abnormalities (4, 5). SOD is equally prevalent in males and females and has an incidence of 1 in 10,000 live births (6, 7). In addition to the varying presentations of optic nerve hypoplasia, varying degrees of endocrine dysfunction are also seen in SOD (8). The predictability of when the hormonal deficiency will present is unknown as it can initially present in the neonatal period or progressively throughout the lifespan (9–11). With early presentation, neonates may struggle with hypoglycemia, conjugated hyperbilirubinemia, micropenis, diabetes insipidus, and failure to thrive (10, 12). There is still much to learn about SOD, and it is a diagnostically challenging disorder due to the complexity and assortment of signs and symptoms. Currently, there is no standard classification system or standard protocols on how to evaluate those with suspected SOD or how frequently to perform
Brought to you by | University of British Columbia - UBC Authenticated Download Date | 7/14/15 1:10 PM
2 Cemeroglu et al.: SOD clinical characteristics
pituitary function tests. In this study, we have retrospectively analyzed the characteristics of patients with the diagnosis of SOD in an attempt to shed some light on the clinical findings of this interesting and relatively rare condition.
Materials and methods Study design and patients We performed an electronic medical record (EMR) retrospective chart review of patients with SOD followed by the Helen DeVos Children’s Hospital Pediatric Endocrinology Clinic between January 1, 2012, and March 31, 2014. ICD-9 codes were used to prescreen potential participants. The EMRs were reviewed to determine whether the patients fit the diagnostic criteria of SOD (4) by having at least two of the three findings including (i) optic nerve hypoplasia, (ii) midline brain abnormalities including agenesis or hypoplasia of the septum pellucidum and/or corpus callosum, and (iii) pituitary hormone abnormalities. Patients with less than two of the diagnostic criteria or patients with inadequate information in the EMR were excluded from the study. Growth hormone deficiency diagnosis was made in newborn patients with a growth hormone level of
Ayse Pinar Cemeroglu*, Tarin Coulas and Lora Kleis
Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study Abstract Background: Septo-optic dysplasia (SOD) is a rare condition with variable clinical pictures and spectrum of findings. Objective: To analyze the spectrum of findings, frequency and age of onset of hypothalamic-pituitary dysfunctions in children with SOD. Method: A retrospective electronic medical record (EMR) chart review was done for patients with SOD seen in a tertiary care center’s pediatric endocrinology clinic between January 1, 2012, and March 31, 2014. The diagnostic criteria for SOD included presence of ≥ 2 of the following: (i) optic nerve hypoplasia, (ii) agenesis/hypoplasia of septum pellucidum and/or corpus callosum and (iii) hypothalamicpituitary dysfunction. Results: Eighty patients fitting the diagnostic criteria of SOD were included in this study. The majority of patients (96%) had optic nerve hypoplasia on magnetic resonance imaging and were diagnosed due to visual issues including nystagmus (36%) or strabismus (13.8%). Hypothalamic-pituitary dysfunction was most common (51%) when optic nerve hypoplasia was present with (36%) or without (15%) dysgenesis of septum pellucidum and/or corpus callosum compared to dysgenesis of septum pellucidum and/or corpus callosum alone (4%). Hypothalamic-pituitary dysfunction was noted in 55% of patients, and most (86%) were diagnosed ≤ 2 years of age. Central hypothyroidism and growth hormone deficiency were most common followed by secondary/tertiary adrenal insufficiency and diabetes insipidus. Conclusions: The risk of hypothalamic-pituitary dysfunction in SOD is highest ≤ 2 years of age and when both optic nerve hypoplasia and dysgenesis of septum pellucidum/ *Corresponding author: Ayse Pinar Cemeroglu, MD, Pediatric Endocrinologist, Associate Professor of Pediatrics, Michigan State University, MI, USA; and Pediatric Endocrinology, Spectrum Health Medical Group, Helen DeVos Children’s Hospital, Grand Rapids, MI, USA, Phone: +616-391-3933, Fax: +616-391-6240, E-mail: [email protected] Tarin Coulas: Michigan State University, Grand Rapids, MI, USA Lora Kleis: Helen DeVos Children’s Hospital, Spectrum Health Medical Group, Pediatric Endocrinology, Grand Rapids, MI, USA
corpus callosum are present, suggesting a need for more frequent follow-up and screening tests for hypothalamicpituitary dysfunction in these patients. Keywords: hypothalamic-pituitary dysfunction; optic nerve hypoplasia; septo-optic dysplasia. DOI 10.1515/jpem-2015-0008 Received January 8, 2015; accepted February 19, 2015
Introduction Septo-optic dysplasia (SOD), previously called de Morsier syndrome, was first described in 1949 when Reeves discovered an association between optic nerve abnormalities and absent septum pellucidum (1, 2). It was not until 1970 that Hoyt then described pituitary abnormalities associated with SOD (3). Although the signs and symptoms of SOD are quite varied, it is classically diagnosed clinically with the presence of two or more components of the triad including (i) optic nerve hypoplasia, (ii) midline brain abnormalities (such as agenesis or hypoplasia of the septum pellucidum and/or corpus callosum), and (iii) pituitary hormone abnormalities (4, 5). SOD is equally prevalent in males and females and has an incidence of 1 in 10,000 live births (6, 7). In addition to the varying presentations of optic nerve hypoplasia, varying degrees of endocrine dysfunction are also seen in SOD (8). The predictability of when the hormonal deficiency will present is unknown as it can initially present in the neonatal period or progressively throughout the lifespan (9–11). With early presentation, neonates may struggle with hypoglycemia, conjugated hyperbilirubinemia, micropenis, diabetes insipidus, and failure to thrive (10, 12). There is still much to learn about SOD, and it is a diagnostically challenging disorder due to the complexity and assortment of signs and symptoms. Currently, there is no standard classification system or standard protocols on how to evaluate those with suspected SOD or how frequently to perform
Brought to you by | University of British Columbia - UBC Authenticated Download Date | 7/14/15 1:10 PM
2 Cemeroglu et al.: SOD clinical characteristics
pituitary function tests. In this study, we have retrospectively analyzed the characteristics of patients with the diagnosis of SOD in an attempt to shed some light on the clinical findings of this interesting and relatively rare condition.
Materials and methods Study design and patients We performed an electronic medical record (EMR) retrospective chart review of patients with SOD followed by the Helen DeVos Children’s Hospital Pediatric Endocrinology Clinic between January 1, 2012, and March 31, 2014. ICD-9 codes were used to prescreen potential participants. The EMRs were reviewed to determine whether the patients fit the diagnostic criteria of SOD (4) by having at least two of the three findings including (i) optic nerve hypoplasia, (ii) midline brain abnormalities including agenesis or hypoplasia of the septum pellucidum and/or corpus callosum, and (iii) pituitary hormone abnormalities. Patients with less than two of the diagnostic criteria or patients with inadequate information in the EMR were excluded from the study. Growth hormone deficiency diagnosis was made in newborn patients with a growth hormone level of
