Can glucocorticoids (corticosteroids) cause pituitary adenoma?

Glucocorticoids and Pituitary Adenomas

Glucocorticoids do not cause pituitary adenomas; rather, they can suppress the hypothalamic-pituitary-adrenal (HPA) axis, potentially masking symptoms of existing pituitary adenomas or causing secondary adrenal insufficiency. 1

Relationship Between Glucocorticoids and the Pituitary

• Exogenous glucocorticoid therapy across all routes of administration (oral, inhaled, topical, intranasal, intra-articular) can cause suppression of the hypothalamo-pituitary-adrenal axis, sometimes referred to as tertiary adrenal insufficiency 1
• This suppression can occur at commonly prescribed doses and in a dose-dependent manner, even with inhaled corticosteroids that were previously thought to be safe within recommended dose ranges 1
• Seven in 1000 people are prescribed long-term oral corticosteroid therapy, creating a large population at risk of adrenal crisis due to HPA axis suppression 1

Pituitary Adenomas and Cortisol Production

• Pituitary adenomas can cause hormonal secretion problems, including hypocortisolism (low cortisol) 2
• In Cushing's disease, ACTH-secreting pituitary adenomas cause hypercortisolism (elevated cortisol) 1
• Corticotroph adenomas (ACTH-producing) are the most common pituitary adenoma diagnosed in early childhood, accounting for 55% of pituitary adenomas in those aged 0-11 years and 30% in those aged 12-17 years 1
• Patients with secondary adrenal insufficiency due to pituitary disorders are deficient in cortisol but continue to secrete aldosterone in response to renin 1

Clinical Implications and Management

• Patients with pituitary adenomas causing hypocortisolism may require hydrocortisone replacement therapy 2
• Higher glucocorticoid replacement doses are associated with increased overall mortality in patients with nonfunctioning pituitary adenomas and insufficiency of the HPA axis 3
• In patients with normal preoperative cortisol levels undergoing removal of a pituitary adenoma, normal morning cortisol values on postoperative days 1 and 2 reliably predict adequate adrenal function in 98% of patients 4
• Patients with Cushing's disease due to ACTH-producing pituitary adenomas may show varying responses to dexamethasone suppression tests, with resistance potentially related to decreased expression of glucocorticoid receptors in the adenoma 5

Important Considerations and Cautions

• Patients taking physiological replacement doses of corticosteroids for either primary or secondary adrenal insufficiency are at significant risk of adrenal crisis and must be given stress doses of hydrocortisone during periods of physiological stress, such as surgery 1
• Daily doses of prednisolone of 5 mg or greater in adults and 10-15 mg/m² hydrocortisone equivalent or greater in children may result in HPA axis suppression if administered for 1 month or more 1
• Documented side effects of steroid therapy include lipodystrophy, hypertension, cardiovascular disease, osteoporosis, impaired wound healing, myopathy, cataracts, peptic ulcers, infection, mood disorders, and diabetogenesis 1
• Clinicians should be aware that exogenous glucocorticoid therapy can mask symptoms of pituitary adenomas by suppressing the HPA axis, potentially delaying diagnosis 1

Conclusion

While glucocorticoids can significantly affect the hypothalamic-pituitary-adrenal axis, there is no evidence in the provided literature that they directly cause pituitary adenomas. The relationship is more about how glucocorticoids interact with existing pituitary pathology or how they can suppress normal pituitary function, rather than being causative of adenoma formation.