Pituitary stalk interruption syndrome: cause, clinical manifestations, diagnosis, and management

Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk, hypoplasia of the adenohypophysis, and ectopic neurohypophysis. PSIS manifestations include a wide spectrum of clinical phenotypes and pituitary hormone deficiencies of variable degree and timing of onset. In this review, recent advances with respect to the cause of PSIS, clinical characteristics leading to earlier diagnosis, and management are outlined.

Diagnosis of PSIS is often delayed probably because clinical findings such as neonatal hypoglycemia, cholestasis, and/or micropenis as well as decreasing growth velocity are not appropriately and timely validated. Recently, molecular defects in various genes have been associated with PSIS albeit in a small number of cases. These findings suggest that PSIS belongs to the spectrum of holoprosencephaly-related defects. Phenotype-genotype discordance and the existence of asymptomatic carriers of a given molecular aberration indicate that penetrance may be modified favorably or unfavorably by the presence of other genetic and/or environmental factors.

PSIS constitutes an antenatal anatomical defect. Neonatal hypoglycemia, cholestasis, and/or micropenis with or without growth deficit should raise the possibility of combined pituitary hormone deficiency, a life-threatening condition in cases of coexisting cortisol deficiency. It is important to search for molecular defects in all PSIS cases, as precise identification of the cause is a prerequisite for genetic counseling.