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Prolactinoma; updates in management
This document summarizes a webinar on prolactinomas and their management. It discusses the anatomy and histology of the pituitary gland and pathological subtypes of prolactinomas according to the new WHO classification. Clinical presentations, investigations including lab tests, visual and radiological assessments are outlined. Medical management using dopamine agonists and surgical management via different approaches are described. Complications like apoplexy and management of invasive prolactinomas are also summarized. The conclusion reiterates that prolactinomas are the second most common pituitary adenomas and various treatment approaches are available depending on the subtype and presentation of individual cases.
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Prolactinoma; updates in management
- 1. Webinar, Tuesday, 14thApril 2020 Prolactinomas:Updatesof Management Khaled Elsayed, MD
- 2. Overview • Anatomy andhistology of the pituitary gland • Prolactinoma : • Pathological subtypes; New WHO Classification • Clinical • Lab Investigations • Visual Assessment • Radiological • Medical management • Surgical management • Apoplexy • Conclusion Items will be presented
- 3. PituitaryGland • Pituitary gland: anterior and posterior lobes • The anterior lobe surrounds the stalk : pars tuberlais • If both lobes are separated , the pars tuberlais remains with the posterior lobe • Pars distalis: major part, secretory cells • Anterior lobe: firmer, easily separated from the dura • Posterior lobe: is softer, but adherent to the dura • Bean shaped, 10 mm length, 5-10 mm height, 10-15 mm width, and 600 mg weight Anatomy and histology of the pituitary gland
- 5. HistologyofPituitaryTumors • Posterior lobe:expression of ADH and Oxytocin • Five different cell types • Growth hormone (GH) producing somatotrophs • Prolactin (PRL) producing lactotrophs • Corticotroph (adrenocorticotrophic ACTH) • Thyrotrophs (thyroid stimulating hormone TSH) • Gonadotrophs (follicular stimulating hormone FSH, and Luteinizing hormone LH)
- 7. Pathologyof Prolactinoma • Mostarise in the lateral or posterior part of the gland • Macroadenomas tend to be aggressive and invasive • Sparsely granulated (chromophobe): • Most common, chromophobic or slightly acidophilic • Calcification in the form of psammoma bodies • Strong staining for PRL, PSA negative, • Densely granulated: • Less common, acidophilic cells • Numerous secretory granules , PRL staining +ve • Acidophil stem cell : • Large chromophobic cells
- 8. UpdatesinPathologicalClassification • Aim ofany classification reflected on outcome and methods of management • First : acromegaly and Cushing’s disease (adenoma) • Staining : hematoxylin and eosin : acidophilic, basophilic and chromophobe; add absence of secretion • WHO 2004: EM and IHC; based on organelles and granules and hormonal expression • Different subtypes of each adenoma… null cell adenoma(immunonegative) • WHO 2017: lineage restricted pituitary transcription factors From beginning till last WHO Classification
- 9. LineageRestrictedTranscriptionFactors • Change ofname from adenoma to Pituitary Neuroendocrine Tumor (PitNET) • Null cell adenoma • Plurihormonal tumors • Atypical Adenoma …… High Risk Adenoma : (male lactotroph, silent corticotroph and Crooke cell adenoma, SG somatotroph, and silent plurihormonal Pit1 • Three linages • PIT1: pituitary specific transcription factor 1: • Lactotroph, Somatotroph, and Thyrotroph • TPIT: pituitary cell restricted factor: • Corticotroph • SF1: splicing transcription factor 1: • Gonadotroph And others
- 11. Clinical • 40% ofadenomas • Micro or Macroadenomas • Male: decreased libido, impotence, infertility • Female: Galactorrhea, oligo/amenorrhea • Macroadenomas: headache, visual compromise, other cranial neuropathies • Apoplexy: • Pituitary hypofunction: in macroadenomas: • Adrenal insufficiency, anorexia, wt loss, hydrocortisone replacement therapy • Hypothyroidism: fatigue, dry skin, … thyroxine replacement
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- 14. LabInvestigations • Mechanism ofprolactin release • Normal ranges: males: 0-20 ng/ml, females 0-25 ng/ml • Hyperprolactinemia: more than 200 ng/ml, in microadenomas: 100-200 ng/ml • Stalk effect: less than 150 ng/ml • Hook effect: false negative in macroadenomas, at dilutions serum 1:100 • Other hormones: cortisol, growth hormone, and free T4
- 15. VisualAssessment • Visual acuity •Visual field assessment • Optomotor function, cavernous sinus invasion • Fundus examination
- 16. RadiologicalDiagnosis • Normal glandappearance • Microadenoma: < 10 mm, Macroadenoma: > 10 mm, Giant > 4 cm • MRI with contrast • Macroadenomas: extensions • Microadenomas: dynamic MRI with contrast , Spoiled Gradient (SPGR) sequence • CT paranasal sinuses: bony anatomic relations for transsphenoidal approach
- 18. Management • Bromocriptine andCabergoline • Doses: • Bromocriptine: 2.5 mg starting dose, increasing up to 10 mg in divided doses (side effects) • Cabergoline: 0.5 - 1.5 mg once or twice a week (less side effects) • Indications: • microadenomas is curative • Macroadenomas : with minimal or without visual compromise • Dopamine Agonists: • Normalizes serum level of prolactin • Tumor shrinkage Medical Treatment
- 19. Surgical • Indications: • Notresponding to treatment : prolactin is not normalized and the tumor does shrink • Intolerable side effects of the drugs • Cystic adenomas • Patients who wish to become pregnant (in case of microadenoma) • To decompress the visual apparatus, cranial nerves and the rest of pituitary gland • To prevent the tumor from progressing or recurring
- 20. SurgicalResults • Cure rateat least 90% by experienced surgeons • Patients achieve normal levels of prolactin • Return menstrual cycle in women and fertility in men • Complete cure : prolactin level in first post operative day is less than 10 ng/ml • Recurrence of hyperprolactinemia can occur up to 5 years post op, prolactin >10 ng/ ml • In this case: small doses of dopamine agonists Microadenoma
- 21. SurgicalResults • Surgical normalizationof prolactin in less than 50% • Helps tumor reduction for better response for medical therapy • In cases of tumor invasion into the cavernous sinus: it helps extra-cavernous resection and the residual for radiosurgery • Staged surgery may be required: transsphenoidal then transcranial Macroadenoma
- 22. SurgicalApproaches • Transsphenoidal • Microscopic •Endoscopic • Transcranial • Subfrontal • Pterional
- 23. PituitaryApoplexy • Apoplexy=Stroke • Haemorrhageor infarction in pituitary adenoma • Mostly in prolactinomas and especially on medical treatment • Sudden onset, may be subacute onset • Increase in size • Mild form: acute headache, meningismus, mild visual affection • Severe : impaired consciousness, visual decline, pituitary hypofunction, ophthalmoplegia, • Clinically evident in less than 10%, subclinical is more evident
- 24. PituitaryApoplexy • Men aremore affected than women: 2:1 • More commonly in the setting of macroadenomas • Predisposing factors: bromocriptine administration or withdrawal, anticoagulation, pregnancy • Full laboratory endocrinological investigation • CT as an emergency tool of investigation • MRI with contrast
- 25. PituitaryApoplexy • Administration ofhydrocortisone to prevent adrenal crisis • Authors advocate conservative therapy: • In isolated stable meningismus or ophthalmoplegia • Others recommend surgical decompression and do not wait metabolic and endocrine correction • Surgery is indicated in cases of impaired consciousness and visual compromise • According to the extension : transcranial or transsphenoidal • Long term hormonal replacement therapy Management
- 26. AdjuvantTherapy • Radiosurgery forresidual tumor in cavernous sinus • Long term hypopituitarism may develop, requires replacement therapy • Usually reserved for elder patients
- 27. InvasiveProlactinomas • Considered invasive:invasion of skull base: sphenoid sinus, oropharynx, clivus, orbit, cavernous sinus, and infratemporal fossa • Higher prolactin level • Diagnostics: high Ki-67, mitosis, and p53 mutations, cellular atypia, • Combined treatment: surgery, radiotherapy, and chemotherapy • Poor prognosis
- 28. ProlactinomaandPregnancy • Macroprolactinoma :surgery before pregnancy • Microprolactinoma : stop medical treatment and followed up, formal visual testing, and MRI at the appearance of symptoms of tumor enlargement • Symptomatic tumor enlargement occurs in 0.5-1% in microadenomas , and 15-35% in macroadenomas • Increased treated with bromocriptine or the patient undergoes surgery in selected cases • Women who wish to breastfed stop medical treatment : lactation has no evidence to increase tumor size Management
- 29. Conclusion • Prolactinomas 2ndmost common adenoma • Micro, Macro, Giant , or Invasive adenomas • Prolactin level, visual assessment, and radiological diagnosis • Medical therapy is the most common initial treatment • Surgery has its indications • Microscopic or endoscopic transsphenoidal , or transcranial • Adjuvant radiosurgery for cavernous reisdual • Apoplexy is a neurosurgical emergency • Rarely prolactinomas are aggressive or invasive.
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