Can Sjögren's Disease Cause Adrenal Insufficiency?
Sjögren's disease does not directly cause clinical adrenal insufficiency, but approximately 17.5-20% of patients develop adrenal autoimmunity with antibodies against 21-hydroxylase, which can lead to subclinical adrenal dysfunction and requires monitoring. 1, 2
Evidence for Adrenal Autoimmunity in Sjögren's Syndrome
The relationship between Sjögren's syndrome and adrenal dysfunction is primarily autoimmune rather than a direct disease manifestation:
Adrenal autoantibodies (anti-21-hydroxylase) are present in 17.5% of primary Sjögren's patients, significantly higher than healthy controls but similar to other autoimmune conditions like autoimmune thyroid disease (28.1%). 1
These patients demonstrate a blunted cortisol response to ACTH stimulation (Synacthen test), indicating subclinical adrenal hyporesponsiveness, even though frank adrenal insufficiency was not detected in the studied cohort. 1
The presence of anti-21-hydroxylase antibodies correlates strongly with B-cell activation markers (interferon-α, BAFF, and IL-21) in salivary gland tissues, suggesting a shared autoimmune mechanism. 1
Hypothalamic-Pituitary-Adrenal Axis Dysfunction
Beyond direct adrenal autoimmunity, Sjögren's patients exhibit central neuroendocrine abnormalities:
Hypoactivity of the HPA axis occurs through both pituitary defects and adrenal gland dysfunction, with pituitary hyporesponsiveness to CRH stimulation and adrenal hyporesponsiveness to endogenous ACTH. 2, 3
Low basal DHEA-sulfate levels (adrenal androgens) are commonly observed, reflecting overall adrenal hypofunction rather than isolated cortisol deficiency. 2
This represents a central deficiency pattern affecting multiple neuroendocrine axes (adrenal, gonadal, and thyroid), not isolated primary adrenal failure. 3
Iatrogenic Adrenal Insufficiency Risk
The most clinically relevant cause of adrenal insufficiency in Sjögren's patients is treatment-related:
Long-term systemic corticosteroid use for moderate-to-severe interstitial lung disease or systemic manifestations carries high risk for secondary adrenal insufficiency, listed as a potential long-term side effect with HIGH strength of evidence. 4
Glucocorticoids should be used at minimum effective dose and duration when treating systemic Sjögren's disease, with steroid-sparing immunosuppressive agents (azathioprine, mycophenolate, methotrexate) considered for maintenance therapy. 5, 6
Clinical Implications and Monitoring
For patients with positive anti-21-hydroxylase antibodies:
- Monitor adrenal function longitudinally with morning cortisol and ACTH levels, as the blunted response suggests potential progression to clinical insufficiency. 1
- Consider annual ACTH stimulation testing in antibody-positive patients, particularly those with symptoms of fatigue, hypotension, or hyponatremia. 1
For patients on chronic corticosteroids:
- Recognize that adrenal suppression develops with prolonged use, requiring gradual taper and stress-dose coverage during illness or surgery. 4
- When tapering from high-dose steroids (>50 mg/day hydrocortisone equivalent), restart mineralocorticoid replacement (fludrocortisone) as the dose falls below this threshold. 4
Common Pitfalls to Avoid
Do not assume fatigue in Sjögren's patients is solely disease-related—screen for adrenal insufficiency with morning cortisol, especially in those with other autoimmune endocrinopathies or on chronic steroids. 1, 2
Do not abruptly discontinue corticosteroids in patients treated for pulmonary or systemic manifestations, as this can precipitate adrenal crisis. 4
Do not overlook the high prevalence of concurrent autoimmune thyroid disease (very common in Sjögren's), which can complicate the clinical picture and must be treated before initiating thyroid hormone replacement in those with concurrent adrenal insufficiency. 7, 2