Why is the retention of gonadotrophin secretion common in children with panhypopituitarism due to septo-optic dysplasia?
Septo-optic dysplasia (De Morsier syndrome) is a developmental anomaly of mid-line brain structures and includes optic nerve hypoplasia, absence of the septum pellucidum and hypothalamo-pituitary abnormalities. We describe seven patients (four female, three male) who had at least two out of the three features necessary for the diagnosis of septo-optic dysplasia. Four patients had hypopituitarism and yet normal gonadotrophin secretion: one of these also had anti-diuretic hormone insufficiency; three had isolated GH deficiency and yet had premature puberty, with the onset of puberty at least a year earlier than would have been expected for their bone age. In any progressive and evolving anterior pituitary lesion it is extremely unusual to lose corticotrophin-releasing hormone/ACTH and TRH/TSH secretion and yet to retain gonadotrophin secretion. GnRH neurons develop in the nasal mucosa and migrate to the hypothalamus in early fetal life. We hypothesise that the arrival of GnRH neurons in the hypothalamus after the development of a midline hypothalamic defect may explain these phenomena. Progress in spontaneous/premature puberty in children with De Morsier syndrome may have important implications for management. The combination of GH deficiency and premature puberty may allow an apparently normal growth rate but with an inappropriately advanced bone age resulting in impaired final stature. GnRH analogues may be a therapeutic option. In conclusion, some patients with De Morsier syndrome appear to retain the ability to secrete gonadotrophins in the face of loss of other hypothalamic releasing factors. The migration of GnRH neurons after the development of the midline defect may be an explanation.
Great Ormond Street Hospital for Children NHS Trust, London, UK.
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Nanduri
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Stanhope
D002648:Child; D002675:Child, Preschool; D005260:Female; D006062:Gonadotropins / Q000378:metabolism*; D013006:Growth Hormone / Q000172:deficiency; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009900:Optic Nerve / Q000002:abnormalities*; D012688:Septum Pellucidum / Q000002:abnormalities*; D013577:Syndrome; D014667:Vasopressins / Q000172:deficiency
D006062:Gonadotropins; D014667:Vasopressins; D013006:Growth Hormone