Growth hormone deficiency of hypothalamic origin in septo-optic dysplasia

Abstract

Hypothalamic pituitary function and growth hormone releasing hormone (GHRH) loading tests in two children with septo-optic dysplasia (SOD) revealed isolated GH deficiency in one and deficiencies of growth hormone, adrenocorticotropic hormone and antidiuretic hormone in the other. Secretion of GH was elicited in the first patient by single i.v. bolus administration of GHRH and after repetitive i.v. infusions of GHRH in the second. With these results we confirmed that the hypopituitarism in our patients with SOD was of hypothalamic origin. Both patients also had infantile spasms.

The role of growth hormone in determining birth size and early postnatal growth, using congenital growth hormone deficiency (GHD) as a model

“…In spite of this, CPHD patients with midline forebrain defects had both greater weight and length SDS than those without midline defects. Although the precise aetiology of pituitary dysfunction in conditions such as HPE and SOD is unknown, abnormal hypothalamic neuro‐anatomy has been postulated in the latter 26,27,43,44 . These patients present with variable phenotypes such as sexual precocity, posterior pituitary dysfunction and abnormal sleep patterns suggestive of a hypothalamic aetiology 43,45 .…”

“…Of the 32 patients with CPHD, there were no significant differences in the prevalence of TSH and ACTH deficiencies between patients in group B [TSH deficiency 90%, ACTH deficiency 70%] and group C [TSH deficiency 91%, ACTH deficiency 91%]. Gonadotrophin secretion was assessed in 19 of the 32 CPHD patients and was abnormal in 63·1% (12/19) of patients, six in group B and six in group C. An additional two patients [patients 27,35] were born with bilateral undescended testes that may reflect gonadotrophin deficiency. Posterior pituitary dysfunction was evident in six patients, all with midline defects (group C).…”

“…[20][21][22][23] Abnormal development of the midline forebrain and hypothalamo-pituitary structures occurs at a very early stage of foetal embryogenesis (4 -6 weeks) in humans, 24 and may therefore affect intrauterine growth. These patients may have both pituitary and hypothalamic abnormalities, [25][26][27][28] and this raises the possibility that these patients may demonstrate more severe growth abnormalities as compared with GH-deficient patients without widespread neuro-anatomical defects. The purpose of this study was to systematically review anthropometric, neuro-imaging and endocrine data in patients with congenital GHD presenting to a single endocrine centre.…”

Genetics of septo-optic dysplasia

“…However, the endocrinopathy may evolve with a progressive loss of endocrine function over time [7]. Commencement of growth hormone treatment in children with SOD involving GH deficiency may be associated with accelerated pubertal maturation [19] and either sexual precocity or failure of pubertal development may occur, with abnormal hypothalamic neuroanatomy or function [20][21][22][23][24]. Other features such as hypoglycemia, diabetes insipidus, and polyuria and polydipsia are less commonly associated [4,25].…”

Septo-Optic Dysplasia – Novel Insights into the Aetiology

“…GH deficiency is the most common endocrinological feature followed by deficiencies of thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) [11], whereas gonadotrophin secretion may be retained in the face of other pituitary hormone deficiencies; however the endocrinopathy may evolve with a progressive loss of endocrine function over time. Either sexual precocity or failure of pubertal development may occur, with abnormal hypothalamic neuroanatomy or function [12,13,14]; other features such as hypoglycaemia and diabetes insipidus are less commonly associated [15]. …”