LACTATION AND PROLACTINOMAS_student central 2020_rev.pptx

LACTATION AND PROLACTINOMAS Dr Anna Crown Consultant Endocrinologist & Honorary Clinical Senior Lecturer TOPICS • Physiology of lactation • Causes of galactorrhoea • Prolactinomas BREAST DEVELOPMENT • Puberty – oestrogen, progesterone – GH (via IGF-I) • alveolar buds •  lobules • Pregnancy –...

LACTATION AND PROLACTINOMAS Dr Anna Crown Consultant Endocrinologist & Honorary Clinical Senior Lecturer TOPICS • Physiology of lactation • Causes of galactorrhoea • Prolactinomas BREAST DEVELOPMENT • Puberty – oestrogen, progesterone – GH (via IGF-I) • alveolar buds •  lobules • Pregnancy – oestrogen, progesterone – hCG, prolactin – Alveolar development • ducts & lobules • Differentiated secretory units (acini) • Colostrum accumulates MILK PRODUCTION • Milk production (lactogenesis) – Secretory intitiation • Progesterone • Occurs during pregnancy • Colostrum – Secretory activation • progesterone / oestrogen • prolactin (cortisol, insulin) • Copious milk production after delivery – Usually 2-3 days post-partum MILK COMPOSITION • Sugar • Lactose & oligosaccharides • Milk fats • triglycerides, cholesterol, phospholipids, steroid hormones • Proteins • Caseins, lactalbumin, lactoferrin, secretory IgA, lysozyme • Minerals • Na, K, Cl, Ca, Mg, Phosphate • Growth factors • Cellular components (esp in colostrum) • Macrophages, lymphocytes, neutrophils, epithelial cells • Phospholipids (membrane fragments) LACTATION • Lactation (galactopoiesis) – Positive feedback loops – Regular removal of milk – Nipple stimulation – Prolactin (anterior pituitary) – Oxytocin (posterior pituitary) PROLACTIN • Lactotroph cells – anterior pituitary • Similarities to GH • Similar receptor to GH – Tyrosine phosphorylation – JAK-STAT signalling PROLACTIN Hypothalamus + 5HT TRH OXT DA Pituitary PRL • Prolactin release inhibited by dopamine • Prolactin release stimulated by 5HT (serotonin), TRH, oxytocin PROLACTIN PROLACTIN IN PREGNANCY PROLACTIN AND SUCKLING LACTATION • Lactational amenorrhoea – Contraceptive efficacy depends on the frequency and duration of breast feeding • Prolactin  – GnRH – LH and FSH, pulsatility – oestrogen / testosterone OXYTOCIN • Nonapeptide • Synthesised in hypothalamic magnicellular neurons – Supraoptic nucleus – Paraventricular nucleus OXYTOCIN • Posterior pituitary – Distal axon terminals of hypothalamic magnocellular neurons • Neurosecretory granules released into capillary system of posterior pituitary OXYTOCIN • Afferent signal from receptors in the nipple when the infant suckles ascend to hypothalamus • + uterine myometrial contraction at birth • + smooth muscle activation in breast – ‘myoepithelial contraction’ • + milk let-down • ? role in maternal behaviour ? The evolutionary perspective • Strategies Mammals lactate for success – Milk Reproductive production strategy involves producing a nutritious secretion from an exocrine gland & encouraging offspring to consume it – changes in the mother’s – Complementary Continued nurturing of offspring after birthbrain • Metabolic with benefits including enhanced brain • Psycho-social / behavioural development – Same hormones! Prof Dave Grattan www.neuroendo.org.uk British Society for Neuroendocrinology Neuroendocrinology Briefings 38 ‘A Mother’s Brain Knows’ (2011) A mother’s brain knows….. • Humans • Other mammals – Brain responds to hormonal changes associated with ovulation, mating, implantation & pregnancy – via prolactin & placental lactogens howtoknowifyouarepregnant.org Prof Dave Grattan www.neuroendo.org.uk British Society for Neuroendocrinology Neuroendocrinology Briefings 38 ‘A Mother’s Brain Knows’ (2011) HYPERPROLACTINAEMIA • • • • Presentation Causes Investigations Management PRESENTATION • • • • •• • •• • • • MEN WOMEN oligo / amenorrhoea Erectile dysfunction –libido risk osteoporosis  galactorrhoea subfertility visual symptoms headaches May not have all these symptoms hypopituitarism May present after stopping contraceptive pill – coincidental Present later Galactorrhoea / gynaecomastia RARE CAUSES • Physiological – Pregnancy – Lactation • Hypothalamic-pituitary disease – Micro / macroPRLoma – Non-functioning adenoma • Drugs • Stress • Other – Polycystic ovarian syndrome – Hypothyroidism ( TRH) – Renal failure, cirrhosis PROLACTIN Hypothalamus + 5HT TRH OXT DA Pituitary PRL • Prolactin release inhibited by dopamine • Prolactin release stimulated by 5HT (serotonin), TRH, oxytocin DRUGS THAT PRL • Mechanisms Antidepressants and antipsychotics – Inhibition of secretion / action of dopamine • DAused antagonists • Drugs for nausea & vertigo • DA receptor blockers – Phenothiazines – Stimulation of central serotonin (5HT) – Metoclopramide pathways – Domperidone • 5HT re-uptake inhibitors • Others INVESTIGATIONS • Pregnancy MRI pituitary test – Microfunction • Renal < 1 cm diameter – Macro > 1 cm diameter U&E, creatinine • • • • • Liver function tests Macroadenoma Thyroid function – Visual fields Prolactin (repeat) – Rest of anterior pituitary function tests LH, FSH Testosterone (men) AIMS OF TREATMENT • Restore fertility • Stop galactorrhoea – Also stop nipple stimulation / ‘checking’ (oxytocin) • Restore regular menstrual periods / libido – Oestrogen / testosteone needed for bone protection – Can use exogenous oestrogen / testosterone (contraceptive pill / HRT / testosterone) • Shrink tumour (macroadenoma) – Recovery of anterior pituitary function – Restore vision PRLoma MANAGEMENT (1) • ‘MEDICAL’ • Dopaminergic drugs – Cabergoline – (Bromocriptine) • Preserve pituitary function • Side-effects – RARE: • Fibrotic reactions – Pulmonary, pericardial, retroperitoneal • Psychiatric disturbances PRLoma MANAGEMENT (2) • ‘Idiopathic MicroPRLomas hyperPRLaemia’ – Assumed Can take COCP to be a/ microPRLoma HRT if fertility not too required small to radiologically – be Candetected discontinue treatment in pregnancy – May involute post-partum – Can trial withdrawal of treatment after ~ 2 years (may not recur) NFA MANAGEMENT • Non-functioning pituitary adenoma – Compression of the pituitary stalk • ‘Disconnection hyperPRLaemia’ • May also occur with hypothalamic masses – May need surgery & radiotherapy • space-occupying effects • risk loss of pituitary function – [prolactin] will with dopaminergic drugs • Need to monitor MRI scan & visual fields CASE 63 year old woman Abnormal CT head scan MacroPRLoma MRI DECEMBER Prolactin = 15,000 miu/L (normal range up to 500) VISUAL FIELDS ANTERIOR PITUITARY FUNCTION TESTS • TSH 3.9 mu/L (0.3 – 4.2) • FT4 7.1 pmol/l (12 – 22) • LH <1 iu/l FSH 1.9 iu/l – low for post-menopausal woman • PRL 15,062 miu/l (range 500) • Random cortisol 509 nmol/l (OK) MRI SCANS: DEC / APRIL SAGITTAL VIEWS Prolactin 15,000 Prolactin 74 MRI SCANS: DEC / APRIL CORONAL VIEWS Prolactin 15,000 Prolactin 74 VISUAL FIELDS MAY Elisa (21) • • • • 2.5 year galactorrhoea On COCP 3-4 years No other medication No PMH / FH of note Elisa (21) • Prolactin 1636, 2005 • TSH 1.27, FT4 15.6 • LH<1 FSH<1 • T Testo 1.2, SHBG >200 What is the explanation of her lab results……? Elisa Microprolactinoma Elisa (management) • Microprolactinoma • Rx – continue COCP – avoid nipple stimulation / checking – may require cabergoline to conceive • Discontinue when pregnancy confirmed Beth (36) • • • • • 8m secondary amenorrhoea Negative pregnancy tests No regular medication / OTC medication No PMH / FH of note Would like children but not yet Beth (36) • Prolactin 1414, 1741 • LH 8 FSH 4.6 • TSH 2.89, FT4 15.1 Beth D Non-functioning pituitary adenoma Stalk compression causing  PRL ( DA) Beth (management) • Non-functioning pituitary adenoma – Stalk compression causing  PRL ( DA) • Rx Transphenoidal hypophysectomy – Risk to vision with further growth • Potential risk to pituitary function – Including future fertility prospects (though would be amenable to treatment) Carol (48) • • • • Galactorrhoea Regular 4-weekly menstrual cycle Long history of depression & anxiety TH: risperidone, trazodone, duloxetine Carol (48) • Prolactin 2210, 3122 • LH 10.8, FSH 14.1 • TSH 3.45, FT4 13.7 • MRI: structurally normal pituitary Carol (management) • Reassurance – Medication-induced hyperprolactinaemia • No treatment – Risk to mental health – Regular MP bones protected • Avoid nipple stimulation / checking TOPICS • Physiology of lactation • Causes of galactorrhoea • HyperPRLaemia / Prolactinomas – – – – Presentation Causes Investigations Management QUIZ! QUIZ • What factors regulate lactation? QUIZ • Prolactin – Secreted from ….. ? – Major inhibitory factor regulating secretion? – Women with PRL present with ….. ? QUIZ • Oxytocin – Synthesised in ….. ? – Released from …… ? – Major stimulant for release? – Stimulates? QUIZ • Causes of PRL? QUIZ • Class(es) of drugs that may cause  PRL • Class of drugs used to treat  PRL THANK-YOU Questions?