Can Partial Empty Sella Cause Hyperprolactinemia?
Yes, partial empty sella syndrome can cause hyperprolactinemia, though the mechanism remains incompletely understood and the association occurs in approximately 10% of cases. 1
Epidemiology and Clinical Evidence
The relationship between empty sella syndrome and hyperprolactinemia is well-documented in the literature:
In a large retrospective series of 213 patients with primary empty sella, 10.3% presented with hyperprolactinemia (22 patients total: 18 women and 4 men), with prolactin levels ranging from mildly to significantly elevated. 1
Hyperprolactinemia associated with empty sella can occur with or without an underlying pituitary microadenoma. In one surgical series, 7 of 8 patients explored had only an empty sella with flattened pituitary tissue and no tumor, while 1 had a coexistent microadenoma. 2
Prolactin levels in empty sella-associated hyperprolactinemia typically range from 33 to 498 ng/mL (approximately 700-10,500 mIU/L), representing mild to moderate elevations rather than the very high levels (>4,000 mIU/L) typically seen with prolactinomas. 2, 1
Proposed Mechanisms
The pathophysiology likely involves pituitary stalk compression or distortion from the herniation of subarachnoid space into the sella, which interrupts the inhibitory dopaminergic tone from the hypothalamus to lactotroph cells. 3
This mechanism is similar to "stalk effect" hyperprolactinemia seen with other mass lesions compressing the pituitary stalk. 3
The flattening and displacement of the pituitary gland against the sellar floor may compromise normal hypothalamic-pituitary portal blood flow. 2
Diagnostic Approach
When evaluating hyperprolactinemia in the setting of empty sella:
First exclude other common causes: hypothyroidism (present in 43% of women and 40% of men with primary hypothyroidism), medications (dopamine antagonists), chronic kidney disease, and liver disease. 3, 4
Screen for macroprolactinemia, as this can coexist with empty sella syndrome and represents a benign condition not requiring treatment. The macroprolactin form may account for the majority of measured prolactin in some cases. 5
MRI of the sella without and with contrast is the gold standard imaging modality to characterize the empty sella and exclude a coexistent pituitary adenoma, which can occur simultaneously. 6
Dynamic testing patterns differ from prolactinomas: Patients with empty sella and hyperprolactinemia typically maintain normal responses to TRH and L-dopa stimulation, whereas prolactinoma patients show impaired responses. 7
Treatment Considerations
Low-dose dopamine agonist therapy (bromocriptine 3.75-5 mg/day or cabergoline) effectively normalizes prolactin levels in empty sella-associated hyperprolactinemia, requiring lower doses than typical prolactinomas (which need 7.5-15 mg/day bromocriptine). 7
However, treatment should only be initiated after:
- Confirming true hyperprolactinemia (not macroprolactinemia) 5
- Excluding reversible causes like hypothyroidism or medications 3, 4
- Documenting symptomatic hypogonadism (amenorrhea, galactorrhea, erectile dysfunction, decreased libido) that warrants intervention 3
Clinical Pitfalls
Radiographic imaging alone cannot reliably distinguish empty sella from pituitary tumor. Lateral skull films and tomography may suggest tumor even when only empty sella is present. 8
Pneumoencephalography may fail to demonstrate air within the sella if the diaphragma sellae remains intact, leading to false-negative results. Modern MRI has largely eliminated this diagnostic challenge. 8
The coexistence of empty sella does not exclude a pituitary microadenoma, so careful MRI evaluation with high-resolution pituitary protocols is essential. 2, 1