Challenges and controversies in the treatment of prolactinomas

Abstract

Recent studies have reported a higher prevalence of pituitary tumors than previously thought. Among these tumors, prolactinomas occur in up to 66% of cases. Since the mid-1980s, the widespread use of dopamine agonists has facilitated the management of the majority of prolactinomas, allowing biological and tumoral control in most cases. The less frequent cases of resistant prolactinomas remain challenging despite a multimodal therapy approach. The understanding of genetic alterations in familial and aggressive pituitary tumors provides new perspectives in the management of some prolactinomas. Genetic screening should be considered, particularly in familial cases but also in young patients with macroprolactinomas, as some mutations can predict potential aggressiveness.

Keywords::

• AIP
• dopamine agonists
• FIPA
• prolactinomas
• resistance

Financial & competing interests disclosure

The authors report receiving research funding in the form of educational grants from Ipsen and Pfizer.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Prolactinomas represent the majority of pituitary adenomas.

• With cabergoline, biological and radiological control is usually rapid and easily achieved.

• Although resistance to medical treatment is rare, a clear definition needs to be validated, allowing better study of these particular cases. In general, resistance to dopamine agonists is more frequent in males, older individuals, those with invasion of the cavernous sinus, those with low dopamine 2 receptor subtype expression and potentially can be associated with germline AIP or MEN1 mutations.

• The use of cabergoline at appropriate doses in the endocrine setting does not have a consistent negative repercussion on cardiac status, although some cases of mild valvulopathy have been reported.

• Withdrawal of medical treatment is still debated. Recurrence rate is variable, according to various studies, with recurrence being more common in larger tumors. Nontumoral hyperprolactinemia and the use of cabergoline can be considered as good prognostic factors to evaluate the possibility of treatment discontinuation.

• Pituitary carcinomas are rare but very challenging to manage, with frequent recurrences and multimodal therapy approaches needed. Temozolomide is a particularly promising drug in these particular cases.

Notes

Reprinted with permission from [120] © Elsevier (1998).