Statement of Principles concerning Cushing syndrome (Balance of Probabilities) (No. 44 of 2018)

The central concept is the "factor" defined in section 9 - the existence of at least one of four specific circumstances that establishes the sufficient causal link between Cushing syndrome and relevant service. The first factor is having a "specified condition" at the time of clinical onset. The schedule defines "specified condition" to include adrenal neoplasm (benign or malignant), ACTH-secreting pituitary neoplasm, macronodular or micronodular adrenal hyperplasia, and neuroendocrine neoplasm (including oat cell or small cell lung carcinoma, carcinoid tumour, islet cell tumour, thymus tumours, medullary thyroid carcinoma, and phaeochromocytoma). These are all endogenous causes of hypercortisolism. The factor does not require the specified condition itself to be service-related - it only requires that the specified condition was present at the time of clinical onset. However, the factor itself must be related to relevant service under section 10, which is a subtle but important point: if the specified condition is itself caused by service, then the Cushing syndrome is linked via the specified condition.

The second factor is having "glucocorticoid therapy as specified" before clinical onset. This is the most detailed and compliance-intensive factor. It defines six alternative sub-categories of glucocorticoid exposure: (a) topical application of high or very high potency glucocorticoids to at least 30% of total skin surface area daily for at least six months; (b) inhaled budesonide or equivalent at least 4,000 micrograms daily for at least six months; (c) oral or injected hydrocortisone to a cumulative dose of at least 1,500 mg at a minimum rate averaging 50 mg/day, or equivalent glucocorticoid therapy (with a table of minimum cumulative doses and daily rates for betamethasone, cortisone, dexamethasone, methylprednisolone, paramethasone, prednisolone, prednisone, and triamcinolone); (d) concurrent use of a glucocorticoid with a drug that inhibits CYP3A4 by at least 30% daily for at least four weeks; (e) concurrent use of a glucocorticoid with a drug from the "specified list of drugs" (a list of 21 antiretroviral, antifungal, and macrolide antibiotics) daily for at least four weeks; (f) clobetasol-containing oral preparation daily for at least four weeks; or (g) glucocorticoid-containing enemas daily for at least six months. Additionally, where the therapy has ceased or decreased, the last dose must have been received within 30 days before clinical onset.

The third factor is treatment with medroxyprogesterone acetate or megestrol acetate for a malignant disease or HIV infection for at least four weeks before clinical onset, and within 30 days of cessation if treatment has stopped. The fourth factor is inability to obtain appropriate clinical management for Cushing syndrome, which applies only to material contribution or aggravation of pre-existing Cushing syndrome, not to initial onset.

The SoP also defines "equivalent glucocorticoid therapy" through dose equivalence tables, "equivalent inhaled glucocorticoid" by specifying beclometasone, ciclesonide, fluticasone propionate, fluticasone furoate, triamcinolone, or therapeutically equivalent doses. "High or very high potency topical glucocorticoid" lists nine named preparations or equivalent potency. "Terminal event" is defined to include pneumonia, respiratory failure, cardiac arrest, circulatory failure, or cessation of brain function, allowing death claims to be linked when Cushing syndrome contributed to such an event.

The SoP directly affects veterans and members of the Australian Defence Force who have rendered "relevant service" as defined in the schedule: eligible war service (other than operational service) under the VEA, defence service (other than hazardous service and British nuclear test defence service) under the VEA, or peacetime service under the MRCA. It does not apply to operational service (which uses the reasonable hypothesis standard under section 120(1) of the VEA) or to hazardous service or British nuclear test defence service. This means a significant number of veterans are excluded from the benefit of this SoP if their service is operational, because those claims are governed by different standard of proof and different SoP requirements (though a separate reasonable hypothesis SoP for Cushing syndrome may exist). The practical effect is that the instrument primarily covers non-operational veterans and peacetime service members, a narrower cohort than the total veteran population.

The instrument also affects clinicians and medical professionals who certify diagnoses and provide evidence of treatment. The precise dosing and duration thresholds require careful documentation. A general practitioner who prescribes prednisolone for a veteran's asthma or prednisone for a skin condition must record not only the drug and dose but also the cumulative total and the average daily rate over the relevant period. If the veteran later claims Cushing syndrome, the medical records must show at least six months of daily use at the specified minimum, or the claim will fail. Similarly, specialists prescribing topical steroids must record the percentage of skin surface area treated and the potency classification.

The Repatriation Commission and the Military Rehabilitation and Compensation Commission are the primary administrative bodies affected. They must apply the SoP to all claims under section 120B VEA or section 339 MRCA. The SoP binds them: if a factor exists and is related to service, they must accept the connection. It also constrains their ability to rely on contrary medical opinion, because the basis for determining the factors is stated to be "sound medical-scientific evidence" and the Authority's view that the link is more probable than not. The Veterans' Review Board and the Administrative Appeals Tribunal are also affected when reviewing decisions, as they must apply the same SoP.

The pharmaceutical industry and compounding pharmacists are indirectly affected. The specified list of drugs includes several antiretroviral and antifungal medications that are commonly used in older HIV and fungal infection treatments. The requirement for concurrent use with glucocorticoids for at least four weeks may increase reporting obligations for prescribers. The inclusion of clobetasol oral preparations and glucocorticoid enemas expands the scope beyond systemic glucocorticoids to certain topically applied preparations with significant systemic absorption.

The instrument imposes no duties on the public; it is a directive to decision-makers. The key duty is on the Repatriation Commission and the Military Rehabilitation and Compensation Commission to apply the factors when determining claims. They must not accept a claim of service-related Cushing syndrome unless at least one factor in section 9 exists and is related to the person's relevant service. They must also apply the definitions strictly. For example, if a veteran was treated with prednisolone but the cumulative dose was 370 mg at an average rate of 10 mg/day, that does not meet the "equivalent glucocorticoid therapy" threshold for prednisolone (minimum cumulative 375 mg, minimum average 12.5 mg/day). The commission must reject the claim on that factor, even if the treating doctor believes the treatment was sufficient to cause Cushing syndrome. That is a limitation on discretion.

The rights of claimants include the right to rely on any of the four factors. The most commonly used factor is likely glucocorticoid therapy as specified, because it covers a wide range of pharmaceutical exposures. The right to use the "inability to obtain appropriate clinical management" factor is limited: it only applies to material contribution or aggravation of pre-existing Cushing syndrome, not to initial onset. A claimant whose Cushing syndrome first arose before service cannot use the inability factor to link the initial condition to service, but may use it to show service worsened the condition. This narrows the scope of that factor significantly.

Claimants also have the right to invoke another SoP if a factor in section 9 refers to an injury or disease covered by another SoP. Section 11 provides that where a factor (for example, having an adrenal neoplasm) refers to a disease for which a separate SoP exists, the factors in that other SoP apply according to its terms. This creates a cascade of SoPs: to prove the factor "adrenal neoplasm", the claimant may need to satisfy the factors in the SoP concerning adrenal neoplasms. That means multiple SoPs may be engaged in a single claim, increasing complexity.

The right to die from Cushing syndrome is also defined. If the person dies from a terminal event contributed to by Cushing syndrome, the death is treated as death from Cushing syndrome for the purposes of the SoP. This is important for dependency claims.

The instrument itself contains no penalties. It is not a criminal or regulatory instrument with fine or imprisonment provisions. Enforcement occurs through the claim determination process: if a claimant fails to prove the existence of a factor, the claim is denied. The real penalty is the denial of entitlement to compensation, including disability pension, permanent impairment payments, and medical treatment costs. For a veteran with Cushing syndrome requiring long-term management, denial can mean tens of thousands of dollars in uncovered medical costs.

The SoP creates an evidentiary barrier. If a claimant's medical records do not contain the exact documentation needed to prove, for example, that the topical glucocorticoid covered at least 30% of skin surface area daily for six months, the claim will be rejected regardless of clinical judgment. This is a de facto penalty for poor record-keeping by the treating doctor. Claimants may also face the cost of obtaining expert medical reports to reconstruct the dosing history, which can be substantial and may not be reimbursed if the claim fails.

There is enforcement potential through the Administrative Appeals Tribunal and the Federal Court. The instrument may be challenged on the ground that it is not based on "sound medical-scientific evidence" or that the Authority acted beyond power under subsection 196B(3). However, the Authority has significant discretion, and courts give considerable deference to its determinations. There is no record in the source of any successful challenge to this particular SoP.

The revocation of the earlier No. 34 of 2009 means that any claim lodged after 28 May 2018 must be determined under this instrument. If the old SoP was more favourable (e.g., had lower dose thresholds or broader definitions), claimants lose that advantage. That is a retrospective effect through the application date: the instrument revokes the old SoP from 28 May 2018, regardless of when the service was rendered or when the condition arose.

The SoP is made under the VEA and interacts directly with section 120B of that Act and section 339 of the MRCA. Section 120B requires that a determination of the Repatriation Medical Authority under subsection 196B(3) must be applied in assessing whether an injury or disease is related to service on the balance of probabilities. This SoP is that determination. It therefore overrides any general medical opinion that might reach a different conclusion on causation. If a doctor believes a veteran's Cushing syndrome was caused by service but none of the factors are present, the claim must be rejected. Conversely, if a factor is present and related to service, the decision-maker must accept the connection, even if the doctor thinks other causes are more likely.

The instrument also interacts with other SoPs. Section 11 provides that if a factor refers to an injury or disease covered by another SoP, the factors in that other SoP apply. For example, adrenal neoplasm is a specified condition factor. To prove adrenal neoplasm, the claimant must satisfy the factors in the SoP for adrenal neoplasm (assuming one exists and is made under the same power). This creates a layering of causation requirements that can be complex. It also means that changes to the adrenal neoplasm SoP automatically flow into this SoP via section 11(2), which says "in accordance with the terms of that Statement of Principles as in force from time to time". So a future amendment to the adrenal neoplasm SoP will update the requirements for this Cushing syndrome SoP without needing a separate amendment.

The instrument does not interact with state workers' compensation, tort law, or private insurance. It is exclusively for Commonwealth veterans' compensation. However, the clinical definitions may be cited in other contexts as authoritative medical standards. The adoption of ICD-10-AM codes means the SoP aligns with hospital coding practices, which may assist in evidence gathering.

The "specified list of drugs" includes many antiretroviral medications used for HIV treatment. This interacts with the VEA and MRCA provisions that cover HIV-positive veterans. It also interacts with common law duties of care for prescribing doctors. A doctor who prescribes a glucocorticoid concurrently with a CYP3A4 inhibitor should be aware that this combination can cause iatrogenic Cushing syndrome and may trigger a compensable claim under veterans' law.

The source only references one amendment: the revocation of the Statement of Principles concerning Cushing's syndrome No. 34 of 2009 made under subsection 196B(3) of the VEA. The earlier instrument was determined on an unknown date and was in force until 27 May 2018. This instrument commences on 28 May 2018 and replaces it. The source does not disclose what changes were made from No. 34 of 2009. It is not possible from the text alone to identify whether thresholds were increased or decreased, whether factors were added or removed, or whether the definition of Cushing syndrome changed. The revocation is a straightforward supersession; the new instrument is not an amendment but a complete replacement.

The instrument itself has not been amended since its commencement. It is a stand-alone determination with no subsequent amending instruments listed. However, as noted, section 11 incorporates other SoPs by reference as in force from time to time, so any amendment to those collateral SoPs will implicitly amend the operation of this SoP without a formal amendment to this instrument. This means the effective content of the SoP can change over time even if the instrument itself remains as originally made.

The authority for making the SoP is subsection 196B(3) of the VEA, which empowers the Repatriation Medical Authority to determine a Statement of Principles "on the balance of probabilities" for the purposes of section 120B. The Authority must satisfy itself that there is sound medical-scientific evidence that it is more probable than not that the condition can be related to relevant service. There is no sunset clause or review date in the instrument. It remains in force until revoked or superseded.

The source contains no reference to any litigation involving this specific instrument. It is a legislative instrument that is rarely litigated directly because it is presumptively valid under the VEA. Challenges to SoPs are possible but must allege a jurisdictional error or that the Authority based the determination on no evidence or irrelevant material. There have been several Federal Court cases dealing with the standard of review for SoPs (e.g., Repatriation Commission v Smith [2005] FCAFC 73, Repatriation Commission v Gorton [2001] FCA 1194), but none specifically concerning Cushing syndrome No. 44 of 2018.

Without any litigation history in the source, one can only note that the instrument is likely to be applied routinely by the Veterans' Review Board and the Administrative Appeals Tribunal. Any appeal from a VRB decision or a Commission decision that applies this SoP would involve the interpretation of its terms. Potential litigation could arise over the meaning of "inability to obtain appropriate clinical management" - what constitutes an inability, and whether it includes reasons such as cost, geographic remoteness, or failure of the Department of Veterans' Affairs to approve treatment. Another likely interpretive issue is the phrase "glucocorticoid therapy as specified" and whether a given course of treatment meets the precise mathematical thresholds, especially when converting doses between different glucocorticoids.

The SoP may also be challenged if a claimant argues that the repugnant condition factor (specified condition) is not itself proven because the underlying neoplasm SoP has become outdated. However, because section 11 incorporates other SoPs as in force from time to time, such a challenge would be directed at the underlying SoP, not this one.

The most significant trap is the requirement that glucocorticoid therapy as specified must be before the clinical onset of Cushing syndrome and, if the therapy has ceased or decreased, the last dose must be within 30 days before clinical onset. A claimant who stopped taking prednisolone six weeks before symptoms appeared will fail on that factor, even if the cumulative dose and average rate were met. The 30-day window is strict and not subject to medical discretion.

The "equivalent glucocorticoid therapy" table sets precise minima. For prednisone, the minimum cumulative dose is 375 mg and the minimum average rate is 12.5 mg/day. A common prescription pattern for an acute condition is 50 mg/day for five days (cumulative 250 mg, rate 50 mg/day) - that fails the cumulative requirement. For chronic conditions, 10 mg/day for 40 days (cumulative 400 mg, average 10 mg/day) meets the cumulative but fails the average rate. The average rate must be calculated over the entire period of treatment, not just a subset.

The "equivalent inhaled glucocorticoid" for budesonide is 4,000 micrograms daily for at least six months. Many maintenance doses for asthma are 400-800 micrograms/day. A cumulative dose over six months of 400 x 180 = 72,000 micrograms, but the average daily requirement is 4,000, not 400. So only patients on very high dose inhaled steroids will qualify. Similarly, topical glucocorticoid requires at least 30% of total body surface area daily for six months - a significant restriction that excludes patients who used topical steroids on limited areas like hands or face.

The factor for medroxyprogesterone acetate or megestrol acetate is limited to use for malignant disease or HIV infection. If used for cachexia from other causes or for endometriosis, the factor does not apply.

The "inability to obtain appropriate clinical management" factor only applies to material contribution or aggravation of pre-existing Cushing syndrome. It cannot be used to establish initial clinical onset. This is a narrow gate. It also requires that the inability itself be related to service (section 10). So a veteran who developed Cushing syndrome before service and then could not obtain proper treatment because of service-related financial or access issues may succeed on aggravation, but only if the inability is service-caused.

The interaction with other SoPs under section 11 means a claimant might need to satisfy two separate SoPs. For example, if the factor is "adrenal neoplasm", the claimant must also satisfy the SoP for adrenal neoplasm. That SoP may have its own factor requirements (e.g., radiation exposure, genetic predisposition) which may be harder to prove.

The instrument does not apply to operational service, hazardous service, or British nuclear test defence service under the VEA. Claimants with those service types cannot use this SoP; they must rely on the reasonable hypothesis standard and a separate SoP (if one exists for that standard). The instrument defines relevant service narrowly, which may catch out claimants who assume all veteran service is covered.

For claimants, compliance requires gathering sufficient medical evidence to satisfy at least one factor. The most straightforward pathway is to document a specified neoplasm (adrenal, pituitary, or neuroendocrine) that caused endogenous Cushing syndrome. This requires imaging (CT, MRI) and possibly biopsy, as well as biochemical confirmation of hypercortisolism. The specified condition must exist at the time of clinical onset, so earlier diagnosis of the neoplasm is helpful.

The glucocorticoid therapy factor requires meticulous reconstruction of all glucocorticoid prescriptions. Claimants should obtain pharmacy dispensing records, doctor's clinical notes, and hospital medication charts. The following data points must be established: the specific glucocorticoid(s) used, the route of administration, the dose per administration, the frequency of administration, the start and stop dates, and any periods of cessation or dose reduction. For topical therapy, the percentage of total skin surface area treated and the potency category must be documented. For inhaled therapy, the daily microgram dose must be averaged over at least six months. For oral or injected therapy, cumulative dose and average daily rate must be calculated. If the therapy was concurrent with a CYP3A4 inhibitor, the specific drug from the specified list must be identified and proof of concurrent daily use for at least four weeks provided. The 30-day window between last dose and clinical onset must be shown by medical records noting the date of symptom onset.

For medroxyprogesterone acetate or megestrol acetate, the claimant must prove that the drug was used for malignant disease or HIV infection, not for other indications. Diagnosis of the underlying condition and treatment records are needed.

The inability to obtain appropriate clinical management factor is difficult to satisfy without a clear record of administrative denials, geographic barriers, or financial inability. Claimants should document all attempts to access treatment, any refusals by the Department or treating doctors, and the impact on their condition. The factor only applies to material contribution or aggravation, so the claimant must also prove that the Cushing syndrome existed before or during service (but did not arise out of service) and that service affected the inability.

For practitioners advising claimants, the best strategy is to review all available medical records against the SoP definitions before lodging a claim. If there is any ambiguity, obtain a retrospective medical opinion that can state on the balance of probabilities that the factor existed. The opinion must apply the SoP's definitions, not just general medical causation. It may be useful to commission a table of glucocorticoid doses and dates to show compliance with the thresholds.

For the Commission, compliance means applying the SoP strictly and not accepting factors by analogy or extrapolation. The definitions are exhaustive. If a drug is not on the specified list, even if it is a known CYP3A4 inhibitor, it cannot support the factor. Similarly, if the dose just misses the minimum, the factor is not met. The Commission should also ensure that where a factor refers to another SoP, that SoP is applied in its current version.