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Titolo:
Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with anovel mutation in the DAX-1 gene
Autore:
Caron, P; Imbeaud, S; Bennet, A; Plantavid, M; Camerino, G; Rochiccioli, P;
Indirizzi:
CHU Rangueil, Serv Endocrinol & Malad Metab, F-31054 Toulouse, France CHU Rangueil Toulouse France F-31054 lad Metab, F-31054 Toulouse, France Univ Pavia, I-27100 Pavia, Italy Univ Pavia Pavia Italy I-27100Univ Pavia, I-27100 Pavia, Italy CHU La Grave, Biochim Lab, Toulouse, France CHU La Grave Toulouse France HU La Grave, Biochim Lab, Toulouse, France CHU Purpan, Serv Pediat & Genet Med, Toulouse, France CHU Purpan Toulouse France n, Serv Pediat & Genet Med, Toulouse, France
Titolo Testata:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
fascicolo: 10, volume: 84, anno: 1999,
pagine: 3563 - 3569
SICI:
0021-972X(199910)84:10<3563:CHDIAH>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONGENITAL ADRENAL HYPOPLASIA; GONADOTROPIN-RELEASING-HORMONE; JAPANESE PATIENTS; DEFICIENCY; EXPRESSION; SECRETION; DIAGNOSIS; FAILURE; AXIS; MEN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Caron, P CHU Rangueil, Serv Endocrinol, 1 Ave J Poulhes, F-31054 Toulouse,France CHU Rangueil 1 Ave J Poulhes Toulouse France F-31054 use, France
Citazione:
P. Caron et al., "Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with anovel mutation in the DAX-1 gene", J CLIN END, 84(10), 1999, pp. 3563-3569

Abstract

We have studied a 20-yr-old male patient with adrenal hypoplasia congenitaand hypogonadotropic hypogonadism (HH) due to a C to A transversion at nucleotide 825 in the DAX-1 gene, resulting in a stop codon at position 197. The same mutation was detected in his affected first cousin (adrenal hypoplasia congenita and HH) and in a heterozygous state in their carrier mothers. The patient had had acute adrenal insufficiency at the age of 2 yr and 6 months, bilateral cryptorchidism corrected surgically at the age of 12 yr, and failure of spontaneous puberty. Plasma testostereone (T) was undetectable (<0.30 nmol/L), gonadotropin levels were low (LH, <0.4 IU/L; FSH, 1.5 IU/L) and not stimulated after iv injection of 100 mu g GnRH. The endogenous LH secretory pattern was apulsatile, whereas free alpha-subunit (FAS) levelsdepicted erratic pulses, suggesting an incomplete deficiency of hypothalamic GnRH secretion. During iv pulsatile GnRH administration(10 mu g/pulse every 90 min for 40 h), each GnRH pulse induced a LH response of low amplitude (0.54 +/- 0.05 UI/L), whereas mean LH (0.45 +/- 0.01 IU/L) and FAS (63 +/- 8 mU/L) levels remained low. Amplitude of LH peaks (0.83 +/- 0.09 IU/L), mean LH (0.53 +/- 0 02 IU/L), and FAS (161 +/- 18 mU/L) levels increased (P< 0.01), whereas the T concentration remained low (0.75 nmol/L) when the pulsatile GnRH regimen was raised to 20 mu g/pulse for a 40-h period, suggesting a partial pituitary resistance to GnRH. Thereafter, plasma T levels remained in prepubertal value after three daily im injections of 5000 IU hCG (3.6 nmoL/L) and after 1-yr treatment with weekly im injections of 1500 IU hCG (1.2 nmol/L), implying Leydig cell resistance to hCG. The patient had agrowth spurt, bone maturation, progression of genital and pubic hair stages, and normalization of plasma T level (16.8 nmol/L) after a 12-month treatment with twice weekly injections of hCG and human menopausal gonadotropin (75 IU International Reference Preparation 2) preparations, suggesting that, in presence of FSH, a Sertoli cell-secreted factor stimulated Leydig cellproduction of T. In conclusion, we report a novel mutation in the DAX-1 gene in patients with AHC and HH. Our results suggest that the hypogonadism is due to a combined hypothalamic-pituitary gonadal defect and imply that the DAX-1 gene may play a critical role in human testicular function.

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Documento generato il 03/12/20 alle ore 15:42:16