Imaging AnalysisPublication Exclusive

Middle-aged man diagnosed with giant invasive prolactinoma

A 52-year-old man was referred to our clinic for the evaluation and management of a large pituitary mass. He went to the ED reporting 2 months of worsening intermittent and severe, squeezing occipital headaches that occurred two to 10 times daily.

A head CT scan in the ED showed a large pituitary macroadenoma demonstrating bony erosion and destruction of the sphenoid and dorsum sella bones of the sella turcica, which cradles the pituitary gland (Figure 1).

Exam, imaging

The patient was referred to the endocrine clinic. On review of systems, he reported no excessive growth or changes in ring or shoe size. He had nonspecific fatigue and an increased need for afternoon naps. He had three children, the youngest aged 13 years. He noted several years of reduced sexual interest and 2 to 3 months of gynecomastia. He reported no nocturia or polydipsia.

Physical exam was unremarkable except for gynecomastia without galactorrhea. In visual testing, peripheral fields on confrontation were normal. Laboratory testing showed an elevated prolactin of more than 17,000 ng/mL (normal, 0-15) and low luteinizing hormone 1 IU/L (normal, 1-9), follicle-stimulating hormone 1 IU/L (normal, 1-18), insulin-like growth factor I 49 µg/L (normal, 61-225) and total testosterone 87 ng/dL (normal, 270-1,070).

Stephanie L. Lee

We ordered an MRI with gadolinium and magnified and fine cuts of the sella. The MRI showed a 3 cm x 3.5 cm x 4.5 cm macroadenoma that diffusely enhanced with gadolinium and invaded into the left cavernous sinus and the superior right cavernous sinus (Figure 2). The tumor encased the left carotid artery. Superior extension of the macroadenoma was concerning for significant compression of the optic chiasm and indentation of the inferior aspect of the frontal lobe. Inferiorly, the tumor eroded into and filled the left sphenoid sinus. Formal visual field testing showed minimal left upper quadrant anopsia.

Diagnosing, treatment

The patient was diagnosed with a giant invasive prolactinoma; such tumors are larger than 4 cm in size and are associated with a serum prolactin greater than 1,000 ng/mL and clinical symptoms caused by the hyperprolactinemia or mass effect. This patient’s tumor fulfills all three of these criteria. Although the mass abutted the optic chiasm, his visual fields were nearly normal.

Figure 1. Sagittal CT scan without contrast. (A) Large invasive pituitary tumor. (B) Normal pituitary (bone window). The large pituitary tumor shows destruction of the bones forming the sella turcica and the clivus. The large mass extends and obliterates the sphenoid sinus. The pituitary (yellow arrow) sits in a depression (floor of the sella; green arrow) of the sphenoid bone bounded anteriorly and inferiorly by the sphenoid sinus and posteriorly by the dorsum sella (red arrow). The inferior extension of these bones is the clivus bone (blue arrow). The normal bone structures are shown on the normal CT scan in panel B.

Reprinted with permission from: Stephanie L. Lee, MD, PhD, ECNU.

The goal of treatment of a macroprolactinoma is to decrease the tumor size, reduce prolactin levels to allow normal gonadal function and improve visual field defects. Dopamine agonists are very effective in more than 90% of patients. Of note, therapy longer than 6 months may be needed to achieve the maximal reduction in prolactin levels in these huge tumors. Thus, the best treatment for prolactinoma even when it is a giant invasive prolactinoma is medical therapy with dopamine agonists. Surgical or gamma knife therapy would be considered only if there were progressive tumor enlargement, progressive vision loss or inability to normalize the prolactin level.

The patient was started on a dopamine agonist, cabergoline, 0.5 mg twice a week. After 1 month, his prolactin decreased to 517 ng/mL. He was symptomatically improved with less frequent headaches and increased energy. His dose of cabergoline was increase to 1 mg twice a week, and 2 months after starting treatment, the prolactin fell further to 165 ng/mL. At 3 months after initiation of therapy, his prolactin fell to 91 ng/mL, and the cabergoline dosage was increased to 1.5 mg twice a week, which has been maintained.

Figure 2. MRI scan of the pituitary with gadolinium contrast. (A) Coronal view. (B) Sagittal view. A large macroadenoma that enhances uniformly with gadolinium is seen replacing the pituitary gland. The tumor invades the cavernous sinus bilaterally and surrounds the carotid artery (C; carotid siphon) in the cavernous sinus. The sphenoid sinus is not seen, and the area inferior to the adenoma is the posterior pharynx (* in A and B). In the sagittal view the mass extends superiorly and deforms the surface of the frontal lobe and inferiorly to obliterate the sphenoid sinus.

A repeat pituitary protocol MRI with gadolinium after 6 months of therapy showed the prolactinoma decreased in size but remained mildly enlarged, measuring 1.6 cm x 0.8 cm x 1.2 cm. The optic chiasm was unremarkable with no mass effect noted. The patient reports no headaches and has regained normal pituitary function, including his pituitary-gonadal axis. There are no plans for transsphenoidal surgery at this time. He will be maintained on life-long dopamine-agonist therapy. With invasive macroprolactinomas, “drug holidays” are not recommended to test for spontaneous tumor regression because such regression is highly unlikely.

A 52-year-old man was referred to our clinic for the evaluation and management of a large pituitary mass. He went to the ED reporting 2 months of worsening intermittent and severe, squeezing occipital headaches that occurred two to 10 times daily.

A head CT scan in the ED showed a large pituitary macroadenoma demonstrating bony erosion and destruction of the sphenoid and dorsum sella bones of the sella turcica, which cradles the pituitary gland (Figure 1).

Exam, imaging

The patient was referred to the endocrine clinic. On review of systems, he reported no excessive growth or changes in ring or shoe size. He had nonspecific fatigue and an increased need for afternoon naps. He had three children, the youngest aged 13 years. He noted several years of reduced sexual interest and 2 to 3 months of gynecomastia. He reported no nocturia or polydipsia.

Physical exam was unremarkable except for gynecomastia without galactorrhea. In visual testing, peripheral fields on confrontation were normal. Laboratory testing showed an elevated prolactin of more than 17,000 ng/mL (normal, 0-15) and low luteinizing hormone 1 IU/L (normal, 1-9), follicle-stimulating hormone 1 IU/L (normal, 1-18), insulin-like growth factor I 49 µg/L (normal, 61-225) and total testosterone 87 ng/dL (normal, 270-1,070).

Stephanie L. Lee

We ordered an MRI with gadolinium and magnified and fine cuts of the sella. The MRI showed a 3 cm x 3.5 cm x 4.5 cm macroadenoma that diffusely enhanced with gadolinium and invaded into the left cavernous sinus and the superior right cavernous sinus (Figure 2). The tumor encased the left carotid artery. Superior extension of the macroadenoma was concerning for significant compression of the optic chiasm and indentation of the inferior aspect of the frontal lobe. Inferiorly, the tumor eroded into and filled the left sphenoid sinus. Formal visual field testing showed minimal left upper quadrant anopsia.

Diagnosing, treatment

The patient was diagnosed with a giant invasive prolactinoma; such tumors are larger than 4 cm in size and are associated with a serum prolactin greater than 1,000 ng/mL and clinical symptoms caused by the hyperprolactinemia or mass effect. This patient’s tumor fulfills all three of these criteria. Although the mass abutted the optic chiasm, his visual fields were nearly normal.

Figure 1. Sagittal CT scan without contrast. (A) Large invasive pituitary tumor. (B) Normal pituitary (bone window). The large pituitary tumor shows destruction of the bones forming the sella turcica and the clivus. The large mass extends and obliterates the sphenoid sinus. The pituitary (yellow arrow) sits in a depression (floor of the sella; green arrow) of the sphenoid bone bounded anteriorly and inferiorly by the sphenoid sinus and posteriorly by the dorsum sella (red arrow). The inferior extension of these bones is the clivus bone (blue arrow). The normal bone structures are shown on the normal CT scan in panel B.

Reprinted with permission from: Stephanie L. Lee, MD, PhD, ECNU.

The goal of treatment of a macroprolactinoma is to decrease the tumor size, reduce prolactin levels to allow normal gonadal function and improve visual field defects. Dopamine agonists are very effective in more than 90% of patients. Of note, therapy longer than 6 months may be needed to achieve the maximal reduction in prolactin levels in these huge tumors. Thus, the best treatment for prolactinoma even when it is a giant invasive prolactinoma is medical therapy with dopamine agonists. Surgical or gamma knife therapy would be considered only if there were progressive tumor enlargement, progressive vision loss or inability to normalize the prolactin level.

The patient was started on a dopamine agonist, cabergoline, 0.5 mg twice a week. After 1 month, his prolactin decreased to 517 ng/mL. He was symptomatically improved with less frequent headaches and increased energy. His dose of cabergoline was increase to 1 mg twice a week, and 2 months after starting treatment, the prolactin fell further to 165 ng/mL. At 3 months after initiation of therapy, his prolactin fell to 91 ng/mL, and the cabergoline dosage was increased to 1.5 mg twice a week, which has been maintained.

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Figure 2. MRI scan of the pituitary with gadolinium contrast. (A) Coronal view. (B) Sagittal view. A large macroadenoma that enhances uniformly with gadolinium is seen replacing the pituitary gland. The tumor invades the cavernous sinus bilaterally and surrounds the carotid artery (C; carotid siphon) in the cavernous sinus. The sphenoid sinus is not seen, and the area inferior to the adenoma is the posterior pharynx (* in A and B). In the sagittal view the mass extends superiorly and deforms the surface of the frontal lobe and inferiorly to obliterate the sphenoid sinus.

A repeat pituitary protocol MRI with gadolinium after 6 months of therapy showed the prolactinoma decreased in size but remained mildly enlarged, measuring 1.6 cm x 0.8 cm x 1.2 cm. The optic chiasm was unremarkable with no mass effect noted. The patient reports no headaches and has regained normal pituitary function, including his pituitary-gonadal axis. There are no plans for transsphenoidal surgery at this time. He will be maintained on life-long dopamine-agonist therapy. With invasive macroprolactinomas, “drug holidays” are not recommended to test for spontaneous tumor regression because such regression is highly unlikely.