Moebius syndrome and hypopituitarism: a case of multiple pituitary hormone deficiency and revision of the literature.

Objectives: Moebius syndrome (MS) is a rare congenital non-progressive rhombencephalic disorder mostly characterised by abducens and facial nerve palsy, but with a multifaceted clinical presentation. Isolated or multiple pituitary hormone deficiencies in the setting of MS have been occasionally reported, but the simultaneous involvement of three or more hypothalamic-pituitary axes has never been described. We hereby report the case of a girl with MS that showed a co-occurrence of GH-, TSH- and ACTH-deficiency. In addition, we provide a systematic revision of all the published cases of hypopituitarism among patients with MS.

Case Presentation: A 6-year-old patient with a MS was referred to our outpatient clinic for faltering growth. The combination of stature below -3.0 SDS, impaired height velocity and pathological response to two GH-stimulation tests prompted the diagnosis of GH deficiency and therefore recombinant human GH was undertaken. Brain MRI highlighted a thin infundibular stalk. By the age of 10 years, she started to complain progressive fatigue and the co-occurrence of remarkably decreased fT4 levels in the setting of non-increased TSH led to diagnose central hypothyroidism. Accordingly, she was started on levothyroxine replacement therapy with timely clinical improvement. At the age of 11.3 years, recurrent symptoms consistent with morning hypoglycaemia prompted the prescription of a low-dose ACTH test, that confirmed an ACTH deficiency, in the setting of a multiple pituitary hormonal impairment.

Conclusions: Patients with MS are potentially at risk for either isolated or multiple pituitary hormones deficiency. Clinicians should lower the threshold for prescribing a dedicated endocrine assessment.