1.1.1. Introduction

Psychological stress may be a factor in precipitating or exacerbating adrenal crisis. A self-reported questionnaire-based study (White et al EJE) reported 1% of incidence of adrenal crisis being related to psychological stress. It is unclear how often this occurs as it is seen very rarely in clinical practice, and when it does is associated with severe sudden stress such as a bereavement. There is considerable variation in people’s experience of psychological stress and its contributing factors. Although some stress is a normal part of life for most people, people with adrenal insufficiency may benefit from reducing their risk of severe psychological stress and adjusting their medicines when these happen, to maintain their health and well-being. It is important that patients do not take extra glucocorticoids when it is not needed as this is associated with symptoms and signs of glucocorticoid excess, that is Cushingoid features and risk of hypertension osteoporosis, Type 2 diabetes, and obesity.

This review examines the evidence for the need for pharmacological treatments, and optimum treatment regimens for managing periods of psychological stress in people with adrenal insufficiency.

1.1.2. Summary of the protocol

For full details see the review protocol in Appendix A.

Table 1

PICO characteristics of review question.

1.1.3. Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in appendix A and the methods document.

Declarations of interest were recorded according to NICE’s conflicts of interest policy.

1.1.4. Effectiveness evidence

1.1.5. Summary of studies included in the effectiveness evidence

No relevant studies were identified for inclusion in this review.

1.1.6. Summary of the effectiveness evidence

No relevant studies were identified for inclusion in this review.

1.1.7. Economic evidence

1.1.8. Economic model

This area was not prioritised for new cost-effectiveness analysis.

1.1.9. Unit costs

Relevant unit costs are provided below to aid consideration of cost effectiveness.

Table 2

Unit costs for pharmacological interventions for psychological stress in children.

Table 3

Unit costs for pharmacological interventions for psychological stress in adults.

1.2.1. The outcomes that matter most

The committee considered all outcomes listed in the protocol to be critical and of equal importance in decision-making. These outcomes included mortality, Health-related Quality of Life, incidence of adrenal crisis, acute and long term cumulative adverse events of drugs, admission to hospital or ITU and psychological morbidities such as incidence of stress or PTSD.

1.2.2. The quality of the evidence

No evidence meeting the review protocol criteria was identified.

1.2.3. Benefits and harms

The committee discussed that there is considerable variation in current clinical practice on whether to adjust glucocorticoid medication when a person is experiencing psychological stress. They noted this is partly due to the wide variation in situations or events that could cause psychological stress, ranging from a mental health crisis, or bereavement. The duration of psychological stress would also vary between a short-term or single event, and much longer periods lasting weeks or months. The committee agreed the variation in how people react to psychological stress makes it difficult to determine whether a person might be at risk of adrenal crisis due to psychological stress. The committee agreed that an occasional increase in glucocorticoid dose was unlikely to lead to side effects, but long-term increases were not advised due to the risk of glucocorticoid excess. An adjustment to the dose of glucocorticoid medication has the potential to reduce the risk of harm to a person experiencing an adrenal crisis due to psychological stress. Overall, the committee agreed that a short-term increase in glucocorticoid for 1-2 days using sick-day dosing rules should be considered for adults in times of acute or extraordinary psychological or emotional stress, and for people under 16 years 1-2 sick day doses may be considered. The recommendation for sick-day dosages was from the review of guidelines from other organisations on the pharmacological management of physiological stress. The quality of these guidelines was assessed using the AGREE II tool and NICE applicability and acceptability checklist. The committee made consensus recommendations, informed by these guidelines. The committee noted a person experiencing a severe mental health crisis may not be able to take an oral preparation and therefore recommended consideration of administering an intramuscular hydrocortisone instead.

1.2.4. Cost effectiveness and resource use

No economic evidence was identified for this review question therefore unit costs were presented to aid the committee’s consideration of cost-effectiveness.

Because the committee noted that current practice was variable in terms of when, and for how long people should increase their oral steroid doses, the committee made recommendations to consider an increase in oral steroid doses for short periods of time (1 to 2 days) when experiencing psychological stress. The latter was defined as periods of sudden, intense psychological and emotional stress such as a bereavement. They also made a consider recommendation for intramuscular hydrocortisone if a person in unable to take oral glucocorticoid during a severe mental health crisis (for example a psychotic episode). This could be administered by a carer using the emergency management kit or by a health care professional. The duration of sick-day rules in people with severe mental health crisis would need to be until the crisis is resolved and would need to be reviewed by a specialist on a case by case.

These recommendations may potentially mitigate the risk of a person experiencing an adrenal crisis due to psychological stress. Of note, the committee were personally not aware of anyone who had experienced an adrenal crisis due to psychological stress alone. However, they acknowledged it was not possible to determine if people never experience an adrenal crisis due to psychological stress because in current practice people will likely increase their oral steroid doses. The committee did however note that in periods of psychological stress people with adrenal insufficiency may experience more pronounced symptoms of their adrenal insufficiency and therefore increasing the dose of an oral steroid will improve a person’s overall quality of life.

An adrenal crisis can be a life-threatening event that significantly impacts a person’s quality of life. There are also high costs associated with an adrenal crisis because hydrocortisone and fluids need to be administered intravenously and this typically requires a hospital admission. The committee discussed the impact of steroids on mood. It was noted that they can sometimes exacerbate a mental health crisis and this needs to be balanced with prescribing increased dosing of glucocorticoids. Sick-day dosing for both physiological and psychological stress is not established current practice and therefore the provision of glucocorticoids to enable sick-day dosing may be a change in practice for some. The recommendations made by the committee are likely to be cost-effective and given that these are consider recommendations, they are not expected to result in a significant resource impact. Of note, the committee highlighted that the recommendation for intramuscular hydrocortisone for those experiencing a severe mental health crisis and are unable to take oral glucocorticoids would apply to a very small proportion of people and therefore would not have a significant resource impact.

1.2.5. Recommendations supported by this evidence review

This evidence review supports recommendations 1.5.1 – 1.5.3.

J.1. Clinical studies

J.2. Health Economic studies

None.