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Reduced steroidogenesis in patients with PCDH 19‐female limited epilepsy
Author(s) -
Trivisano Marina,
Lucchi Chiara,
Rustichelli Cecilia,
Terracciano Alessandra,
Cusmai Raffaella,
Ubertini Grazia Maria,
Gian Germana,
Bertini Enrico Silvio,
Vigevano Federico,
Gecz Jozef,
Biagini Giuseppe,
Specchio Nicola
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13772
Subject(s) - neuroactive steroid , pregnenolone sulfate , pregnenolone , endocrinology , medicine , allopregnanolone , adrenocorticotropic hormone , pregnanolone , dehydroepiandrosterone sulfate , epilepsy , chemistry , stimulation , hormone , steroid , gabaa receptor , receptor , androgen , psychiatry
Summary Patients affected by protocadherin 19 ( PCDH 19)–female limited epilepsy ( PCDH 19‐ FE ) present a remarkable reduction in allopregnanolone blood levels. However, no information is available on other neuroactive steroids and the steroidogenic response to hormonal stimulation. For this reason, we evaluated allopregnanolone, pregnanolone, and pregnenolone sulfate by liquid chromatographic procedures coupled with electrospray tandem mass spectrometry in 12 unrelated patients and 15 age‐matched controls. We also tested cortisol, estradiol, progesterone, and 17 OH ‐progesterone using standard immunoassays. Apart from estradiol and progesterone, all the considered hormones were evaluated in basal condition and after stimulation with adrenocorticotropic hormone ( ACTH ). A generalized decrease in blood levels of almost all measured neuroactive steroids was found. When considering sexual development, cortisol and pregnenolone sulfate basal levels were significantly reduced in postpubertal girls affected by PCDH 19‐ FE . Of interest, ACTH administration did not recover pregnenolone sulfate serum levels but restored cortisol to control levels. In prepubertal girls with PCDH 19‐ FE , by challenging adrenal function with ACTH we disclosed defects in the production of cortisol, pregnenolone sulfate, and 17 OH ‐progesterone, which were not apparent in basal condition. These findings point to multiple defects in peripheral steroidogenesis associated with and potentially relevant to PCDH 19‐ FE . Some of these defects could be addressed by stimulating adrenocortical activity.