Top

Published in:

01-02-2020 | Prolactinoma

Biochemical diagnosis in prolactinomas: some caveats

Author: Stephan Petersenn

Published in: Pituitary | Issue 1/2020

Abstract

Prolactinomas are the most frequently seen pituitary adenomas in clinical practice. A correct biochemical diagnosis of hyperprolactinemia is a prerequisite for further investigation but may be hampered by analytical difficulties as well as a large number of potentially overlapping conditions associated with increased prolactin levels. Suspicion should rise in patients whose symptoms and biochemical results do not match. Assay problems, macroprolactinemia, and high-dose hook effect are discussed as possible reasons for false positive or false negative prolactin levels. Physiological and pathological causes of hyperprolactinemia and their implications for interpreting prolactin results are reviewed.

Saleem M, Martin H, Coates P (2018) Prolactin biology and laboratory measurement: an update on physiology and current analytical issues. Clin Biochem Rev 39:3–16PubMedPubMedCentral

Bernard V, Young J, Chanson P, Binart N (2015) New insights in prolactin: pathological implications. Nat Rev Endocrinol 11:265–275PubMed

Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, Cappabianca P, Colao A, Fahlbusch R, Fideleff H, Hadani M, Kelly P, Kleinberg D, Laws E, Marek J, Scanlon M, Sobrinho LG, Wass JA, Giustina A (2006) Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 65:265–273

Seppälä M, Ranta T, Hirvonen E (1976) Hyperprolactinaemia and luteal insufficiency. Lancet 1:229–230PubMed

Garde AH, Hansen AM, Skovgaard LT, Christensen JM (2000) Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone sulfate, hemoglobin A(1c), IgA, prolactin, and free testosterone in healthy women. Clin Chem 46:551–559PubMed

Overgaard M, Pedersen SM (2017) Serum prolactin revisited: parametric reference intervals and cross platform evaluation of polyethylene glycol precipitation-based methods for discrimination between hyperprolactinemia and macroprolactinemia. Clin Chem Lab Med 55:1744–1753PubMed

Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA, Endocrine S (2011) Diagnosis and treatment of hyperprolactinemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96:273–288PubMed

Hattori N (2003) Macroprolactinemia: a new cause of hyperprolactinemia. J Pharmacol Sci 92:171–177PubMed

Wallace IR, Satti N, Courtney CH, Leslie H, Bell PM, Hunter SJ, McCance DR, Sheridan B, Atkinson AB (2010) Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant. J Clin Endocrinol Metab 95:3268–3271PubMed

10.

Smith TP, Suliman AM, Fahie-Wilson MN, McKenna TJ (2002) Gross variability in the detection of prolactin in sera containing big big prolactin (macroprolactin) by commercial immunoassays. J Clin Endocrinol Metab 87:5410–5415PubMed

11.

Fahie-Wilson M, Smith TP (2013) Determination of prolactin: the macroprolactin problem. Best Pract Res Clin Endocrinol Metab 27:725–742PubMed

12.

Samson SL, Hamrahian AH, Ezzat S (2015) American Association of Clinical Endocrinologists, American College of Endocrinology Disease state clinical review: clinical relevance of macroprolactin in the absence or presence of true hyperprolactinemia. Endocr Pract 21:1427–1435PubMed

13.

Kavanagh L, McKenna TJ, Fahie-Wilson MN, Gibney J, Smith TP (2006) Specificity and clinical utility of methods for the detection of macroprolactin. Clin Chem 52:1366–1372PubMed

14.

Olukoga AO, Kane JW (1999) Macroprolactinaemia: validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition. Clin Endocrinol (Oxf) 51:119–126

15.

Suliman AM, Smith TP, Gibney J, McKenna TJ (2003) Frequent misdiagnosis and mismanagement of hyperprolactinemic patients before the introduction of macroprolactin screening: application of a new strict laboratory definition of macroprolactinemia. Clin Chem 49:1504–1509PubMed

16.

Beltran L, Fahie-Wilson MN, McKenna TJ, Kavanagh L, Smith TP (2008) Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms. Clin Chem 54:1673–1681PubMed

17.

Ram S, Harris B, Fernando JJ, Gama R, Fahie-Wilson M (2008) False-positive polyethylene glycol precipitation tests for macroprolactin due to increased serum globulins. Ann Clin Biochem 45:256–259PubMed

18.

Petakov MS, Damjanović SS, Nikolić-Durović MM, Dragojlović ZL, Obradović S, Gligorović MS, Simić MZ, Popović VP (1998) Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect. J Endocrinol Invest 21:184–188PubMed

19.

Schöfl C, Schöfl-Siegert B, Karstens JH, Bremer M, Lenarz T, Cuarezma JS, Samii M, von zur Mühlen A, Brabant G (2002) Falsely low serum prolactin in two cases of invasive macroprolactinoma. Pituitary 5:261–265PubMed

20.

Unnikrishnan AG, Rajaratnam S, Seshadri MS, Kanagasapabathy AS, Stephen DC (2001) The ‘hook effect’ on serum prolactin estimation in a patient with macroprolactinoma. Neurol India 49:78–80PubMed

21.

Barkan AL, Chandler WF (1998) Giant pituitary prolactinoma with falsely low serum prolactin: the pitfall of the “high-dose hook effect”: case report. Neurosurgery 42:913–915 (discussion 915)PubMed

22.

Lennartsson AK, Jonsdottir IH (2011) Prolactin in response to acute psychosocial stress in healthy men and women. Psychoneuroendocrinology 36:1530–1539PubMed

23.

Hackney AC, Saeidi A (2019) The thyroid axis, prolactin, and exercise in humans. Curr Opin Endocr Metab Res 9:45–50PubMedPubMedCentral

24.

Daly W, Seegers CA, Rubin DA, Dobridge JD, Hackney AC (2005) Relationship between stress hormones and testosterone with prolonged endurance exercise. Eur J Appl Physiol 93:375–380PubMed

25.

Hu Y, Ding Y, Yang M, Xiang Z (2018) Serum prolactin levels across pregnancy and the establishment of reference intervals. Clin Chem Lab Med 56:803–807

26.

Molitch ME (2008) Drugs and prolactin. Pituitary 11:209–218PubMed

27.

Smith SM, O’Keane V, Murray R (2002) Sexual dysfunction in patients taking conventional antipsychotic medication. Br J Psychiatry 181:49–55PubMed

28.

Haddad PM, Wieck A (2004) Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 64:2291–2314PubMed

29.

Kapur S, Seeman P (2001) Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: a new hypothesis. Am J Psychiatry 158:360–369PubMed

30.

Byerly M, Suppes T, Tran QV, Baker RA (2007) Clinical implications of antipsychotic-induced hyperprolactinemia in patients with schizophrenia spectrum or bipolar spectrum disorders: recent developments and current perspectives. J Clin Psychopharmacol 27:639–661PubMed

31.

Madhusoodanan S, Parida S, Jimenez C (2010) Hyperprolactinemia associated with psychotropics—a review. Hum Psychopharmacol 25:281–297PubMed

32.

Hutchinson J, Murphy M, Harries R, Skinner CJ (2000) Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. The Lancet 356:1003–1004

33.

Luciano AA, Sherman BM, Chapler FK, Hauser KS, Wallace RB (1985) Hyperprolactinemia and contraception: a prospective study. Obstet Gynecol 65:506–510PubMed

34.

Reyniak JV, Wenof M, Aubert JM, Stangel JJ (1980) Incidence of hyperprolactinemia during oral contraceptive therapy. Obstet Gynecol 55:8–11PubMed

35.

Bourgeois AL, Auriche P, Palmaro A, Montastruc JL, Bagheri H (2016) Risk of hormonotherapy in transgender people: literature review and data from the French Database of Pharmacovigilance. Ann Endocrinol (Paris) 77:14–21

36.

Holley JL (2004) The hypothalamic-pituitary axis in men and women with chronic kidney disease. Adv Chronic Kidney Dis 11:337–341PubMed

37.

Hou SH, Grossman S, Molitch ME (1985) Hyperprolactinemia in patients with renal insufficiency and chronic renal failure requiring hemodialysis or chronic ambulatory peritoneal dialysis. Am J Kidney Dis 6:245–249PubMed

38.

Lo JC, Beck GJ, Kaysen GA, Chan CT, Kliger AS, Rocco MV, Chertow GM, FHN Study (2017) Hyperprolactinemia in end-stage renal disease and effects of frequent hemodialysis. Hemodial Int 21:190–196PubMed

39.

Saha MT, Saha HH, Niskanen LK, Salmela KT, Pasternack AI (2002) Time course of serum prolactin and sex hormones following successful renal transplantation. Nephron 92:735–737PubMed

40.

Yavuz D, Topçu G, Ozener C, Akalin S, Sirikçi O (2005) Macroprolactin does not contribute to elevated levels of prolactin in patients on renal replacement therapy. Clin Endocrinol (Oxf) 63:520–524

41.

Farthing MJ, Green JR, Edwards CR, Dawson AM (1982) Progesterone, prolactin, and gynaecomastia in men with liver disease. Gut 23:276–279PubMedPubMedCentral

42.

Morgan MY, Jakobovits AW, Gore MB, Wills MR, Sherlock S (1978) Serum prolactin in liver disease and its relationship to gynaecomastia. Gut 19:170–174PubMedPubMedCentral

43.

McClain CJ, Kromhout JP, Elson MK, Van Thiel DH (1981) Hyperprolactinemia in portal systemic encephalopathy. Dig Dis Sci 26:353–357PubMed

44.

Corenblum B, Shaffer EA (1989) Hyperprolactinemia in hepatic encephalopathy may result from impaired central dopaminergic neurotransmission. Horm Metab Res 21:675–677PubMed

45.

Ress C, Maeser PA, Tschoner A, Loacker L, Salzmann K, Staudacher G, Melmer A, Zoller H, Vogel W, Griesmacher A, Tilg H, Kaser I (2014) Serum prolactin in advanced chronic liver disease. Horm Metab Res 46:800–803PubMed

46.

Potter E, Nicolaisen AK, Ong ES, Evans RM, Rosenfeld MG (1981) Thyrotropin-releasing hormone exerts rapid nuclear effects to increase production of the primary prolactin mRNA transcript. Proc Natl Acad Sci USA 78:6662–6666PubMedPubMedCentral

47.

Cave WT, Paul MA (1980) Effects of altered thyroid function on plasma prolactin clearance. Endocrinology 107:85–91PubMed

48.

Foord SM, Peters JR, Dieguez C, Jasani B, Hall R, Scanlon MF (1984) Hypothyroid pituitary cells in culture: an analysis of thyrotropin and prolactin responses to dopamine (DA) and DA receptor binding. Endocrinology 115:407–415PubMed

49.

Davis JR, Lynam TC, Franklyn JA, Docherty K, Sheppard MC (1986) Tri-iodothyronine and phenytoin reduce prolactin messenger RNA levels in cultured rat pituitary cells. J Endocrinol 109:359–364PubMed

50.

Hekimsoy Z, Kafesçiler S, Güçlü F, Ozmen B (2010) The prevalence of hyperprolactinaemia in overt and subclinical hypothyroidism. Endocr J 57:1011–1015PubMed

51.

Sharma LK, Sharma N, Gadpayle AK, Dutta D (2016) Prevalence and predictors of hyperprolactinemia in subclinical hypothyroidism. Eur J Intern Med 35:106–110PubMed

52.

Raber W, Gessl A, Nowotny P, Vierhapper H (2003) Hyperprolactinaemia in hypothyroidism: clinical significance and impact of TSH normalization. Clin Endocrinol (Oxf) 58:185–191

53.

Morley JE, Dawson M, Hodgkinson H, Kalk WJ (1977) Galactorrhea and hyperprolactinemia associated with chest wall injury. J Clin Endocrinol Metab 45:931–935PubMed

Title: Biochemical diagnosis in prolactinomas: some caveats
Author: Stephan Petersenn
Publication date: 01-02-2020
Publisher: Springer US
Keywords: Prolactinoma
Hyperprolactinemia
Chronic Kidney Disease
Hypothyroidism
Published in: Pituitary / Issue 1/2020
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI: https://doi.org/10.1007/s11102-019-01024-z

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Biochemical diagnosis in prolactinomas: some caveats

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

Dopamine agonists in prolactinomas: when to withdraw?

Prolactinomas in males: any differences?

Aggressive prolactinomas: how to manage?

Dopamine agonist resistant prolactinomas: any alternative medical treatment?

Diagnosis and management of prolactinomas: current challenges

Prolactinomas in pregnancy: considerations before conception and during pregnancy

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page