While cortisol dysregulation gets the most attention for its link to weight and stress, it is also connected to medical conditions like hypertension, reproduction issues, PTSD, addiction, depression, and autism.

Hypertension

A primary function of cortisol is regulation of blood pressure. Thus, when cortisol is dysregulated, blood pressure is often affected. In cases of Cushing’s syndrome, when there is an excess of glucocorticoids, a common response (nearly 80% of cases) is the development of hypertension (high blood pressure). Nearly 30% of hypertension cases are thought to occur in response to cortisol dysregulation, specifically, This increase in cortisol related to hypertension is due to stimulation by ACTH.

Reproduction

Cortisol is not only involved in fat tissues, but it can also play a role in the function of reproductive organs.  The ovaries have GRs and they are influenced directly by the HPA through glucocorticoids, primarily cortisol (Andersen C. , 2002). In addition to the cortisol-binding protein (CBP), sex-hormone-binding globulin (SHBG) may also bind to cortisol. However, this interaction is not nearly as strong as the bond between CBP and cortisol. Like in other tissues, cortisol expression is regulated by 11β-HSD enzymes, which fluctuate over the course of the menstrual cycle.

Post-traumatic Stress Disorder

Being the stress hormone, it may come as no surprise that cortisol levels are altered in individuals with post-traumatic stress disorder (PTSD). In a meta-analysis examining the relationship between cortisol and PTSD, it was determined that while in general there is no difference in cortisol levels between people with PTSD and those without, a difference could be seen within subgroups of people (Meewisse, Reitsma, Vries, Gersons, & Olff, 2007). For example, when comparing cortisol levels collected from plasma, people with PTSD had lower levels. Women experiencing PTSD also had lower levels of cortisol than those without the disorder. Thus, suggesting a role for cortisol regulation in PTSD.

Addiction

HPA and cortisol response can also be significantly altered by drug use and addiction. Substances such as alcohol, nicotine or illegal drugs cause a small HPA response. And so it is likely that constant high intake of drugs can lead to dysregulation of the HPA. During heavy use, the HPA is chronically activated and can remain activated during withdrawal and for weeks. The circadian rhythm of HPA activity is also altered. And although, it may return back to a normal rhythm once the substance is no longer being used, HPA response, and thus cortisol response, to normal stimuli is remains blunted.

Depression

Stress has been linked to depression, and it is believed that treatment with antidepressants may treat depression in part by correcting dysregulation of HPA activity. People with depression have been found to secrete higher amounts of ACTH and cortisol and have a higher concentration of CRH in their cerebral spinal fluid —the fluid located in the ventricles of the brain, around the spinal cord, and other regions within the nervous system. These individuals have also been shown to have a higher number of CRH secreting nerve cells in regions connected to the HPA such as the limbic system (a region in the brain related to emotion). Furthermore, depression has been linked to other diseases associated with cortisol dysregulation. For example, several studies have linked Type 2 diabetes to an increased risk for major depressive disorder (MDD) (Demakakos, Pierce, & Hardy, 2010; Rustad, Musselman, & Nemeroff, 2011). In turn, the risk of developing diabetes is 60% higher in people with depression (Mezuk B, 2008). Taken together, the evidence suggests that cortisol dysregulation is a contributing factor in depression.

Autism

Autism is a neurodevelopmental disorder that presents as impaired social communication, limited interests, and repetitive behaviors. HPA dysregulation has also been implicated in autism disorders. As mentioned above, cortisol levels follow a diurnal (daily waking hours) rhythm. They rise in the morning and slowly decline throughout the day. Many studies have found that children with autism were more likely to show a disruption in this oscillation (Yamazaki, Saito, Okada, Fujieda, & Yamashita, 1975; Hill, Wagner, Shedlarski, & Sears, 1977; Hoshino, et al., 1987; Corbett, Schupp, Levine, & Mendoza, 2009; Richdale & Prior, 1992). Despite abnormal fluctuations in cortisol levels, the amount of cortisol secreted is similar to those with regularly regulated cortisol. People with autism also typically display slow HPA response activity to stress. The HPA also recovers from stress more slowly.