Ongoing care and monitoring of people with adrenal insufficiency
Evidence review N
NICE Guideline, No. 243
1. Ongoing care and monitoring
1.1. Review question
- What ongoing care and monitoring should be offered to people with adrenal insufficiency?
- What ongoing care and monitoring should be offered to people with adrenal insufficiency who are receiving end-of-life care?
1.1.1. Introduction
Ongoing care and monitoring
People with primary and secondary adrenal insufficiency need lifelong glucocorticoids, and for primary adrenal insufficiency mineralocorticoid replacement as well. People with tertiary adrenal insufficiency may be able to stop glucocorticoid replacement, but a proportion will need to continue lifelong. There are consequences of both over and under treatment with glucocorticoids and mineralocorticoids.
Signs and symptoms of glucocorticoid under-replacement include weight loss, early satiety, decreased appetite, nausea, fatigue that is significantly affecting the person’s ability to carry out activities of daily living, worsening pigmentation (in primary adrenal insufficiency), muscle weakness. Additional signs and symptoms in children and young people include faltering growth and early puberty.
Signs and symptoms of glucocorticoid over-replacement (for people who are on a higher dose than standard replacement) include weight gain, increased appetite, disturbed sleep, skin thinning, new or worsening diabetes, new or worsening hypertension, cushingoid appearance, skin infections, acne, thrush, frequent or low-impact fractures, height loss, fragility fractures.
There is variation in practice, both in frequency of ongoing monitoring of people with adrenal insufficiency, and in what tests might be performed.
The purpose of this review is to determine the optimal frequency of monitoring and what needs to be monitored for consequences of over- or under-treatment with glucocorticoids to improve outcomes for people with adrenal insufficiency,
Ongoing care and monitoring for people receiving end-of-life care
Glucocorticoids are essential for life in people with adrenal insufficiency. For people coming towards the end of their life comfort and symptom control become priorities rather than prolonging life. It can be difficult to take oral medication, or multiple doses towards end-of-life and so it may be necessary to adjust replacement regimen of glucocorticoids to once daily dosing, use of dispersible medications rather than tablets, or use of subcutaneous or intramuscular preparations. It also is not appropriate to be performing invasive monitoring and blood tests at end-of-life. Patients’ wishes should be taken into account, and they may choose to stop all medication when they are actively dying.
The purpose of this review is to determine what ongoing care and monitoring should be offered to people who are receiving end-of-life care.
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
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
1.1.4.1. Included studies
A search was conducted for randomised controlled trials (RCTs) and observational studies comparing monitoring strategies for people with adrenal insufficiency and people with adrenal insufficiency who are receiving end-of-life care.
No relevant RCTs or observational studies were identified.
1.1.4.2. Excluded studies
See the excluded studies list in Appendix J.
1.1.5. Summary of studies included in the effectiveness evidence
No relevant published evidence was identified.
1.1.6. Economic evidence
1.1.6.1. Included studies
No health economic studies were included.
1.1.6.2. Excluded studies
No relevant health economic studies were excluded due to assessment of limited applicability or methodological limitations.
See also the health economic study selection flow chart in Appendix G.
1.1.7. Economic model
This area was not prioritised for new cost-effectiveness analysis.
1.2. The committee’s discussion and interpretation of the evidence
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, complications of AI, incidence of vascular events or fractures or diabetes and measures of activities of daily living.
1.2.2. The quality of the evidence
No evidence was identified for ongoing care and monitoring of people with adrenal insufficiency including those who are receiving end-of-life care. Recommendations were made by consensus of the committee to reflect current practice.
1.2.3. Benefits and harms
The committee agreed that it was important to make recommendations despite the lack of evidence as adrenal insufficiency is a complex condition.
The committee didn’t wish to specify the frequency of reviews as these would vary widely depending on patient needs as well as the type of adrenal insufficiency they have. For example: newly diagnosed people with primary adrenal insufficiency may require more frequent monitoring until the health care professional is satisfied that the person understands the condition and how to manage it. The committee acknowledged this should be part of shared decision-making between clinical staff and the person. People who are symptomatic and have rapidly changing clinical needs will also need more frequent monitoring until their condition has stabilised. However, people with secondary or tertiary adrenal insufficiency who are confident with self-management or have stable clinical needs may need less frequent monitoring, as this group of people will still have some residual HPA axis function and therefore be at much lower risk of having an adrenal crisis.
Health care professionals would consider the most appropriate mode of follow-up and monitoring according to the person’s needs. For example, some may need to be seen face-to-face and others may be followed up remotely through telephone consultations. A shared decision model such as Patient Initiated Follow Up (PIFU) may be used to aid discussion with the patient such as the frequency and mode of follow up.
The committee agreed the appropriate specialist team providing ongoing care should be defined based on the needs of the individual.
Health care professionals should be aware of signs and symptoms of under-replacement of glucocorticoids which may include weight loss, nausea and fatigue. These can be quite broad and non-specific; therefore, it is important to investigate whether these can be attributed to under replacement of glucocorticoids or other reasons. For example, fatigue can occur just in the short term while patients are adjusting to steroids and should not be a reason to initiate a change in dosing. However, sudden onset fatigue or fatigue that is significantly affecting the person’s ability to undertake activities of daily living should not be ignored.
Signs and symptoms indicating over-replacement of glucocorticoids particularly in patients on supraphysiological (higher than standard) doses may include unexplained weight gain, new or worsening diabetes or hypertension. Cushingoid appearance/ Cushing’s syndrome is particularly indicative of over-replacement. This usually manifests as weight gain with increased fat on the chest and tummy, but thin arms and legs with muscle wasting and reduced muscle strength, a build-up of fat on the back of the neck and shoulders, and a red, puffy, rounded face, bruising and red stretch marks particularly found with the use of dexamethasone.
Treatment for people with primary adrenal insufficiency also includes mineralocorticoids which can also cause undesirable effects if over- or under-used and need to be carefully monitored. These include light headedness or salt craving (under replacement) and swollen ankles or high blood pressure (over replacement).
The committee noted that whilst measuring renin may be beneficial to some patients, this doesn’t need to be routinely screened if there are no symptoms indicating any issues with fludrocortisone dosing. Renin levels have not been shown to correlate with symptoms.
Cortisol day series do not need to be performed routinely as the levels don’t correlate to symptoms, especially fatigue. Some people may have very low afternoon cortisol levels but will be fine. Therefore, clinicians need to be careful of interpreting low levels in this context. In addition, most of the new assays don’t correlate with the traditional thresholds that were based on the old literature. Consequently, cortisol day series values may be misleading.
An important aim of ongoing reviews is to make sure that people with adrenal insufficiency understand their condition, how to manage it and how to avoid having an adrenal crisis. Therefore, healthcare professionals should make sure that they discuss this with their patients and emphasise the importance of medication adherence and knowing what to do in emergency situations. The impact of the condition on a patient’s psychological well-being and activities of daily living should not be underestimated and should be discussed during each review.
Children
For children, the committee agreed appointments with the specialist team should be at least every six months, but similarly to adults, this would need to be adjusted according to patient needs. An annual face-to-face hospital appointment should be offered to measure height and weight of children to ensure the condition is being managed well. These measurements can be taken by any member of the multidisciplinary team including a specialist nurse. Progression to and through puberty for example, frequency and regularity of menstrual periods should be monitored as both over- and under-replacement of glucocorticoids can have an impact on puberty progression. The committee discussed more frequent monitoring may be needed during periods of rapid growth when dosages of medication may need to be changed when transitioning to adult services, if there are concerns with medicines adherence, or whether the child and their family or carers are able to safely manage the condition.
For people at the end of life, the committee agreed cross referring to the guidelines on end-of-life care for adults and end-of-life care for children and young people with life-limiting conditions was appropriate. Decisions on withdrawing active treatment should be made as part of shared decision-making and may not mean withdrawing steroids but may include changes to how medication is administered such as by injection rather than orally.
1.2.4. Cost effectiveness and resource use
No health economic evidence or clinical evidence was identified for this review question, therefore the committee made recommendations reflective of current practice. As the recommendations made are reflective of current practice no significant resource will be associated with this review question.
1.2.5. Recommendations supported by this evidence review
This evidence review supports recommendations1.8.1 – 1.8.15.
References
- 1.
- National Institute for Health and Care Excellence. Developing NICE guidelines: the manual. London. National Institute for Health and Care Excellence, 2014. Available from: https://www
.nice.org .uk/process/pmg20/chapter/introduction [PubMed: 26677490]
Appendices
Appendix A. Review protocols
A.2. Health economic review protocol (PDF, 131K)
Appendix B. Literature search strategies
The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual.1
For more information, please see the Methodology review published as part of the accompanying documents for this guideline.
B.1. Clinical search literature search strategy (PDF, 197K)
B.2. Health Economics literature search strategy (PDF, 158K)
Appendix C. Effectiveness evidence study selection
Appendix D. Effectiveness evidence
No evidence included.
Appendix E. Forest plots
None.
Appendix F. GRADE and/or GRADE-CERQual tables
None.
Appendix G. Economic evidence study selection
Download PDF (166K)
Appendix H. Economic evidence tables
None.
Appendix I. Health economic model
No original economic modelling was undertaken for this review question.
Appendix J. Excluded studies
J.1. Clinical studies
Table 5
Studies excluded from the clinical review.
J.2. Health Economic studies
None.
Final
Evidence reviews underpinning recommendations 1.8.1 to 1.8.15 in the NICE guideline
This evidence review was developed by NICE
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