Clinical and genetic heterogeneity of combined pituitary hormone deficiency and its overlap with congenital hypogonadotropic hypogonadismo

• Grant number: 24/04888-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2024
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ana Claudia Latronico Xavier
• Grantee: Ana Claudia Latronico Xavier
• Principal researcher abroad: Nelly Pitteloud
• Institution abroad: Centre Hospitalier Universitaire Vaudois, Switzerland
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Pinheiro Machado Canton ; Fernanda de Azevedo Correa

Abstract

Combined pituitary hormone deficiency (CPHD) is a rare condition affecting the development ofthe pituitary gland with subsequent hormone deficiencies and has an estimated prevalence of1:8000 births. Despite the accumulated knowledge of the genetic causes of CPHD, the diagnosticyield is only around 10 to 15%, prompting researchers to pursue new genes involved in thisdisease. CPHD shares clinical and genetic features with congenital hypogonadotropichypogonadism (CHH), a rare hypothalamic disease characterized by absent puberty andinfertility. This overlap needs further elucidation through systematic detailed phenotyping inlarge cohorts of CPHD. Further, CPHD was thought to be a pituitary defect, but recent data pointtowards an additional hypothalamic defect that can be revealed through short-term pulsatileGnRH therapy.This project will focus on a collaboration between two research groups-one in Sao Paulo, Braziland the other in Lausanne, Switzerland. Both groups have expertise in clinical endocrinology,human genetics, and bioinformatics with the aims to: (i) investigate the clinical and geneticoverlap between CPHD and CHH; (ii) unmask a possible dual defect, hypothalamic and/orpituitary, in patients with CPHD and gonadotropins deficiency; and (iii) identify novel CPHD genesusing family-based genetic studies. This proposal will lead to new discoveries regarding ontologyof syndromes, pathophysiology of the development of the pituitary, and personalized diagnosisand treatment for patients with CPHD. (AU)