Rapid reduction with cystic transformation of invasive giant prolactinoma following short term low dose cabergoline

Sir,

Dopamine agonists are the treatment of choice for prolactinomas and surgery is warranted only when the response to medical therapy is poor, not tolerated, or in those with compromised vision or with extensive invasion.[1] Giant prolactinomas (GPs) represent a rare end of the spectrum of prolactinomas, more common in males, which have large size (>40 mm), predominant suprasellar and cranial invasion, with very high prolactin levels (>1000 ng/ ml).[1] It has been suggested previously that patients with GPs often require larger than the conventional doses of cabergoline with frequent dose escalation for clinical and biochemical response.[2]

MRI of the brain in a 60-year-old man complaining of headache, vomiting, blurring of vision, and erectile dysfunction for 6 months revealed pituitary macroadenoma (442 × 531 × 338 mm) with destruction and effacement of sella, invasion into bilateral cavernous sinuses, frontal lobe, left temporal lobe (solid black arrow), pons, compressing the optic chiasma and third ventricle (hollow black arrow) [Figures 1a and 2–4]. Perimetry showed bitemporal hemianopia. Hormonal evaluation revealed elevated serum prolactin (1592 ng/ml), low serum testosterone (252 ng/ dl; normal range 288-915 ng/ml), LH (<0.1 mIU/L) and FSH (0.14 mIU/L), with normal IGF-1 (136 ng/ml; normal range 81-225 ng/ml), 8 am cortisol (23 μg/dl) and thyroid function (FT4-1.12 ng/ dl; TSH-2.31 μIU/ml). A diagnosis of invasive GP with secondary hypogonadism was made and cabergoline was started at 0.25 mg/week and increased to 1 mg/week over 3 weeks as the patient refused surgery. There was rapid resolution of headache over 2 weeks, with improvement in vision over 3 months. Serum prolactin reduced to 192 ng/ml at 8 months followed by normalization (12 ng/ml) at 14 months of therapy. Repeat pituitary imaging after 14 months revealed normal-sized anterior pituitary (13 × 7 × 6 mm) with irregular margins located posteriorly in the sella (99.31% size reduction) with anterior sella containing cystic areas with contrast enhancement of margins suggestive of cystic degeneration of prolactinoma (white arrow) [Figures 1b and 5–7]. Repeat hormonal evaluation showed normal serum 8 am cortisol (13 μg/dl) and thyroid function (FT4 - 1.24 ng/dl; TSH - 2.21 μIU/ml) with low IGF-1 (66 ng/ml; normal range 75-212 ng/ml), normal testosterone (472 ng/dl). He was on thrice-weekly intramuscular testosterone. Cabergoline was continued at 0.5 mg/week.

Figure 1.

(a) T1W MRI of brain showing pituitary macroadenoma involving bilateral cavernous sinus, frontal lobe, temporal lobe, and compressing the optic chiasma. (b) MRI of brain showing resolution of pituitary macroadenoma with cystic transformation

Figure 2.

Invasive giant prolactinoma invading the frontal lobe anteriorly (black arrow) and impinging on the pons posteriorly (white arrow)

Figure 4.

Invasive giant prolactinoma showing invasion into the left temporal lobe (black arrow) and posteriorly compressing the pons (white arrow)

Figure 5.

Posterior cuts of coronal sections of MRI brain (Dec 2011) showing normal-sized pituitary (solid white arrow) surrounded by cystic fluid (hollow white arrow)

Figure 7.

T2W MRI brain sagittal section (Dec 2011) showing enlarged effaced partially empty sella predominantly containing CSF (white arrow) with normal pituitary seen posteriorly (black arrow)

Figure 3.

MRI brain (sagittal section) showing invasive giant prolactinoma with effacement of sella with predominant suprasellar component extending anteriorly, superiorly and posteriorly

Figure 6.

A further posterior cut of coronal section showing the normal-sized pituitary with irregular margins

Complete surgical resection and cure is difficult for macroprolactinomas due to the common involvement of the surrounding structures.[3] Normal prolactin, resumption of menses and cessation of galactorrhea was observed in only 31% patients with macroprolactinoma undergoing surgery.[3] Several recent reports have suggested encouraging results of dopamine agonists in the management of GPs. Shimon, et al. showed that cabergoline for 1-50 months normalized prolactin in 8 out of 10 patients with GPs.[1] In another study of 10 patients of GPs, after a mean 39 months of cabergoline, 5 patients had normal prolactin, and the remaining 5 had a 94% reduction from baseline.[4] Acharya, et al. demonstrated normalization of serum prolactin in 7 out of 10 patients of GP with 49% reduction in size following mean therapy of 8.8 months. An important observation in that study was an improvement/normalization of visual field defects in all the 7 patients who had this defect.[5]

Hence, the idea of presenting this case is to highlight that cabergoline should be the first-line therapy and the treatment of choice even in patients with invasive GPs with extensive locoregional spread and visual field compromise as outcomes are usually excellent.