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 )