Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviours . Inspite of the fact that many studies aimed at determining the neurobiological basis of this disorder, its cause remains obscure .
The limbic system deserves special attention in autism because this brain region is a basis for emotions and social interactions (which are abnormal in autism). Since the limbic system influences the functions of the hypothalamus and the pituitary gland, it is logical to postulate that analyzing blood levels of pituitary hormones may reflect possible alterations of the limbic system functioning in individuals with autism .
In the current study, serum cortisol levels were lower and plasma ACTH levels were higher in individuals with autism, compared to normal subjects with 10% and 16% having low cortisol and high ACTH respectively. In addition, 10% did not show adequate cortisol response to ACTH stimulation. Serum cortisol and ACTH levels were analyzed in several studies but the results were inconsistent. Marinovic-Curin and co-workers  found lower cortisol, higher ACTH and inadequate cortisol response after ACTH stimulation among their autistic patients in comparison to controls which goes with our results. Other studies that did not perform an ACTH stimulation test did not find a difference in cortisol levels among autistic patients and controls [22, 30] with only ACTH being significantly higher among cases than controls  or found significantly lower cortisol levels among autistic patients than controls . In addition, Tani and associates  found lower cortisol and higher ACTH levels among patients with Asperger syndrome than controls. The difference between our findings and other studies could reflect variations in methods for hormone measurement. Also, our samples were collected in an earlier time period (9 am) and larger numbers of autistics and controls took part in our study compared to previous reports.
Cortisol has an important role in proper emotional development and functioning. Thus, abnormal cortisol levels were found in chronic depression and suicide prone behaviour . In addition, lower levels of cortisol were found among holocaust victims with posttraumatic stress disorder and were pointer to "vulnerability" for its development . Also, primary disorders of cortisol metabolism (Cushing syndrome and Addison disease), as well as cortisol supplement therapy are often associated with emotional disturbances . Our finding of lower cortisol levels among individuals with autism is hard to interpret. Some authors hypothesized that individuals with autism display heightened response to stressors, namely venipuncture procedure so that anxiety and situational stress could explain the raised ACTH values  but elevated ACTH in our study was accompanied by lower cortisol levels which is in contradiction to such a conclusion. Also, the stress of venipuncture procedure was the same in both groups and so, the observed differences may be related to autism pathophysiology rather than to acute stress. There are many studies of the plasma levels of B-endorphin in autistic patients and most of them found higher levels of this hormone in individuals with autism [36–38]. Since ACTH and B-endorphin are secreted in equi-molar quantities from same precursor, pro-opiomelanocortin, from the anterior pituitary, other studies [30, 36] showing elevated B-endorphin levels in autistic individuals support our finding of elevated ACTH. Finally, we hypothesize that lower cortisol and higher ACTH levels may signal a state of low basal functioning of HPA axis in autistic individuals. This was confirmed in our study by failure of 10% of autistic patients to show an adequate cortisol response to ACTH stimulation which was supported by another study . Suggested mechanisms include either an abnormality in delivery of ACTH to adrenal cortex receptors, or in biosynthesis of cortisol, or in negative feedback inhibition of HPA axis by cortisol and ACTH [30–32]. This hypothesis also, sheds light on the fact that HPA axis dysfunction might have a role in the pathophysiology of autism and its clinical symptomatology especially impaired behavioral and social interactions .
Moreover, the current study revealed significantly lower morning basal cortisol, higher ACTH and lower cortisol response after ACTH stimulation as the autistic severity increased. In addition, CARS score correlated positively with ACTH and negatively with each of basal and stimulated cortisol. This means that the extent of the HPA axis dysfunction was closely linked to autistic severity which was confirmed by another study .
In the current study, all hormonal parameters did not differ significantly according to the IQ of autistic subjects. Similarly, Marinovic-Curin etal, 2003  and Tordjman etal 1997  concluded that IQ itself did not appear to influence the hormonal levels significantly bearing in mind that they did not confirm their results by performing an ACTH stimulation test. To the best of our knowledge, we could not trace data in literature to explain the mechanism by which low plasma cortisol could affect cognitive functions in autistic children. On the other hand, another study  concluded that, generally speaking, increased cortisol levels due to stress-induced HPA axis over activity have been associated with cognitive impairment as stress-induced HPA axis overactivity and increased cortisol levels may cause hippocampal damage and, subsequently, cognitive decline. Furthermore, patients with Cushing's syndrome more often present with cognitive impairment . Finally, one of the side-effects of treatment with synthetic corticosteroids is cognitive deterioration 
Also, the current study revealed that hormonal profile did not differ significantly between autistic children with and without EEG abnormalities which was also supported by Marinovic-Curin and associates .
In addition, the current study demonstrated that hormonal profile did not significantly differ between autistic patients with and without self injurious behavior which was also confirmed by another study . Inspite of the previous fact, there is evidence of an association between low HPA axis activity and antisocial behavior since cortisol, which is the final product of the HPA axis, is an important factor for proper emotional and social development and functioning [42, 43].