SAGE IVD recommended including the prolactin test category in the third EDL:
• as a disease-specific IVD for use in clinical laboratories (EDL 3, Section II.b, within a new subsection for endocrine disorders);
• using an immunoassay format;
• to diagnose and monitor hyperprolactinaemia (including prolactinoma). The group further requested the addition of a note to the test category entry in the EDL stating that it is only recommended for use in specialized health care settings.

Prolactinoma is a pituitary tumour that responds to medical treatment and, if necessary, to surgical treatment. PRL testing is a simple test that is commonly used in clinical practice to diagnose and follow up on prolactinoma and conditions associated with hyperprolactinaemia, such as infertility and menstrual irregularities. While the EML does not include any medicines for managing hyperprolactinaemia, PRL testing for it is included in the guidelines of many professional societies. There is limited evidence regarding the test’s impact on health outcomes or cost. SAGE IVD raised concerns about the potential to overuse PRL testing as well as the potential for abnormal results that are not associated with hyperprolactinaemia. PRL testing requires appropriate laboratory infrastructure and quality assurance. And, depending on the type of assay used, PRL testing can also be affected by biotin ingested by the patient. Importantly, SAGE IVD emphasized the need to interpret PRL results with care, not least because macroprolactin, which is present in 3.7% of the general population, causes high levels of PRL but is inactive. The group noted that laboratory procedures such as precipitation by polyethylene glycol are required to estimate the amount of biological active monomeric PRL.

The main goal of the test for prolactin is to diagnose hyperprolactinaemia (including caused by a prolactinoma) and to follow up patients treated for hyperprolactinaemia (including prolactinoma). Guidelines suggest that prolactin measurement using immunoassays for detecting hyperprolactinaemia is appropriate. Both guidelines and reviews repeatedly emphasize that prolactin measurement alone is insufficient to further subclassify the etiologic cause of hyperprolactinaemia (e.g. pituitary tumour, drugs, idiopathic). For that, anamnesis and other tests such as biomarker measurement (thyroid-stimulating hormone (TSH), free T4 and creatinine) and MRI scans are needed. The claims made on the diagnostic accuracy of PRL testing for hyperprolactinaemia are not made in terms of traditional diagnostic test accuracy measures, although they do suggest that it is adequate. The submission only lists one study with diagnostic test accuracy of PRL for etiologic causes of hyperprolactinaemia. Claims made of impact on health outcomes or costs assume that a root cause of hyperprolactinaemia is identified, and are circumstantial. No evidence-based conclusion can be drawn for the effect of PRL testing on health outcomes or costs.

World Health Organization. (‎2021)‎. The selection and use of essential in vitro diagnostics: report of the third meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2020 (‎including the third WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/339064