Hyposecretion of the Adrenal Androgen Dehydroepiandrosterone Sulfate (DHEA-S) in the Majority of the Alopecia Areata Patients: Is it a Primitive and Pathogenic Perturbation of Hypothalamic-Pituitary-Adrenal Axis?

Abstract

Sir, Basic and clinical research suggest that disturbed neuro-endocrine function may be involved in the pathogenesis and course of autoimmune diseases. Hormones, such as those of hypothalamic-pituitary-adrenal Axis (HPA), are known to operate a modulation of immune responses.[1] In this report, we looked into the basal serum levels of four hormones: prolactin, ACTH, cortisol, dehydroepiandrosterone sulfate (the stable metabolite of the active steroid DHEA) by means of RIA method, to investigate if it could be a gross HPA axis perturbation in severe cases of alopecia areata disease (involvement >25% of scalp hair) as it appears in other autoimmune illness, such as in rheumatoid arthritis, systemic lupus erythematosus, Sjogren disease[2] and Hashimoto's thyroiditis[3] the last one so often associated to alopecia areata.[4] We studied a total of 142 patients - 55 males and 87 females- average age 34 years, not in systemic steroid therapy [Table 1]; they are members of the “Associazione Mediterranea Alopecia Areata” (www.alopecia-italy.com). We confirmed the normal value of prolactin level[5] and did not find significant imbalance of basal level of ACTH and cortisol, but DHEA-S in the majority of the patients was found reduced in comparison to age and sex matched controls: 69.1% of males (M) and 74.7% of females (F) are below the media of the control values – 165.80±98.69 mcg/dl (M) and 101.36±97.22 mcg /dl (F) versus 228.07±151.81 mcg/dl (M- control) and 134.49±104.64 mcg/dl (F -control) - Student's t-test P<0.00002 and Mood's median-test P<0.0000001 respectively-. 63.6% of M and 64.4% of F are in the range of deficiency values - given by mean minus s.d./3: <177, 47 mcg/dl for M and <99,60 mcg /dl for F [Figure 1]- irrespective of their age, clinical forms and duration of the disease. At the moment, we cannot determine with certainty whether this deficit is pre-existing or subsequent to the onset of pathology, but the low DHEA-S secretion also found in the majority of the patients in the remission phase and those with recent onset of the pathology -whereas cortisol and ACTH were in the normal range- could be indicative of a primitive deficit of DHEA-S production. These results confirm the old data from Vinocurow[6] and Montagnani:[7] they found in 85% of patients a hypoadrenalism through dosing of urinary steroids, independently from the clinical form of Alopecia. Many studies have shown that DHEA/DHEA-S has significant immunomodulating activity and could be useful in restoring immune regulation in patients with chronic autoimmune diseases,[8] probably through its capacity to modulate the mechanisms of natural immunity, such as NK cells, that can control the activation of T autoreactive linphocytes, event that appears in some autoimmune diseases, including alopecia areata.[9] On the other hand, DHEA is a neurohormone with antidepressive - ansiolytic activity and low DHEA-S secretion is considered as indicative of chronic stress response,[10] whose involvement in the pathogenesis of AA is to be considered.[11] Our preliminary therapeutic data suggest the clinical usefulness in some patients of the normalitation of the defective level of DHEA-S, but it is mandatory to investigate in a consistent number of cases affected from severe chronic/relapsing AA if the administration of DHEA could be a new additive relatively safe and inexpensive resource for the stabilization of this desperating disease, as it is suggested for other autoimmune pathologies.[8] Table 1 Case study Figure 1 DHEA-S mean values in sample (normal mean and median: males=228.07±151.81 mcg/dl; females=134.49±104.64 mcg/dl): Sample mean: males=165.80±98.69 mcg/dl (n=55, Student's t-test P<0.00002), females=101.36±97.22 mcg/dl (n=87, not normally distributed, therefore, given the median=73.8, Mood's median-test P<0.0000001).