Giant Prolactinoma in Men: Clinical Features and Therapeutic Outcomes

Abstract

The aim of the study was to evaluate the clinical features and long-term therapeutic outcome of giant prolactinoma (gPRLoma) in men and to compare them with those of a group of male patients with non-gPRL macroprolactinomas (non-gPRLomas). A retrospective and multicenter study of gPRLomas in men diagnosed in a 20-year period was performed. Clinical data and treatment outcome were registered. The diagnosis of gPRLoma was established when the maximal tumor diameter was ≥40 mm or the tumor had ≥20 mm of suprasellar extension associated to hyperprolactinemia (PRL>1000 ng/ml). Non-gPRLoma was considered when tumor diameter was  ≥ 10 mm and<40 mm associated to hyperprolactinemia (PRL≥200 ng/ml). Twenty-three patients with gPRLoma (age 38.3±13.5 years) followed for at least 3 months (follow-up 87.1±60.5 months, range 3–211 months) were evaluated. A group of 42 patients with non-gPRLoma (age 42±16.6 years; NS; follow-up 89±65.9 months, range 3–222 months; NS) served as a control group. More than half (56.5%) of the gPRLoma patients were younger than 40 years at diagnosis. Visual disturbances were significantly more common in gPRLoma than in non-gPRLoma patients (65.2 vs. 25.6%; p=0.004). Prevalence of hypopituitarism was similar in both groups of patients (73.9% vs. 80.9%; gPRLoma vs non-gPRLoma; NS). Serum PRL concentrations were significantly higher in gPRLoma than in non-gPRLoma patients [median (IR), 3978 ng/ml (1179–9012) vs. 907 ng/ml (428–3119); p<0.001]. Maximum tumor diameter in gPRLomas was 4.8±0.8 cm and 2.4±0.7 cm in non-gPRLoma (p<0.001). All patients were treated with dopamine agonists (DA). Twelve (52.2%) gPRLoma patients and 32 (73.8%) non-gPRLoma patients were treated with DA as monotherapy (p=0.045). Surgery was used in 12 (52.2%) gPRLoma patients and in 12 (28.6%) non-gPRLoma patients (p=0.054). Lastly, radiotherapy was used in 5 (21.7%) gPRLoma patients and in 6 (14.2%) non-gPRLoma patients (NS). At last visit, PRL was similar in both groups of patients [16 ng/ml (4–30) vs. 11 ng/ml (4–25); gPRLomas vs. non-gPRLomas; ns] and tumor size decreased significantly (p<0.001) in both groups of patients. Clinical cure (maintained normoprolactinemia without therapy for>1 year and no radiological evidence of pituitary tumor) was achieved in 2 (8.7%) gPRLoma patients and in 2 (4.8%) non-gPRLoma patients (NS). gPRLomas in men are usually diagnosed at a mean age of 40 years, an age similar to that of non-gPRLomas. The only clinical difference with non-gPRLomas is their greater prevalence of visual disturbances. The therapeutic approaches and tumor outcomes were similar to those obtained in patients with non-gPRLomas. Complete cure in gPRLoma is rare, but similar to that achieved in non-gPRLomas, reached in less than 10% of patients.

Key words

giant prolactinoma - men - macroprolactinoma - prolactin - hypopituitarism

• References

• 1 Molitch ME. Medical treatment of prolactinomas. Endocrinol Metab Clin North Am 1999; 28: 143-169
• 2 Mindermann T, Wilson CB. Age-related and gender-related occurrence of pituitary adenomas. Clin Endocrinol (Oxf) 1994; 41: 359-364
• 3 Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J. Sex-related difference in the growth of prolactinomas: A clinical and proliferation marker study. J Clin Endocrinol Metab 1997; 82: 2102-2107
• 4 Davis JR, Sheppard MC, Heath DA. Giant invasive prolactinoma: A case report and review of nine further cases. Q J Med 1990; 74: 227-238
• 5 Shrivastava RK, Arginteanu MS, King WA, Post KD. Giant prolactinomas: Clinical management and long-term follow up. J. Neurosurg 2002; 97: 299-306
• 6 Corsello SM, Ubertini G, Altomare M, Lovicu RM, Migneco MG, Rota CA, Colosimo C. Giant prolactinomas in men: Efficacy of cabergoline treatment. Clin Endocrinol (Oxf) 2003; 58: 662-670
• 7 Moraes AB, Silva CM, Vieira Neto L, Gadelha MR. Giant prolactinomas: The therapeutic approach. Clin Endocrinol (Oxf) 2013; 79: 447-456
• 8 Shimon I, Jallad RS, Fleseriu M, Yedinak CG, Greenman Y, Bronstein MD. Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors. Eur J Endocrinol 2015; 172: 707-713
• 9 Maiter D, Delgrange E. Therapy of endocrine disease: the challenges in managing giant prolactinomas. Eur J Endocrinol 2014; 170: R213-R227
• 10 Raverot G, Burman P, McCormack AI, Heaney AP, Petersenn S, Popovic V, Trouillas J, Dekkers O. European Society of Endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol 2018; 178: G1-G24
• 11 Shimon I, Benbassat C, Hadani M. Effectiveness of long-term cabergoline treatment for giant prolactinoma: Study of 12 men. Eur J Endocrinol 2007; 156: 225-231
• 12 Almalki MH, Buhary B, Alzahrani S, Alshahrani F, Alsherbeni S, Alhowsawi G, Aljohani N. Giant prolactinomas: Clinical manifestations and outcomes of 16 Arab cases. Pituitary 2015; 18: 405-409
• 13 Espinosa E, Sosa E, Mendoza V, Ramirez C, Melgar V, Mercado M. Giant prolactinomas: Are they really different from ordinary macroprolactinomas?. Endocrine 2016; 52: 652-659
• 14 Shimon I, Sosa E, Mendoza V, Greenman Y, Tirosh A, Espinosa E, Popovic V, Glezer A, Bronstein MD, Mercado M. Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas. Pituitary 2016; 19: 429-436
• 15 Andujar-Plata P, Villar-Taibo R, Ballesteros-Pomar MD, Vidal-Casariego A, Perez-Corral B, Cabezas-Agricola JM, Alvarez-Vazquez P, Serramito R, Bernabeu I. Long-term outcome of multimodal therapy for giant prolactinomas. Endocrine 2017; 55: 231-238
• 16 Delgrange E, Raverot G, Bex M, Burman P, Decoudier B, Devuyst F, Feldt-Rasmussen U, Andersen M, Maiter D. Giant prolactinomas in women. Eur J Endocrinol 2013; 170: 31-38
• 17 Iglesias P, Bernal C, Villabona C, Castro JC, Arrieta F, Diez JJ. Prolactinomas in men: A multicentre and retrospective analysis of treatment outcome. Clin Endocrinol (Oxf) 2012; 77: 281-287
• 18 Chattopadhyay A, Bhansali A, Masoodi SR. Long-term efficacy of bromocriptine in macroprolactinomas and giant prolactinomas in men. Pituitary 2005; 8: 147-154
• 19 Yu C, Wu Z, Gong J. Combined treatment of invasive giant prolactinomas. Pituitary 2005; 8: 61-65
• 20 Cho EH, Lee SA, Chung JY, Koh EH, Cho YH, Kim JH, Kim CJ, Kim MS. Efficacy and safety of cabergoline as first line treatment for invasive giant prolactinoma. J Korean Med Sci 2009; 24: 874-878