Metformin, estrogen replacement therapy and gonadotropin inhibition fail to improve insulin sensitivity in a girl with aromatase deficiency.
BACKGROUND
Insulin resistance (IR), abnormal lipid profile, and other features of the metabolic syndrome have been described in CYP19 gene knockout mice and in aromatase-deficient adult men but not in prepubertal affected girls.


OBJECTIVE
To study insulin sensitivity, as well as the effects of estrogen, metformin and GnRHa treatment on glucose homeostasis, in an aromatase-deficient girl.


METHODS
Clinical, metabolic and hormonal follow-up data, from 8 to 12 years of age, is presented.


RESULTS
At 9 years of age, IR (HOMA 5.6) and glucose intolerance was detected, along with high serum testosterone (2.28 nmol/l), androstenedione (4.92 nmol/l) and FSH (13.4 mIU/ml) levels. Estrogen replacement was ineffective to suppress gonadotropin and androgen levels, as well as IR. Under metformin therapy, she developed type 2 diabetes and acanthosis nigricans. GnRHa administration for 1 year resulted in marked decreases in gonadotropin and serum androgens, but severe IR persisted.


CONCLUSIONS
Postnatal estrogen replacement and a marked decrease of endogenous androgens failed to improve IR and glucose tolerance. We propose that, in females, the increment of androgens and/or lack of estrogens during fetal life might alter the mechanism of fetal programming of insulin sensitivity.
Guercio
Gabriela
G
Endocrine Service, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
Di Palma
Maria Isabel
MI
Pepe
Carolina
C
Saraco
Nora I
NI
Prieto
Mariana
M
Saure
Carola
C
Mazza
Carmen
C
Rivarola
Marco A
MA
Belgorosky
Alicia
A
D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000378:metabolism; D001141:Aromatase / Q000172:deficiency*; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D015914:Estrogen Replacement Therapy; D025461:Feedback, Physiological; D005260:Female; D005333:Fetus / Q000503:physiopathology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008687:Metformin / Q000627:therapeutic use*; D011247:Pregnancy
D000726:Androgen Antagonists; D000728:Androgens; D007987:Gonadotropin-Releasing Hormone; D008687:Metformin; D001141:Aromatase