The contribution of autoimmune phenomena to dysfunction of hypophysis or hypothalamus is far to be unraveled and also the specific pathways of hypophysitis are poorly understood until now, mostly for the pediatric population. Primary hypophysitis is rare in children and often regarded as an autoimmune disorder, following the evidence of lymphoplasmacytic infiltration in the pituitary gland, detection of anti-pituitary antibodies (APA) and anti-hypotalamus antibodies (AHA) by indirect immunofluorescence on cryostatic sections of human or primate hypophysis and hypothalamus, and coexistence with other autoimmune disorders. The rarity of this condition and the lack of ad hoc studies make hard any assessment of the real incidence of hypophysitis in pediatric patients, and also the role of APA and AHA has been poorly investigated in children with idiopathic hypopituitarism. Potential target autoantigens studied in autoimmune hypophysitis have been various pituitary-specific factors, chaperone proteins, alpha-enolase, secretogranins, chorionic somatomammotropin and intracellular transcription factors. Many clinical features both endocrine and neurologic or systemic can herald the onset of autoimmune hypophysitis. Antidiuretic hormone deficiency with central diabetes insipidus and growth retardation are the most significant presenting symptoms in children with hypophysitis, requiring a careful differential diagnosis with other causes of hypopituitarism, including tumors of the sellar region, differently from adults in whom adrenal insufficiency, hypogonadism, headache or diplopia might be the leading manifestations. Growth hormone deficiency is found in 3/4 of pediatric cases. Five histologic variants of primary hypophysitis have been described: lymphocytic, granulomatous, xanthomatous, IgG4-related and necrotizing: lymphocytic hypophysitis is the most frequent variant in the pediatric sceneries. Children with diagnosis of hypophysitis are also at risk of developing germinomas later in life, and require an extended follow-up in the long-term. Therapeutic options should be differentiated according to the rapidity of disease progression and modality of clinical onset, as acute pictures might require corticosteroids or immunosuppressant agents, while chronic forms may need a conservative management or appropriate hormone replacement therapies. This review updates and summarizes the most recent information related to the autoimmune involvement of hypophysis and hypothalamus in children, discusses the correlations between APA, AHA and disease activity, as well as the recommendations for treatment of primary hypophysitis from the pediatric perspective.
- Autoimmune hypophysitis