Nonfunctional Pituitary Adenomas

From Lewis Blevins, MD – We really shouldn’t call them nonfunctional pituitary adenomas. They are living tissue and thus “functioning.” The term comes from the fact that they are not producing any hormones in excess and thus not overdriving the pituitary target glands. Further, they sure can cause dysfunction of the pituitary gland that can wreak havoc in the lives of affected patients.

Some have proposed calling them non-secreting pituitary adenomas. Others have suggested the term endocrine inactive adenomas. These are also misnomers. In fact, many of these tumors secrete hormones that are biologically inactive. For example, 45% of all ACTH producing tumors are thought to be nonfunctioning tumors because the ACTH they produce either is not appropriately secreted or does not have biological activity and thus cannot overdrive the adrenal glands to produce cortisol. Interestingly, some of these tumors, when they recur, will cause Cushing syndrome. Further, a small fraction of tumors that produce growth hormone secrete a biologically inactive molecule. Some patients will have elevations in the IGF one though they do not look acromegalic. We often refer to these tumor subtypes as “silent” but that term obviously doesn’t work either.

The fact of the matter is that most of the “nonfunctional” pituitary adenomas are gonadotroph adenomas in that they are derived from the LH and FSH producing cells of the pituitary gland. A very small proportion of these actually overdrive either the ovaries or the testicles.

As mentioned above, another proportion of these tumors are actually “clinically silent” ACTH or growth hormone producing tumors. Prolactinomas and TSH producing adenomas are not usually clinically silent. I have, however, seen an occasional patient who had no symptoms or signs of a prolactinoma, with only a very mild elevation in prolactin, but proved to have an atypical prolactinoma or acidophil stem cell adenoma.

There is indeed a “null cell” adenoma of the pituitary gland and, if one were to be a purist, would say this is probably the only true non-secreting pituitary adenoma. Well, maybe the rare oncocytoma also counts.

Also, there are other tumor types involving the pituitary gland. Occasionally, a patient will have an intrasellar craniopharyngioma or glioma. Posterior pituitary tumors are uncommon but seen periodically. The most common one is a choristoma. Further, some Rathke’s cleft cysts are suspected of being pituitary adenomas and are deemed to be “nonfunctional,” which, of course they are, but they are not tumors.

Frankly, I don’t know what is best to call these tumors that are not over producing hormones in amounts that overdrive a target gland. Attempts to get away from calling them “nonfunctional” have not been successful.

We do indeed classify pituitary tumors according to size. Those less than 1 cm are called microadenomas whereas those greater than 1 cm are macroadenomas. The term giant adenoma is reserved for those 4 cm or greater in any dimension. Of course, the term invasive is added to any tumor that crosses a tissue plane. Pituitary carcinoma is a term reserved for a tumor that has spread to another area. More on this topic later. We certainly classify tumors according to cell type based on immunochemistry and correlations with the clinical presentation. Immunochemistry allows us to define those tumors that are hormone producing and yet clinically silent. It defines most of the nonfunctional tumors are gonadotroph adenomas.

My advice, if you’re told that you have a “nonfunctional” pituitary adenoma, is to ask precisely what that means! It may actually be clinically important because you may develop Cushing syndrome if your silent ACTH producing tumor recurs. Or, perhaps someday we will have good medical therapies for the gonadotroph adenomas. Further, your survival might be effective if you have a tumor that appears to be nonfunctional but produces low levels of growth hormone elevating the IGF-I. It is best to be fully aware of your diagnosis so that you can make plans for the future.
Read more about clinically significant pituitary tumors in this article from Touch Endocrinology


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