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      Prolactinomas and nonfunctioning adenomas: preoperative diagnosis of tumor type using serum prolactin and tumor size

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          Abstract

          OBJECTIVE

          Prolactinoma and nonfunctioning adenoma (NFA) are the most common sellar pathologies, and both can present with hyperprolactinemia. There are no definitive studies analyzing the relationship between the sizes of prolactinomas and NFAs and the serum prolactin level. Current guidelines for serum prolactin level cutoffs to distinguish between pathologies are suboptimal because they fail to consider the adenoma volume. In this study, the authors attempted to describe the relationship between serum prolactin level and prolactinoma volume. They also examined the predictive value that can be gained by considering tumor volume in differentiating prolactinoma from NFA and provide cutoff values based on a large sample of patients.

          METHODS

          A retrospective analysis of consecutive patients with prolactinomas (n = 76) and NFAs (n = 217) was performed. Patients were divided into groups based on adenoma volume, and the two pathologies were compared.

          RESULTS

          A strong correlation was found between prolactinoma volume and serum prolactin level (r = 0.831, p < 0.001). However, there was no significant correlation between NFA volume and serum prolactin level (r = −0.020, p = 0.773). Receiver operating characteristic curve analysis of three different adenoma volume groups was performed and resulted in different serum prolactin level cutoffs for each group. For group 1 (≤ 0.5 cm 3), the most accurate cutoff was 43.65 μg/L (area under the curve [AUC] = 0.951); for group 2 (> 0.5 to 4 cm 3), 60.05 μg/L (AUC = 0.949); and for group 3 (> 4 cm 3), 248.15 μg/L (AUC = 1.0).

          CONCLUSIONS

          Prolactinoma volume has a significant impact on serum prolactin level, whereas NFA volume does not. This finding indicates that the amount of prolactin-producing tissue is a more important factor regarding serum prolactin level than absolute adenoma volume. Hence, volume should be a determining factor to distinguish between prolactinoma and NFA prior to surgery. Current serum prolactin threshold level guidelines are suboptimal and cannot be generalized across all adenoma volumes.

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          Most cited references28

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          Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.

          In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.
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            Management of clinically non-functioning pituitary adenoma.

            Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts.
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              Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma.

              The differentiation of a pituitary non-functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy. Serum PRL levels have been suggested as a useful diagnostic indicator. However, values between 2500 and 8000 mU/l are a grey area and are currently associated with diagnostic uncertainty. We wished therefore, to investigate the serum PRL values in a large series of patients presenting with apparently non-functioning pituitary macroadenomas. All patients presenting to the Department of Endocrinology in Oxford with clinically non-functioning pituitary macroadenomas (later histologically verified) between 1990 and 2005 were studied. Information documented in the notes on the medications and on the presence of conditions capable of affecting the serum PRL levels at the time of blood sampling was also collected. Two hundred and twenty-six patients were identified (median age at diagnosis 55 years, range 18-88 years; 146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12 silent ACTH adenomas). All tumours had suprasellar extension. At the time of blood sampling 41 subjects were taking medications capable of increasing serum PRL. Hyperprolactinaemia was found in 38.5% (87/226) of the patients. The median serum PRL values in the total group were 386 mU/l (range 16-3257) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-3257) and in those not taking drugs capable of increasing serum PRL 363 mU/l (range 16-2565) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-2565). Serum PRL 2000 mU/l, two were taking oestrogen preparations. Based on a large series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never encountered in nonfunctioning pituitary macroadenomas. Values above this limit in the presence of a macroadenoma should not be surrounded by diagnostic uncertainty (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the most likely diagnosis and a dopamine agonist should be considered as the treatment of choice.
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                Author and article information

                Journal
                Journal of Neurosurgery
                Journal of Neurosurgery Publishing Group (JNSPG)
                0022-3085
                1933-0693
                June 2019
                June 2019
                : 1-8
                Affiliations
                [1 ]1University of Louisville School of Medicine, University of Louisville, Louisville, Kentucky;
                [2 ]2Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and
                [3 ]3Pacific Neuroscience Institute at the John Wayne Cancer Institute, Santa Monica, California
                Article
                10.3171/2019.3.JNS19121
                b915d24c-708e-46d6-bd52-3f978c237058
                © 2019
                History

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