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Prolactin-secreting pituitary tumors. Rosario Pivonello Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy. Epidemiology.
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Prolactin-secreting pituitary tumors Rosario Pivonello Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy
Epidemiology • 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.
Clinical presentation Women Galactorrhea Oligo-amenhorrea Infertility Hypogonadism Smaller tumors Men Galactorrhea Decreased libido Erectyle dysfunction Hypogonadism Larger tumors Both Headache Visual impairment
Objectives 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 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 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.
Basal 1 week 4 weeks 550 μg/L 55 μg/L 1180 μg/L Early Changes of Prolactinomas After Cabergoline
Basal 1 week 1 month
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) Spontaneous Regression of Prolactinomas Vast majority microprolactinomas
Cabergoline Withdrawal: Inclusion Criteria • 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 Colao et al. N Engl J Med. 2003;349:2023.
Recurrence rate 100 75 Recurrence of hyperprolactinemiaafter withdrawal (%) 50 NTH 25 Micro MRI negative Remnant micro Macro MRI negative Remnant macro P=0.0009 0 0 12 24 36 48 60 Months Colao et al. N Engl J Med. 2003;349:2023.
Summary 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.
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