From the Guidelines
Adrenal diseases such as Cushing's syndrome, Addison's disease, and pheochromocytoma present with distinct clinical features that reflect their underlying hormonal imbalances, and their diagnosis involves a stepwise approach with screening tests, confirmatory tests, and localization studies. Cushing's syndrome manifests with central obesity, moon face, buffalo hump, purple striae, hypertension, hyperglycemia, and muscle weakness due to excess cortisol, and diagnosis involves screening with 24-hour urinary free cortisol, overnight dexamethasone suppression test, or late-night salivary cortisol, followed by confirmatory tests and imaging to determine the source 1. Addison's disease presents with fatigue, weight loss, hyperpigmentation, hypotension, salt craving, and electrolyte abnormalities due to insufficient cortisol and aldosterone, and diagnosis requires morning cortisol levels, ACTH stimulation test, and antibody testing to confirm primary adrenal insufficiency 1. Pheochromocytoma typically causes episodic hypertension, headaches, sweating, and palpitations due to catecholamine excess, and diagnosis involves measuring plasma or 24-hour urinary metanephrines and catecholamines, followed by CT or MRI imaging to locate the tumor 1.
Some key points to consider in the diagnosis of adrenal diseases include:
- Screening for autonomous cortisol secretion in all patients with adrenal incidentalomas using 1 mg dexamethasone suppression testing 1
- Screening for primary aldosteronism with an aldosterone-to-renin ratio in patients with hypertension and/or hypokalemia 1
- Screening for pheochromocytoma with plasma or 24-hour urinary metanephrines in patients with signs/symptoms of catecholamine excess or adrenal incidentalomas with >10 HU on non-contrast CT 1
- The use of non-contrast CT as first-line imaging to distinguish benign lesions from those which require further radiologic investigation 1
- The importance of a multidisciplinary review by endocrinologists, surgeons, and radiologists when the imaging is not consistent with a benign lesion, there is evidence of hormone hypersecretion, the tumor has grown significantly during follow-up imaging, or adrenal surgery is being considered 1
Early recognition of these conditions is crucial as they can lead to significant morbidity if untreated, and the diagnostic approach generally follows a stepwise pattern: screening tests to establish the presence of hormonal abnormalities, confirmatory tests to verify the diagnosis, and localization studies to determine the exact source of the problem, enabling appropriate treatment planning.
From the Research
Clinical Presentation of Adrenal Disease
The clinical presentation of adrenal disease can vary depending on the specific condition. For Cushing's syndrome, the clinical presentation may include weight gain, hypertension, and glucose intolerance 2, 3, 4.
Diagnostic Approaches for Adrenal Diseases
- Cushing's syndrome:
- Overnight dexamethasone suppression test (DST) can be used for differential diagnosis, with a sensitivity of 78% and 100% specificity 2.
- Low-dose dexamethasone suppression test can correctly identify 98% of patients with ACTH-dependent Cushing's syndrome and distinguish between pituitary and ectopic causes with a sensitivity of 82% and a specificity of 79% 4.
- Midnight cortisol and midnight ACTH levels can also be used for diagnosis and localization of Cushing's syndrome, with a sensitivity of 100% at cut offs of 138 nmol/l and below 5.
- Addison's disease:
- No specific studies are provided in the given evidence.
- Pheochromocytoma:
- No specific studies are provided in the given evidence.
Diagnostic Tests for Cushing's Disease
- 11 p.m. salivary cortisol level can be used as an initial screening tool for the diagnosis of Cushing syndrome 6.
- 24-hour urinary free cortisol test and/or a low-dose dexamethasone suppression test can be used for confirmation 6.
- Corticotropin-releasing hormone (CRH) stimulation test can be used to help rule out pseudo-Cushing states and clarify the underlying disease 6.
- Magnetic resonance (MR) imaging of the pituitary gland can be performed to detect a pituitary neoplasm, and inferior petrosal sinus sampling can be used to diagnose Cushing disease in experienced hands 6.