In a patient with isolated ACTH deficiency, does a flattened pituitary gland and a CSF‑filled sella indicate a secondary empty sella caused by an underlying condition?

Can Isolated ACTH Deficiency Cause Empty Sella?

Yes, isolated ACTH deficiency can be associated with a flattened pituitary gland and CSF-filled sella (empty sella syndrome), and this finding may indicate an underlying pathologic process affecting the pituitary gland. 1

Understanding the Association

The relationship between isolated ACTH deficiency and empty sella is well-documented but represents an uncommon presentation:

• Empty sella syndrome has been reported in multiple cases of isolated ACTH deficiency, suggesting a potential causal relationship where the structural abnormality may be responsible for the selective hormonal deficit 1
• Approximately 30% of patients with empty sella demonstrate some degree of hypopituitarism upon testing, though isolated ACTH deficiency represents a rare subset of these cases 2, 3, 4
• The empty sella finding in isolated ACTH deficiency may represent primary empty sella syndrome where herniation of CSF into the sella compresses and flattens the pituitary gland, potentially causing selective corticotroph dysfunction 1

Potential Underlying Conditions

Several mechanisms can lead to this presentation:

• Lymphocytic hypophysitis is a recognized cause of isolated ACTH deficiency in adults and may result in subsequent pituitary atrophy and empty sella appearance 5
• Autoimmune etiology should be considered, particularly in adults presenting with isolated ACTH deficiency and structural pituitary changes 5
• Antiphospholipid syndrome has been reported in association with isolated ACTH deficiency and empty sella, suggesting vascular compromise as a potential mechanism 6
• Post-traumatic injury can lead to isolated ACTH deficiency, though this typically has a clear clinical history 5

Diagnostic Approach

MRI with high-resolution pituitary protocols is the preferred imaging modality to characterize the empty sella and can confirm the diagnosis even without IV contrast 7, 2, 3, 4

Essential Hormonal Evaluation

You must perform comprehensive pituitary function testing to confirm true isolated ACTH deficiency:

• Morning baseline measurements should include cortisol, ACTH, TSH, free T4, prolactin, IGF-1, and sex hormones (testosterone in men, estradiol/FSH/LH in women) 2
• All other pituitary hormone axes must be normal to establish the diagnosis of isolated ACTH deficiency—this is a critical diagnostic criterion 5, 8
• Dynamic testing with insulin tolerance test (ITT) is the gold standard for confirming ACTH deficiency, or alternatively use 1 mcg cosyntropin stimulation test when ITT is contraindicated 2, 5
• Prolonged ACTH stimulation test (over several days) typically shows preserved or partial adrenal response in secondary adrenal insufficiency, distinguishing it from primary adrenal failure 1, 5, 8

Key Diagnostic Pitfalls

• Do not assume primary adrenal insufficiency based solely on low cortisol—measure ACTH simultaneously, as isolated ACTH deficiency presents with low or inappropriately normal ACTH levels 5, 9
• Beware of falsely elevated TSH that may suggest primary hypothyroidism when it actually reflects isolated ACTH deficiency—the low cortisol can cause mild TSH elevation 9
• Hyponatremia in isolated ACTH deficiency is typically mild and associated with normal-to-high potassium (unlike primary adrenal insufficiency with hyperkalemia), because mineralocorticoid production is preserved 5

Clinical Implications

The presence of empty sella with isolated ACTH deficiency suggests:

• A structural or inflammatory process has affected the pituitary, even if other hormone axes remain intact 1
• The condition may be progressive—approximately 30% of empty sella patients have some hypopituitarism, and careful reevaluation at 24-36 months is recommended if initially normal 4
• Autoimmune or vascular etiologies should be investigated, particularly in younger patients or those with suggestive clinical features 5, 6

Management Recommendations

• Glucocorticoid replacement therapy with hydrocortisone 20 mg daily (0.30 mg/kg) or cortisone acetate 25 mg daily (0.35 mg/kg) is the standard treatment 5
• Mineralocorticoid replacement is not necessary because aldosterone production remains intact in isolated ACTH deficiency 5
• Endocrinology referral is indicated for all patients with confirmed isolated ACTH deficiency to guide hormone replacement and monitor for development of additional pituitary deficiencies 2, 3
• Patient education on stress-dosing and emergency injectable steroids is mandatory, along with obtaining a medical-alert bracelet 2