Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea.
OBJECTIVE
To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls.


METHODS
Cross-sectional study.


METHODS
Umeå University Hospital, Umeå, Sweden.


METHODS
Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls.


METHODS
None.


METHODS
We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer.


RESULTS
Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels.


CONCLUSIONS
The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.
Lindahl
Magnus S
MS
Department of Women's and Children's Health, Uppsala University Hospital, Uppsala, Sweden.
Olovsson
Matts
M
Nyberg
Sigrid
S
Thorsen
Kim
K
Olsson
Tommy
T
Sundström Poromaa
Inger
I
D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage*; D000328:Adult; D000568:Amenorrhea / Q000097:blood* / Q000150:complications; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007027:Hypothalamic Diseases / Q000097:blood* / Q000150:complications; D053577:Interleukin-1 Receptor Accessory Protein / Q000097:blood*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D016896:Treatment Outcome
D016207:Cytokines; D053577:Interleukin-1 Receptor Accessory Protein; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone