Deficit in anterior pituitary function and variable immune deficiency (DAVID) in children presenting with adrenocorticotropin deficiency and severe infections.
BACKGROUND
Among 22 independent patients from the GENHYPOPIT network who had ACTH deficiency and no identified mutation of TPIT, three of them (13.6%) displayed common variable immunodeficiency (CVID), characterized by defective Ig production.


OBJECTIVE
Our objective was to describe an as yet unrecognized disease association.


METHODS
We considered the hypothesis of ACTH deficiency being associated with antipituitary autoimmunity or lymphocytic hypophysitis. In the context of a functional network between the immune and endocrine systems, we also tested the hypothesis of a common genetic cause using a candidate gene approach.


METHODS
This was a multicentric study in three academic hospitals.


METHODS
We report four patients from three unrelated families presenting with ACTH deficiency and CVID.


METHODS
Detection of antipituitary autoantibodies, and sequencing of candidate genes (LIF, IKAROS, EOS) were the main outcome measures.


RESULTS
All patients including a pedigree with two affected siblings had ACTH deficit diagnosed from 5-15 yr, with symptomatic hypoglycemia, and CVID diagnosed from 2-8 yr revealed by recurrent infections. Three of the four patients had a hypoplastic pituitary. One patient had low IGF-I and subnormal GH response to stimulation, suggesting that secretion of other pituitary hormones may also be affected. All patients proved negative for pituitary autoantibodies and had no alteration in any of the genes tested.


CONCLUSIONS
The remarkable association of two rare disorders affecting two functionally related systems in four patients from three independent pedigrees including a familial case provides strong evidence of the existence of a disease association: deficit in anterior pituitary function and variable immune deficiency, or DAVID.
Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, Aix-Marseille Université, 13344 Marseille, France.
Marie-Hélène
MH
Quentien
Brigitte
B
Delemer
Dimitris T
DT
Papadimitriou
Pierre-François
PF
Souchon
Roland
R
Jaussaud
Anne
A
Pagnier
Martine
M
Munzer
Nicolas
N
Jullien
Rachel
R
Reynaud
Noémie
N
Galon-Faure
Alain
A
Enjalbert
Anne
A
Barlier
Thierry
T
Brue
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000172:deficiency*; D000328:Adult; D020274:Autoimmune Diseases of the Nervous System / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007239:Infections / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D010375:Pedigree; D010641:Phenotype; D010900:Pituitary Diseases / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D010903:Pituitary Gland, Anterior / Q000378:metabolism / Q000473:pathology; D010908:Pituitary Hormones, Anterior / Q000097:blood / Q000172:deficiency*; D012720:Severity of Illness Index; D057127:Single-Chain Antibodies / Q000235:genetics; D055815:Young Adult
D010908:Pituitary Hormones, Anterior; D057127:Single-Chain Antibodies; D000324:Adrenocorticotropic Hormone