From the Guidelines
To diagnose suspected hypothalamic dysfunction, I recommend evaluating ACTH, cortisol, TSH, free T4, and electrolytes, with consideration of additional tests such as LH, testosterone, FSH, and estrogen in specific cases, as well as MRI brain imaging with pituitary or sellar cuts in patients with new hormonal deficiencies or severe symptoms. When evaluating suspected hypothalamic dysfunction, the initial workup should include assessment of the pituitary-hypothalamic axis through laboratory tests, as outlined in the guidelines for managing immune-related adverse events 1. The key tests to consider are:
- ACTH and cortisol levels, particularly in the morning, to assess the integrity of the hypothalamic-pituitary-adrenal axis
- TSH and free T4 to evaluate thyroid function
- Electrolytes to assess for any imbalances that could indicate hypothalamic dysfunction Additional tests may be necessary based on patient symptoms, such as:
- LH and testosterone in males with fatigue, loss of libido, and mood changes
- FSH and estrogen in premenopausal females with similar symptoms or oligomenorrhea
- Consideration of standard-dose ACTH stimulation testing for indeterminate results, such as morning cortisol levels between 3 and 15 mg/dL 1 Imaging studies are also crucial, particularly MRI of the brain with focus on the pituitary or sellar region, in patients with new hormonal deficiencies, multiple endocrine abnormalities, severe headaches, or complaints of vision changes, as well as in those presenting with diabetes insipidus 1. These tests are essential for identifying structural abnormalities that could be causing the hypothalamic dysfunction and for guiding further management.
From the Research
Lab Tests for Hypothalamic-Pituitary Axis Dysfunction
The following lab tests are used to diagnose suspected hypothalamic-pituitary axis dysfunction:
- Insulin tolerance test (ITT) 2, 3, 4, 5, 6
- Glucose suppression test for acromegaly 2
- Dexamethasone suppression test for Cushing's disease 2
- Basal thyroid function tests 2
- Serum oestradiol or testosterone 2
- Basal gonodotrophins 2
- Overnight water deprivation test for assessment of neurohypophyseal function 2
- GH stimulation testing 2
- TRH or LHRH testing 2
- Metyrapone test 3
- ACTH stimulation test 3, 4
- GHRP-6 Test 5
- Human-corticotrophin releasing hormone (h-CRH) test 6
Specific Tests for Adrenal Insufficiency
For diagnosing adrenal insufficiency, the following tests are used:
- ITT 3, 4, 5, 6
- Metyrapone test 3
- ACTH stimulation test 3, 4
- GHRP-6 Test 5
- h-CRH test 6
- Serum cortisol measurement at 0800 h 6
- 24-h urinary free cortisol 6
Comparison of Tests
The ITT is considered the gold standard for diagnosing adrenal insufficiency, but it may be hazardous and unpleasant to perform 3, 4, 5, 6. Alternative tests such as the metyrapone test, ACTH stimulation test, and GHRP-6 Test have been proposed, but their diagnostic reliability and accuracy may vary 3, 4, 5. The h-CRH test and serum cortisol measurement at 0800 h may also be useful in evaluating adrenal function 6.