Statement of PrinciplesconcerningADRENAL INSUFFICIENCY(Reasonable Hypothesis)(No. 58 of 2026)The Repatriation Medical Authority determines the following Statement of Principles under section 370CB of the Military Rehabilitation and Compensation Act 2004.Dated 4 September 2026Dr Anthony Lynham AOChairpersonby and on behalf ofThe Repatriation Medical AuthorityContents1 Name2 Commencement3 Authority4 Repeal5 Application6 Definitions7 Kind of injury, disease or death to which this Statement of Principles relates8 Basis for determining the factors9 Factors that must exist10 Relationship to service11 Factors referring to an injury or disease covered by another Statement of PrinciplesSchedule 1 - Dictionary1 DefinitionsNameThis is the Statement of Principles concerning adrenal insufficiency (Reasonable Hypothesis) (No. 58 of 2026).CommencementThis instrument commences on 5 October 2026.AuthorityThis instrument is made under section 370CB of the Military Rehabilitation and Compensation Act 2004.RepealThe Statement of Principles concerning adrenal insufficiency (Reasonable Hypothesis) (No. 71 of 2018) (Federal Register of Legislation No. F2018L01182) made under section 370CB of the MRCA is repealed.ApplicationThis instrument applies to a claim to which section 338 of the Military Rehabilitation and Compensation Act 2004 applies.DefinitionsThe terms defined in the Schedule 1 - Dictionary have the meaning given when used in this instrument.This Statement of Principles is about adrenal insufficiency and death from adrenal insufficiency.Meaning of adrenal insufficiencymeans an endocrine disease characterised by biochemically-demonstrated deficient production of adrenal cortical hormones, sufficient to produce clinical symptoms and signs, and to necessitate glucocorticoid, mineralocorticoid or adrenal androgen replacement therapy; andincludes drug-induced adrenal insufficiency; andexcludes heritable and congenital forms of adrenal insufficiency.Note 1: Adrenal cortical hormones are mineralocorticoids, cortisol and adrenal androgens.Note 2: Clinical symptoms and signs of adrenal insufficiency are nonspecific and may include nausea, vomiting, abdominal cramps and diarrhoea, fatigue, myalgias, arthralgias, weakness, fever, dizziness, weight loss, amenorrhoea, decreased libido and depression.Note 3: Adrenal insufficiency may be acute or chronic. Acute adrenal insufficiency may present as an adrenal crisis. Primary adrenal insufficiency is also known as Addison disease.While adrenal insufficiency attracts ICD 10 AM code E27.1, E27.2, E27.3, E27.4, E89.6, A18.7 or A39.1, in applying this Statement of Principles the meaning of adrenal insufficiency is that given in subsection (2).For subsection (3), a reference to an ICD-10-AM code is a reference to the code assigned to a particular kind of injury or disease in The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM), Tenth Edition, effective date of 1 July 2017, copyrighted by the Independent Hospital Pricing Authority, ISBN 978-1-76007-296-4.Death from adrenal insufficiencyFor the purposes of this Statement of Principles, adrenal insufficiency, in relation to a person, includes death from a terminal event or condition that was contributed to by the person's adrenal insufficiency.Note: terminal event is defined in the Schedule 1 – Dictionary.Basis for determining the factorsThe Repatriation Medical Authority is of the view that there is sound medical-scientific evidence that indicates that adrenal insufficiency and death from adrenal insufficiency can be related to relevant service under the MRCA.Note: MRCA and relevant service are defined in the Schedule 1 – Dictionary.Factors that must existAt least one of the following factors must as a minimum exist before it can be said that a reasonable hypothesis has been raised connecting adrenal insufficiency or death from adrenal insufficiency with the circumstances of a person's relevant service:having an acute, severe stressor in the 7 days immediately preceding clinical onset of adrenal crisis;Note: acute, severe stressor and adrenal crisis are defined in the Schedule 1 - Dictionaryhaving an autoimmune disorder involving the adrenal glands at the time of clinical onset or clinical worsening;amyloidosis;iron overload; orsarcoidosis.Note: iron overload is also defined in the Schedule 1 - Dictionaryboth adrenal glands; ora single functional adrenal gland, where there is only one functional adrenal gland; orparaneoplastic syndrome;having infection with human immunodeficiency virus before clinical onset or clinical worsening;both adrenal glands, orwhere there is only one functional adrenal gland; oras surgical treatment for Cushing syndrome or primary Aldosteronism;within the 1 year before the clinical onset or clinical worsening;both adrenal glands, ora single functional adrenal gland, where there is only one functional adrenal gland;within the 1 year before clinical onset or clinical worsening;Note: Common causes of adrenal haemorrhage or infarction include trauma to the adrenal gland, heparin-induced thrombocytopaenia, anticoagulant therapy, antiphospholipid syndrome, sepsis, COVID-19 infection, malignancy and haematological disorder.both adrenal glands, ora single functional adrenal gland, where there is only one functional adrenal gland;at the time of clinical onset or clinical worseningabiraterone;aminoglutethimide;azole antifungals (including fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole);busulfan;chlorpromazine;etomidate;imipramine;metyrapone;mifepristone;mitotane;osilodrostat;rifampicin;suramin; ortreosulfan.taking an immune checkpoint inhibitor within the 1 year before clinical onset or clinical worsening;Note: immune checkpoint inhibitor is defined in the Schedule 1 - Dictionarytaking glucocorticoid therapy, before clinical onset or clinical worsening, and where the glucocorticoid therapy has ceased or decreased, the last dose of the therapy was taken within the 1 year before clinical onset or clinical worsening;Note: glucocorticoid therapy is defined in the Schedule 1 – Dictionary.for a continuous period of at least 4 weeks before clinical onset or clinical worsening; andwhere such treatment has ceased, the last dose was received within the 3 months before clinical onset or clinical worsening;having hypopituitarism with adrenocorticotrophic hormone deficiency, at the time of clinical onset or clinical worsening;having a critical illness or injury within the 1 year before clinical onset or clinical worsening;Note: critical illness or injury is defined in the Schedule 1 - Dictionary.taking an opioid, at an average daily morphine equivalent dose of at least 60 milligrams or methadone to treat opioid use disorder, for at least the 3 months immediately preceding clinical onset or clinical worsening;having an acute, severe stressor in the 7 days immediately preceding clinical worsening;Note: acute, severe stressor is defined in the Schedule 1 - Dictionaryinability to obtain appropriate clinical management for adrenal insufficiency before clinical worsening.The existence in a person of any factor referred to in section 9, must be related to the relevant service rendered by the person.The clinical worsening aspect of factors set out in section 9 apply only to material contribution to, or aggravation of, adrenal insufficiency where the person's adrenal insufficiency was suffered or contracted before or during (but did not arise out of) the person's relevant service.Factors referring to an injury or disease covered by another Statement of PrinciplesIn this Statement of Principles:if a factor referred to in section 9 applies in relation to a person; andthat factor refers to an injury or disease in respect of which a Statement of Principles has been determined under section 370CB of the Military Rehabilitation and Compensation Act 2004;then the factors in that Statement of Principles apply in accordance with the terms of that Statement of Principles as in force from time to time.Schedule 1 - DictionaryNote: See Section 61 DefinitionsIn this instrument:acute, severe stressor means a physical or psychological stimulus or event that causes a sudden, intense psychological or physical response.Note: Examples of acute, severe stressors include but are not limited to, vomiting or diarrhoea, febrile illness or infection (such as influenza, gastroenteritis, lower respiratory tract infection, or urinary tract infection), physical activity of 5 METS or more, extreme heat of at least 40 degrees Celsius and or dehydration, an acute, severe, emotional stressor or an abrupt cessation or lowering of glucocorticoid therapy.Note: MET (metabolic equivalent) is a unit of measure of the level of physical capability of the cardiorespiratory system. For example, 1 MET = cardiorespiratory effort associated with a person sitting, 3-4 METs = cardiorespiratory effort associated with a person walking at average walking pace (5 km/h) or light gardening.adrenal crisis means a constellation of symptoms that indicate severe adrenal insufficiency of rapid onset causing acute haemodynamic decompensation. Characteristic symptoms and signs are hypotension, tachycardia, hypovolaemia (shock), lethargy, hypoglycaemia, disorientation, impaired consciousness, seizures and coma.Note 1: Adrenal crisis is a medical emergency that requires treatment with injectable hydrocortisone and fluid support. Adrenal crisis is also known as an Addisonian crisis.Note 2: Adrenal crisis may be the first presentation of undiagnosed adrenal insufficiency, or may complicate existing chronic adrenal insufficiency.adrenal insufficiency—see subsection 7(2).critical illness or injury means:(a) any physical injury or illness requiring mechanical ventilation support or admission to an intensive care unit;(b) acute renal tubular necrosis;(c) adult respiratory distress syndrome;(d) 2nd degree burns covering a total burn area of 50-70%, or 3rd degree burns covering an area >20% of total body surface;(e) disseminated intravascular coagulation;(f) multiple organ failure; or(g) septicaemia.equivalent glucocorticoid therapy means a glucocorticoid in the following table, at the doses specified in the table, or a therapeutically equivalent dose of another glucocorticoid:GlucocorticoidMinimum cumulativedose (milligrams)Minimum averagerate (milligrams/day)betamethasone | 18 | 0.6cortisone | 750 | 25dexamethasone | 22 | 0.7methylprednisolone | 120 | 4paramethasone | 60 | 2prednisolone | 150 | 5prednisone | 150 | 5triamcinolone | 120 | 4equivalent inhaled glucocorticoid means:(a) 1,000 micrograms of beclomethasone dipropionate (standard particle inhaler);(b) 400 micrograms of beclomethasone dipropionate (extra fine particle inhaler);(c) 640 micrograms of ciclesonide;(d) 400 micrograms of fluticasone furoate;(e) 1,000 micrograms of fluticasone propionate;(f) 4,000 micrograms of triamcinolone; or(g) a therapeutically equivalent dose of another inhaled glucocorticoid.glucocorticoid therapy means:applying a high or very high potency topical glucocorticoid to at least 10% of total skin surface area, daily, for a continuous period of at least 3 months; or(b) inhaling at least 1,600 micrograms of budesonide, or equivalent inhaled glucocorticoid, daily, for a continuous period of at least 3 months; or(c) taking:(i) hydrocortisone, orally or by injection:to a cumulative dose of at least 600 milligrams; andat a minimum dose rate averaging 20 milligrams per day, or(ii) equivalent glucocorticoid therapy, orally or by injection; or(d) using a glucocorticoid concurrently with a drug, daily, for at least 4 weeks, where that drug can inhibit the activity of the metabolising enzyme cytochrome P450 3A4 by at least 30% (moderate to strong inhibition);Note: examples of moderate to strong cytochrome P450 3A4 inhibitors include atazanavir, azole antifungals, clarithromycin, cobicistat, erythromycin, fosamprenavir, ritonavir.(e) using an ocular glucocorticoid, daily, for a continuous period of at least 6 months; or(f) using an intranasal glucocorticoid, at an average daily dose exceeding 400 micrograms of betamethasone 0.1%, or equivalent intranasal glucocorticoid, for a continuous period of at least 6 months; or(g) using glucocorticoid containing enemas, daily, for a continuous period of at least 3 months; or(h) having an epidural or extradural injection of glucocorticoid or at least 2 glucocorticoid injections into a peripheral joint within a 3-month period; or(i) swallowing oral preparations containing glucocorticoids, daily for a continuous period of at least 6 months; or(j) taking any glucocorticoid therapy that causes Cushing syndrome.Note: equivalent glucocorticoid therapy, equivalent inhaled glucocorticoid, high or very high potency topical glucocorticoid are also defined in the Schedule 1 – Dictionary.high or very high potency topical glucocorticoid means:(a) betamethasone dipropionate 0.05%;(b) betamethasone valerate 0.1%;(c) clobetasol proprionate 0.05%;(d) diflucortolone valerate 0.1%;(e) fluocinolone acetonide 0.025%;(f) methylprednisolone 0.1%;(g) mometasone 0.1%;(h) triamcinolone acetonide 0.5%; or(i) another topical glucocorticoid of equivalent potency.immune checkpoint inhibitor means a form of cancer immunotherapy that uses monoclonal antibodies targeting the immune checkpoint proteins. Examples include ipilimumab, atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, tislelizumab, nivolumab and pembrolizumab.iron overload means an accumulation of excess iron in tissues and organs which has been confirmed by elevated ferritin or transferrin saturation levels. Causes include haemochromatosis or blood transfusions.MRCA means the Military Rehabilitation and Compensation Act 2004.relevant service means:warlike service;non warlike service;British nuclear test defence service;hazardous service.terminal event means the proximate or ultimate cause of death and includes the following:pneumonia;(b) respiratory failure;(c) cardiac arrest;(d) circulatory failure; or(e) cessation of brain function.