J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-13008 | DOI: 10.4274/jcrpe.galenos.2023.2023-1-23

Pituitary Stalk Interruption Syndrome – Clinical Presentation and Management of a Potentially Life-threatening Disease in Newborns

Ira Winkler¹, Elisabeth Steichen², Klaus Kapelari², Peter Wöckinger¹, Vera Neubauer¹, Ursula Kiechl-Kohlendorfer¹, Elke Griesmaier^1
1Department of Paediatrics II (Neonatology), Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
²Department of Paediatrics I, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria

Pituitary stalk interruption syndrome (PSIS) is a rare congenital disease resulting in hypopituitarism of variable degree. Serious courses, due to severe combined pituitary insufficiency, are even rarer and associated with a very early manifestation immediately after birth. First clinical signs are elusive and lead to delayed diagnosis and treatment, often resulting in lifethreatening complications. Objective of the current report is to point out early leading symptoms and key issues of neonatal manifested PSIS to increase the awareness, improve the clinical management and thereby enable an early diagnosis and treatment to prevent further complications. This report presents and compares the clinical course and management of two male newborns with manifested PSIS. Early leading symptoms were the same in both patients, including recurrent hypoglycaemia, hyponatraemia, jaundice, cholestasis, sucking weakness and genital abnormalities. Patient 1 developed an infection-induced adrenal crisis, persistent substitution-dependent thrombocytopenia and convulsions due to severe hypoglycaemia in delayed PSIS diagnosis. In patient 2, due to recognised above-mentioned symptoms, endocrine testing and a subsequent cerebral magnetic resonance imaging were performed early and he was diagnosed and treated before major complications occurred. Genetic testing was performed in both patients. GLI2 gene mutation (NM_005270.5: c.2537del; p.(Pro846Argfs*66)) heterozygous was detected in patient 1. No mutation was found in patient 2. Conclusively, the early diagnosis of neonatal PSIS is indispensable in the treatment and prevention of the possible severe clinical manifestation of this orphan disease. Therefore, increased awareness for early leading symptoms and proper clinical management are crucial.

Keywords: Pituitary stalk interruption syndrome, hypopituitarism, neonatal manifestation, clinical management in newborns, neonatal cerebral magnetic resonance imaging, haematological abnormalities, GLI2 mutation

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