Pituitary Tumor Neither Shrinking nor Growing


Question

I would appreciate suggestions regarding treatment for the following case.

Patient is Male age 44.

June 2010 – Prolactin level at 251 ng/ml with total testosterone 197 ng/dl and TSH 6.65 ulU/ml normal T3 and T4 . Subsequent MRI revealed tumor 1.9 x 1.8 x 1.5 cm with extension into the left cavernous sinus and rightward displacement of the pituitary gland and stalk deviation. Cortisol and other hormones for pituitary reserve were normal. Initial diagnosis of Prolactinoma with treatment of .5mg of Cabergoline in addition to Levothyroxine, and Testosterone replacement therapy.

July 2010 – Prolactin levels dropped to 12.3, testosterone and TSH normal.

Dec 2010 – Prolactin 10.8, testosterone and TSH normal. MRI results – no gross change in lesion, measurement 2.0 x 1.5 x 1.6 cm.

April 2011 – Prolactin 11.2, testosterone and TSH normal.

Patient came under my care in Sept 2011.

Sept 2011 – Prolactin 8.3 ng/mL. MRI shows no change in size of the tumor. Complete MRI text.. “Pituitary: Stable size and morphology of the sella turcica. Intrasellar lesion is reidentified resulting in some expansion of the sella turcica. Gross stability in height and morphology of this intrasellar lesion relative to 12/30/2010. Again, portions of the lesion extend into the suprasellar cistern on the left side. Deviation of the pituitary stalk to the right is noted. Probable involvement of the medial aspect of the left cavernous sinus again noted, stable. Preserved flow voids of the cavernous and supraclinoid segments of the bilateral internal carotid arteries. Stable signal characteristics of this lesion. Soft tissue signal intensity noted on the unenhanced coronal T1 images. The T2 signal characteristics are also stable. Avid enhancement following contrast administration. This lesion currently measures 2.0 x 1.6 x 1.5 cm in the respective craniocaudal, AP and transverse dimensions. Suprasellar Cistern: No impingement on the optic chiasm present.Hypothalamus: No mass, signal abnormality, or abnormal enhancement.Cavernous Sinus: Signal voids of cavernous internal carotid arteries present. Meckel cave is bilaterally fluid filled.Brain: Ventricles and sulci are age appropriate. Midline and basal cisterns are preserved. No focal signal abnormality, mass effect, or abnormal enhancement present. No change.Skull/Extracranial Structures: No mass, signal abnormality, or abnormal enhancement.Impression: 1. No change from 12/30/2010. 2. Intrasellar solid mass reidentified with some stable extension into the suprasellar cistern on the left side in the medial aspect of the left cavernous sinus. 3. Routine whole brain MRI images unremarkable. Negative for acute CVA or enhancing intra-axial mass.”

At this point prolactin levels are normal on cabergoline0.5mg twice weekly dosage, the tumor is stable at 2 cm in its maximal dimension wit normal thyroid and testosterone levels on replacement . He had normal visual fields examination. He came to me looking for a third opinion. My diagnoses is a non functioning pituitary adenoma that caused elevation of the prolactin level by compression; since the tumor is not shrinking with normal prolactin level and therefore my recommendation will be surgery.

Would you consider a prolactin producing tumor that is resistant to treatment ? even though his prolactin level is now normal.

would increasing dosage present any chance of reducing the size of the tumor? Is surgery the best path of treatment at this time?

Thank you again for your support. M. Montoya , M.D.

Response

Based on pre-treatment data, your patient could most likely harbor a macroprolactinoma, as hyperprolactinemia secondary to pituitary stalk disconnection very seldom is above 100 ng/mL 1, unless associated with macroprolatinemia2. Furthermore, in the case of nonfunctioning pituitary macroadenomas we should expect very low or even undetectable serum prolactin levels during cabergoline therapy instead of normal values, even in low doses.

Concerning treatment, first of all I would suggest to withdraw testosterone therapy and, if still low, introduce clomiphene instead 3. As neurophtalmologic evaluation and MRI ruled out chiasma compression, medical treatment with cabergoline (in the same dose, as no clear data on the benefits of increasing doses in tumor shrinkage is available when prolactin is already within the normal range). Some prolactinomas may exhibit shrinkage in the long-term treatment. Of course surgery can be performed at any time. I also would advice to follow the patient with echocardiograms, as the issue of cardiac valvular disease in prolactinoma patients on cabergoline is still under debate 4.

Marc ello Bronstein, MD|

Wass JA , Karavitaki N . Nonfunctioning pituitary adenomas: the Oxford experience. Nonfunctioning pituitary adenomas: the Oxford experience. Nat Rev Endocrinol. 2009 Sep;5(9):519-22

Glezer A , Soares CR, Vieira JG, Giannella-Neto D, Ribela MT, Goffin V, Bronstein MD. Human macroprolactin displays low biological activity via its homologous receptor in a new sensitive bioassay. J Clin Endocrinol Metab. 2006 Mar;91(3):1048-55

Ribeiro RS, Abucham J . Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment. Eur J Endocrinol. 2009 Jul;161(1):163-9