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      Diagnostic pitfalls of hyperprolactinemia: the importance of sequential pituitary imaging

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          The 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.


          Receiver 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.


          Non-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.

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          Most cited references 24

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          Pathology and Genetics of Tumour of Endocrine Organs

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            Hyperprolactinemia and prolactinomas.

            Any process interfering with dopamine synthesis, its transport to the pituitary gland, or its action at the level of lactotroph dopamine receptors can cause hyperprolactinemia. As described in this article, considering the complexity of prolactin regulation, many factors could cause hyperprolactinemia, and hyperprolactinemia can have clinical effects not only on the reproductive axis. Once any drug effects are excluded, prolactinomas are the most common cause of hyperprolactinemia. The most frequent symptom is hypogonadism in both genders. Medical and surgical therapies generally have excellent results, and most prolactinomas are well controlled or even cured in some cases.
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              Clinical versus subclinical pituitary apoplexy: presentation, surgical management, and outcome in 21 patients.

              A retrospective review of 16 consecutive patients with pituitary apoplexy treated over a 10-year period is reported. Eight men and 8 women (mean age, 48 years) underwent transsphenoidal decompression after an average duration of symptoms of 19 days. The diagnosis of pituitary apoplexy was made by the sudden onset of headache (88%), nausea (56%), or meningismus (13%), with or without visual disturbances (75%), in the setting of a sellar tumor on computed tomographic or magnetic resonance imaging scans. Thirteen of 16 patients showed significant improvement of symptoms after surgery (average follow-up, 2.5 years). In addition, 5 patients with clinically silent yet extensive pituitary hemorrhage were treated. Although extensive pituitary hemorrhage often produced fulminant apoplexy, it also presented insidiously over many days with few, if any, clinical signs. Rapid diagnosis, endocrine replacement, and transsphenoidal decompression constituted effective therapy. Magnetic resonance imaging (after at least 12 hours of symptoms) was superior to computed tomography in detecting hemorrhage.

                Author and article information

                [ ]Department of Neurosurgery, Kohnan Hospital, 4-20-1 Nagamachi Minami, Taihaku-ku, Sendai, Miyagi, 982-8523 Japan
                [ ]Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                20 August 2014
                20 August 2014
                : 7
                : 1
                25142896 4148930 3082 10.1186/1756-0500-7-555
                © Kawaguchi et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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