Evaluation of therapy with cabergoline in men with macroprolactinoma

Elżbieta Andrysiak‑Mamos, Agnieszka Kaźmierczyk‑Puchalska, Ewa Żochowska, Elżbieta Sowińska-Przepiera, Leszek Sagan, Ireneusz Kojder, Anhelli Syrenicz

Abstract


Introduction: Pituitary gland adenomas producing prolactin are one of the commonest hormonally active tumours. Pharmacological treatment using of dopamine receptors agonists is the therapy of choice in a case of prolactinoma. Bromocriptine, which causes numerous side‑effects is the most commonly used drug. Recently, good results of therapy have been achieved with cabergoline – a selective dopamine receptor agonist with prolonged time of action.

The aim of the study was to evaluate therapy with cabergoline of men with macroprolactinoma based on clinical, hormonal and radiological examinations.

Material and methods: Ten men aged 18–65 (mean 41.9 ±15.01 years) with the presence of a pathological mass in the pituitary gland sized between 16.7 and 40.5 mm (mean 29.8 ±9.38 mm) and an elevated prolactin (PRL) level of between 37.3 and 4700 ng/mL (mean 1608.2 ±1771.6 ng/mL) were included in the study. The PRL and other trophic hormones levels were evaluated after 1, 3, 6 and 12 months, and tumour size was evaluated by magnetic resonance imaging examination after 12 months of therapy with cabergoline.

Results: Therapy with cabergoline led to remission of headaches, visual acuity correction, and a significant improvement in libido and erection in all patients. In 90% of patients, PRL normalisation was achieved, just the initial months of therapy. The mean PRL serum concentrations were before, and after 1, 3, 6 and 12 months of therapy respectively, 1608.2 ±1771.6 ng/mL and 263.4 ±223.4, 136.1 ±244.7, 91.31 ±105.5 and 27.5 ±57.7 ng/mL. A significant tumour size reduction was observed: from 29.8 ±9.4 mm to 23.2 ±9.4 mm, a mean reduction of about 6 mm, or 25.1% (from 4–48.5%). No significant correlation between the mean tumour size and PRL level was observed before or during the treatment. A decreased testosterone level before the therapy was proven, and its gradual increase during the treatment was observed, but after 12 months no normal mean testosterone concentration was achieved.

Conclusions: 1. The administration of cabergoline to patients with macroprolactinoma is effective in reaching PRL level normalisation as well as in tumour size reduction. 2. Therapy with cabergoline significantly decreases the clinical symptoms of hyperprolactinemia and neurological and ophtalmological changes associated with the presence of a pathological lesion in the pituitary gland. 3. Tumour size is not a predictive factor for the effectiveness of therapy with cabergoline.


Keywords


macroprolactinoma; cabergoline; therapy evaluation

Full Text:

PDF

References


Gillam M.P., Molitch M.E., Lombardi G., Colao A.: Advances in the treatment of prolactinomas. Endocr Rev. 2006, 27 (5), 485–534.

Kars M., Dekkers O.M., Pereira A.M., Romijn J.A.: Update in prolactinomas. Neth J Med. 2010, 68 (3), 104–112.

Mindermann T., Wilson C.B.: Age‑related and gender‑related occurrence of pituitary adenomas. Clin Endocrinol (Oxf). 1994, 41 (3), 359–364.

Fernandez A., Karavitaki N., Wass J.A.: Prevalence of pituitary adenomas: a community‑based, cross‑sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf ). 2010, 72 (3), 377–382.

Ciccarelli A., Daly A.F., Beckers A.: The epidemiology of prolactinomas. Pituitary. 2005, 8 (1), 3–6.

De Rosa M., Zarrilli S., Di Sarno A., Milano N., Gaccione M., Boggia B. et al.: Hyperprolactinemia in men: clinical and biochemical features and response to treatment. Endocrine. 2003, 20 (1–2), 75–82.

Coppola A., Cuomo M.A.: Prolactinoma in the male. Physiopathological, clinical, and therapeutic features. Minerva Endocrinol. 1998, 23 (1), 7–16.

Walsh J.P., Pullan P.T.: Hyperprolactinaemia in males: a heterogeneous disorder. Aust NZ J Med. 1997, 27 (4), 385–390.

Corona G., Mannucci E., Fisher A.D., Lotti F., Ricca V., Balercia G. et al.: Effect of hyperprolactinemia in male patients consulting for sexual dysfunction. J Sex Med. 2007, 4 (5), 1485–1493.

Colao A., Sarno A.D., Cappabianca P., Briganti F., Pivonello R., Somma C.D. et al.: Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol. 2003, 148 (3), 325–331.

Melmed S., Casanueva F.F., Hoffman A.R., Kleinberg D.L., Montori V.M., Schlechte J.A. et al.: Endocrine Society. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin

Endocrinol Metab. 2011, 96 (2), 273–288.

Braucks G.R., Naliato E.C., Tabet A.L., Gadelha M.R., Violante A.H.: Clinical and therapeutic aspects of prolactinoma in men. Arq Neuropsiquiatr. 2003, 61 (4), 1004–1010.

Delgrange E., Raverot G., Bex M., Burman P., Decoudier B., Devuyst F. et al.: Giant prolactinomas in women. Eur J Endocrinol. 2013, 22, 170 (1), 31–38.

Maiter D., Delgrange E.: Therapy of endocrine disease: the challenges in managing g iant prolactinomas. Eur J Endocrinol. 2014, 170 (6), R213–227.

Wong A., Eloy J.A., Couldwell W.T., Liu J.K.: Update on prolactinomas. Part 2: Treatment and management strategies. J Clin Neurosci. 2015, 22 (10), 1568–1574.

Krysiak R., Okopień B., Marek B., Szkróbka W.: Gruczolak przysadki wydzielający prolaktynę. Przegl Lek. 2009, 66 (4), 198–205.

Child D.F., Nader S., Mashiter K., Kjeld M., Banks L., Fraser T.R.: Prolactin studies in “functionless” pituitary tumours. Br Med J. 1975, 1 (5958), 604–606.

Molitch M.E., Elton R.L., Blackwell R.E., Caldwell B., Chang R.J., Jaffe R. et al.: Bromocriptine as primary therapy for prolactin‑secreting macroadenomas:

results of a prospective multicenter study. J Clin Endocrinol Metab. 1985, 60 (4), 698–705.

Van‘t Verlaat J.W., Croughs R.J., Hendriks M.J., Bosma N.J.: Results of primary treatment with bromocriptine of prolactinomas with extrasellar extension. Can J Neurol Sci. 1990, 17 (1), 71–73.

Waśko R., Bocian‑Sobkowska J., Krzyżagórska E., Horst‑Sikorska W., Kozak W.: Wyniki leczenia bromokryptyną chorych z guzami przysadki typu prolaktinoma. Now Lek. 1994, 63 (5), 16–23.

Di Sarno A., Landi M.L., Cappabianca P., Di Salle F., Rossi F.W., Pivonello R. et al.: Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab. 2001, 86 (11), 5256–5261.

Cho K.R., Jo K.I., Shin H.J.: Bromocriptine therapy for the treatment of invasive prolactinoma: the single institute experience. Brain Tumor Res Treat. 2013, 1 (2), 71–77.

Colao A., Di Sarno A., Guerra E., De Leo M., Mentone A., Lombardi G.: Drug insight: Cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women. Nat Clin Pract Endocrinol Metab. 2006, 2 (4), 200–210.

Molitch M.E.: Pharmacologic resistance in prolactinoma patients. Pituitary. 2005, 8 (1), 43–52.

Biller B.M.K., Molitch M.E., Vance M.L., Cannistraro K.B., Davis K.R., Simons J.A. et al.: Treatment of prolactin secreting macroadenoma with once‑ weekly dopamine agonist cabergoline. J Clin Endocrinol Metab. 1996, 81 (6), 2338–2343.

Colao A., Di Sarno A., Landi M.L., Scavuzzo F., Cappabianca P., Pivonello R. et al.: Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab. 2000, 85 (6), 2247–2252.

Rastogi A., Bhansali A., Dutta P., Singh P., Vijaivergiya R., Gupta V. et al.: A comparison between intensive and conventional cabergoline treatment of newly diagnosed patients with macroprolactinoma. Clin Endocrinol (Oxf). 2013, 79 (3), 409–415.

Verhelst J., Abs R., Maiter D., van den Bruel A., Vandeweghe M., Velkeniers B. et al.: Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab. 1999, 84 (7), 2518–2522.

Colao A., Di Sarno A., Sarnacchiaro F., Ferone D., Di Renzo G., Merola B. et al.: Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J Clin Endocrinol Metab. 1997, 82 (3), 876–883.

Webster J.: Clinical management of prolactinomas. Baillieres Best Pract Res Clin Endocrinol Metab. 1999, 13 (3), 395–408.

Delgrange E., Maiter D., Donckier J.: Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine. Eur J Endocrinol. 1996, 134 (4), 454–456.

Wang A.T., Mullan R.J., Lane M.A., Hazem A., Prasad C., Gathaiya N.W. et al.: Treatment of hyperprolactinemia: a systematic review and meta‑analysis. Syst Rev. 2012, 24 (1), 33.

Wong A., Eloy J.A., Couldwell W.T., Liu J.K.: Update on prolactinomas. Part 1: Clinical manifestations and diagnostic challenges. J Clin Neurosci. 2015, 22 (10), 1562–1567.

Alsubaie S., Almalki M.H.: Cabergoline treatment in invasive giant prolactinoma. Clin Med Insights Case Rep. 2014, 19, 7, 49–51.

Ferrari C., Paracchi A., Mattei A.M., de Vincentiis S., D’Alberton A., Crosignani P.: Cabergoline in the long‑term

therapy of hyperprolactinemic disorders. Acta Endocrinol (Copenh). 1992, 126 (6), 489–494.

Colao A., Vitale G., Cappabianca P., Briganti F., Ciccarelli A., De Rosa M. et al.: Outcome of cabergoline treatment in men with prolactinoma: effects

of a 24‑month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis. J Clin Endocrinol Metab. 2004, 89 (4), 1704–1711.

Bevan J.S., Webster J., Burke C.W., Scanlon M.F.: Dopamine agonists and pituitary tumor shrinkage. Endocr Rev. 1992, 13 (2), 220–240.

Kopczak A., Renner U., Karl Stalla G.:. Advances in understanding pituitary tumors. F1000Prime Rep. 2014, 2 (6), 5.

Vilar L., Fleseriu M., Bronstein M.D.: Challenges and pitfalls in the diagnosis of hyperprolactinemia. Arq Bras Endocrinol Metabol. 2014, 58 (1), 9–22.

Zgliczyński W., Zdunowski P.: Hyperprolactinaemia – pitfalls in PRL assessment. Endokrynol Pol. 2005, 56 (6), 980–985.

Waśko R., Dymalska‑Kubasik L., Horst‑Sikorska W., Sowiński J.: Norprolac – a new drug in the treatment of prolactinoma type adenomas resistant to bromocriptine therapy. Endokrynol Pol. 1999, 50 (2), 139–146.

Zgliczyński W., Jeske W., Janik J. et al.: The use of Norprolac (Novartis) – a selective agonist of D2‑

dopamine receptor‑in treatment of macroprolactinoma. Endokrynol Pol. 2000, 51 (2), 225–236.

Pinzone J.J., Katznelson L., Danila D.C., Pauler D.K., Miller C.S., Klibanski A. et al.: Primary medical therapy of micro‑ and macroprolactinomas in men. J Clin Endocrinol Metab. 2000, 85 (9), 3053–3057.

Ono M., Miki N., Kawamata T., Makino R., Amano K., Seki T. et al.: Prospective study of high‑dose cabergoline treatment of prolactinomas in 150 patients. J Clin Endocrinol Metab. 2008, 93 (12), 4721–4727.

Corsello S.M., Ubertini G., Altomare M., Lovicu R.M., Migneco M.G., Rota C.A. et al.: Giant prolactinomas in men: efficacy of cabergoline treatment. Clin Endocrinol (Oxf). 2003, 58 (5), 662–670.

Pontikides N., Krassas G.E., Nikopoulou E., Kaltsas T.: Cabergoline as a first‑line treatment in newly diagnosed macroprolactinomas. Pituitary. 2000, 2 (4), 277–281.

Colao A., Di Sarno A., Landi M.L., Cirillo S., Sarnacchiaro F., Facciolli G. et al.: Long‑term and low‑dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab. 1997, 82 (11), 3574–3579.

Menucci M., Quiñones‑Hinojosa A., Burger P., Salvatori R.: Effect of dopaminergic drug treatment on surgical findings in prolactinomas. Pituitary. 2011, 14 (1), 68–74.

Manuchehri A.M., Sathyapalan T., Lowry M., Turnbull L.W., Rowland‑Hill C., Atkin S.L.: Effect of dopamine agonists on prolactinomas and normal pituitary

assessed by dynamic contrast enhanced magnetic resonance imaging (DCE‑ MRI). Pituitary. 2007, 10 (3), 261–266.

Vroonen L., Jaffrain‑Rea M.L., Petrossians P., Tamagno G., Chanson P., Vilar L. et al.: Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol. 2012, 167 (5), 651–662.

Maiter D., Primeau V.: 2012 update in the treatment of prolactinomas. Ann Endocrinol (Paris). 2012, 73 (2), 90–98.

Shimon I., Benbassat C., Hadani M.: Effectiveness of long‑term cabergoline treatment for giant prolactinoma: study of 12 men. Eur J Endocrinol. 2007, 156 (2), 225–231.

Bolko P., Jaskuła M., Waśko R., Wołuń M., Sowiński J.: The assessment of cabergoline efficacy and tolerability in patients with pituitary adenomas prolactinoma type. Pol Arch Med Wewn. 2003, 109 (5), 489–495.

Badal J., Ramasamy R., Hakky T., Chandrashekar A., Lipshultz L.: Case report: Persistent erectile dysfunction in a man with prolactinoma. F1000Res. 2015, 15, 4, 13.

De Rosa M., Zarrilli S., Vitale G., Di Somma C., Orio F., Tauchmanova’ L. et al.: Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence. J Clin Endocrinol Metab. 2004, 89 (2), 621–625.

Ciccarelli A., Guerra E., De Rosa M., Milone F., Zarrilli S., Lombardi G. et al.: PRL secreting adenomas in male patients. Pituitary. 2005, 8 (1), 39–42.

De Rosa M., Colao A., Di Sarno A., Ferone D., Landi M.L., Zarrilli S. et al.: Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur J Endocrinol. 1998, 138 (3), 286–293.

De Rosa M., Zarrilli S., Di Sarno A., Milano N., Gaccione M., Boggia B. et al.: Hyperprolactinemia in men: clinical and biochemical features and response to treatment. Endocrine. 2003, 20 (1–2), 75–82.

De Rosa M., Ciccarelli A., Zarrilli S., Guerra E., Gaccione M., Di Sarno A. et al.: The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males. Clin Endocrinol (Oxf). 2006,

(3), 307–313.




DOI: https://doi.org/10.21164/pomjlifesci.95

Copyright (c) 2015

License URL: https://creativecommons.org/licenses/by-nc-nd/3.0/pl/