Prolactinoma in childhood and adolescence—Tumour size at presentation predicts management strategy: Single centre series and a systematic review and meta‐analysis

Abstract

Objective To report the clinical presentation, management and outcomes of young patients with prolactinomas (<20 years) and conduct a systematic review and meta‐analysis. Patients and Design Clinical, biochemical and radiological data (1996‐2018) were collected from our centre. A systematic review and meta‐analysis of published literature (1994‐2019) on prolactinoma (age <20 years) were conducted. Both random and fixed effects meta‐analysis were used to pool outcomes across studies. Results 1 Case series Twenty‐two patients (14 females) were identified; median age at diagnosis 15.7 years (range 13‐19); 12 patients (6 females) had a macroprolactinoma. Seven patients (macroprolactinoma‐6) had associated pituitary hormone deficiencies at presentation. Five patients (4 males) underwent surgical resection due to poor response to cabergoline or apoplexy. Patients undergoing surgery had larger tumours (p < .02) and higher serum prolactin concentration (p < .005). All patients with macroprolactinoma >20 mm required surgical intervention. Results 2 Systematic review and meta‐analysis We selected 11 studies according to strict inclusion criteria describing 275 patients. Macroprolactinoma was more common in girls (78.7% [95% CI 70.5‐85.9]) than boys and was more frequent than microprolactinoma (56.6% [95% CI 48.4‐64.5]). In males, only 6/57 (10.5%) of tumours were microprolactinoma as compared to 102/198 (51.5%) microprolactinoma in females (risk difference −0.460; [95% CI −0.563 to −0.357]; p < .001). Surgery was first‐line therapy in 18.9% patients, with another 15.4% requiring it as a second line (overall 31.3%). Conclusions Macroprolactinoma, particularly if >20 mm, usually requires multimodal therapy including surgical intervention. While overall prolactinomas in <20 years age group are more common in females, the proportion of macroprolactinoma vs microprolactinoma is greater in males, particularly for large invasive tumours. Microprolactinoma is a rare diagnosis in adolescent males.

Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomes

“…19 Moreover, >80% of patients with macroadenomas in our study were 276 female, and this contrasts with the occurrences of sporadic macroprolactinomas in children and adolescents, 277 which are more common in males. 21 Furthermore, ~50% of patients with macroadenomas did not respond 278 to medical therapy and required surgical treatment. This is consistent with a report of pituitary adenomas 279 in MEN1 patients, compared to non-MEN1 pituitary tumors, being less responsive to medical therapy and 280 more aggressive, 22 although another study, which excluded pediatric patients, reported that MEN1-related 281 prolactinomas rarely required surgery.…”

The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) gene

“…Prolactinomas are the most frequently encountered pituitary adenoma in clinical practice ( 1 , 20 ). In children, adolescents and young adults, prolactinomas are also the most common pituitary adenoma ( 21 ). Most present as microadenomas in fertile women that are responsive to labelled doses of cabergoline ( 2 ).…”

A scoping review to understand the indications, effectiveness, and limitations of cabergoline in radiological and biochemical remission of prolactinomas

“…[ 38 39 40 ] However, prolactinomas perform differently with medical management in patients lesser than 20 years of age, where macroproactinemia requires multimodal therapy, including surgical intervention. [ 44 ]…”

“…In the systematic review and meta-analysis of 22 patients aged less than 20 years with prolactinoma, the authors found that macroprolactinoma (size > 20 mm) is more likely to require multimodality therapy, including surgical intervention. [ 44 ] These patients usually have larger tumors and prolactin levels, and are usually not responsive to cabergoline therapy. However, even giant prolactinomas are shown to be responsive to cabergoline therapy in adults.…”