What tests are recommended for patients with suspected secondary lymphoedema, such as Addison's disease or Cushing's syndrome?

From the Guidelines

For patients with suspected secondary lymphoedema related to endocrine disorders like Addison's disease or Cushing's syndrome, the most recommended tests include serum cortisol levels, 24-hour urinary free cortisol, overnight dexamethasone suppression test, and serum electrolytes, as well as imaging studies like CT or MRI of the adrenal glands and pituitary, with the priority of determining the diagnosis of hypercortisolism and its aetiology, as supported by the most recent guideline 1.

When evaluating patients with suspected secondary lymphoedema due to endocrine disorders, it is crucial to follow established algorithms for diagnosing Cushing syndrome and determining its cause. The initial step involves confirming the presence of hypercortisolism, which can be achieved through tests such as 24-hour urinary free cortisol collection, late-night salivary cortisol, or serum cortisol circadian rhythm studies, as outlined in the consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: part 2, specific diseases 1.

Key points to consider in the diagnostic process include:

• Serum cortisol levels: Morning cortisol levels can help identify adrenal insufficiency in Addison's disease, while elevated cortisol levels may indicate Cushing's syndrome.
• 24-hour urinary free cortisol: This test is essential for confirming hypercortisolism in patients with suspected Cushing's syndrome.
• Overnight dexamethasone suppression test: This test helps confirm the diagnosis of Cushing's syndrome by assessing the suppression of cortisol production after dexamethasone administration.
• Imaging studies: CT or MRI of the adrenal glands and pituitary can help identify underlying tumors or abnormalities that may be causing the endocrine disorder.

The ACTH stimulation test is particularly valuable for diagnosing Addison's disease, as patients will show an inadequate cortisol response to synthetic ACTH. For Cushing's syndrome, determining the ACTH dependency is crucial, which can be supported by a normal or elevated 09:00 h plasma ACTH, as recommended in the guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: part 2, specific diseases 1.

In cases where Cushing's syndrome is confirmed, and the source of ACTH excess needs to be determined, bilateral inferior petrosal sinus sampling (BSIPSS) may be offered to confirm a central source of ACTH excess, especially in the absence of an identified adenoma on pituitary MRI, as recommended in the consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: part 2, specific diseases 1.

Proper diagnosis of the underlying endocrine disorder is critical because these conditions can cause fluid retention and impaired lymphatic function, leading to secondary lymphoedema. Targeted treatment of the underlying condition, rather than just managing the lymphoedema symptoms, is essential for improving patient outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

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From the Research

Secondary Lymphoedema Tests

For patients with suspected secondary lymphoedema, such as Addison's disease or Cushing's syndrome, the following tests are recommended:

• Imaging techniques, including MR and ICG lymphography, as well as ultra-high-frequency ultrasound examinations, to assess the lymphatic system 2
• Functional lymphoscintigraphy, such as Tc-99, to evaluate lymphatic drainage 2
• Measurement of plasma adrenocorticotropin (ACTH), renin activity, and aldosterone to diagnose primary adrenocortical insufficiency (PAI) 3
• Rapid ACTH injection test as an indirect screening test for adrenocortical insufficiency 3

Diagnostic Workup

The diagnostic workup for lymphoedema includes:

• Clinical suspicion and physical examination 2, 4
• Limb volume measurement of >10% in the affected limb compared to the unaffected limb to confirm a lymphoedema diagnosis 4
• Integrated medical, psychological assessment, and physical examination 4

Management

The management of lymphoedema involves:

• Complex Decongestive Therapy (CDT) followed by self-management using skincare, self-lymphatic drainage massage, exercise, and compression 4
• (Super)microsurgery to restore regional lymphatic drainage in the context of intensified conservative therapy 2
• Suction-assisted lipectomy to produce long-term, stable reductions in circumference and improvement in quality of life 2