Background: Few studies have described the phenotypic spectrum of Septo-Optic Dysplasia (SOD). The aim of this study was to evaluate the range of H-P structural abnormalities and the endocrine morbidity of children with SOD and related disorders.
Methods: Retrospective longitudinal single centre study of children with SOD (n:171), Multiple Pituitary Hormone Deficiency (MPHD) (n:53) and Optic Nerve Hypoplasia (ONH) (n:35).
Results: Of SOD patients, 39/171 (23%) did not develop hypopituitarism over a median (25th, 75th centiles) follow-up of 6.20 (3.41, 8.06) years, although 73% had a small anterior pituitary (SAP). Half of patients with ONH had SAP, but preserved pituitary function at 10.22 (5.96, 12.98) years of follow-up. Compared to SOD, MPHD were significantly more likely to manifest anterior pituitary deficiencies and to develop these earlier [Hazard Ratio (HR) 0.28 to 0.63], with a higher prevalence of Ectopic Posterior Pituitary (EPP) (80%vs41.6%; P<0.0001) and Pituitary Stalk Interruption Syndrome (PSIS) (46.9%vs29.5%; P=0.03). Diabetes Insipidus (DI) (22%vs5.4%; P<0.006) and Posterior Pituitary Absence (PPA) (21.6%vs6%; P<0.02) were more frequent in SOD. MPHD developed the first deficit earlier [HR 0.616 (0.44, 0.86); P=0.0044]. The time to first deficiency was significantly associated with the number of pituitary deficits that subsequently developed [HR 1.59 (1.36, 1.85)] and with the presence of EPP [HR 2.11 (1.41, 3.15)] and PPA [HR 2.54 (1.53, 4.21)], in both groups. In SOD only, there was an association between Pituitary Stalk Absence (PSA) and ACTH, GH and TSH deficiencies, as shown by the interaction HR of 3.02 (1.16, 7.84), 2.7 (1.10, 6.61) and 3.04 (1.23, 7.56), respectively. Among DI patients, 6/26 (23%) SOD and 3/5 (60%) MPHD had a normal PP and 3/26 (11.5%) SOD and 1/5 (20.0%) MPHD had EPP. Among patients without DI, 18/128 (14.1%) SOD and 2/45 (4.4%) MPHD had PPA. Unusual MRI abnormalities (pituitary enlargement or pituitary stalk thickening) were documented in SOD only.
Conclusions: SOD patients present with a wide spectrum of radiological H-P abnormalities and with heterogeneous endocrine phenotypes, whilst MPHD tend to develop multiple anterior pituitary deficits at early stages of life with a higher prevalence of EPP and PSIS. PSA is associated with the development of specific anterior pituitary deficits in SOD only. SAP and PPA have low predictive value for the development of anterior and posterior pituitary deficits. MRI findings can predict the evolution of endocrine deficits only to some extent, hence life-long surveillance is essential in all groups.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology