Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Lucknow
On Sep 2018




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On Aug 2018




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"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : March | Volume : 16 | Issue : 3 | Page : BC12 - BC15 Full Version

Prevalence of Macroprolactinaemia in Women with Hyperprolactinaemia: A Retrospective Study


Published: March 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/52702.16123
Flavia Almeida, Alap Christy, Varsha Birla, Raj Jatale, Kirti Chadha

1. Senior Manager, Department of Clinical Chemistry, Metropolis Healthcare Ltd., Mumbai, Maharashtra, India. 2. Head, Department of Clinical Chemistry, Metropolis Healthcare Ltd., Mumbai, Maharashtra, India. 3. Clinical Biochemist, Department of Clinical Chemistry, Metropolis Healthcare Ltd., Mumbai, Maharashtra, India. 4. Statistician, Department of Medical Affairs, Metropolis Healthcare Ltd., Mumbai, Maharashtra, India. 5. Chief Scientific Officer, Department of Medical Affairs, Metropolis Healthcare Ltd., Mumbai, Maharashtra, India.

Correspondence Address :
Ms. Flavia Almeida,
Unit No. 409-416, 4th Floor, Commercial I, A-Wing, Nr. Kohinoor Mall, Kohinoor City,
Kirol Road, Off LBS Marg, Opp. Holy Cross School, Kurla (W),
Mumbai, Maharashtra, India.
E-mail: flavia@metropolisindia.com

Abstract

Introduction: Macroprolactinaemia causes asymptomatic hyperprolactinaemia in many patients which leads to misdiagnosis, inappropriate investigation and needless treatment in these patients. Though immunoassays for prolactin are sturdy and reliable, they are prone to interference from macroprolactin. Polyethylene Glycol (PEG) precipitation is used as a screening test for macroprolactinaemia.

Aim: To find out the prevalence of macroprolactin in women with hyperprolactinaemia, this will help in evaluation and treatment of such patients.

Materials and Methods: This retrospective study was conducted at a Global Reference Laboratory in Mumbai over a period of three and a half years from January 2018 to May 2021. Total available data of 1,15,149 women with age above 18 years were included in the study. Prolactin concentrations were measured before and after PEG precipitation. Macroprolactinaemia was characterised by percentage recovery and post PEG prolactin concentrations. Continuous variables were expressed as Mean±Standard Deviation (SD), range and categorical variables as number and percentage. The differences in categorical variables were assessed with Chi-square test or Fisher’s-exact test.

Results: Out of total 1,15,149 women, 36,247 (31.48%) women were observed to have hyperprolactinaemia. Prevalence of macroprolactinaemia using recovery criteria of ≤50% was 7.88%. Amongst the women diagnosed with hyperprolactinaemia maximum women were between 18-30 years age group i.e., 22,639 (62.46%). Macroprolactin and age were found to be statistically significant (p<0.05). Infertility, Oligomenorrhoea/amenorrhoea, and thyroid disorders was seen more frequently in hyperprolactinaemia than in macroprolactinaemia. Twelve women with prolactin values above 100 ng/mL were found to have macroprolactinaemia.

Conclusion: Macroprolactin determination with the PEG precipitation method might prevent unnecessary tests and treatments during the diagnosis process and follow-up of patients.

Keywords

Infertility, Monomeric prolactin, Polyethylene glycol precipitation, Prolactin, Screening

Prolactin is a 198-amino acid protein {23- kilodalton (kDa)} produced in the lactotroph cells of the anterior pituitary gland. Prolactin is an important hormonal test used for female and, male reproductive health. Prolactin stimulates breast growth development during pregnancy for the production of breast milk (1). The primary control of prolactin is inhibitory instead of stimulatory and the principle prolactin inhibitory factor is dopamine that regulates prolactin secretion (2). Low levels of prolactin are usually not a concern in women or men. However, very high levels of prolactin, known as hyperprolactinaemia, can indicate a deeper issue (2).

Human prolactin exists in multiple forms: monomeric prolactin having a molecular weight of 23 kDa, dimeric prolactin or big prolactin with a molecular weight of 50-60 kDa and polymeric form big-big prolactin (Macroprolactin) having a molecular weight of 150-170 kDa (3). Monomeric prolactin is the biologically and immunologically active form of prolactin accounting for 80-95% of the total prolactin in cases with normoprolactinaemia and true hyperprolactinaemia. Dimeric prolactin makes <10% and macroprolactin is 1% of the total prolactin (4).

Macroprolactin is a complex of monomeric prolactin with an Immunoglobulin G (IgG) antibody with a prolonged half-life leading to hyperprolactinaemia which is suspected in asymptomatic individuals or in patients without symptoms. Many women with macroprolactinaemia are asymptomatic with normal menstrual cycle but however have clinical symptoms of hyperprolactinaemia due to the rise in the levels of monomeric prolactin (1),(5). The prolactin-IgG complex has limited bioavailability and bioactivity because it cannot cross the endothelial lining and reach target organs. Prevalence of macroprolactinaemia is reported to be 26% in patients with hyperprolactinaemia (6).

General symptoms of excess prolactin in premenopausal women are oligomenorrhoea, amenorrhoea and galactorrhoea. Other symptoms in women with hyperprolactinaemia are menstrual irregularities, decreased libido, anovulation, infertility, chronic hyperandrogenism, prolonged hypoestrogenism, decreased bone mass and osteopenia (5). The causes of hyperprolactinaemia can be either physiological or pathological like- pregnancy, stress, hypothyroidism, pituitary tumours, nipple stimulation, certain foods, medicines given for depression and high blood pressure (2). Since the prevalence of oligomenorrhoea and galactorrhoea is 57% and 29% in macroprolactinaemia, most often patients are misdiagnosed as hyperprolactinaemia leading to unnecessary treatment and mismanagement (1),(6),(7).

In Indian subcontinent small and medium sized laboratories do not perform macroprolactin test in cases of hyperprolactinaemia. Hence misdiagnosed cases are started on unnecessary treatment. Presently there is only one Indian study on hyperprolactinaemia by Turankar S et al., done on 30 women (8). As not many such studies are done in Indian Subcontinent on a larger sample size, this study would help laboratory as well as clinicians to take the right clinical decision which will help in evaluation and treatment of such patients. Hence, this study was designed to understand the exact prevalence of macroprolactinaemia to create awareness on laboratory testing for macroprolactin.

Material and Methods

This retrospective study was conducted at a Global Reference Laboratory in Mumbai over a period of three and a half years from January 2018 to May 2021. Data was collected and analysed in July 2021. The study was conducted retrospectively from the data available in Laboratory Information System (LIS) of the laboratory. Approval on usage of Laboratory Information Management System (LIMS) and survey based patient data for scientific research and publication was obtained from Conscience Independent Ethics Committee (ECR/233/Indt/GJ/2015/RR-21) wide approval reference (02062021/09:44).

Inclusion criteria: Total available data of 1,15,149 female patients aged more than 18 years were included in the study irrespective of clinical history.

Exclusion criteria: All male patients and females below 18 years were excluded from the study.

Sample size: During the period from January 2018 to May 2021 there were a total of 1,15,149 females for prolactin requests, all were included.

Information about the patient’s age, gender, clinical history details was taken from the Test Requisition Form (TRF). Clinical history of only 839 patients was available. The patients were divided into two groups, group A with values within normal reference interval for prolactin and group B with values above reference interval for prolactin (group A ≤23.3 ng/mL, group B >23.3 ng/mL).

Laboratory Method

1. Prolactin was analysed by Electrochemiluminescence Immunoassay (ECLIA) method.
2. PEG precipitation method is used to detect the presence of macroprolactin in the sera of patients with hyperprolactinaemia as it precipitates the lgG and therefore the macroprolactin as well. After addition of 25% PEG to the serum specimen the sample is spun down. The supernatant is taken off and re-assayed for prolactin. If a significant difference is observed from the original result, then macroprolactin is to be suspected. (2).
3. Presence of macroprolactinaemia is expressed as prolactin recovery (% Recovery) and prolactin concentration after PEG treatment (post PEG prolactin ng/mL). Pseudohyperprolactinaemia is defined with post PEG prolactin within post PEG reference intervals and true hyperprolactinaemia above the upper limit of the post PEG reference interval. (9).
4. Samples with a prolactin value of >50 ng/mL were subjected to the PEG precipitation test (10),(11) (Table/Fig 1).

Interpretation

1. The total prolactin reference ranges are 4.79-23.3 ng/mL for women (12).
2. A recovery of >50% is considered to be a negative screen for macroprolactin.
3. A recovery of ≤50% is a positive screen indicating possible macroprolactin interference. Macroprolactin may be present and further characterisation is required (Table/Fig 2) (2),(3),6].
4. Serum prolactin (Monomeric post PEG) reference range is 3.5-17 ng/mL (6).

Statistical Analysis

All statistical analysis was performed using “R Studio version 1.4.1103”. A two-tailed p-value of <0.05 was considered as statistically significant. Continuous variables were expressed as Mean±SD, range and categorical variables as number and percentage. Shapiro-Wilks test was used to determine whether data sets differed from a normal distribution. The differences in categorical variables were assessed with Chi-square test or Fisher’s-exact test. For continuous variable differences between two groups was examined using unpaired t-test.

Results

Distribution of total prolactin age wise: During the period from January 2018 to May 2021 there were a total of 1,15,149 female prolactin requests. The mean age was found to be 30.12 years and 68,337 patients (59.35%) were in range between 18-30 years age group (Table/Fig 3). Out of total 68,337 patients, 22,639 (62.63%) patients having hyperprolactinaemia were between 18-30 years.

Prevalence of hyperprolactinaemia: Out of the total 1,15,149 patients, 36,247 women (31.48%) were observed to have hyperprolactinaemia with prolactin values above the reference range and 78,902 (68.52%) had prolactin with normal limits (Table/Fig 4).

Prevalence of clinical symptoms: Among the 839 prolactin patients whose clinical history was available, thyroid disorders was the most prevalent clinical history observed followed by patients on medicines in patients screened for prolactin. A total of 94 (33.22%) was thyroid disorders followed by 82 (28.98%) women on medication history in group B (Table/Fig 5).

Incidence of macroprolactinaemia in women with hyperprolactinaemia: During the study period, 1,15,149 prolactin requests were received out of which 8,705 (7.56%) had prolactin >50 ng/mL and were advised for macroprolactin. Out of these 5,763 were tested for macroprolactin as this retrospective study was conducted in a reference laboratory and patients did not gave consent for the test. There were 454 (7.88%) samples with post PEG recovery of ≤50% and these were defined as containing macroprolactin. A recovery >50% was present in most of the patients (92.12%), indicating that the predominant form was little Prolactin (PRL) which cannot be precipitated with PEG (Table/Fig 6).

Characteristics and PRL levels of patients with macroprolactinaemia (recovery ≤50% and recovery >50%): After PEG precipitation prolactin values reduced from 71.94-10.45 ng/mL in patients with macroprolactinaemia and from 70.85-30.10 in patients with monomeric prolactin predominance.

No significant difference was found for age but statistically significant difference was found for prolactin values between samples with recovery >50% and ≤50%. About 167 (93.30%) of the patients with monomeric prolactin predominance had prolactin values above 100 ng/mL in >50% recovery and 12 (6.7%) of the hyperprolactinaemic patients with PRL levels above 100 ng/mL had macroprolactinaemia in ≤50% recovery (Table/Fig 7).

Association of macroprolactin with age: Significant difference was observed between macroprolactin and age (Table/Fig 8).

Incidence of pseudohyperprolactinaemia: In present study, 454 patients (7.88%) patients were found to have macroprolactin leading to pseudohyperprolactinaemia. Recovery criterion of ≤50% defined these patients as Macroprolactinaemic.

A total of 52 (11.45%) of them had PRL-monomeric above the upper limit of the post PEG reference interval (true hyperprolactinaemia) and macroprolactin was also present. A total of 83 (1.56%) women had post PEG prolactin monomeric within the reference interval and macroprolactin was absent. However, 402 (88.55%) women had post PEG monomeric within normal reference interval but macroprolactin was present. As macroprolactin is present with increased monomeric form and further workup has to be done to identify causes of hyperprolactinaemia. A total of 5226 women had post PEG prolactin monomeric above the upper limit of the reference limit and macroprolactin was absent. If no clinical symptoms are seen no further investigation is required (Table/Fig 9).

Discussion

In present retrospective study, 7.88% of the patients with hyperprolactinaemia had the prevalence of macroprolactenaemia. This was similar to the findings by Barth JH et al., who reported macroprolactin incidence of 5% and also similar to recent studies by Sánchez-Eixerés MR et al., where the prevalence of hyperprolactinaemia was found to be 9% (13),(14).

Macroprolactinaemia should be considered as differential diagnosis of hyperprolactinaemia. It can avoid unnecessary and costly diagnostic investigations, inappropriate treatments. Although patients with macroprolactinaemia are usually asymptomatic there are a number of women with macroprolactinaemia presenting hyperprolactinaemic clinical symptoms due to the rise in the levels of monomeric prolactin, that cannot be differentiated from the patients with true hyperprolactinaemia (1),(15). Macroprolactin can interfere with all commercial prolactin immunoassays leading to falsely elevated prolactin levels in terms of macroprolactinaemia. Therefore, PEG induced precipitation of macroprolactin is used as a screening technique for hyperprolactinaemic sera (16).

According to a study done in the United Kingdom by Olukoga AO and Kane JW (17), the prevalence of macroprolactin was 15% and this was lower than the prevalence of 25% reported in another study by Fahie-Wilson MN and Soule SG., 1997) (3). As per studies done in Turkey by Muhtaroglu S et al., the prevalence of macroprolactinaemia is approximately 4% of the general population and the frequency of macroprolactinaemia in other countries is detected in 4-46% of patients with hyperprolactinaemia depending on the immunoassay method platforms and population tested (18). In present study, the finding of low prolactin recovery after PEG is indicative of the presence of macroprolactin, which has been accurately validated by Fahie-Wilson MN and Soule SG (3).

Out of the total available 1,15,149 data of female patients in present study 68,337 (59.35%) were between 18-30 years age group. The mean age for prolactin was found to be 30.12 years and prevalence of hyperprolactinaemia was highest 22,639 (62.46%) among this age group. A recent study by Palubska S et al., also concluded that hyperprolactinaemia mostly affects women in the reproductive age between 25-34 years (19).

Hyperprolactinaemia, the presence of abnormally high levels of prolactin in the blood and hypothyroidism are found to be closely interrelated. As per study by Turankar S et al., some of the women with high prolactin levels have been diagnosed with hypothyroidism (8). Similarly in present study, thyroid disorders (33.22%) have been found to be the most prevalent clinical characteristic in hyperprolactinaemic women. Clinical symptoms of infertility, irregular menses and thyroid disorders occurred more frequently in hyperprolactinaemia as compared to macroprolactinaemia in present study. This was in accordance with a study published by Toldy E et al., (20).

Therefore, present study helped to differentiate such cases based on macroprolactin estimation. Also, in present study the correlation between monomeric prolactin and macroprolactinaemia was 11.45% therefore, the presence of macroprolactinaemia may include pituitary pathology when post PEG prolactin is above reference range (1),(16).

Limitation(s)

This was a retrospective data analysis based study so lack of detailed history for the subjects was limited. So, further investigation towards the causative classification of macroprolactinaemia is required.

Conclusion

The present retrospective study demonstrates that 7.88% of the patients with hyperprolactinaemia have macroprolactinaemia. This in house study provides an assessment of macroprolactin as a cause of hyperprolactinaemia. This finding supports the inclusion of macroprolactinaemia screening in the differential diagnosis of hyperprolactinaemia to avoid unnecessary expensive examination. Detecting macroprolactinaemia favours a definitive diagnosis to be made in many cases that would otherwise be labelled idiopathic hyperprolactinaemia.

References

1.
Kasum M, Orešković S, Čehić E, Å unj M, Lila A, Ejubović E. Laboratory and clinical significance of macroprolactinaemia in women with hyperprolactinaemia. Taiwan J Obstet Gynecol. 2017;56(6):719-24. [crossref] [PubMed]
2.
Richa V, Rahul G, Sarika A. Macroprolactin; a frequent cause of misdiagnosed hyperprolactinaemia in clinical practice. J Reprod Infertil. 2010;11(3):161-67.
3.
Fahie-Wilson MN, Soule SG. Macroprolactinaemia: Contribution to hyperprolactinaemia in a district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Ann Clin Biochem. 1997;34(Pt 3):252-58. [crossref] [PubMed]
4.
Lu CC, Hsieh CJ. The importance of measuring macroprolactin in the differential diagnosis of hyperprolactinaemic patients. Kaohsiung J Med Sci. 2012;28(2):94-99. [crossref] [PubMed]
5.
Kasum M, Pavičić-Baldani D, Stanić P. Importance of macroprolactinaemia in hyperprolactinaemia. Eur J Obstet Gynecol Reprod Biol. 2014;183:28-32. [crossref]
6.
Beltran L, Fahie-Wilson MN, McKenna TJ. Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: Evaluation and validation on common immunoassay platforms. Clin Chem. 2008;54(10):1673-81. [crossref] [PubMed]
7.
Suliman AM, Smith TP, Gibney J. Frequent misdiagnosis and mismanagement of hyperprolactinaemic patients before the introduction of macroprolactin screening: Application of a new strict laboratory definition of macroprolactinaemia. Clin Chem. 2003;49(9):1504-09. [crossref] [PubMed]
8.
Turankar S, Sonone K, Turankar A. Hyperprolactinaemia and its comparison with hypothyroidism in primary infertile women. J Clin Diagn Res. 2013;7(5):794-96. [crossref] [PubMed]
9.
Å ostarić M, Bokulić A, Marijančević D. Optimizing laboratory defined macroprolactin algorithm. Biochem Med (Zagreb). 2019;29(2):020706. [crossref] [PubMed]
10.
Melmed S, Casanueva FF, Hoffman AR. Endocrine Society. Diagnosis and treatment of hyperprolactinaemia: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273-88. [crossref] [PubMed]
11.
Serri O, Chik CL, Ur E. Diagnosis and management of hyperprolactinaemia. CMAJ. 2003;169(6):575-81.
12.
Reference Interval Study for Children and randomly selected adults Elecsys Fertility Tests, Roche 2015-7.
13.
Barth JH, Lippiatt CM, Gibbons SG. Observational studies on macroprolactin in a routine clinical laboratory. Clin Chem Lab Med. 2018;56(8):1259-62. [crossref] [PubMed]
14.
Sánchez-Eixerés MR, Mauri M, Alfayate R. Prevalence of macroprolactin detected by Elecsys 2010. Horm Res. 2001;56(3-4):87-92. [crossref] [PubMed]
15.
Gibney J, Smith TP, McKenna TJ. The impact on clinical practice of routine screening for macroprolactin. J Clin Endocrinol Metab. 2005;90(7):3927-32. [crossref] [PubMed]
16.
Chutpiboonwat P, Yenpinyosuk K, Sridama V. Macroprolactinaemia in patients with hyperprolactinaemia: An experience from a single tertiary center. Pan Afr Med J. 2020;36:8. [crossref] [PubMed]
17.
Olukoga AO, Kane JW. Macroprolactinaemia: Validation and application of the polyethylene glycol precipitation test and clinical characterisation of the condition. Clin Endocrinol (Oxf). 1999;51(1):119-26. [crossref] [PubMed]
18.
Muhtaroglu S, Barlak Keti D, Hacioglu A. Macroprolactin: An overlooked reason of hyperprolactinaemia. Journal of Laboratory Medicine. 2019;43(3):163-68. [crossref]
19.
Palubska S, Adamiak-Godlewska A, Winkler I. Hyperprolactinaemia- a problem in patients from the reproductive period to the menopause. Prz Menopauzalny. 2017;16(1):01-07. [crossref] [PubMed]
20.
Toldy E, Löcsei Z, Szabolcs I. Macroprolactinaemia: The consequences of a laboratory pitfall. Endocrine. 2003;22(3):267-73. [crossref]

DOI and Others

DOI: 10.7860/JCDR/2022/52702.16123

Date of Submission: Oct 05, 2021
Date of Peer Review: Dec 21, 2021
Date of Acceptance: Jan 31, 2022
Date of Publishing: Mar 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Oct 08, 2021
• Manual Googling: Jan 27, 2022
• iThenticate Software: Feb 07, 2022 (16%)

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