Download Adrenocorticotropic hormone deficiency associated with combined

Adrenocorticotropic hormone deficiency associated with combined variable immunodeficiency : a new
syndrome ?
Quentien MH1, Delemer B2, Papadimitriou DT3, Souchon PF2, Pagnier A3, Enjalbert A1, Brue T1.
1
ICNE UMR6544, Université de la Méditerranée, Marseille; 2Départements d'Endocrinologie et d'Endocrinologie
pédiatrique, Centre Hospitalier et Université de Reims; 3Département d'Endocrinologie pédiatrique, Centre Hospitalier
et Université de Grenoble.
Understanding molecular mechanisms by which pituitary hormones deficiency occured is a central issue in
endocrinology. In this purpose was created the GENHYPOPIT network, an international multicentric study, based on
mutational screen and sequence analysis to determine the underlying gene mutations responsible of pituitary hormones
deficiency. Among patients listed in this network, 17 had ACTH deficiency, a desease characterized by low or absent
cortisol production secondary to low plasma ACTH. Interestingly, 3 of them displayed common variable
immunodeficiency (CVID), characterized by defective antibody formation. Scattered cases with this association were
reported before. For the first time our work evidenced a familial case, allowing to define this association as a new
syndrome. Increasing evidences outlined the idea of a functional network between the immune system and endocrine
system. In this context we screened genes expressed in cells of the immune system and in the pituitary, particularly in
cells expressing ACTH. Up to date we analysed three genes : LIF is a cytokine not only involved in pituitary
development but also in POMC expression and is critical in neuroimmune transduction of central and immune signals to
the adrenal axis. Ikaros, a zinc-finger transcription factor, directly regulates corticotroph and melanotroph lineages
development as well as differentiation and maturation of the leukocytes system. Eos, an Ikaros-related protein, is also
expressed in pituitary and may have function independent of Ikaros outside the lymphoid compartment. Up to now, no
mutation were identified in the coding exons of these different genes, but it is still interesting to study these genes in
other patients displaying such a phenotype. Sequencing of the complex network of regulatory elements in Ikaros gene
and of this circuitry partners might be a good approach to identify a single genetic cause to this ACTH deficiency
combined with a CVID.