This competitive renewal project proposes to extend studies of the hypothalamic-pituitary-adrenal axis in fibromyalgia syndrome previously undertaken by the PI. Her initial data suggested reduced adrenocorticotropin (ACTH) and epinephrine responses to graded hypoglycemic challenge, and blunting of the normal diurnal cortisol rhythm in patients with fibromyalgia when compared to normal controls. The PI postulates that the decreased ACTH response to hypoglycemic challenge is the result of impaired CRH release, this also results in decreased sympathoadrenal response to hypoglycemia. The PI further proposes that the diurnal cortisol rhythm in patients with fibromyalgia is abnormal due to a shift in the circadian phase.
In Specific Aim 1, the PI and her colleagues propose to assess hypothalamic CRH-pituitary ACTH activity at baseline and in response to three stimuli: hypoglycemia, metapyrone-induced glucocorticoid administration, and an immune stimulus with tetanus toxoid vaccine.
In Specific Aim 2, sypathoadrenal responses to hypoglycemia, the cold pressor test, metapyrone vs. placebo will be compared in patients with fibromyalgia and controls.
In Specific Aim 3, the circadian phase (measured by core body temperature and melatonin levels) will be compared in women with fibromyalgia and healthy controls. Additional studies of the relationship between disrupted sleep pattern and night-time secretion of ACTH and cortisol and cytokines are planned if the circadian phase is not shifted.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Special Emphasis Panel (ZRG5-CFS (01))
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Ader, Deborah N
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Brigham and Women's Hospital
United States
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Vijayan, Sujith; Klerman, Elizabeth B; Adler, Gail K et al. (2015) Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia. J Neurophysiol 114:1923-30
Faghih, Rose T; Dahleh, Munther A; Adler, Gail K et al. (2015) Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing. IEEE Trans Biomed Eng 62:2379-88
Faghih, Rose T; Dahleh, Munther A; Adler, Gail K et al. (2014) Deconvolution of serum cortisol levels by using compressed sensing. PLoS One 9:e85204
Dean 2nd, Dennis A; Adler, Gail K; Nguyen, David P et al. (2014) Biological time series analysis using a context free language: applicability to pulsatile hormone data. PLoS One 9:e104087
Adler, G K; Bonyhay, I; Curren, V et al. (2010) Hypoglycaemia increases aldosterone in a dose-dependent fashion. Diabet Med 27:1250-5
Kubzansky, Laura D; Adler, Gail K (2010) Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease. Neurosci Biobehav Rev 34:80-6
Togo, Fumiharu; Natelson, Benjamin H; Adler, Gail K et al. (2009) Plasma cytokine fluctuations over time in healthy controls and patients with fibromyalgia. Exp Biol Med (Maywood) 234:232-40
Szmuilowicz, Emily D; Adler, Gail K; Ricchiuti, Vincent et al. (2007) Relationships between endogenous sex hormone concentrations and vascular function in postmenopausal women. J Clin Endocrinol Metab 92:4738-41
Szmuilowicz, Emily D; Adler, Gail K; Williams, Jonathan S et al. (2006) Relationship between aldosterone and progesterone in the human menstrual cycle. J Clin Endocrinol Metab 91:3981-7
McCall-Hosenfeld, Jennifer S; Goldenberg, Don L; Hurwitz, Shelley et al. (2003) Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia. J Rheumatol 30:809-14

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