Why is a contrast‑enhanced pituitary magnetic resonance imaging (MRI) the first step in an adult with newly diagnosed secondary adrenal insufficiency (low cortisol with inappropriately low or normal adrenocorticotropic hormone)?

Rationale for Pituitary MRI in Secondary Adrenal Insufficiency

Contrast-enhanced pituitary MRI is essential in newly diagnosed secondary adrenal insufficiency to identify the underlying pituitary or hypothalamic pathology causing ACTH deficiency, guide treatment decisions, and detect potentially life-threatening structural lesions requiring urgent intervention. 1

Primary Diagnostic Rationale

MRI with pituitary protocol is the gold-standard imaging study because it directly visualizes the pituitary gland, infundibulum, and surrounding structures to identify the cause of ACTH deficiency. 1, 2 The biochemical diagnosis of secondary adrenal insufficiency—low cortisol with inappropriately low or normal ACTH—confirms hypothalamic-pituitary axis dysfunction but does not reveal the underlying structural cause. 3

Key Structural Pathologies Detected

• Pituitary adenomas (both functioning and non-functioning) are among the most common causes of secondary adrenal insufficiency, and MRI identifies these lesions with superior sensitivity compared to all other imaging modalities. 1

• Hypophysitis presents with pituitary enlargement, stalk thickening, suprasellar convexity, and heterogeneous enhancement on MRI—findings that precede clinical symptoms and guide management decisions about immunosuppression versus hormone replacement. 4

• Other structural lesions including pituitary hemorrhage, infiltrative diseases (sarcoidosis, hemochromatosis), metastatic disease, and craniopharyngiomas require identification for appropriate treatment planning. 3

Technical Imaging Specifications

High-resolution T1-weighted coronal and sagittal sequences performed before and after gadolinium administration maximize detection of microadenomas and other subtle pathology. 1 Thin-section imaging with dedicated pituitary protocols is mandatory because:

• Microadenomas (<10 mm) appear as hypo-enhancing lesions on post-contrast sequences and may be missed without proper technique. 1

• Dynamic contrast-enhanced MRI further increases sensitivity for small lesions and clarifies their relationship to the pituitary stalk and cavernous sinus. 1

• 3D spoiled gradient-echo T1 sequences provide the highest sensitivity for detecting hormone-secreting adenomas. 1

Clinical Decision-Making Impact

MRI findings directly influence management by distinguishing surgical candidates from those requiring medical therapy alone. 4, 5

• Patients with mass lesions causing stalk compression or chiasmal involvement may benefit from transsphenoidal surgery to decompress structures and potentially restore pituitary function. 5

• Hypophysitis with significant pituitary enlargement may warrant pulse-dose corticosteroids (prednisone 1 mg/kg/day) in addition to physiologic replacement, particularly when there is threatened optic chiasm compression. 4

• Empty sella or atrophic changes suggest long-standing disease requiring lifelong hormone replacement without surgical intervention. 6

Detection of Multiple Pituitary Hormone Deficiencies

MRI should be performed in all patients with new hormonal deficiencies, particularly those with multiple endocrine abnormalities, new severe headaches, or visual complaints. 4 Secondary adrenal insufficiency rarely occurs in isolation:

• Central hypothyroidism coexists in >75% of patients with hypophysitis, and MRI abnormalities help confirm the diagnosis when combined with biochemical findings. 4

• Approximately 50% of patients present with panhypopituitarism (adrenal insufficiency plus hypothyroidism plus hypogonadism), making comprehensive pituitary evaluation essential. 4

• Diabetes insipidus, when present, most commonly indicates metastatic disease to the pituitary and mandates urgent MRI with contrast. 4

Timing and Urgency Considerations

MRI should be obtained before initiating high-dose corticosteroid therapy when possible, as steroid treatment can alter pituitary appearance and complicate interpretation. 4 However, this should never delay emergency treatment of suspected adrenal crisis. 4

For patients with severe symptoms (grade 3-4), MRI should be performed urgently to exclude mass lesions requiring immediate neurosurgical intervention, while simultaneously initiating stress-dose corticosteroids and fluid resuscitation. 4

Common Pitfalls to Avoid

• CT scanning is markedly less sensitive than MRI for microadenomas and should not be used as the initial imaging study—it misses up to 17.6% of lesions <5 mm even with optimal technique. 1, 2

• Plain radiography of the sella is insensitive and nonspecific because many adenomas occur with a normal-appearing sella on X-ray. 1

• Non-contrast MRI alone may miss subtle enhancement patterns that distinguish adenomas from normal gland, so gadolinium administration is strongly recommended. 1, 2

• Failure to use dedicated pituitary protocols with thin-section imaging significantly reduces diagnostic sensitivity for small lesions. 1

Integration with Hormonal Assessment

MRI findings must be interpreted in conjunction with comprehensive anterior pituitary hormone testing (prolactin, IGF-1, TSH/free T4, morning cortisol/ACTH, gonadal hormones) to distinguish functioning from non-functioning lesions and assess the full extent of pituitary dysfunction. 1 This combined biochemical-radiological approach:

• Identifies hormone-secreting adenomas that may require specific medical therapy (e.g., dopamine agonists for prolactinomas). 2

• Detects clinically silent hormone excess (up to 46% of apparently non-functioning adenomas show GH immunostaining). 1

• Establishes baseline for surgical planning and postoperative monitoring when intervention is indicated. 1