Accurate Characterization of Double Pituitary Adenomas is Key in Cushing’s Patients, Study Reports

Proper characterization of the features of double pituitary adenomas in patients with Cushing’s disease is key for an accurate diagnosis and successful surgical removal, a study highlights.

The study, “Double Pituitary Adenomas in a Large Surgical Series,” was published in the journal Pituitary.

Most pituitary adenomas — tumors that are normally benign and slow-growing — arise from a single cell type and produce a single hormone. However, up to one-third of these adenomas produce more than one pituitary hormone. This can be due to either a single cell type capable of producing two or more hormones, or two or more cell types inside a single tumor, each producing different hormones.

Double or multiple pituitary adenomas are rare. They can be either synchronous (appearing at the same time) or asynchronous, as a recurrence of a previously removed adenoma. They can also be clearly separate masses or contiguous, or bordering, masses.

To better characterize double pituitary adenomas, researchers analyzed the medical records of 3,270 patients who had operations for pituitary tumors at the Military Institute of Medicine in Warsaw, Poland, between 2003 and 2018. Of these patients, 22 had a double pituitary adenoma, corresponding to 0.67% of the total population — within the reported prevalence range of 0.2 to 2.6%.

Magnetic resonance imaging (MRI) revealed double pituitary adenomas in 11 patients, all showing two separate tumors during surgery. In the remaining patients, contiguous adenomas were confirmed by histological examination.

One patient diagnosed with adrenocorticotrophic hormone (ACTH)-dependent hypercortisolemia, or excess cholesterol levels, showed no tumors on a preoperative MRI. However, two distinct tumors were found in separate surgeries. Their removal led to Cushing’s remission.

In another patient, a second pituitary adenoma was removed three years after the removal of the first adenoma.

In most cases, the adenomas were hormonally active, meaning they secreted hormones, and more than one hormone was produced. The main clinical finding was acromegaly, when the pituitary gland produces too much growth hormone (12 patients), followed by Cushing’s disease (in three).

In Cushing’s cases, ACTH-secreting adenomas coexisted with prolactin-secreting tumors in two patients and with a growth hormone-secreting tumor in one case.

There was one case of secondary hyperthyroidism and one case of hyperprolactinemia (overproduction of prolactin) with secondary amenorrhea, which refers to the absence of menstruation. Three patients had non-functioning pituitary adenomas, meaning they did not secrete any active hormones, diagnosed due to vision problems.

Over an average follow-up of 74.2 months, all but two patients with acromegaly achieved remission of their altered levels of pituitary hormones.

“Double pituitary adenoma is a rare entity that can pose a significant challenge especially in the setting of Cushing’s disease,” the scientists wrote. “Recognition and exact localization of double pituitary adenomas prior to surgery are essential to avoid the failure of surgery by missing the causative lesion, which is of special importance in the course of treating Cushing’s disease.”