Predictive Value of Circulating Gonadal and Adrenal Steroids For Respiratory Function in Patients with Amyotrophic Lateral Sclerosis (ALS).

GARGIULO MONACHELLI G; SIVORI M; MEYER M; SICA, R.E.P; DENICOLA AF; GONZALEZ DENISELLE MC

San Diego

Congreso; American Academy of Neurology 65th Annual Meeting; 2013

American Academy of Neurology

Objective: To analyze serum levels of adrenal and gonadal steroids in ALS patients and controls, and to search for a relationship between these steroids and respiratory parameters in ALS.Background: Changes of circulating steroids exist in patients with ALS and animal models of motor neuron degeneration and influence progression. For instance, in the SOD1 mouse model of familial ALS, ovariectomy leads to a significant acceleration of the disease. Changes of steroids may also influence respiratory function. Lastly, ALS has been recently considered a hormonal condition.Design/Methods: Serum levels of gonadal and adrenal steroids were measured in 52 subjects (28 ALS and 24 controls) using radioimmunoassay procedures. We also evaluated ALS functional and strength scales, and respiratory parameters: forced vital capacity (FVC%), maximal inspiratory pressure (MIP%) and maximal expiratory pressure (MEP%), at diagnosis. Steroid levels and steroid ratios were correlated with respiratory parameters (including FVC% decline) at blood sample collection. The need for non-invasive ventilation (NIV) and survival time were also recorded.Results: The results showed that female patients demonstrated higher testosterone levels than female controls. Furthermore, with increasing age testosterone declined in controls but not in ALS patients, suggesting a differential metabolic behavior. The ratio dehydroepiandrosterone sulfate (DHEAS)/cortisol positively correlated with FVC%, MIP% and MEP%. The correlation analysis of free testosterone and progesterone/free testosterone (PROG/FT) ratio showed a negative and positive relationships respectively, with greater FVC% decline. Multiple regression analysis showed that elevated cortisol levels and higher age significantly decreased the time to NIV in 1.4 and 1.8 months, respectively.Conclusions: Determination of the steroid profile was sexually dimorphic in ALS: testosterone levels were higher in female ALS patients with respect to female controls. Overall testosterone levels did not decline with increasing age in ALS, whereas control levels did. DHEA-PROG correlated with better respiratory function and cortisol-testosterone behaved oppositely. Regarding respiratory function, certain hormones may serve a protective function while others may have a negative influence.