The Hypothalamus-Pituitary-Adrenal axis (HPA-axis) with its end product cortisol mediates the physiological response to stress thereby promoting mobilization of energy. The cortisol levels follow a diurnal rhythm with a distinct awakening response. Regulation of the HPA-axis differs among persons with certain psychiatric disorders when compared with controls. Some reports concern Attention-Deficit/Hyperactivity Disorder (ADHD) but findings are inconclusive. The main aim of the present thesis was to investigate diurnal levels of saliva cortisol in school aged children with ADHD and age matched non-affected comparisons, also taking early adversity, perceived stress and ADHD-medication into consideration. Children with ADHD had lower cortisol levels at awakening, 30 minutes later and before going to bed than comparisons. When the study group was split into three different age groups similar results were found only for children above 10 years of age. Within the ADHD group, subtype of ADHD or co-occurring symptoms did not affect the cortisol levels. Furthermore, children in the ADHD group had to a higher degree been exposed to foetal and childhood psychosocial adversity than comparisons. Since exposure to early adversity has been associated with both ADHD and HPA-axis functioning, such exposures could theoretically explain the low cortisol levels in ADHD via early programming of the HPA-axis. However, no relation was found between exposures to psychosocial adversity and diurnal cortisol levels. Neither did continuous medication with stimulants or atomoxetine explain the low cortisol levels. Possibly, medication may rather increase the levels. Finally, children with ADHD scored higher on perceived stress, measured by the Pressure-Activation-Stress (PAS) scale, than the comparison group. Female sex was also associated with higher stress in both groups, as well as increasing age in the comparison group. As with psychosocial adversity, no association was found between the higher PAS-scores and the lower cortisol levels, indicating the complexity of the stress regulating system. The results indicate a down-regulated or displaced HPA-axis with lower cortisol levels in children with ADHD. Stress related fragility – with more exposure to early stressors, higher perceived stress and lower diurnal cortisol levels – seem to accompany ADHD during childhood.

Myxedema coma and pituitary apoplexy are well-known life-threatening endocrine emergencies. The coincidence of these entities is exceedingly rare. Myxedema coma occurring as a result of pituitary lesion is a much less seen entity. A high index of suspicion is often required for early diagnosis as it is of particular importance in improving survival outcomes. We present a rare case of a patient with myxedema coma presenting as bradycardia and hypotension secondary to pituitary apoplexy, which was confirmed on magnetic resonance imaging (MRI). The patient was managed conservatively with levothyroxine and stress doses of steroid, with the resolution of hemodynamic changes and a decrease in the size of the suprasellar mass.

Bipolar disorders and recurrent depressions are two common psychiatric disorders with a life time prevalence of approximately 1% and 8%, respectively. Despite treatment these patients suffer from affective symptoms up to 50% of the time, resulting in lower well-being. The average life length is also reduced with 10-15 years, mainly attributable to suicide and cardiovascular disease. Increased stress is one of many factors that have been shown to be linked to an increased risk for developing affective disorders and some comorbid somatic conditions such as metabolic disturbances and cardiovascular disease. An increased stress level is known to cause hyperactivity of the hypothalamic-pituitary-adrenal-axis (HPA-axis) with increased cortisol secretion. Hyperactivity of the HPA-axis (or hypercortisolism) is one of the most replicated neurobiological finding in depression. In other stress related disorders it has however been shown that prolonged stress over long periods of time can lead to a state of low HPA-axis activity, hypocortisolism. Since persons with recurrent affective disorders such as bipolar disorder and recurrent depression are exposed to a high degree of recurrent and chronic stress it could be expected that in addition to hypercortisolism, a state of hypocortisolism could also develop in these disorders, potentially exerting an influence upon the psychological and somatic wellbeing among these patients. The major aim of this thesis was to evaluate whether hypocortisolism is related to relevant psychiatric and somatic phenotypes in recurrent affective disorders. In bipolar disorder, individuals with hypocortisolism exhibited a higher degree of depression and low quality of life compared to patients with normal HPA-axis activity. In recurrent depression, individuals with hypocortisolism exhibited shorter leukocyte telomere length than patients with normal or high HPA-axis activity, which is an indication of an accelerated aging process. In a sample of both bipolar and recurrent depression patients, hypocortisolism was associated with an increased proportion of obesity, dyslipidemia and metabolic syndrome compared with patients with normal or high HPA-axis activity. Patients with recurrent depression showed a higher occurrence of hypocortisolism than the control sample representative of the general population. Patients with bipolar disorder showed a similar occurrence of hypocortisolism as the control sample. Among bipolar disorder patients with a low degree of lifetime with lithium prophylaxis, there was an inverse correlation between age and HPA-axis activity. In contrast, among patients with a higher degree of lifetime with lithium prophylaxis as well as among the controls, there was no correlation between age and HPA-axis activity. Accordingly, hypocortisolism was most common among older patients with a low degree of lifetime with lithium prophylaxis. In conclusion, hypocortisolism in both recurrent depression and bipolar disorder was associated with multiple clinically-relevant phenotypes. Additionally it was shown for bipolar disorder patients that increasing age was a risk factor for hypocortisolism and that prophylactic lithium treatment was a protective factor. It is argued that the protective effect of lithium towards the HPA-axis is attributable to its mood-stabilizing effect, which in turn reduces the chronic stress level. These results provide new insight into the role of hypocortisolism and chronic stress in recurrent affective disorders warranting further studies and hopefully providing clues to improved treatment strategies.

Many studies have shown steroid hormone changes in adrenal incidentalomas with subclinical hypercortisolism and various forms of Cushing's syndrome. The aim of our work was to measure, using novel steroid GC-MS/MS measurement procedure, complex picture of many steroids in these patients. With the knowledge of these changes we could better explain causal pathophysiologic changes. In the study on patients with adrenal incidentalomas we described complex steroid changes in patients with subclinical hypercortisolism. Previous studies showed decrease of DHEAS in subclinical hypercortisolism. We confirmed this finding and described a decrease in other androgens and their metabolites. We also evaluated their sensitivity and specificity when compared to routinely used parameters for diagnosis of subclinical hypercortisolism. Furthermore, we looked at the alterations in all measured steroids and their changes in the 1 mg dexamethasone suppression test. In another study, we analyzed steroid changes in various forms of Cushing's syndrome. We confirmed the decrease of adrenal androgens in the ACTH independent forms and mild increase in the ACTH dependent forms. We also described elevations of mineralocorticoid precursors in central and ectopic forms of ACTH secretion. In the distinction of ectopic and central...