Diagnostic pitfalls of hyperprolactinemia: the importance of sequential pituitary imaging

Abstract

BackgroundThe purpose of this study is to confirm whether the serum prolactin cut-off value is definitive to distinguish prolactinoma and non-functioning pituitary adenoma with hyperprolactinemia. We retrospectively reviewed patients with non-functioning pituitary adenoma, including gonadotroph cell adenoma, null cell adenoma and prolactinoma who were surgically treated at Kohnan hospital between June 2005 and March 2012. The patients without endocrinological/neurological symptom and with the tumor larger than 40 mm in diameter were excluded. According to previously reported cut-off value of serum prolactin, mild hyperprolactinemia, which is considered non-definitive (border zone) concentration between prolactinoma and non-functioning pituitary adenoma, were defined as 90 – 200 ng/ml. Ninety-five prolactinoma patients and 212 patients with non-functioning pituitary adenoma were analyzed. The serum prolactin concentration, tumor size, and clinical characteristics were statistically compared.ResultsReceiver operating characteristic (ROC) curve analysis was performed, indicating that cut-off value of serum prolactin concentration to distinguish between non-functioning pituitary adenoma and prolactinoma was 38.6 ng/ml. Although it was statistically good accuracy (the area under the curve; 0.96, sensitivity; 0.99 and specificity; 0.81), the result did not fit the clinical situation as many false-positive cases (40 of 212, 18.9%) were included. Among them, mild hyperprolactinemia were shown in 9 (4.2%) and 53 (55.8%) non-functioning pituitary adenoma and prolactinoma, respectively. Four of 9 border zone patients with non-functioning pituitary adenoma were initially treated with dopamine agonists. Sequential head magnetic resonance imaging revealed no tumor shrinkage in all of them despite serum prolactin concentration was decreased. Surgery was chosen for them 24.6 months in average after the introduction of medication.ConclusionsNon-negligible number of patients with non-functioning pituitary adenoma presented unexpectedly high concentration of prolactin, fraught with a potential risk of misdiagnosis. While this equivocal population is not the majority, the prolactin cut-off value is not safely applicable. Especially for the patients with border zone prolactin concentration, meticulous follow up with sequential pituitary imaging is important.

Triple Synchronous Tumors Presenting as Right Nasolabial Basal Cell Carcinoma, Papillary Thyroid Carcinoma and Prolactinoma: A Rare Case Report

“…Significant elevation of prolactin is >200 ug/L (>200 ng/mL) and is almost invariably indicative of a prolactin secreting pituitary adenoma. 23 , 24 A “stalk effect” secondary to a large sellar mass as in this case may also increase serum prolactin levels due to obstruction of inhibitory dopamine flow from the hypothalamus. The elevation would usually fall between 96-200ng/mL and would not be too elevated, thus this was ruled out.…”

“…The elevation would usually fall between 96-200ng/mL and would not be too elevated, thus this was ruled out. 24 All other causes for hyperprolactinemia were ruled out in this case. Evaluation of the hormones involved in the hypothalamus-pituitary-endocrine gland axis is imperative (Table 2).…”

Identification of an optimal prolactin threshold to determine prolactinoma size using receiver operating characteristic analysis

“…For a PRL cut-off value of 204 μg/L (4338 mU/L), both sensitivity and specificity of diagnosing a macro adenoma were optimal. While several studies assess the cut-off PRL value that could differentiate between a prolactinoma and a non-functioning pituitary adenoma 9 , 14 , 15 , and cut-off differentiating between a prolactinoma and “stalk effect” hyperprolactinemia, to the best of our knowledge, this is the first study reporting on a value that distinguishes micro- from macro- prolactinomas. In other studies, the cut off for distinguishing a true macroprolactinoma from a non-functioning pituitary adenoma (NFPA) was typically > 189 μg/L (> 4000 mU/L) 16 .…”

Role of prolactin/adenoma maximum diameter and prolactin/adenoma volume in the differential diagnosis of prolactinomas and other types of pituitary adenomas

“…However, in clinical practice, the optimal PRL level for the differential diagnosis of prolactinoma and other types of pituitary adenoma is far from 250 µg/l. Kawaguchi et al (28) reported that the optimal PRL level for the differential diagnosis of prolactinoma and non-functioning adenomas was 38.6 µg/l, which is substantially lower than 100-200 ng/ml. Karavitak et al (6) demonstrated that the PRL level of non-functional pituitary adenomas did not exceed 2,000 mIU/l (1 µg/l=21.2 mIU/l), and 2,000 mIU/l was considered as the upper PRL limit of non-functional pituitary adenomas.…”