{"id":"F2018L00555","name":"Statement of Principles concerning Cushing syndrome (Reasonable Hypothesis) (No. 43 of 2018)","slug":"statement-of-principles-concerning-cushing-syndrome-reasonable-hypothesis-no-43-of-2018","collection":"legislative_instrument","jurisdiction":"commonwealth","status":"in_force","isInForce":true,"actNumber":null,"makingDate":null,"administeringDepartment":null,"currentVersion":{"id":439606,"registerId":"F2018L00555-fast-fetch-1775955565979","compilationNumber":null,"startDate":"2026-04-12","status":"InForce","reasons":null,"registeredAt":null},"sections":[{"sectionNumber":"1","sectionType":"section","heading":"Statement of Principles concerning Cushing syndrome (Reasonable Hypothesis) (No. 43 of 2018)","content":"---\nmeta-content-style-type: text/css\nmeta-content-type: application/xhtml+xml; charset=utf-8\nmeta-generator: Aspose.Words for .NET 20.2\n---\n\n?xml version=\"1.0\" encoding=\"utf-8\" standalone=\"no\"?>\n\n\n\n \n\nStatement of Principles\n\nconcerning\n\nCUSHING SYNDROME (Reasonable Hypothesis)\n\n(No. 43 of 2018)\n\nThe Repatriation Medical Authority determines the following Statement of Principles under subsection 196B(2) of the Veterans' Entitlements Act 1986.\n\n \n\nDated 27 April 2018\n\n \n\n \n\n \n\n \n\n \n\n| The Common Seal of the Repatriation Medical Authority was affixed to this instrument at the direction of:
|\n| --- |\n| 
Professor Nicholas Saunders AO
Chairperson
|\n\n\n \n\n \n\n\nContents\n\n1 Name\n\n2 Commencement\n\n3 Authority\n\n4 Revocation\n\n5 Application\n\n6 Definitions\n\n7 Kind of injury, disease or death to which this Statement of Principles relates\n\n8 Basis for determining the factors\n\n9 Factors that must exist\n\n10 Relationship to service\n\n11 Factors referring to an injury or disease covered by another Statement of Principles\n\nSchedule 1 - Dictionary\n\n1 Definitions\n\n \n\n\n\n\n1 Name\n\nThis is the Statement of Principles concerning Cushing syndrome (Reasonable Hypothesis) (No. 43 of 2018).\n\n2 Commencement\n\n This instrument commences on 28 May 2018.\n\n3 Authority\n\nThis instrument is made under subsection 196B(2) of the Veterans' Entitlements Act 1986.\n\n4 Revocation\n\nThe Statement of Principles concerning Cushing's syndrome No. 33 of 2009 made under subsection 196B(2) of the VEA is revoked.\n\n5 Application\n\nThis instrument applies to a claim to which section 120A of the VEA or section 338 of the Military Rehabilitation and Compensation Act 2004 applies.\n\n6 Definitions\n\nThe terms defined in the Schedule 1 - Dictionary have the meaning given when used in this instrument.\n\n7 Kind of injury, disease or death to which this Statement of Principles relates\n\n(1) This Statement of Principles is about Cushing syndrome and death from Cushing syndrome.\n\nMeaning of Cushing syndrome\n\n(2) For the purposes of this Statement of Principles, Cushing syndrome means an endocrine disorder resulting from an excess of endogenous or exogenous glucocorticoids.\n\nNote: Features of Cushing syndrome may include proximal muscle weakness, facial plethora, wasting of the extremities with increased fat in the abdomen (centripetal fat) and face (\"moon facies\"), wide (> 1 cm) purplish striae, bruising with no obvious trauma, supraclavicular fat pads and dorsocervical fat pad (\"buffalo hump\").\n\n(3) While Cushing syndrome attracts ICD‑10‑AM code E24.0, E24.2, E24.3, E24.8 or E24.9, in applying this Statement of Principles the meaning of Cushing syndrome is that given in subsection (2).\n\n(4) 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.\n\nDeath from Cushing syndrome\n\n(5) For the purposes of this Statement of Principles, Cushing syndrome, in relation to a person, includes death from a terminal event or condition that was contributed to by the person's Cushing syndrome.\n\nNote: terminal event is defined in the Schedule 1 – Dictionary.\n\n8 Basis for determining the factors\n\nThe Repatriation Medical Authority is of the view that there is sound medical‑scientific evidence that indicates that Cushing syndrome and death from Cushing syndrome can be related to relevant service rendered by veterans, members of Peacekeeping Forces, or members of the Forces under the VEA, or members under the MRCA.\n\nNote: MRCA, relevant service and VEA are defined in the Schedule 1 – Dictionary.\n\n9 Factors that must exist\n\nAt least one of the following factors must as a minimum exist before it can be said that a reasonable hypothesis has been raised connecting Cushing syndrome or death from Cushing syndrome with the circumstances of a person's relevant service:\n\n(1) having a specified condition at the time of the clinical onset of Cushing syndrome;\n\nNote: specified condition is defined in the Schedule 1 - Dictionary. \n\n(2) having glucocorticoid therapy as specified before the clinical onset of Cushing syndrome, and where the glucocorticoid therapy as specified has ceased or decreased, the last dose of the therapy was received within the 30 days before the clinical onset of Cushing syndrome;\n\nNote: glucocorticoid therapy as specified is defined in the Schedule 1 - Dictionary.\n\n(3) being treated with medroxyprogesterone acetate or megestrol acetate for a malignant disease or human immunodeficiency virus infection:\n\n(a) for at least four weeks before the clinical onset of Cushing syndrome; and\n\n(b) where treatment has ceased, the clinical onset of Cushing syndrome has occurred within 30 days of cessation;\n\n(4) inability to obtain appropriate clinical management for Cushing syndrome.\n\n10 Relationship to service\n\n(1) The existence in a person of any factor referred to in section 9, must be related to the relevant service rendered by the person.\n\n(2) The factor set out in subsection 9(4) applies only to material contribution to, or aggravation of, Cushing syndrome where the person's Cushing syndrome was suffered or contracted before or during (but did not arise out of) the person's relevant service.\n\n11 Factors referring to an injury or disease covered by another Statement of Principles\n\nIn this Statement of Principles:\n\n(1) if a factor referred to in section 9 applies in relation to a person; and\n\n(2) that factor refers to an injury or disease in respect of which a Statement of Principles has been determined under subsection 196B(2) of the VEA;\n\nthen 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.\n\n \n\n \n\nSchedule 1 - Dictionary \n\nNote: See Section 6\n\n1 Definitions\n\nIn this instrument:\n\n adrenal neoplasm means a primary neoplasm, either benign (adenoma) or malignant (carcinoma), arising from the adrenal gland.\n\n Cushing syndrome—see subsection 7(2).\n\n 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:\n\n| Glucocorticoid | Minimum cumulative
dose (milligram) | Minimum average
rate (milligram/day) |\n| --- | --- | --- |\n| betamethasone | 45 | 1.5 |\n| cortisone | 1 875 | 62.5 |\n| dexamethasone | 55 | 1.8 |\n| methylprednisolone | 300 | 10 |\n| paramethasone | 150 | 5 |\n| prednisolone | 375 | 12.5 |\n| prednisone | 375 | 12.5 |\n| triamcinolone | 300 | 10 |\n\n\n equivalent inhaled glucocorticoid means:\n\n(a) 2 000 micrograms of beclometasone;\n\n(b) 1 600 micrograms of ciclesonide;\n\n(c) 2 500 micrograms of fluticasone propionate;\n\n(d) 1 000 micrograms of fluticasone furoate;\n\n(e) 10 000 micrograms of triamcinolone; or\n\n(f) a therapeutically equivalent dose of another inhaled glucocorticoid.\n\n glucocorticoid therapy as specified means:\n\n(a) applying a high or very high potency topical glucocorticoid to at least 30% of total skin surface area, daily, for at least six months; or\n\n(b) inhaling at least 4 000 micrograms of budesonide, or equivalent inhaled glucocorticoid, daily, for at least six months; or\n\n(c) taking:\n\n(i) hydrocortisone, orally or by injection:\n\n(A) to a cumulative dose of at least 1 500 milligrams; and\n\n(B) at a minimum dose rate averaging 50 milligrams per day, or\n\n(ii) equivalent glucocorticoid therapy, orally or by injection; or\n\n(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); or\n\n(e) using a glucocorticoid concurrently with a drug from the specified list of drugs, daily, for at least four weeks; or\n\n(f) using a clobetasol containing oral preparation, daily, for at least four weeks; or\n\n(g) using glucocorticoid containing enemas, daily, for at least six months.\n\nNote: equivalent glucocorticoid therapy, equivalent inhaled glucocorticoid, high or very high potency topical glucocorticoid and specified list of drugs are also defined in the Schedule 1 – Dictionary.\n\n high or very high potency topical glucocorticoid means:\n\n(a) betamethasone dipropionate 0.05%;\n\n(b) betamethasone valerate 0.1%;\n\n(c) clobetasol proprionate 0.05%;\n\n(d) diflucortolone valerate 0.1%;\n\n(e) fluocinolone acetonide 0.025%;\n\n(f) methylprednisolone 0.1%;\n\n(g) mometasone 0.1%;\n\n(h) triamcinolone acetonide 0.5%; or\n\n(i) another topical glucocorticoid of equivalent potency.\n\n MRCA means the Military Rehabilitation and Compensation Act 2004.\n\n neuroendocrine neoplasm means a non-pituitary neoplasm that secretes polypeptides functionally equivalent to adrenocorticotrophic hormone (ACTH) or corticotropin-releasing hormone (CRH), and includes oat cell or small cell lung carcinoma, carcinoid tumour, islet cell tumour, tumours of the thymus, medullary carcinoma of the thyroid, and phaeochromocytoma.\n\n relevant service means:\n\n(a) operational service under the VEA;\n\n(b) peacekeeping service under the VEA;\n\n(c) hazardous service under the VEA;\n\n(d) British nuclear test defence service under the VEA;\n\n(e) warlike service under the MRCA; or\n\n(f) non-warlike service under the MRCA.\n\nNote: MRCA and VEA are also defined in the Schedule 1 - Dictionary.\n\n specified condition means one of the following:\n\n(a) adrenal neoplasm;\n\n(b) adrenocorticotrophic hormone (ACTH) secreting neoplasm of the pituitary gland;\n\n(c) macronodular adrenal hyperplasia;\n\n(d) micronodular adrenal hyperplasia; or\n\n(e) neuroendocrine neoplasm.\n\nNote: adrenal neoplasm and neuroendocrine neoplasm are also defined in the Schedule 1 - Dictionary.\n\n specified list of drugs means:\n\n(a) amprenavir;\n\n(b) atazanavir;\n\n(c) boceprevir;\n\n(d) clarithromycin;\n\n(e) darunavir;\n\n(f) delavirdine;\n\n(g) erythromycin;\n\n(h) fosamprenavir;\n\n(i) indinavir;\n\n(j) isoniazid;\n\n(k) itraconazole;\n\n(l) ketoconazole;\n\n(m) lopinavir;\n\n(n) nelfinavir;\n\n(o) posaconazole;\n\n(p) ritonavir;\n\n(q) saquinavir;\n\n(r) telaprevir;\n\n(s) telithromycin;\n\n(t) tipranavir; or\n\n(u) voriconazole.\n\n terminal event means the proximate or ultimate cause of death and includes the following:\n\n(a) pneumonia;\n\n(b) respiratory failure;\n\n(c) cardiac arrest;\n\n(d) circulatory failure; or\n\n(e) cessation of brain function.\n\n VEA means the Veterans' Entitlements Act 1986.\n\n \n\n \n","sortOrder":0}],"analysis":{"flash_summary":{"complexity_score":5,"scope_assessment":{"changed":true,"description":"The instrument expressly revokes the prior Statement (No.33 of 2009) (section 4) and replaces it with a Statement that specifies measurable exposure and treatment criteria (section 9; Schedule 1). It adds precise glucocorticoid dose/equivalence tables, defined inhaled and topical thresholds, a specified list of interacting drugs, and clarifies inclusion of death from terminal events (section 7(5); Schedule 1). These changes narrow and concretise how service‑connection may be established compared with a more general prior formulation, and affect how claims are evidenced and decided (see sections 8–11)."},"complexity_factors":["Dense medical and pharmacological definitions with precise numeric thresholds and equivalences (Schedule 1: equivalent glucocorticoid therapy; equivalent inhaled glucocorticoid; glucocorticoid therapy as specified).","Dose tables and minimum cumulative/average rate requirements require clinical calculation and conversion between agents (Schedule 1 table).","Multiple conditional and temporal rules (30‑day windows for onset after cessation; minimum durations such as 4 weeks or 6 months) increase evidentiary complexity (see section 9(2),(3) and Schedule 1 glucocorticoid therapy as specified).","Lists of interacting drugs and enzyme‑inhibition rules (specified list of drugs; cytochrome P450 3A4 inhibition) add pharmacokinetic dependency (Schedule 1).","Cross‑references to other statutes and other Statements of Principles create dependencies on external instruments and evolving law (sections 3, 5 and 11; references to VEA, MRCA and other Statements).","Legal standard is 'reasonable hypothesis' tied to 'material contribution' or 'aggravation' requiring factual and medical linkage assessments (sections 8–10).","Inclusion of death via proximate terminal events broadens causation analysis to downstream fatal events (section 7(5); terminal event in Schedule 1).","Revocation of the prior 2009 Statement means decision‑makers must apply the new definitions and criteria to ongoing and new claims (section 4)."],"plain_english_summary":"This instrument sets the medical criteria the Repatriation Medical Authority uses to decide whether Cushing syndrome (and death from it) can be linked to a person's relevant service for claims under the VEA or MRCA. It replaces the earlier 2009 Statement.\n\nIt defines Cushing syndrome, and lists specific exposure and treatment thresholds (including quantified glucocorticoid, inhaled and topical doses, interacting drugs), specified medical conditions, and lack of access to appropriate clinical management as factors that may raise a reasonable hypothesis connecting the condition to service."},"flash_summary_failed":{"failed":true,"reason":"Unauthenticated. Configure AI_GATEWAY_API_KEY or use a provider module. Learn more: https://ai-sdk.dev/unauthenticated-ai-gateway","source":"analysis-cron"},"kimi_summary":{"content_quality":"ok","complexity_score":6,"scope_assessment":{"changed":false,"description":"The instrument maintains its original purpose as a medical-determination tool for a specific endocrine disorder within the veterans' compensation scheme. While it updates medical criteria (replacing the 2009 version with new drug lists and dosing thresholds), it does not expand beyond its core function of defining service-connection factors for Cushing syndrome claims."},"complexity_factors":["Multiple nested definitions: 15+ defined terms in Schedule 1, with some definitions referring to other defined terms (e.g., 'glucocorticoid therapy as specified' incorporates 'equivalent glucocorticoid therapy', 'equivalent inhaled glucocorticoid', 'high or very high potency topical glucocorticoid', and 'specified list of drugs')","Detailed quantitative thresholds: Complex dosing tables with specific cumulative doses and daily rates for 8 different glucocorticoids, plus microgram thresholds for inhaled steroids","Temporal conditions: Multiple time-based requirements (30 days, 4 weeks, 6 months) that vary by factor and include 'cessation' clauses","Cross-referencing structure: Section 11 creates dynamic incorporation of other Statements of Principles by reference, meaning the instrument interacts with an entire scheme of similar documents","Conditional logic in section 9(4): Special limitation restricting the 'inability to obtain appropriate clinical management' factor to aggravation cases only, creating an exception to the general rule","Medical-legal hybrid language: Requires understanding of both pharmacology (cytochrome P450 3A4 inhibition, therapeutic equivalence) and veterans' compensation law (VEA/MRCA service types)"],"plain_english_summary":"This Statement of Principles defines when Cushing syndrome can be accepted as service-related under the \"reasonable hypothesis\" test, replacing the 2009 version with updated medical evidence. It governs claims by veterans, peacekeepers, and current/former defence members under the Veterans' Entitlements and Military Rehabilitation and Compensation Acts.\n\nClaims succeed if service-related factors—such as certain tumours or hormonal conditions, significant glucocorticoid or specific hormone exposure, or lack of appropriate care—are plausibly linked to onset."}},"importantCases":[],"_links":{"self":"/api/acts/statement-of-principles-concerning-cushing-syndrome-reasonable-hypothesis-no-43-of-2018","history":"/api/acts/statement-of-principles-concerning-cushing-syndrome-reasonable-hypothesis-no-43-of-2018/history","analysis":"/api/acts/statement-of-principles-concerning-cushing-syndrome-reasonable-hypothesis-no-43-of-2018/analysis","conflicts":"/api/acts/statement-of-principles-concerning-cushing-syndrome-reasonable-hypothesis-no-43-of-2018/conflicts","importantCases":"/api/acts/statement-of-principles-concerning-cushing-syndrome-reasonable-hypothesis-no-43-of-2018/important-cases","documents":"/api/acts/statement-of-principles-concerning-cushing-syndrome-reasonable-hypothesis-no-43-of-2018/documents"}}