Abnormal puberty in paediatric Cushing's disease: relationship with adrenal androgen, sex hormone binding globulin and gonadotrophin concentrations.
OBJECTIVE
Paediatric Cushing's disease is frequently associated with abnormal puberty. We addressed the hypothesis that prepubertal patients show excessive virilization and pubertal patients show suppression of LH and FSH secretion.


METHODS
Serum androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), testosterone (T), and sex hormone binding globulin (SHBG) were determined at diagnosis and converted to standard deviation scores. LH, FSH concentrations were also determined. Severity of CD was assessed from the sleeping midnight cortisol concentration. Puberty was staged and excessive virilization defined as advance in pubic hair stage for breast stage or testicular volume (TV).


METHODS
Twenty-seven CD patients (17 male, 10 female), median age 13.4 years (range 5.9-17.8) were studied.


RESULTS
In the CD group as a whole, A4, DHEAS, T standard deviation scores (SDS) values were normal. SHBG SDS values (n = 19) were low (median -1.93, -4.32-0.86) correlating with BMI (r = -0.49). A4, DHEAS, T, SHBG, LH and FSH did not correlate with midnight cortisol, but A4 and T SDS correlated with ACTH at 09.00 h (both r = 0.51). Thirteen patients (11 male, 2 female) had excessive virilization with increased A4 (P = 0.033), DHEAS (P = 0.008), testosterone (P = 0.033) and decreased SHBG (P = 0.004) compared with subjects without excessive virilization. Pubertal boys (TV > or = 4 ml) (n = 7) and girls (breasts > or = stage 2) (n = 8) had low median LH and FSH. Boys had an LH concentration of 1.2 mU/l (0.3-3.5), FSH, 0.9 mU/l (0.2-6.4) and median T SDS, -1.95 (-3.8-4.65), while girls had an LH concentration of 1 mU/l (0.3-7.4).


CONCLUSIONS
Many patients had abnormal puberty and excessive virilization associated with increased adrenal androgens and decreased SHBG. Pubertal patients had low LH and FSH suggesting impaired pituitary-gonadal axis function.
Dupuis
C C
CC
Department of Endocrinology, Barts and the Royal London School of Medicine and Dentistry, London, UK.
Storr
H L
HL
Perry
L A
LA
Ho
J T F
JT
Ahmed
L
L
Ong
K K
KK
Dunger
D B
DB
Monson
J P
JP
Grossman
A B
AB
Besser
G M
GM
Savage
M O
MO
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000150:complications*; D011629:Puberty, Precocious / Q000097:blood / Q000209:etiology*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood; D014770:Virilism / Q000097:blood / Q000209:etiology
D000728:Androgens; D006065:Gonadotropins, Pituitary; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D000735:Androstenedione; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone