| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Letters |
1
Departments of Medical Biochemistry, and Medicine, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, United Kingdom
2
UKNEQAS for Peptide Hormones, Department of Clinical Biochemistry, Royal Infirmary, Edinburgh EH3 9YW,, United Kingdom
a Address correspondence to this author at: Department of Medical Biochemistry, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, United Kingdom. Fax 44-2920-748383.
To the Editor:
Macroprolactin is a complex of prolactin with immunoglobulin (IgG) that in vivo appears to have limited or no biological activity, possibly because of the failure of the high-molecular weight complex to cross capillary walls (1). The predominant form of prolactin in serum in the general population is monomeric prolactin, but the prevalence of macroprolactin in serum is not known. However, when samples with increased prolactin are further investigated, it has been reported that up to 26% of these samples contain macroprolactin as the predominant form (2)(3). Immunoassays for prolactin have variable reactivity with macroprolactin; therefore, its presence should be considered in the differential diagnosis of hyperprolactinemia. This clinical problem is illustrated by the following two patients who were referred, from the same local hospital, to our endocrine center for the investigation of hyperprolactinemia.
Clinical case 1.
A 38-year-old female volunteer in a clinical
trial had serum prolactin concentrations of 1168–1748
mIU/L (reference interval <420 mIU/L) on three occasions at
her local hospital. She had occasional headaches, but regular menstrual
cycles and no galactorrhea or other clinical symptoms of the
hyperprolactinemic syndrome. On referral to our endocrine center,
imaging of her pituitary revealed no evidence of a prolactinoma,
although a small incidental tentorial meningioma was seen. Testing with
the dopamine antagonist, domperidone, (10 mg, administered
intravenously) produced a normal increase in serum prolactin 30 min
after administration (basal prolactin, 663 mIU/L, increasing to 5220
mIU/L; prolactin measured at our endocrine center). No treatment was
given, but serum prolactin measured 1 year later at her local hospital
was still increased at 2220 mIU/L.
Clinical case 2.
A 43-year-old female presented with a history
of irregular menstrual periods, recent weight gain, dryness of skin,
and facial hair, but no galactorrhea or visual problems. Domperidone
testing gave a normal response, and a computed tomography scan
revealed no abnormality. However, it was noticed that her serum
prolactin was increased at her local hospital but not significantly
increased on referral to our center. In July 1995, her serum prolactin
at our endocrine center was 510 mIU/L, whereas in August and September
1996, her serum prolactin at her local hospital was 1729 and 2134
mIU/L. A sample collected in October 1996 and measured in each
laboratory was 733 mIU/L at our endocrine center and 2322 mIU/L at her
local hospital. Serum prolactin, in this and clinical case 1, was
measured at her local hospital by a radioimmunoassay procedure and at
our endocrine center by a two-site immunochemiluminometric assay on the
Bayer Chiron ACS:180.
This discrepancy between the two assays prompted an investigation into
the response of other assays to this patient’s sample, utilizing the
United Kingdom External Quality Assessment Scheme (UKNEQAS). An aliquot
of serum from the second clinical case was distributed by UKNEQAS to 70
laboratories in the United Kingdom, which use 21 different methods for
prolactin measurement. The method mean prolactin concentrations varied
from 556 mIU/L to 2055 mIU/L, depending on the method used. The mean
prolactin concentrations by the main methods are shown in Fig. 1
for the patient specimen and for two hyperprolactinemic pools,
one with exogenous prolactin and one endogenous. Gel
filtration studies of samples from both patients showed that
macroprolactin was the predominant form of prolactin in their sera.
|
All methods for measuring prolactin will show some cross-reactivity with macroprolactin, and the extent to which it contributes to the measured prolactin concentration depends on the choice of reagent antibody. Because the presence of macroprolactin does not appear to contribute to the hyperprolactinemic syndrome in the majority of patients, it is important to raise awareness of the problem in clinical chemistry laboratories and with physicians. We recommend that manufacturers of prolactin reagents state in their product leaflets to what extent macroprolactin interferes in their prolactin assay and have available a validated method to confirm the presence of macroprolactin. It is also important that manufacturers address the problem with prolactin assays to minimize reaction with macroprolactin. In the meantime, polyethylene glycol (PEG) precipitation has been shown to be a valid screening test for macroprolactin when used with the Wallac DELFIA assay (2). It cannot, however, be used for all methods because of interference from PEG, and it needs to be validated with other assay systems before being brought into use.
Confirmation of the presence of macroprolactin can be made by gel filtration chromatography, but this is time-consuming, costly, and beyond the scope of most clinical laboratories. Laboratories in the United Kingdom have been using mainly PEG precipitation techniques to identify macroprolactinemia, but we urge equipment manufacturers to address this problem. As highlighted in these two clinical cases, macroprolactin needs to be identified early in a patient’s work-up to avoid unnecessary, costly, and invasive procedures.
References
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  L. Kavanagh, T. J. McKenna, M. N. Fahie-Wilson, J. Gibney, and T. P. Smith Specificity and Clinical Utility of Methods for the Detection of Macroprolactin Clin. Chem., July 1, 2006; 52(7): 1366 - 1372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hekim, H. Alfthan, J. T. Leinonen, and U.-H. Stenman Effect of Incubation Time on Recognition of Various Forms of Prolactin in Serum by the DELFIA Assay Clin. Chem., December 1, 2002; 48(12): 2253 - 2256. [Full Text] [PDF]
|
|
|
|
|
|
G. Gilson, P. Schmit, J. Thix, J.-P. Hoffman, and R.-L. Humbel Prolactin Results for Samples Containing Macroprolactin Are Method and Sample Dependent Clin. Chem., February 1, 2001; 47(2): 331 - 333. [Full Text] [PDF]
|
|
|
|
|
|
M. N. Fahie-Wilson and R. John Detection of Macroprolactin Causing Hyperprolactinemia in Commercial Assays for Prolactin Dr. John responds: Clin. Chem., December 1, 2000; 46(12): 2022 - 2023. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
