Prolactin-secreting

pituitary tumorsRosario PivonelloDepartment of Molecular and Clinical

Endocrinology and Oncology, Federico II University, Naples, Italy

• Prolactinomas are the most frequent pituitary tumors,with an estimated prevalence in the adult population of 100 per million population

• Their frequency varies with age and sex, occurring most frequently in females between 20 and 50 yr old, when the ratio between the sexes is estimated to be 10:1.

• After the fifth decade of life, the frequency of prolactinomas is similar in both sexes.

• Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility.

Epidemiology

Clinical presentationWomen

GalactorrheaOligo-amenhorreaInfertilityHypogonadism

Smaller tumors

Men

GalactorrheaDecreased libido

Erectyle dysfunctionHypogonadism

Larger tumorsBoth

HeadacheVisual impairment

Tumor removal, preservation of normal residual function, and prevention of recurrences

Restoration of normal secretion

Relief of symptoms directly caused by PRL excess

Prevention of complications (hypogonadism, osteoporosis)

Colao and Lombardi. Lancet. 1998;352:1455.

Patients With Micro-, Macroadenomas, and Idiopathic Hyperprolactinemia Primarily Treated With Various Dopamine

Agonists

Dopamine Agonist Total

No. With Normal PRL

% With Normal PRL

Bromocriptine1 997 757 76

Pergolide2 98 85 87

Cabergoline3 612 544 89

1. Fossati, Friesen, Bergh, Badano, Crosignani, Horowitz, Molitch, Liuzzi, van der Heijden, Brue, Webster, Pascal-V, Pinzone, DiSarno, Sabuncu.

2. Horowitz, Kleinberg, L’Hermite, Freda.3. Ferrari, Ferrari, Webster, Pascal-V, Muratori, Verhelst, Pinzone, Di Sarno, Sabuncu.

Efficacy in PRL Normalization and Tumor Size in Patients With Macroprolactinoma

Bromocriptine(n=27)1

Pergolide(n=22)2

Cabergoline (n=26)3

Baseline PRL(µg/L)

2260 2938 1013

Normal PRL (% of pts)

66 68 100

≥50% tumor shrinkage (% of pts)

64 86 96

Time of assessment (mo)

12 mo 27 mo 24 mo

1. Molitch et al. J Clin Endocrinol Metab. 1985;60:698; 2. Freda et al. J Clin Endocrinol Metab. 2000;85:8; 3. Colao et al. J Clin Endocrinol Metab. 2000;85:2247.

Basal1180 μg/L

1 week550 μg/L

4 weeks55 μg/L

Early Changes of Prolactinomas After Cabergoline

Basal

1 week

1 month

Remission after cabergoline withdrawal

32% (Koppelman et al. Ann Intern Med. 1984;100:115)

33% (Jeffcoate et al. Clin Endocrinol (Oxf). 1996;45:299)

35% (Schlechte et al. J Clin Endocrinol Metab. 1989;68:412)

>55% (Sisam et al. Fertil Steril. 1987;48:67)

Normalization of PRL levels Tumor size at MRI No tumor Residual tumor but ≥50% tumor reduction of baseline size in

presence of a ≥5 mm distance from optic chiasm and in the absence of invasion of one or both cavernous sinuses or any other cerebral area

Follow-up after withdrawal at least 24 months

Cabergoline Withdrawal: Inclusion Criteria

Colao et al. N Engl J Med. 2003;349:2023.

Recurrence rate

0 12 24 36 48 600

25

50

75

100

NTHMicro MRI negativeRemnant microMacro MRI negativeRemnant macro P=0.0009

Months

Recu

rren

ce o

f hyp

erpr

olac

tinem

iaaft

er w

ithdr

awal

(%)

Colao et al. N Engl J Med. 2003;349:2023.

SummarySummary

Recurrence after cabergoline withdrawal was low in patients achieving tumor disappearance and did not differ in NTH (24%), micro-(26.2%) and macroprolactinomas (32.6%)

Recurrence of hyperprolactinemia was higher in patients still presenting small remnant tumors at MRI (41.5% in micro- and 77.5% in macroprolactinomas)

In no case of recurrence of hyperprolactinemia did tumor regrow or symptoms reappear

Colao et al. N Engl J Med. 2003;349:2023.Colao et al. N Engl J Med. 2003;349:2023.

Cardiac valve regurgitation after cabergoline withdrawal

Colao et al., JCEM 2008

Colao et al., JCEM 2008

No controversies on macroprolactinomas: 1st treatment is pharmacotherapy (cabergoline). Surgery indicated in patients with resistant adenomas

In young patients with microprolactinoma, the surgical choice should be offered based on the high likelihood of definitive cure (risk of tricuspid regurgitation!)

Patients fully responsive to bromocriptine or cabergoline who showed the disappearance of the tumor in MRI could be withdrawn from the drug and followed up.

There is an increased risk for asymptomatic tricuspid regurgitation that should be investigated more carefully

Conclusions

Thanks