UpToDate: Giant Prolactinoma

Giant prolactinoma

Their definition should be restricted to pituitary adenomas with a diameter of 40 mm or more, significant extrasellar extension, very high prolactin concentrations (usually above 1000 µg/L), and no concomitant GH or ACTH secretion.


They represent only 2-3 % of all prolactinomas.

Giant prolactinoma are rare tumours. They are much more frequent in young to middle-aged men than in women with a male to female ratio of about 9:1. 1) 2).


Endocrine symptoms are often present but overlooked for a long period of time and diagnosis is eventually made when neurological complications arise from massive extension into the surrounding structures, leading to cranial nerve palsy, hydrocephalus, temporal lobe epilepsy or exophthalmos.

Prolactin concentrations are usually in the range of 1,000 to 100,000 µg/L, but may be underestimated by the so-called ‘high dose hook effect’.


Sexual dysfunction is a hallmark of prolactinomas in males. Tumors that co-secrete prolactin and LH are extremely rare and and only a case reported in an adult male. In this case, normal testosterone was maintained by intact LH levels even in the face of the highest prolactin level reported to date 3).


As in every prolactinoma, dopamine agonists are the first-line treatment allowing rapid alleviation of neurologic symptoms in the majority of the cases, a significant reduction of tumour size in three-fourths; of the patients and PRL normalization in 60-70%. These extensive tumours are usually not completely resectable and neurosurgery has significant morbidity and mortality. It should therefore be restricted to acute complications such as apoplexy or leakage of cerebrospinal fluid (often induced by medical treatment), or to patients with insufficient tumoral response or progression. Irradiation and temozolomide are useful adjuvant therapies in a subset of patients with aggressive/invasive tumours which are not controlled despite combined medical and surgical treatments. Because of these various challenges, it needs a multidisciplinary management in expert centres 4).

Case series

In 42 cases, male patients accounted for 71.4% of this series and were relatively younger (35.70±2.42 vs. 52.00±3.55 years, p=0.0011) and harbored bigger tumors (14.57 vs. 7.74 cm3, p=0.0179) compared to females. Almost all of these tumors showed suprasellar extension (97.6%) and cavernous sinus invasion (92.9%). Dopamine agonist represented an efficient method to control PRL concentrations (98.8%) and reduce tumor burdens (81.2 %). PRL normalization was detected in 13 out of the 27 patients initially treated with bromocriptine (BRC) whereas none of the 14 patients with first-line operation gained a normalization of PRL concentration after surgery. Although there was no reliable predictor of tumor response, First PRL reduction was a predictive criterion for the nadir PRL level during the long-time period of follow-up for first-line bromocriptine treatment. In conclusion, patients with giant prolactinomas did not gain more benefits from initial surgery. Dopamine agonist (BRC) should be first-line treatment for giant prolactinomas whereas operation merely served as a remedy for acute compression symptoms and dopamine agonist resistance. Consecutive monitoring of serum PRL levels in the early stage of initial BRC treatment is useful for evaluation of therapeutic effect and further therapeutic decision 5).

16 patients (43.7 % women); mean age at diagnosis: 42.1 ± 21 years. The most frequent presentation was compressive symptoms. The delay in diagnosis was higher in women (median of 150 months vs. 12 in men; p = 0.09). The mean maximum tumor diameter at diagnosis was 56.9 ± 15.5 mm, and mean prolactin levels were 10,995.9 ± 12,157.8 ng/mL. Dopamine agonists were the first-line treatment in 11 patients (mean maximum dose: 3.9 ± 3.2 mg/week). Surgery was the initial treatment in five patients and the second-line treatment in six. Radiotherapy was used in four cases. All patients but one, are still with dopamine agonists. After a mean follow-up of 9 years, prolactin normalized in 7/16 patients (43.7 %) and 13 patients (81 %) reached prolactin levels lower than twice the upper limit of normal. Mean prolactin level at last visit: 79.5 ± 143 ng/mL. Tumor volume was decreased by 93.8 ± 11.3 %, and final maximum tumor diameter was 18.4 ± 18.8 mm. Three patients are actually tumor free. Giant prolactinomas are characterized by a large tumor volume and extreme prolactin hypersecretion. Multimodal treatment is frequently required to obtain biochemical and tumor control 6).



Shrivastava RK, Arginteanu MS, King WA, Post KD. Giant prolactinomas:clinical management and long-term follow up. J Neurosurg. 2002;97:299–306. doi: 10.3171/jns.2002.97.2.0299.

Corsello SM, Ubertini G, Altomare M, Lovicu RM, Migneco MG, Rota CA, Colosimo C. Giant prolactinomas in men: efficacy of cabergoline treatment. Clin Endocrinol. 2003;58:662–670. doi: 10.1046/j.1365-2265.2003.01770.x.

Tamagno G, Daly AF, Deprez M, Vroonen L, Andris C, Martin D, Beckers A. Absence of hypogonadism in a male patient with a giant prolactinoma: a clinical paradox. Ann Endocrinol (Paris). 2008 Feb;69(1):47-52. Epub 2007 Dec 20. PubMed PMID: 18082643.

Maiter D, Delgrange E. The challenges in managing giant prolactinomas. Eur J Endocrinol. 2014 Feb 17. [Epub ahead of print] PubMed PMID: 24536090.

Lv L, Hu Y, Yin S, Zhou P, Yang Y, Ma W, Zhang S, Wang X, Jiang S. Giant Prolactinomas: Outcomes of Multimodal Treatments for 42 Cases with Long-Term Follow-Up. Exp Clin Endocrinol Diabetes. 2018 Jun 25. doi: 10.1055/a-0597-8877. [Epub ahead of print] PubMed PMID: 29940665.

Andujar-Plata P, Villar-Taibo R, Ballesteros-Pomar MD, Vidal-Casariego A, Pérez-Corral B, Cabezas-Agrícola JM, Álvarez-Vázquez P, Serramito R, Bernabeu I. Long-term outcome of multimodal therapy for giant prolactinomas. Endocrine. 2016 Oct 4. PubMed PMID: 27704480.

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