Hyperprolactinemia resident survival guide: Difference between revisions

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==Overview==
==Overview==
[[Hyperprolactinemia]] is defined as high circulating levels of [[prolactin]] in the blood. The cut-off values of serum [[prolactin]] for [[hyperprolactinemia]] are greater than 20 ng/ml in men and postmenopausal women and greater than 30ng/ml in premenopausal women.<ref name="pmid21296991">{{cite journal| author=Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA | display-authors=etal| title=Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2011 | volume= 96 | issue= 2 | pages= 273-88 | pmid=21296991 | doi=10.1210/jc.2010-1692 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21296991  }} </ref> [[Prolactin]] [[hormone]] is produced by lactotroph cells located in the anterior lobe of the [[pituitary gland]]. It is responsible for [[lactation]] and the development of [[breasts]] in females during pregnancy. Elevated levels of [[prolactin]] cause [[galactorrhea]], menstrual irregularities, and failure to conceive in females and erectile dysfunction, [[hypogonadism]], and [[infertility]] in males. This section provides a short and straight to the point overview of the [[hyperprolactinemia]].
[[Hyperprolactinemia]] is defined as high circulating levels of [[prolactin]] in the blood. The cut-off values of serum [[prolactin]] for [[hyperprolactinemia]] are greater than 20 ng/ml in men and postmenopausal women and greater than 30ng/ml in premenopausal women.<ref name="pmid21296991">{{cite journal| author=Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA | display-authors=etal| title=Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2011 | volume= 96 | issue= 2 | pages= 273-88 | pmid=21296991 | doi=10.1210/jc.2010-1692 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21296991  }} </ref> [[Prolactin]] [[hormone]] is produced by lactotroph cells located in the anterior lobe of the [[pituitary gland]]. It is responsible for [[lactation]] and the development of [[breasts]] in females during [[pregnancy]]. Elevated levels of [[prolactin]] cause [[galactorrhea]], menstrual irregularities, and failure to conceive in females and [[erectile dysfunction]], [[hypogonadism]], and [[infertility]] in males. This section provides a short and straight to the point overview of the [[hyperprolactinemia]].


==Causes==
==Causes==
===Life Threatening Causes===
===Life Threatening Causes===
Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.
Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.
* Severe burns on the chest can cause hyperprolactinemia due to neural stimulation similar to suckling. <ref name="pmid562902">{{cite journal| author=Morley JE, Dawson M, Hodgkinson H, Kalk WJ| title=Galactorrhea and hyperprolactinemia associated with chest wall injury. | journal=J Clin Endocrinol Metab | year= 1977 | volume= 45 | issue= 5 | pages= 931-5 | pmid=562902 | doi=10.1210/jcem-45-5-931 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=562902  }} </ref>
* Severe [[burn|burns]] on the chest can cause [[hyperprolactinemia]] due to neural stimulation similar to [[Breastfeeding|suckling]]. <ref name="pmid562902">{{cite journal| author=Morley JE, Dawson M, Hodgkinson H, Kalk WJ| title=Galactorrhea and hyperprolactinemia associated with chest wall injury. | journal=J Clin Endocrinol Metab | year= 1977 | volume= 45 | issue= 5 | pages= 931-5 | pmid=562902 | doi=10.1210/jcem-45-5-931 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=562902  }} </ref>


===Common Causes===
===Common Causes===
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* [[Lactation]]<ref name="pmid5024994">{{cite journal| author=Tyson JE, Hwang P, Guyda H, Friesen HG| title=Studies of prolactin secretion in human pregnancy. | journal=Am J Obstet Gynecol | year= 1972 | volume= 113 | issue= 1 | pages= 14-20 | pmid=5024994 | doi=10.1016/0002-9378(72)90446-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5024994  }} </ref>
* [[Lactation]]<ref name="pmid5024994">{{cite journal| author=Tyson JE, Hwang P, Guyda H, Friesen HG| title=Studies of prolactin secretion in human pregnancy. | journal=Am J Obstet Gynecol | year= 1972 | volume= 113 | issue= 1 | pages= 14-20 | pmid=5024994 | doi=10.1016/0002-9378(72)90446-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5024994  }} </ref>
* [[Prolactinoma]]<ref name="pmid840242">{{cite journal| author=Kleinberg DL, Noel GL, Frantz AG| title=Galactorrhea: a study of 235 cases, including 48 with pituitary tumors. | journal=N Engl J Med | year= 1977 | volume= 296 | issue= 11 | pages= 589-600 | pmid=840242 | doi=10.1056/NEJM197703172961103 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=840242  }} </ref>
* [[Prolactinoma]]<ref name="pmid840242">{{cite journal| author=Kleinberg DL, Noel GL, Frantz AG| title=Galactorrhea: a study of 235 cases, including 48 with pituitary tumors. | journal=N Engl J Med | year= 1977 | volume= 296 | issue= 11 | pages= 589-600 | pmid=840242 | doi=10.1056/NEJM197703172961103 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=840242  }} </ref>
* Injury to dopaminergic neurons in the hypothalamus ([[sarcoidosis]], [[craniopharyngioma]], and metastatic brain carcinoma)<ref name="pmid840242">{{cite journal| author=Kleinberg DL, Noel GL, Frantz AG| title=Galactorrhea: a study of 235 cases, including 48 with pituitary tumors. | journal=N Engl J Med | year= 1977 | volume= 296 | issue= 11 | pages= 589-600 | pmid=840242 | doi=10.1056/NEJM197703172961103 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=840242  }} </ref>
* Injury to dopaminergic neurons in the [[hypothalamus]] ([[sarcoidosis]], [[craniopharyngioma]], and metastatic brain carcinoma)<ref name="pmid840242">{{cite journal| author=Kleinberg DL, Noel GL, Frantz AG| title=Galactorrhea: a study of 235 cases, including 48 with pituitary tumors. | journal=N Engl J Med | year= 1977 | volume= 296 | issue= 11 | pages= 589-600 | pmid=840242 | doi=10.1056/NEJM197703172961103 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=840242  }} </ref>
* Section of the hypothalamic-pituitary stalk
* Section of the hypothalamic-pituitary stalk
* Antipsychotics ([[risperidone]], [[haloperidol]], and [[phenothiazine]])<ref name="pmid11048906">{{cite journal| author=David SR, Taylor CC, Kinon BJ, Breier A| title=The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. | journal=Clin Ther | year= 2000 | volume= 22 | issue= 9 | pages= 1085-96 | pmid=11048906 | doi=10.1016/S0149-2918(00)80086-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11048906  }} </ref>
* Antipsychotics ([[risperidone]], [[haloperidol]], and [[phenothiazine]])<ref name="pmid11048906">{{cite journal| author=David SR, Taylor CC, Kinon BJ, Breier A| title=The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. | journal=Clin Ther | year= 2000 | volume= 22 | issue= 9 | pages= 1085-96 | pmid=11048906 | doi=10.1016/S0149-2918(00)80086-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11048906  }} </ref>
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{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | C01 | | | |C01= <div style="float: left; text-align: left; height: 6em; width: 15em; padding:1em;"> Measure serum [[prolactin]]. Elevated serum [[prolactin]] }}
{{Family tree | | | | C01 | | | |C01= <div style="float: left; text-align: left;"> Measure serum [[prolactin]]. Elevated serum [[prolactin]] }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | |!| | | | | }}
{{Family tree | | | | D01 | | | |D01= Mesure serum TSH. TSH levels elevated?}}
{{Family tree | | | | D01 | | | |D01= <div style="float: left; text-align: left;"> Mesure serum [[Thyroid-stimulating hormone|TSH]]. [[Thyroid-stimulating hormone|TSH]] levels elevated?}}
{{familytree | | |,|-|^|-|.| }}
{{familytree | | |,|-|^|-|.| }}
{{familytree | | E01 | | |E02|E01= Yes | E02= No}}
{{familytree | | E01 | | |E02|E01= Yes | E02= No}}
{{familytree | | |!| | | |!| }}
{{familytree | | |!| | | |!| }}
{{familytree | | F01 | | |F02|F01= Treat [[hypothyroidism]] | F02= Perform the MRI with the contrast of the brain. Does it show any mass in the hypothalamic-pituitary region? }}
{{familytree | | F01 | | |F02|F01= <div style="float: left; text-align: left;">Treat [[hypothyroidism]] | F02= <div style="float: left; text-align: left;">Perform the [[Magnetic resonance imaging|MRI]] with the contrast of the [[brain]]. Does it show any mass in the hypothalamic-pituitary region? }}
{{familytree | | |!| | |,|-|^|-|.| }}
{{familytree | | |!| | |,|-|^|-|.| }}
{{familytree | | G01 | |G02 | | G03 |G01= Levels of TSH and [[prolactin]] should be reassessed after 6-12 weeks. | G02=Yes. The levels of other pituitary hormones should be evaluated: Plasma [[Adrenocorticotropic hormone|corticotropins]] (ACTH), Serum TSH, Insulin-like growth factors, [[Follicle-stimulating hormone]], [[Luteinizing hormone]], Estradiol/ Testosterone | G03= No}}
{{familytree | | G01 | |G02 | | G03 |G01= <div style="float: left; text-align: left;"> Levels of TSH and [[prolactin]] should be reassessed after 6-12 weeks. | G02= Yes | G03= No}}
{{familytree | | | | | |!| | | | | }}
{{familytree | | | | | |H01| | | |H01= <div style="float: left; text-align: left;"> The levels of other pituitary hormones should be evaluated: Plasma [[Adrenocorticotropic hormone|corticotropins]] (ACTH), Serum TSH, Insulin-like growth factors, [[Follicle-stimulating hormone]], [[Luteinizing hormone]], Estradiol/ [[Testosterone (transdermal)|Testosterone]] }}
{{Family tree/end}}
{{Family tree/end}}


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{{Family tree | B01 | | | | B02 |B01=<div style="float: left; text-align: left; height: 13em; width: 19em; padding:1em;">The drug of choice for [[prolactinoma]] are:  
{{Family tree | B01 | | | | B02 |B01=<div style="float: left; text-align: left; height: 13em; width: 19em; padding:1em;">The drug of choice for [[prolactinoma]] are:  
* [[Dopamine agonist|Dopamine agonists]] as they decrease [[prolactin]] secretion and reduce the size of the [[prolactinoma]].   
* [[Dopamine agonist|Dopamine agonists]] as they decrease [[prolactin]] secretion and reduce the size of the [[prolactinoma]].   
* [[Cabergoline]] is the preferred drug because of its efficacy and lower incidence of nausea and side effects compared to [[bromocriptine]]. |B02= Transsphenoidal surgery is done in:
* [[Cabergoline]] is the preferred drug because of its efficacy and lower incidence of [[Nausea and vomiting|nausea]] and side effects compared to [[bromocriptine]]. |B02= <div style="float: left; text-align: left; height: 13em;"> Transsphenoidal surgery is done in:
* Patients with unsuccessful treatment with [[Dopamine agonist|dopamine agonists]].  
* Patients with unsuccessful treatment with [[Dopamine agonist|dopamine agonists]].  
* A female patient with a known history of lactotroph macroadenoma who wishes to conceive. }}
* A female patient with a known history of lactotroph macroadenoma who wishes to conceive. }}
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{{Family tree | C01 | | | | C02 |C01=<div style="float: left; text-align: left; height: 14em; width: 16em; padding:1em;">
{{Family tree | C01 | | | | C02 |C01=<div style="float: left; text-align: left; height: 14em; width: 16em; padding:1em;">
*The preferred initial dose of [[cabergoline]] for microadenoma is 0.25mg twice a week or 0.5mg once a week.
*The preferred initial dose of [[cabergoline]] for microadenoma is 0.25mg twice a week or 0.5mg once a week.
*The medicine should be given at dinner or bedtime to reduce the incidence of nausea and drowsiness. |C02= Transsphenoidal surgery has a high success rate in reducing serum [[prolactin]] to a normal level. }}
*The medicine should be given at dinner or bedtime to reduce the incidence of [[Nausea and vomiting|nausea]] and [[Somnolence|drowsiness]]. |C02= Transsphenoidal surgery has a high success rate in reducing serum [[prolactin]] to a normal level. }}
{{Family tree/end}}
{{Family tree/end}}


==Do's==
==Do's==
* “Hook effect” should be kept in consideration while assessing serum [[prolactin]] levels. Patients with macroadenoma can have artifactually low values of serum [[prolactin]] between 20 to 200 mcg/L in patients with high levels of serum [[prolactin]] i.e. 5000 mcg/L.<ref name="pmid9591215">{{cite journal| author=Petakov MS, Damjanović SS, Nikolić-Durović MM, Dragojlović ZL, Obradović S, Gligorović MS | display-authors=etal| title=Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect. | journal=J Endocrinol Invest | year= 1998 | volume= 21 | issue= 3 | pages= 184-8 | pmid=9591215 | doi=10.1007/BF03347299 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9591215  }} </ref> This artifact is avoided by repeating the assay by dilution of serum.  
* While assessing [[serum]] [[prolactin]] levels "hook effect” should be considered. Patients with macroadenoma can have artifactually low values of serum [[prolactin]] between 20 to 200 mcg/L in patients with high levels of serum [[prolactin]] i.e. 5000 mcg/L.<ref name="pmid9591215">{{cite journal| author=Petakov MS, Damjanović SS, Nikolić-Durović MM, Dragojlović ZL, Obradović S, Gligorović MS | display-authors=etal| title=Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect. | journal=J Endocrinol Invest | year= 1998 | volume= 21 | issue= 3 | pages= 184-8 | pmid=9591215 | doi=10.1007/BF03347299 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9591215  }} </ref> This artifact is avoided by repeating the assay by dilution of serum.  
* Cabergoline is preferred by women who wish to conceive as it is safe in early pregnancy.<ref name="pmid8829257">{{cite journal| author=Robert E, Musatti L, Piscitelli G, Ferrari CI| title=Pregnancy outcome after treatment with the ergot derivative, cabergoline. | journal=Reprod Toxicol | year= 1996 | volume= 10 | issue= 4 | pages= 333-7 | pmid=8829257 | doi=10.1016/0890-6238(96)00063-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8829257  }} </ref> Though bromocriptine is also a safe choice with more evidence of reduced events of congenital defects.<ref name="pmid7062462">{{cite journal| author=Turkalj I, Braun P, Krupp P| title=Surveillance of bromocriptine in pregnancy. | journal=JAMA | year= 1982 | volume= 247 | issue= 11 | pages= 1589-91 | pmid=7062462 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7062462  }} </ref>
* Cabergoline is preferred by women who wish to conceive as it is safe in early pregnancy.<ref name="pmid8829257">{{cite journal| author=Robert E, Musatti L, Piscitelli G, Ferrari CI| title=Pregnancy outcome after treatment with the ergot derivative, cabergoline. | journal=Reprod Toxicol | year= 1996 | volume= 10 | issue= 4 | pages= 333-7 | pmid=8829257 | doi=10.1016/0890-6238(96)00063-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8829257  }} </ref> Though bromocriptine is also a safe choice with more evidence of reduced events of congenital defects.<ref name="pmid7062462">{{cite journal| author=Turkalj I, Braun P, Krupp P| title=Surveillance of bromocriptine in pregnancy. | journal=JAMA | year= 1982 | volume= 247 | issue= 11 | pages= 1589-91 | pmid=7062462 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7062462  }} </ref>
* Patients with [[hyperprolactinemia]] with normal serum [[prolactin]] levels should be monitored for regular intervals after discontinuing [[cabergoline]]. There is a recurrence of [[hyperprolactinemia]] in these patients.<ref name="pmid14627787">{{cite journal| author=Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G| title=Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 21 | pages= 2023-33 | pmid=14627787 | doi=10.1056/NEJMoa022657 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14627787  }} </ref>
* [[Physician]] should monitor patients with [[hyperprolactinemia]] with normal serum [[prolactin]] levels for regular intervals after discontinuing [[cabergoline]]. There is a chance of recurrence of [[hyperprolactinemia]] in patients after disconticontinuing [[cabergoline]].<ref name="pmid14627787">{{cite journal| author=Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G| title=Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 21 | pages= 2023-33 | pmid=14627787 | doi=10.1056/NEJMoa022657 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14627787  }} </ref>


==Don'ts==
==Don'ts==
* Certain medications like [[risperidone]], [[domperidone]], [[methyldopa]], [[metoclopramide]], [[verapamil]], and [[cimetidine]] raise serum [[prolactin]] levels. These medications can blunt the effects of dopamine agonists.
* [[Physician]] should prescribe certain medications like [[risperidone]], [[domperidone]], [[methyldopa]], [[metoclopramide]], [[verapamil]], and [[cimetidine]] with caution in patients with [[hyperprolactinemia]] as it raise serum [[prolactin]] levels. These medications can blunt the effects of [[dopamine]] agonists.
* The patients should be monitored for side effects. [[Cabergoline]] treatment in [[prolactinoma]] patients for more than three months can result in impulse control disorders. [[Hypersexuality]] is common in males and compulsive eating disorders in females.<ref name="pmid30848825">{{cite journal| author=Dogansen SC, Cikrikcili U, Oruk G, Kutbay NO, Tanrikulu S, Hekimsoy Z | display-authors=etal| title=Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study. | journal=J Clin Endocrinol Metab | year= 2019 | volume= 104 | issue= 7 | pages= 2527-2534 | pmid=30848825 | doi=10.1210/jc.2018-02202 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30848825  }} </ref>
* The patients should be monitored for side effects. [[Cabergoline]] treatment in [[prolactinoma]] patients for more than three months can result in impulse control disorders. [[Hypersexuality]] is common in males and compulsive eating disorders in females.<ref name="pmid30848825">{{cite journal| author=Dogansen SC, Cikrikcili U, Oruk G, Kutbay NO, Tanrikulu S, Hekimsoy Z | display-authors=etal| title=Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study. | journal=J Clin Endocrinol Metab | year= 2019 | volume= 104 | issue= 7 | pages= 2527-2534 | pmid=30848825 | doi=10.1210/jc.2018-02202 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30848825  }} </ref>


Latest revision as of 20:00, 15 October 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mydah Sajid, MD[2]

Overview

Hyperprolactinemia is defined as high circulating levels of prolactin in the blood. The cut-off values of serum prolactin for hyperprolactinemia are greater than 20 ng/ml in men and postmenopausal women and greater than 30ng/ml in premenopausal women.[1] Prolactin hormone is produced by lactotroph cells located in the anterior lobe of the pituitary gland. It is responsible for lactation and the development of breasts in females during pregnancy. Elevated levels of prolactin cause galactorrhea, menstrual irregularities, and failure to conceive in females and erectile dysfunction, hypogonadism, and infertility in males. This section provides a short and straight to the point overview of the hyperprolactinemia.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

Common Causes

Diagnosis

Shown below is an algorithm summarizing the diagnosis of hyperprolactinemia according to an Endocrine Society Clinical Practice guidelines:[1][11]

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inquire about any present illness like hypothyroidism, chronic renal failure, and the use of medications known to cause hyperprolactinemia.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure serum prolactin. Elevated serum prolactin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mesure serum TSH. TSH levels elevated?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
Perform the MRI with the contrast of the brain. Does it show any mass in the hypothalamic-pituitary region?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Levels of TSH and prolactin should be reassessed after 6-12 weeks.
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The levels of other pituitary hormones should be evaluated: Plasma corticotropins (ACTH), Serum TSH, Insulin-like growth factors, Follicle-stimulating hormone, Luteinizing hormone, Estradiol/ Testosterone
 
 
 

Treatment

Shown below is an algorithm summarizing the treatment of hyperprolactinemia:[1][12][13][14]

 
 
 
The prolactinoma are treated in the following patients:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The drug of choice for prolactinoma are:
 
 
 
Transsphenoidal surgery is done in:
  • Patients with unsuccessful treatment with dopamine agonists.
  • A female patient with a known history of lactotroph macroadenoma who wishes to conceive.
    •  
     
     
     
     
     
     
     
     
     
     
     
    • The preferred initial dose of cabergoline for microadenoma is 0.25mg twice a week or 0.5mg once a week.
    • The medicine should be given at dinner or bedtime to reduce the incidence of nausea and drowsiness.
     
     
     
    		Transsphenoidal surgery has a high success rate in reducing serum prolactin to a normal level.

    Do's

    • While assessing serum prolactin levels "hook effect” should be considered. Patients with macroadenoma can have artifactually low values of serum prolactin between 20 to 200 mcg/L in patients with high levels of serum prolactin i.e. 5000 mcg/L.[15] This artifact is avoided by repeating the assay by dilution of serum.
    • Cabergoline is preferred by women who wish to conceive as it is safe in early pregnancy.[16] Though bromocriptine is also a safe choice with more evidence of reduced events of congenital defects.[17]
    • Physician should monitor patients with hyperprolactinemia with normal serum prolactin levels for regular intervals after discontinuing cabergoline. There is a chance of recurrence of hyperprolactinemia in patients after disconticontinuing cabergoline.[18]

    Don'ts

    References

    1. ↑ 1.0 1.1 1.2 Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA; et al. (2011). "Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 96 (2): 273–88. doi:10.1210/jc.2010-1692. PMID 21296991.
    2. ↑ Morley JE, Dawson M, Hodgkinson H, Kalk WJ (1977). "Galactorrhea and hyperprolactinemia associated with chest wall injury". J Clin Endocrinol Metab. 45 (5): 931–5. doi:10.1210/jcem-45-5-931. PMID 562902.
    3. ↑ 3.0 3.1 Tyson JE, Hwang P, Guyda H, Friesen HG (1972). "Studies of prolactin secretion in human pregnancy". Am J Obstet Gynecol. 113 (1): 14–20. doi:10.1016/0002-9378(72)90446-2. PMID 5024994.
    4. ↑ 4.0 4.1 Kleinberg DL, Noel GL, Frantz AG (1977). "Galactorrhea: a study of 235 cases, including 48 with pituitary tumors". N Engl J Med. 296 (11): 589–600. doi:10.1056/NEJM197703172961103. PMID 840242.
    5. ↑ David SR, Taylor CC, Kinon BJ, Breier A (2000). "The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia". Clin Ther. 22 (9): 1085–96. doi:10.1016/S0149-2918(00)80086-7. PMID 11048906.
    6. ↑ McCallum RW, Sowers JR, Hershman JM, Sturdevant RA (1976). "Metoclopramide stimulates prolactin secretion in man". J Clin Endocrinol Metab. 42 (6): 1148–52. doi:10.1210/jcem-42-6-1148. PMID 777023.
    7. ↑ Sowers JR, Sharp B, McCallum RW (1982). "Effect of domperidone, an extracerebral inhibitor of dopamine receptors, on thyrotropin, prolactin, renin, aldosterone, and 18-hydroxycorticosterone secretion in man". J Clin Endocrinol Metab. 54 (4): 869–71. doi:10.1210/jcem-54-4-869. PMID 7037817.
    8. ↑ Steiner J, Cassar J, Mashiter K, Dawes I, Fraser TR, Breckenridge A (1976). "Effects of methyldopa on prolactin and growth hormone". Br Med J. 1 (6019): 1186–8. doi:10.1136/bmj.1.6019.1186. PMC 1639736. PMID 1268617.
    9. ↑ Newey PJ, Gorvin CM, Cleland SJ, Willberg CB, Bridge M, Azharuddin M; et al. (2013). "Mutant prolactin receptor and familial hyperprolactinemia". N Engl J Med. 369 (21): 2012–2020. doi:10.1056/NEJMoa1307557. PMC 4209110. PMID 24195502.
    10. ↑ Snyder PJ, Jacobs LS, Utiger RD, Daughaday WH (1973). "Thyroid hormone inhibition of the prolactin response to thyrotropin-releasing hormone". J Clin Invest. 52 (9): 2324–9. doi:10.1172/JCI107421. PMC 333037. PMID 4199418.
    11. ↑ Majumdar A, Mangal NS (2013). "Hyperprolactinemia". J Hum Reprod Sci. 6 (3): 168–75. doi:10.4103/0974-1208.121400. PMC 3853872. PMID 24347930.
    12. ↑ Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD; et al. (2006). "Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas". Clin Endocrinol (Oxf). 65 (2): 265–73. doi:10.1111/j.1365-2265.2006.02562.x. PMID 16886971.
    13. ↑ Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF (1994). "A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group". N Engl J Med. 331 (14): 904–9. doi:10.1056/NEJM199410063311403. PMID 7915824.
    14. ↑ Randall RV, Laws ER, Abboud CF, Ebersold MJ, Kao PC, Scheithauer BW (1983). "Transsphenoidal microsurgical treatment of prolactin-producing pituitary adenomas. Results in 100 patients". Mayo Clin Proc. 58 (2): 108–21. PMID 6681646.
    15. ↑ Petakov MS, Damjanović SS, Nikolić-Durović MM, Dragojlović ZL, Obradović S, Gligorović MS; et al. (1998). "Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect". J Endocrinol Invest. 21 (3): 184–8. doi:10.1007/BF03347299. PMID 9591215.
    16. ↑ Robert E, Musatti L, Piscitelli G, Ferrari CI (1996). "Pregnancy outcome after treatment with the ergot derivative, cabergoline". Reprod Toxicol. 10 (4): 333–7. doi:10.1016/0890-6238(96)00063-9. PMID 8829257.
    17. ↑ Turkalj I, Braun P, Krupp P (1982). "Surveillance of bromocriptine in pregnancy". JAMA. 247 (11): 1589–91. PMID 7062462.
    18. ↑ Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G (2003). "Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia". N Engl J Med. 349 (21): 2023–33. doi:10.1056/NEJMoa022657. PMID 14627787.
    19. ↑ Dogansen SC, Cikrikcili U, Oruk G, Kutbay NO, Tanrikulu S, Hekimsoy Z; et al. (2019). "Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study". J Clin Endocrinol Metab. 104 (7): 2527–2534. doi:10.1210/jc.2018-02202. PMID 30848825.


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