1 / 44

General approach to management of hyperprolactinaemia

General approach to management of hyperprolactinaemia. Dr. But Wai Man. Prolactin. Polypeptide hormone consisted of 199 aminoacids with 3 intramolecular disulfide bonds Encoded by a single gene on chromosome 6, 5 coding exons Secreted by lactotrophic cells in anterior pituitary gland.

suzannenewton
Download Presentation

General approach to management of hyperprolactinaemia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. General approach to management of hyperprolactinaemia Dr. But Wai Man

  2. Prolactin • Polypeptide hormone consisted of 199 aminoacids with 3 intramolecular disulfide bonds • Encoded by a single gene on chromosome 6, 5 coding exons • Secreted by lactotrophic cells in anterior pituitary gland

  3. Prolactin receptor • Identified as a member of the cytokine receptor superfamily • Single –chain transmembrane receptor • Functions by binding a single prolactin molecule and then dimerizing with a second receptor molecule

  4. Functions of prolactin • Important role in a variety of reproductive functions • Essential factor for normal production of breast milk following child birth • Hyperprolactinaemia disrupts normal pulsatile secretion of gonadotrophic-releasing hormone, altered LH and FSH secretion and impaired gonadal steroidogenesis, leads to infertility and gonadal dysfunction

  5. Control of prolactin secretion • Secretion is mainly under inhibitory control by hypothalamic dopamine • Circadian variation. Levels rise after the onset of sleep, nocturnal peak of 2x daytime concentration

  6. HyperprolactinaemiaClinical manifestations • Galactorrhoea 90%: affect mammary gland development • Amenorrhoea/Oligomenorrhoea: In women, • prolactin-secreting tumors is usually small, headache and neurological deficits are rare

  7. In men, tend to be large, and may cause cranial-nerve dysfunction, visual loss and panhypopituitarism • loss of libido and erection dysfunction • Galactorrhea and gynaecomastia are uncommon N Engl J Med 78; 299: 847-52 In both men and women Low bone density Weight gain Mood and behaviour changes

  8. Causes • Pregnancy 10X • Dopamine antagonist drug therapy ( phenothiazines and metoclopramide, • TCA, monamine oxidase inhibitors, oestrogen, verapamil, methyldopa • Stress eg venepuncture/ exercise • Polycystic ovarian syndrome • Pituitary-secreting microadenomas/macroadenomas • Pituitary stalk disruption by interfering with the normal suppression of prolactin by hypothalamic dopamine • Chronic renal failure

  9. Evaluation Biological evaluation of related hormonal axes: • Careful drug history and physical examination • TFT, RFT • PCO • and exclusion of pregnancy

  10. Levels of prolactin

  11. Macroprolactinaemia • High molecular-weight prolactin-immunoglobulin complexes • Polyethylene glycol precipitation of complexes allows the measurement of free monmeric prolactin • Not thought to have pathological significance

  12. Evaluation for hypothalamic-pituitary pathology • Clinical examination: assessment of visual fields • Imaging : MRI /CT • Pituitary microadenoma < 10mm • Pituitary macroadenoma > 10 mm • Pituitary stalk lesions • Hypothalamic tumours, granulomas

  13. Pituitary microadenoma • 20% of the normal population at autopsy • 50% of MRI imaging • No lesion suggesting microadenoma < 2mm, lactotroph hyperplasia • Hypopituitarism in structural lesion

  14. Prolactin secreting pituitary tumors • Benign tumors • Commonest pituitary tumors, 40% • >90% are small, intrasellar tumors that rarely increase in size JCEM 89; 68: 412-8

  15. Treatment of prolactin-secreting pituitary adenoma • Medical • Surgical • Radiotherapy

  16. Indication • To suppressive abnormal lactation • To restore ovarian function • Protection against development of osteoporosis • Rx may not be required in a few women with modest elevations of prolactin, may retain normal ovarian function and have few symptoms

  17. Dopamine agonist • Primary treatment of choice • Normalise prolactin levels, restoration of pituitary function and tumor shinkage in 80-90% over several weeks JCEM 1997 82 996-1000 • Tumour shinkage by at least 25% of volume in 80% of patients with large macroadenoma • Improvement in pressure symptoms within 48 hrs • In men, 50% may require testosterone replacement, withhold until prolactin levels are normalised

  18. Duration of treatment • Early studies showed remission is rare after interruption of therapy, life long treatment Clin Endo 1991; 34: 173-174 • Recent studies showed increase in remission and therapeutic withdrawal is recommended J Royal College of Physicians 1997; 31: 628-636

  19. List of studies assessing dopamine agonist withdrawal

  20. Remission • Long term follow up studies of untreated patients have shown that prolactinomas are very indolent • Short term therapy appears to induce cytostatic effects including reduction in organelle size and reduction in the volume of prolactin cells JCEM 55, 11798-1183 • Long-term therapy induces cytocidal effects such as necrosis, fibrosis and inflammatory cell infiltration JCEM 58, 1179-1183

  21. Pregnancy • Warned that restoration of ovulatory menstral cycle within weeks • Advised to use mechanical form of contraception until 2 regular menstrual flow • Stop dopamine agonist as soon as pregnancy is confirmed for microadenoma, risk of pituitary enlargement is low <2% • Bromocriptine can cross placenta and suppress pituitary prolactin secretion, but no apparent risk of congenital abnormality or misscarriage JCEM 97 82 996-1000

  22. For macroadenoma, bromocriptine is advised during pregnancy to avoid significant tumor expansion as risk of enlargement is 15-30% (J Reprod Med 99; 44: 1121-6) • Some recommend debulking for macroadenoma which have extended beyond the sella before pregnancy and bromocriptime prescribed throughoutpregnancy (Am J O&G 83; 146:935-8) • Cabergoline should not be used as a therapy for infertility until more information is available

  23. Surgery • Not first line option as outcomes reported are variable • Experienced center cure rate 85-90%, recurrence and complication <10% and hypopituitarism <1% JCEM 1995 81 1711-1719 • Prolactin decrease to very low values immediately after surgery and gradually to low-normal over wks, recurrence rate is very low Meta 1986 35 905-912 • Success is less likely (<50%) in macroadenoma which has extended beyond the sella JCEM 1995 81 1711-1719

  24. Indications for pituitary surgery • Resistance or intolerance to optimal medical therapy • For patients with intrasellar tumor for whom long-term drug treatment is not acceptable • Surgical decompression may be required for tumors pressing on optic chiasm • Avoid in cases o f extrasellar expanding tumors without optic chiasm compression because of low success rate

  25. Hormonal therapy • Fertility is not a concern • For hypogonadism • Prevent progressive bone loss

  26. Macroadenomas • Tend to grow, absolute indication for therapy • Managed with dopamine agonist • Confined to the sella should be managed as micraoadenoma as unlikely enlarged sufficiently to cause serious complications

  27. Higher doses • Decrease in prolactin levels within 2-3 wks and precedes a decrease in the size of the tumor and restoration of anterior pituitary function • Visual field assessment 1 month after the initiation of therapy • MRI repeated 6 months later • Prolactin measured yearly

  28. Hyperprolactinaemia and antipsychotic drugs

  29. Hyperprolactinaemia and antipsychotic drugs • 34% of men and 75% of women showed hyperprolactinaemia (Curr Med Res Opin 2004;20:(2) 189-97) • Hypogonadism is common. Mean levels were in the hypogonadal range for women and 6.4% of men were hypogonadal (Br J Psy 2004;184:503-8) • Sexual dysfunction in 45% compared with 17% of GP clinic control (Br J Psy 2004;184:503-8)

  30. Effects of long term prolactin raising antipsychotic medication on bone mineral density in patients with schizophrenia • Male and post-menopausal female patients with schizophrenia on long-term prolactin –raising antipsychotic drugs (>10yr) • British J of Psychiatry 2004; 184; 503-508

  31. Results • Hyperprolactinaemia was present in 62% of the overall group (60% in male and 64% in female) • 57% of the men and 32% of the women had reduced bone mineral density

  32. Antipsychotic drugs A new risk factor for osteoporosis in young women with schizophrenia • To study the effect of prolactin-raising and prolactin-sparing antipsychotic drugs (olanzapine) on bone density of premenopausal females • Jof clinical psychopharmacology 2005; 25 (1):26-31

  33. Results • Low BMD in 65% of prolactin-raising group, compared with 17% in prolactin-sparing group • Hyperprolactinaemia was associated with low BMD; 95% with low BMD had hyperprolactinemia and only 11% of the group with normal prolactin had abnormal BMD

  34. Relative percentage distribution of low BMD in prolactin-sparing and prolactin –raising groups

  35. Relative percentage distribution of bone loss in normal prolactin and hyperprolactinemia

  36. Thanks you

More Related