Diurnal variation of hypothalamic function and chronic subthalamic nucleus stimulation in Parkinson's disease.
BACKGROUND
Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life in patients with advanced Parkinson's disease (PD), but is associated with neuropsychiatric side effects and weight gain in some individuals. The pathomechanisms of these phenomena are still unknown. Considering anatomical and functional connections of the STN with the hypothalamic-pituitary (HP) system, we prospectively investigated whether chronic STN-DBS alters HP functioning in 11 PD patients.


METHODS
Basal hormone levels of the HP-adrenal (HPA), HP-gonadal and HP-somatotropic axis were determined before surgery as well as 3 and 6 months after electrode implantation. In addition, 24-hour cortisol profiles and dexamethasone suppression tests were obtained. Postoperative hormone changes were correlated with individual neuropsychological test performance, psychiatric status and anthropometric measures.


RESULTS
While PD patients experienced weight gain (p = 0.025) at follow-up, most neuropsychological data and basal HP hormone levels did not change over time. HPA regulation and diurnal rhythmicity of cortisol remained intact in all patients. The 24-hour mean cortisol levels decreased 6 months after surgery (p = 0.002) correlating with improved postoperative depression (p = 0.02).


CONCLUSIONS
Chronic application of high-frequency electrical stimuli in the STN was not associated with HP dysfunction in patients with advanced PD. The diurnal variability of peripheral cortisol secretion as one important element of the endogenous biological clock remained intact. Evening cortisol levels decreased after surgery reflecting a favorable regulation of the cortisol setpoint. STN-DBS can be considered safe from a neuroendocrine perspective, but the origin of unwanted side effects warrants further elucidation.
Department of Neurology, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
Carola
C
Seifried
Sandra
S
Boehncke
Jannika
J
Heinzmann
Simon
S
Baudrexel
Lutz
L
Weise
Thomas
T
Gasser
Karla
K
Eggert
Wolfgang
W
Fogel
Horst
H
Baas
Klaus
K
Badenhoop
Helmuth
H
Steinmetz
Rüdiger
R
Hilker
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology*; D046690:Deep Brain Stimulation; D003907:Dexamethasone; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000097:blood / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy*; D010912:Pituitary-Adrenal Function Tests; D011569:Psychiatric Status Rating Scales; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000502:physiology*; D013739:Testosterone / Q000097:blood
D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D006854:Hydrocortisone