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Table of Contents    
Year : 2011  |  Volume : 59  |  Issue : 6  |  Page : 944-945

Microsurgical management of prolactinomas - Clinical and hormonal outcomes

1 Department of Clinical Biochemistry, Dr. Vivek's Health Centre, Chennai, India
2 Department of Biochemistry and Neurology, Institute of Neurological Sciences, Global Hospitals and Health City, Chennai, India

Date of Submission29-Oct-2011
Date of Decision29-Oct-2011
Date of Acceptance14-Dec-2011
Date of Web Publication2-Jan-2012

Correspondence Address:
S Vivekanandan
Department of Clinical Biochemistry, Dr. Vivek's Health Centre, Chennai
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.91400

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How to cite this article:
Vivekanandan S, Nayak D. Microsurgical management of prolactinomas - Clinical and hormonal outcomes. Neurol India 2011;59:944-5

How to cite this URL:
Vivekanandan S, Nayak D. Microsurgical management of prolactinomas - Clinical and hormonal outcomes. Neurol India [serial online] 2011 [cited 2020 Aug 15];59:944-5. Available from:

Editor′s Note This letter has been sent to the authors for their views and clarifications. In spite of repeated reminders the authors failed to respond.


We read the article "Microsurgical management of prolactinomas-Clinical and hormonal outcomes" as well as the accompanying editorial comment [1] and would like to add the following comments:

This paper reports the post-surgical hormonal outcome in the medical therapy ineffective prolactinoma subgroup. Because serum prolactin was the treatment outcome marker, the lack of mention of the methodology used to measure prolactin levels, and the presence or absence of macroprolactin is a flaw in an otherwise fine study.

The manifestation of clinical effects of hyperprolactinemia requires a) raised prolactin concentration requires to cross the vasculature and b) prolactin requires to interact with its receptors. Serum prolactin circulates as a monomer with molecular weight of 23 kDa, more than 95% of which crosses the vasculature, binds with its receptors, and triggers molecular events resulting in clinical signs and symptoms. When prolactin complexes with big immunoglobulin molecule IgG (mostly autoantibodies) in the circulation (<5%) [2] and/or gets polymerized to big-big prolactin molecular complex in the circulation (usually <1%), these macroprolactin variants (when elevated called macroprolactinemia) do not cross the vasculature and thus cannot interact with tissue prolactin receptor to initiate biological (molecular) events. Hence, they are not clinically relevant even when the subject has relevant clinical signs and symptoms secondary to a completely different pathology. Macroprolactinemia may account for up to 20% of all cases of hyperprolactinemia in the general population. [2],[3]

In addition, serum prolactin is measured universally by immunometric assay principle using an anti-prolactin antibody. The anti-prolactin antibody from different prolactin assay kit manufacturers can recognize and measure 100% of prolactin monomers (23 kDa) (as the kits are configured to measure the variants as total circulating prolactin concentration). But the degree of recognition and measurement of the prolactin variants varies among kits, [3],[4] as the kits are not configured to measure the monomers as total circulating prolactin concentration. It is only by laboratory screening tests such as polyethylene glycol (PEG) precipitation test that the existence of macroprolactin can be detected. The interested readers are advised to refer cited articles for more information. [5],[6]

One of the surgical indications mentioned in this paper is the failure to achieve prolactin level normalization. [1] The authors have not mentioned whether they have considered the possibility of these patients (some) having macroprolactin(emia) and have not discussed this either in the methodology or in the discussion. The editorial also does not discuss this. [7] It is well known that the presence of macroprolactin is a relevant cause in patients with hyperprolactinemia and one of the reasons for the failure to achieve prolactin level normalization is the coexistence of macroprolactin.

Interestingly, the possible association of macroprolactin (emia) with pituitary lesion has been reported by Vassilatou et al. [8] in a young man with macroprolactinemia and magnetic resonance imaging (MRI) documenting microadenoma. When macroprolactin(emia) coexists with pituitary microadenoma, it is (sometimes) difficult to resolve whether the tumor is prolactin secreting, contributing to raised serum prolactin, or is non-functioning. This is especially important taking into account that approximately 10% of healthy subjects have radiographic evidence of a pituitary adenoma. [9] In addition, macroprolactinemia has also been described in cases of histologically confirmed pituitary adenomas. [9] Furthermore, persistent macroprolactin(emia) has been observed even after a successful surgical removal of a pituitary microadenoma. [9],[10]

It has been suggested that the diagnostic algorithm of hyperprolactinemic states should include both suitable macroprolactin screening test (such as PEG precipitation test) [to confirm macroprolactin(emia)] and MRI imaging. [11] In cases of hyperprolactinemia without an identifiable cause, such as gonadal dysfunction, and in persisting hyperprolactinemia despite appropriate medical or surgical treatment, search for macroprolactin constitutes a useful diagnostic step. [12] We feel that had the authors tested for macroprolactin(emia) routinely for all their patients, it would have revealed that some of the medical and surgical failures may actually have been due to the presence of circulating macroprolactin.

  References Top

1.Sinha S, Sharma BS, Mahapatra AK. Microsurgical management of prolactinoma: Clinical and hormonal outcome in a series of 172 patients. Neurol India 2011;59:327-9.  Back to cited text no. 1
2.Hattori N. Macroprolactinaemia: Prevalence and aetiologies in a large group of hospital workers. Clin Endocrinol 2009;71:702-8.  Back to cited text no. 2
3.Sadideen H, Swaminathan R. Macroprolactin: What is it and what is its importance? Int J Clin Pract 2006;60:457-61.  Back to cited text no. 3
4.Gibney J, Smith TP, McKenna TJ. Clinical relevance of macroprolactin. Clin Endocrinol (Oxf) 2005;62:633-43.  Back to cited text no. 4
5.Wallace R, Satti N, Courtney CH, Leslie H, Bell PM, Hunter SJ, et al. Ten-year clinical follow-up of a cohort of 51 Patients with macroprolactinemia establishes it as a benign variant. J Clin Endocrinol Metab 2010;95:3268-71.  Back to cited text no. 5
6.McKenna TJ. Should macroprolactin be measured in all hyperprolactinaemic sera? Clin Endocrinol 2009;71:466-9.  Back to cited text no. 6
7.Behari S. Management of prolactinomas: The fine print between the lines! Editorial comment. Neurol India 2011;59:501-3.  Back to cited text no. 7
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8.Vassilatou E, Schinochoritis P, Marioli S, Tzavara I. Macroprolactinemia in a young man and review of the literature. HORMONES 2003, 2:130-4  Back to cited text no. 8
9.Hauache OM, Rocha AJ, Maia AC Jr, Maciel RM, Vieira JG. Screening for macroprolactinaemia and pituitary imaging studies. Clin Endocrinol (Oxf) 2002;57:327-31.  Back to cited text no. 9
10.Donadio F, Barbieri A, Angioni R, Mantovani G, Beck-Peccoz P, Spada A, et al. Patients with macroprolactinaemia: Clinical and radiological features. Eur J Clin Invest 2007;37:552-7.  Back to cited text no. 10
11.Fahie-Wilson. M. In Hyperprolactinemia, testing for macroprolactin is essential. Clin Chem 2003;49:1434-6.  Back to cited text no. 11
12.Suliman AM, Smith TP, Gibney J, Mckenna TJ. Frequent misdiagnosis and mismanagement of hyperprolactinemic patients before the introduction of macroprolactin screening: Application of a new strict laboratory definition of macroprolactinemia. Clin Chem 2003;49:1504-9.  Back to cited text no. 12


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