What is the role of a pituitary hormone panel in the investigation of adrenal insufficiency (low cortisol)?

From the Guidelines

A pituitary hormone panel for investigating low cortisol should include ACTH, TSH, free T4, prolactin, LH, FSH, IGF-1, and morning cortisol levels, as recommended by the most recent guidelines 1. This comprehensive panel helps determine whether the low cortisol is due to primary adrenal insufficiency or secondary adrenal insufficiency caused by pituitary dysfunction. The ACTH level is particularly important as it will be elevated in primary adrenal insufficiency (Addison's disease) but low or inappropriately normal in secondary adrenal insufficiency. Additional testing may include an ACTH stimulation test (Synacthen test) where synthetic ACTH (250 mcg) is administered and cortisol levels are measured at baseline, 30 minutes, and 60 minutes post-administration. A normal response shows cortisol rising above 18-20 μg/dL, as noted in the guidelines 1. Timing of collection is crucial, with samples ideally taken in the morning (8-9 AM) when cortisol levels are naturally highest. Patients should avoid taking glucocorticoids before testing as they can interfere with results, as highlighted in the guidelines 1. If pituitary pathology is suspected, an MRI of the pituitary gland should be considered to identify potential tumors or other structural abnormalities, as recommended in the guidelines 1. Some key points to consider when evaluating patients with low cortisol include:

• Evaluating ACTH, cortisol, TSH, free T4, and electrolytes, as recommended in the guidelines 1
• Considering standard-dose ACTH stimulation testing for indeterminate results, as noted in the guidelines 1
• Evaluating LH and testosterone in males, FSH, and estrogen in premenopausal females with fatigue, loss of libido and mood changes, or oligomenorrhea, as recommended in the guidelines 1
• Considering MRI brain w/wo contrast with pituitary or sellar cuts in all patients with new hormonal deficiencies and particularly those with multiple endocrine abnormalities, new severe headaches, or complaints of vision changes, as recommended in the guidelines 1

From the Research

Pituitary Hormone Panel for Investigation in Low Cortisol

• The pituitary hormone panel is used to investigate low cortisol levels, which can be caused by various factors, including hypopituitarism or adrenal insufficiency 2, 3.
• The panel typically includes measurements of adrenocorticotrophic hormone (ACTH), cortisol, and other hormones to assess the hypothalamic-pituitary-adrenal (HPA) axis 2.
• A low dose ACTH test (LDST) is often used to diagnose central adrenal insufficiency (CAI), with a cutoff value of 18 μg/dL (500 nmol/L) for a normal response 3, 4.
• However, newer specific cortisol assays may have lower thresholds for a normal response, with recommended cutoffs ranging from 14 to 15 μg/dL depending on the assay used 4.
• The ACTH stimulation test can also be used to distinguish between subtypes of primary aldosteronism, although its clinical usefulness is still being debated 5.
• Measurement of cortisol-binding globulin (CBG) concentration and calculation of free cortisol or free cortisol index can help avoid false interpretations of dynamic tests of the HPA axis based on plasma total cortisol 2.
• Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for adrenal insufficiency, and consider the clinical context and potential biases in epidemiological studies when interpreting results 3, 4, 5.