Hyperprolactinemia

Prolactin ( PRL ) is a polypeptide hormone containing 198 amino acids and with a molecular weight of 22kDa. Hyperprloactinemia is elevated serum PRL.

Women → 500 milliunits/ L or < 25 micrograms /L
Men → 400 milliunits / L or 20 micrograms / L

Prolactin levels of over 3000 mII/L suggest the presence of a Prolactinoma.

PRL is synthesized and secreted by lactotroph cells in the anterior pituitary Also secreted by various extrapituitary tissues including several brain regions , lymphocytes , mammary epithelial cells , tumours , decidua , myometrium , lacrimal glands , thymus and the spleen Secretion is pulsatile → levels fluctuate throughout the day and the menstrual cycle Unique hormone – predominantly negative mode of regulation by the hypothalamus
○ no hypothalamus derived releasing hormone
○ controlled by inhibitory effect of DOPAMINE released from the hypothalamus Acts to induce and maintain lactation of the primed breast ( Mammogenic & lactogenic ) Nonpeurperal hyperprolactinemia is caused by lactotroph adenomas → PROLACTINOMA. Prolocatinomas account for 40 % of all pituitary tumours

Causes- physiological Coitus Exercise Lactation Pregnancy Sleep Stress. Pathological- Granulomas Infiltration Irradiation Rathke’s cyst Trauma
○ pituitary stalk section
○ suprasellar surgery Tumours
○ craniopharyngioma
○ germinoma
○ hypothalamic metasteses
○ meningioma
○ suprasellar pituitary mass Acromegaly Idiopathic Lymphocytic hypophysitis of parasellar mass Macroadenoma Macroprolactinemia Plurihormonal adenoma Prolactinoma Surgery Trauma Chest- neurogenic wall trauma , surgery , herpes zoster Chronic renal failure Cirrhosis Primary hypothyroidism Cranial radiation Epileptic seizures PCOS Multiple endocrine neoplasia. drug related- Antipsychotics 
○ phenothiazines
○ thioxanthenes
○ butyrophenones
○ atypical antipsychotics

Usually < 100 mcgm/L
Dose dependent
At the start of treatment
Highest with amisulpride and risperidone
 Drugs that block dopamine receptors
○ metoclopramide
○ domperidone
○ risperidone
○ tricylcic antidepressants
○ cimetidine
 Interfere with synthesis and storage of Dopamine
○ methyldopa
○ MAOIs
 Anti-depressants- SSRIs , nefazodone , bupropion , venlafaxine
 Opiates , opiate antagonists and cocaine
 Antihypertensives
○ verapamil
○ methyldopa
 Estrogen – Oral contraceptives
Oral contraceptive withdrawal
 Prolactinomas are the
 commonest functioning
 pituitary tumour. Vast majority 
are less than 10 mm – Microprolactinoma

Presentation- Females ↑ PRL can cause disorders of gonadotrophin sex steroid function – result
○ menstrual cycle derangement ( oligomenorrhoea and amenorrhoea , anovulation )
○ sexual dysfunction
○ inappropriate lactation or glactorrhoea
○ ↓↓ libido , hirsuitism 

Post-menopausal women –> Galactorrhoea less common due to lack of oestrogen 
Osteopenia and Osteoporosis , hirsuitism and acne
 Males ↑ PRL causes secondary hypogonadism and infertility by suppression of GnRH pulses and a ↓↓ in LH and FSH levels
○ patients may have low or normal testosterone levels
○ abnormal sperm counts and morphology
○ diminished libido and impotence
○ galactorrhoea , gynaecomastia , ↓↓ bone density Macroadenoma -Headache and visual field defect
○ only when macroadenomas with suprasellar extension impinge on optic chiasm
○ bitemporal hemianopia or upper temporal quadrantanopia Hypopituitarism Cranial nerve palsy ( invasion of cavernous sinus ) Rarely CSF leak or secondary meningitis Serum PRL > 4000 U/L is diagnostic of a macroprolactinoma Drug related -Usually only mild to moderate elevation in PRL Risperidone and metoclopramide can cause more than mild elevations Neuroleptics / Antipsychotic medications are the commonest cause If possible discontinue or substitute the medication and recheck in 3 Days Discuss first with Psychiatry team/Prescribing consultant – before considering changing/ discontinuing medications

Treatment-Dopamine agonists as bromocriptine , cabergoline

For tumors of any size

References Diagnosis and management of hyperprolactinemia Omar Serri et al CMAJ .2003 Sep 16(6) : 575-581 Hyperprolactinemia E medicine Donald Shenerberger et al May 2017 Hyperprolactenemia , Galacatorrhoea , and Pituitary Adenomas : Etiology , Differential Diagnosis , Natural History , Management Roger A. Lobo Comprehensive Gynecology , 39 , 853-864.e1 Hyperprolactinemia Ming Li MD , PhD et al Conn’s Current Therapy 2018 Interpreting raised serum prolactin results BMJ 2014 ;348:g3207 Diagnosis and Treatment of Hyperprolactinemia; an Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab , February 2011 , 96 (2):273-288 Prolocatinomas -Oxford Handbook of Endocrinology and Diabetes The epidemiology of hyperprolactinaemia over 20 years in the Tayside region of Scotland : the Prolactin Epidemiology , Audit and Research Study ( PROLEARS ) Clin Endocrinol ( Oxf ) Jan ; 86 (1) : 60-67 ( Abstract )


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