From the Guidelines
The HPA axis lab workup should include evaluating ACTH, cortisol, TSH, free T4, and electrolytes, with consideration of standard-dose ACTH stimulation testing for indeterminate results, as recommended by the 2021 ASCO guideline update 1. When evaluating the HPA axis, it is essential to consider the timing of specimen collection, with morning cortisol and ACTH levels drawn between 7-9 AM when cortisol is naturally at its peak.
- The initial workup should include:
- Evaluating ACTH (AM) and cortisol (AM) levels
- Measuring TSH and free T4 levels
- Assessing electrolyte levels
- For indeterminate results, such as AM cortisol between 3 mg/dL and 15 mg/dL, standard-dose ACTH stimulation testing should be considered 1.
- Additional testing may be necessary, including:
- Evaluating LH and testosterone in males, FSH, and estrogen in premenopausal females with fatigue, loss of libido, and mood changes, or oligomenorrhea
- Performing MRI brain with or without contrast with pituitary or sellar cuts in all patients with new hormonal deficiencies, particularly those with multiple endocrine abnormalities, severe headaches, or complaints of vision changes 1.
From the Research
HPA Axis Lab Work Up
- The hypothalamic-pituitary-adrenal (HPA) axis is a complex neuroendocrine system that can be affected by various diseases and syndromes, including Cushing's syndrome and adrenal insufficiency 2.
- Evaluation of patients with possible Cushing's syndrome begins with ruling out exogenous steroid use, followed by screening for elevated cortisol using a 24-hour urinary free cortisol test, late-night salivary cortisol test, or dexamethasone suppression test 3.
- Laboratory tests for HPA axis dysfunction may include:
- Plasma corticotropin levels to distinguish between adrenal and pituitary causes of hypercortisolism
- Pituitary magnetic resonance imaging to identify pituitary tumors
- Bilateral inferior petrosal sinus sampling to confirm the source of excess corticotropin production
- Adrenal or whole-body imaging to identify adrenal tumors or other sources of excess cortisol production 3, 4
- For the diagnosis of adrenal insufficiency, the normal cortisol response to adrenocorticotropic hormone (ACTH) stimulation is considered to be ≥18 μg/dL (500 nmol/L) using older serum cortisol assays, but newer specific cortisol assays may have lower thresholds for a normal response 5.
- New cutoffs for the biochemical diagnosis of adrenal insufficiency after ACTH stimulation using specific cortisol assays have been proposed, ranging from 14 to 15 μg/dL depending on the assay used 5.
- The choice of laboratory tests and interpretation of results should be individualized based on the patient's clinical presentation and medical history, and should be performed in consultation with an endocrinologist or other qualified healthcare professional 2, 3, 6, 4.