Hypopituitarism and Gamma Knife Radiotherapy

Does radiotherapy cause hypotituitarism when treating pituitary adenoma(s)?

Sometimes tumors cause damage to the pituitary gland which results in hypopituitarism and panhypopitituarism. Surgery to remove the tumor(s) can also cause damage to the pituitary which leads to hypopitutiarism. Sometimes, depending on tumor placement and the amount of pituitary removed, the pituitary regains total function. Nothing is cut-and-dry with this due to the numerous factors surrounding tumors and their removal.

This article takes a look at the effect of radiotherapy on the pituitary. Is hypopituitarism a "given" with radiotherapy or can it be avoided? According to the authors, this depends on the total dose, the fraction size of each irradiation, and the time between each fraction.

Since Gamma Knife is a single-fraction radiosurgery, all radiation is delivered in one dose.

Radiation-induced hypopituitarism occurs in a significant number of patients treated for pituitary adenomas with either stereotactic radiosurgery (SRS), which involves a single dose of stereotactic radiotherapy, as well as following fractionated stereotactic radiotherapy (FSRT).

The authors point out the risk is difficult to establish due to the multiple factors involved, which include:

• surgery
• variations in dosages of radiation
• technique used (SFR vs. FSRT)
• accuracy of placement and imaging
• pre-existing hypopituitarism
• lack of consisten protocol for diagnosing hypopituitarism

They also point out hypopituitarism is "more likely to occur following stereotactic irradiation for
secretory adenomas, as higher doses are generally required to achieve hormonal control." This includes gamma knife.

Since hypopitituarism can include multiple hormones, which are the most apt to be affected? Growth hormone (GH) has the greatest vulnerability. "With higher radiation doses (30–50 Gy), however,the frequency of GH insufficiency substantially increases and can be as high as 50–100%."

Patients irradiated for pituitary tumors have an increased risk for gonadotrophin deficiency with the data presenting "severity from subtle subclinical) abnormalities in secretion detected only by
GnRH testing to severe impairment associated with diminished circulating sex hormone levels."

Normal ACTH deficiency "dramatically increases (27–35%) after intensive irradiation [6, 9, 12] and more so (31–60%) in patients with pituitary adenomas [20, 25, 26]." TSH deficiency follows almost identically with patients irradiated for pituitary tumors.

Women tend to develop hyperprolactemia after SRS/GK which tends to normalize over time. The article was not very clear on this and just briefly touched on it. There didn't seem to be much data on it, either.

More on GK later this week.

Ken H. Darzy, Stephen M. Shalet (2008). Hypopituitarism following radiotherapy Pituitary, 12 (1), 40-50 DOI: 10.1007/s11102-008-0088-4