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      The Curious Case of Prolactin Hormone

      , 1

      Indian Journal of Dermatology

      Medknow Publications & Media Pvt Ltd

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          Abstract

          Sir, This is with reference to the article “Serum prolactin levels in psoriasis and its association with disease activity: A case-control study” published by Keen et al.[1] This study although carefully conducted raised a few questions. It is recommended that the blood sample for the estimation of prolactin (PRL) levels should be obtained without excessive venipuncture stress.[2] It is not known if such a precaution was taken. The exclusion criteria employed in the study needs detailed scrutiny. A plethora of factors[2] can affect PRL levels and studies on PRL estimation should carefully exclude these confounding factors to avoid overestimation and possible false association. Known cases of renal, hepatic, endocrinopathy (prolactinoma and hypothyroidism) or psychiatric disease were excluded, but it is not specified whether screening tests such as thyroid function tests were done. Pretesting before inclusion is essential because clinical features of thyroid disease are often non-specific; hence, history and clinical examination are not sufficient to rule out hypothyroidism The author's exclusion criteria, although exhaustive, miss out on a few drugs known to cause hyperprolactinemia, such as oral contraceptive pills, and anticonvulsants[2] Stress being an established exacerbating factor for psoriasis is also known to increase PRL levels.[2] Psychiatric comorbidity in psoriasis is well known and although known cases of psychiatric disease were excluded, some of them may be undiagnosed cases of depression or anxiety which could have caused an overestimation of PRL levels Control for physiological confounding factors such as coitus or exercise which could cause PRL elevation appears to be poor.[2 3] History of coitus on the night prior to sample collection and history of exercise on the morning of sample collection was not elaborated. Even though monomeric 23 kDa form of PRL is the predominant form, its big variants (50 and 150 kDa) known as “big prolactin” or macroprolactin represent dimers, trimers, polymers of PRL, or prolactin–immunoglobulin immune complexes (PRL–IgG complexes),[3] which remain reactive to varying degrees in all PRL immunoassays. Interestingly, they exhibit little, if any, biological activity in vivo and consequently its presence is considered clinically irrelevant.[4 5] In this study, levels of PRL were quantitatively estimated using electro-chemiluminescence immunoassay (ECLIA).[1] Though generally robust and reliable, such immunoassays are susceptible to interference from PRL–IgG autoantibody complex or macroprolactin.[5] Polyethylene glycol precipitation is an inexpensive way to detect the presence of macroprolactin in the serum.[3] All sera subjected to PRL estimation should be sub-fractionated using polyethylene glycol precipitation to provide a more meaningful clinical measurement of the bioactive monomeric PRL content.[5] The patients received topical treatment for 6 weeks following which reduction in the PRL levels was observed, but post-treatment PASI scores were not reported. In addition, it is not specified as to what treatment was prescribed. Topical corticosteroids are still a popular choice of topical treatment for psoriasis. A literature search showed no studies evaluating the effect of topical steroids on PRL levels. Nevertheless, it is noteworthy that studies have shown reduction in PRL secretion or levels following systemic steroids.[3] If steroids were applied over larger areas, consequent systemic absorption might have affected PRL levels.

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          Most cited references 5

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          Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline.

          The aim was to formulate practice guidelines for the diagnosis and treatment of hyperprolactinemia. The Task Force consisted of Endocrine Society-appointed experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, The European Society of Endocrinology, and The Pituitary Society reviewed and commented on preliminary drafts of these guidelines. Practice guidelines are presented for diagnosis and treatment of patients with elevated prolactin levels. These include evidence-based approaches to assessing the cause of hyperprolactinemia, treating drug-induced hyperprolactinemia, and managing prolactinomas in nonpregnant and pregnant subjects. Indications and side effects of therapeutic agents for treating prolactinomas are also presented.
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            Hyperprolactinemia

            Prolactin (PRL) is an anterior pituitary hormone which has its principle physiological action in initiation and maintenance of lactation. In human reproduction, pathological hyperprolactinemia most commonly presents as an ovulatory disorder and is often associated with secondary amenorrhea or oligomenorrhea. Galactorrhea, a typical symptom of hyperprolactinemia, occurs in less than half the cases. Out of the causes of hyperprolactinemia, pituitary tumors may be responsible for almost 50% of cases and need to be investigated especially in the absence of history of drug induced hyperprolactinemia. In women with hyperprolactinemic amenorrhea one important consequence of estrogen deficiency is osteoporosis, which deserves specific therapeutic consideration. Problem in diagnosing and treating hyperprolactinemia is the occurrence of the ‘big big molecule of prolactin’ that is biologically inactive (called macroprolactinemia), but detected by the same radioimmunoassay as the biologically active prolactin. This may explain many cases of very high prolactin levels sometimes found in normally ovulating women and do not require any treatment. Dopamine agonist is the mainstay of treatment. However, presence of a pituitary macroadenoma may require surgical or radiological management.
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              Determination of prolactin: the macroprolactin problem.

              Serum prolactin is frequently measured when investigating patients with reproductive disorders and elevated concentrations are found in up to 17% of such cases. Clinical laboratories rely predominantly on automated analysers to quantify prolactin levels using sandwich immunometric methodologies. Though generally robust and reliable, such immunoassays are susceptible to interference from a high molecular mass prolactin/IgG autoantibody complex termed macroprolactin. While macroprolactin remains reactive to varying degrees in all prolactin immunoassays, it exhibits little if any biological activity in vivo and consequently its presence is considered clinically irrelevant. Macroprolactinaemia, defined as hyperprolactinaemia due to excess macroprolactin with normal concentrations of bioactive monomeric prolactin, may lead to misdiagnosis and mismanagement of hyperprolactinemic patients if not recognised. Current best practice recommends that all sera with elevated total prolactin concentrations are sub-fractionated using polyethylene glycol precipitation to provide a more meaningful clinical measurement of the bioactive monomeric prolactin content. Manufacturers of prolactin assays should strive to minimise interference from macroprolactin in their assays. Clinical laboratories should introduce screening procedures to exclude macroprolactinaemia in all patients identified as having hyperprolactinaemia. Clinicians should be aware of this potential diagnostic pit fall and insist on PEG screening of all hyperprolactinaemic sera.
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                Author and article information

                Journal
                Indian J Dermatol
                Indian J Dermatol
                IJD
                Indian Journal of Dermatology
                Medknow Publications & Media Pvt Ltd (India )
                0019-5154
                1998-3611
                May-Jun 2015
                : 60
                : 3
                : 310
                Affiliations
                From the Department of Dermatology, MGM Medical College, Kamothe, India. E-mail: shaurya023@ 123456gmail.com
                [1 ] Consultant Endocrinologist, Fortis Hiranandani Hospital, Vashi, Navi Mumbai, Maharashtra, India
                Article
                IJD-60-310
                10.4103/0019-5154.156399
                4458952
                Copyright: © Indian Journal of Dermatology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Correspondence

                Dermatology

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