Causes of Hyperprolactinemia in Acromegalic Patients and Clinical Correlations

Research Article

Austin J Endocrinol Diabetes. 2021; 8(1): 1080.

Causes of Hyperprolactinemia in Acromegalic Patients and Clinical Correlations

Matos T1, Gomes V1, Faria C2,3, Gomes A1,4, Nobre E1,4 and Bugalho MJ1,4*

1Endocrinology, Diabetes and Metabolism Department, North Lisbon University Hospital Center, Portugal

2Neurosurgery Department, North Lisbon University Hospital Center, Portugal

3Institute of Molecular Medicine Joao Lobo Antunes, Faculty of Medicine, University of Lisbon, Portugal

4Faculty of Medicine, University of Lisbon, Portugal

*Corresponding author: Bugalho MJ, Serviço de Endocrinologia, Diabetes e Metabolismo, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Av. Prof. Egas Moniz MB, 1649-028 Lisboa, Portugal

Received: January 22, 2021; Accepted: February 26, 2021; Published: March 05, 2021


Hyperprolactinemia in acromegalic patients may result either from cosecretion of growth hormone and prolactin by the tumour or from pituitary stalk compression. The occurrence of both conditions is possible. This study was designed aiming 1) to estimate the prevalence of each cause of hyperprolactinemia and its respective clinical course; 2) to compare the outcomes of patients with tumours staining only for growth hormone against tumours staining for both growth hormone and prolactin. 75 acromegalic patients submitted to transsphenoidal surgery between 1989 and 2018 were included. Patients were divided based on preoperative prolactin levels and immunostaining pattern. Statistical analysis was performed with SPSS version 23.

Hyperprolactinemia was documented in 22 out of 36 patients (61%). Stalk compression was the only underlying cause of hyperprolactinemia in 45% of cases. The levels of prolactin were not associated with the immunostaining pattern for prolactin. Clinical differences were not observed between hyperprolactinemic and normoprolactinemic patients, except for a higher frequency of cavernous sinus invasion (64% vs 29%, p=0,064), that reached the level of significance for the subgroup with macroadenomas staining exclusively for growth hormone (p=0,031). In the present series, no clinical differences were noticed between patients with tumours staining only for growth hormone or staining for both growth hormone and prolactin.

Hyperprolactinemia resulting from stalk compression is likely to anticipate a less favourable course of disease, since it is associated with larger tumours and a higher frequency of cavernous sinus invasion. On the contrary, positive immunostaining for prolactin was not a marker of worse prognosis.

Keywords: Acromegaly; Hyperprolactinemia; Immunostaining; Growthhormone; Prolactin


Acromegaly is a chronic disorder resulting from excessive Growth Hormone (GH) secretion. GH hypersecretion stimulates IGF-1 overproduction which in large part mediates the somatic and metabolic effects of GH, leading to a multisystemic disease characterized by somatic overgrowth, multiple comorbidities, premature mortality, and physical disfigurement [1,2]. More than 90% of acromegaly cases are caused by a GH-secreting pituitary adenoma arising from somatotroph cells [2]. Surgery, preferentially through an endoscopic endonasal approach, is recommended as the first line therapy for most patients. However, the optimal treatment approach should be chosen depending on the size, extension of the pituitary adenoma (particularly to the cavernous sinus) and patient characteristics [1,3]. Surgical remission rates can be greater than 85% for microadenomas, however these figures can decrease to 20-30 % for macroadenomas [4-6]. For patients with disease persistence, medical therapy is often indicated with the first-generation Somatostatin Receptor Ligands (SRLs) octreotide and lanreotide. As second-line therapy, both second-generation SRLs such as pasireotide or the GH receptor antagonist pegvisomant are alternatives. Dopamine agonists have a limited efficacy and are likely to be useful in patients with modest elevations of GH and IGF1. Radiosurgery or stereotactic fractionated radiation therapy can also play a role for selected patients [3,4,7]. In a number of patients, a multimodal approach is the most adequate solution.

Hyperprolactinemia has been reported in about 30 to 40% of acromegalic patients. High levels of Prolactin (PRL) can result from co-secretion of GH and PRL by the tumour, from pituitary stalk compression or even from both conditions [8]. Indeed, about 25% somatotrophic adenomas also secrete PRL. These tumours include dimorphous adenomas (mixed somatotroph-lactotroph adenoma) and monomorphous adenomas (mammosomatotroph adenoma) [9]. The aims of the current study were: 1) to estimate the prevalence of each cause of hyperprolactinemia, among a cohort of acromegalic patients from a single center, and follow its evolution after surgery; 2) to compare the clinical presentation and course of acromegalic patients with tumours staining only for GH against tumours staining for both GH and PRL.

Materials and Methods

Study cohort

We retrospectively reviewed medical records of 75 patients with acromegaly submitted to transsphenoidal surgery between January 1989 and December 2018 (endoscopic approach, since 2011), at Hospital de Santa Maria, in Lisbon, Portugal. Inclusion criteria: pre and post-operative clinical, laboratory and imaging data as well as immunohistochemical study. Exclusion criteria: use of medications likely to induce hyperprolactinemia, radiotherapy prior to surgery and adenomas staining for hormones other than GH and PRL.

Histopathology and laboratory data

Analysis was performed based on the pathology reports included in the patients’ files. GH and IGF-1 were measured using an immunometric chemiluminescence assay. IGF1 results were interpreted according to the reference range defined for age and gender. Serum PRL was measured using an electro-chemiluminescence assay and results interpreted according to a reference range adjusted for gender. As a consequence of the retrospective nature of the study, the reference ranges have changed throughout the years. Criteria for biochemical remission were defined as a normal serum IGF-1 for age and gender, as well as a random GH below 1ng/mL [1].

Neuroradiological studies

Pituitary adenomas were classified according to the tumour diameter described on magnetic resonance imaging and/or computed tomography scan. Tumours with diameter <1 centimetre were defined as microadenomas and ≥1 centimetre as macroadenomas [10]. Additionally, cavernous sinus invasion was evaluated.

Statistical analysis

Statistical analysis was performed with SPSS version 23. Chisquare test was used for comparison of categorical variables, whereas Student’s T and Mann-Whitney tests were used for continuous variables. Differences were considered statistically significant when p-value was <0.05.


Forty, out of 75 patients, met the study inclusion criteria. The ratio Female/Male was 1,9. Macroadenomas were present in 36 patients. Prior to surgery, PRL was evaluated in 36 patients. Hyperprolactinemia was documented in twenty-two patients (61%), with a median level of 40,3ng/mL. Furthermore, 10 patients (28%) despite presenting hyperprolactinemia did not disclose immunostaining for PRL. All patients in the latter group had macroadenomas. On the other hand, 6 patients, corresponding to 33, 3% of those with positive staining for PRL, had normal values of serum PRL, (Table 1).