Pituitary Disease Resident Tutorial 2017

Transcription

1 Pituitary Disease Resident Tutorial 2017 Sarat Sunthornyothin MD Division of Endocrinology and Metabolism King Chulalongkorn Memorial Hospital Pituitary Anatomy hypophyseal portal system direct arterial supply from int. carotid a. 1. Sup. hypophyseal a. 2. Inf. hypophyseal a. Pituitary Gland Pituita (latin) = phlegm JAMA Feb 7;317(5):

2 Control of Pituitary Hormones Pituitary Imaging Sellar Masses Pituitary tumor Functioning pituitary adenoma Prolactin, GH, Cushing s, TSH, gonadotroph Non functioning pituitary adenoma Null cell adenoma, gonadotroph Pituitary carcinoma Other mass lesions Rathke s Cyst Craniopharyngioma Metastases Hypophysitis Meningioma 2

3 Pituitary Apoplexy Greek : apoplexia : (ἀποπληξία) to strike Sudden impairment of brain function Pituitary : pituita : phlegm It was believed in the 1500's and 1600's that the pituitary gland channeled mucus to the nose Clinical syndrome consisting of a constellation of signs and symptoms that occur with rapid expansion of the contents of the sella turcica *** CLINICAL DIAGNOSIS *** Pituitary Apoplexy Pituitary apoplexy is a clinical syndrome due to abrupt hemorrhaging and/or infarction of the pituitary gland, generally within a pituitary adenoma. prevalence : 6.2 per 100,000 Incidence: 0.17 per 100,000 per year 2% and 12% of patients with adenoma 45% non functioning adenoma Most common: 5 th 6 th decade male preponderance ( : 1) 26% with precipitating factors Endocrine Reviews, December 2015, 36(6): Pituitary Apoplexy: Precipitating factors Conditions Head trauma Hypotension Medications Anticoagulants Dopamine agonist Procedures Angiography esp. cerebral angiogram Surgery (cardiac and orthopedic surgery) Pituitary dynamic testing TRH / GnRH/ GHRH/ CRH stimulation test Insulin induced hypoglycemia Others History of irradiation History of hypertension intra or postoperative hypotension, cardiopulmonary bypass, anticoagulation and/or microemboli leading to infarction imbalance between the increased metabolic demand induced by the stimulation and the ability of increased blood flow at the level of the pituitary adenoma 3

4 Clinical Manifestations Headache of sudden and severe onset like a thunderclap in a clear sky Dural traction meningeal irritation from extravasation of blood and necrotic material into the subarachnoid space usually retroorbital but can be bifrontal or diffuse Hormonal deficits * Adrenal insufficiency * Chronic Hypothyroid from pre existing pituitary lesions Hormonal excess: pre existing functioning pituitary tumor Endocrine Reviews, December 2015, 36(6): Clinical Manifestations Visual disturbances Visual field defect Ocular palsy Subarachnoid hemorrhage Cerebral ischemia : focal neurological deficits mechanical compression of the carotid artery cerebral vasospasm Pituitary Tumor Apoplexy Prolactin may be an indicator of pituitary function recovery Degree / risk of hypopituitarism related to intrasellar pressure 4

5 Pituitary Apoplexy Score (PAS) Clin Endocrinol (Oxf). 2011;74:9 20 (17) Pathophysiology Pituitary apoplexy is mostly associated with pituitary macroadenoma Pituitary adenoma Less blood supply than normal pituitary Reduced angiogenesis and microvasculature pituitary tumor ischemia / infarction Tumor outgrows blood supply Increased fragility of tumor blood vessels Compression of vessels against the sellar diaphragm by the expanding tumor mass MRI Findings Stage Substance T1 T2 Hyperacute (1 2hr) blood Hypo iso Hyper hypo Acute (>3hr) deoxyhb iso Very hypo Subacute (< 1 wk) methb Hyper Focal or heterogeneous Hypo to hyper Chronic (> 1 wk) protein Hyper Hyper Rarely shows pure hemorrhage; usually mixed infarction/ hemorrhagic infarction Thickening of sphenoid mucosal sinus from venous congestion Related to degree of hypopituitarism J Neurosurg. 2006; 104:

6 Hormonal Deficit Corticotropin deficiency: most common deficit (50% 80%) **** empiric parenteral corticosteroid ***** After serum blood draw for cortisol given to all patients with signs of PA, without waiting for diagnostic confirmation Cortisol < 15 mcg/dl : adrenal insufficiency in critical acute settings Pituitary Apoplexy: Treatment No treatment mortality > 50% Clinical suspicious is very important Blood draw for hormone measurement Supportive hemodynamic treatment Glucocorticoid : stress dose (200 mg of hydrocortisone) Imaging study after initial treatment and hemodynamically stable Conservative or Surgery Conservative therapy can be used in selected patients minimal symptoms improve dramatically after administration of glucocorticoids Factors to choose treatment options Patient s presentation clinical stability initial response to glucocorticoids availability of an experienced neurosurgeon Imaging findings single large hypodense area within the tumor on CT might be associated with better subsequent tumor shrinkage than are several small hypodense areas Simple infarction is less severe than hemorrhagic infarct 6

7 Hormonal Management Glucocorticoid preoperative Thyroid hormone if symptomatic or very low DI : not common (10%) and often transient Re evaluate postoperative 2 4 weeks Glucocorticoid may be tested early postop. Thyroid, sex hormone Outcomes after Apoplexy Ocular palsy resolved 75% 100% of patients without surgery, 31% 57% of patients with surgery Visual field defect resolved 50% normalized, 30% improved after Sx Similar outcome in conservative treatment Worse outcome in severe deficit Better outcome if surgery within first week Hormonal deficit Only 20% does not require hormone replacement after apoplexy Similar outcome for surgical and conservative group UK Guideline Apoplexy Clin Endocrinol (Oxf) Jan;74(1):

8 Pituitary Apoplexy : Summary Clinical diagnosis: high degree of suspicion Hydrocortisone therapy as soon as the diagnosis is suspected Conservative treatment is an option Surgery if Severely reduced VA Severe, persistent, deteriorating VF defect Deteriorating level of consciousness Not improved or worsening with conservative treatment Surgery should be performed within first week Pitfalls of Management Delay in diagnosis Delay in hydrocortisone treatment Need patient education for self adjustment of glucocorticoid dose No testosterone replacement How to prescribe IM, transdermal gel, oral How to follow up Testosterone level, CBC, PSA Consult urology PSA increase > 1.4 in first 12 month PSA > 4 Abn. digital rectal exam Hypothalamic Pituiary Control Neuropeptides are released into the specialized blood supply to the pituitary to regulate its secretion 8

9 Pituitary Adenoma JAMA Feb 7;317(5): Prevalence of Pituitary Adenoma JAMA Feb 7;317(5): Prolactinoma 9

10 Prolactin Regulation Stimulatory TRH, E, EGF Inhibitory Dopamine hypogonadism Prolactin Regulation Predominant effect: Inhibitory Dopaminergic neuron Dopamine D 2 receptor Stimulatory : Prl Releasing Factors Peripheral neural control Hyperprolactinemia inh prolactin Prl inh. Kisspeptin expression Kisspeptin stim GnRH neuron Nat Rev Endocrinol May;11(5):

11 Symptoms of Hyperprolactinemia Female Amenorrhea, Oligomenorrhea infertility Galactorrhea Osteoporosis Male Hypogonadism Gynecomastia Osteoporosis Symptoms from mass effect Visual field defect Apoplexy CN defect CSF rhinorrhea Causes of Hyperprolactinemia Antihistamine Opiate and opiate antagonist Prolactin Measurement Single measurement at any time of the day Avoid excessive venipuncture No need for stimulation test (TRH, L dopa, domperidone) PRL > 500 ng/ml macroprolactinoma PRL > 250 ng/ml usually indicate prolactinoma Some drug induced hyperprl can have PRL > 200 ng/ml Risperidone, metoclopramide Usually drug induced hyperprl; PRL < 100 ng/ml Minimal hyperprolactinemia maybe a prolactinoma, but a non prolactin secreting mass should first be considered 11

12 Prolactin Measurement Nat Clin Pract Endo&Met Mar 2007 Circulating Forms of PRL MACROPROLACTIN Found in 40% of patients with hyperprolactinemia Found in 4% of normal population Galactorrhea 20% oligo/amenorrhea 45% pituitary adenomas 20% 12

13 Heterophile Antibody Interference Heterophile Ab are antibodies induced by external antigens (heterophile Ag) Heterophile Ab Interference Hook Effect Reading can be normal or slightly elevated. Happen in very big tumor (Actual PRL is extremely high) Unless using the assay not affected by this condition: 2 steps method 13

14 Inaccurate Result of Prolactin Falsely high Macroprolactinemia Heterophile antibody Physiologic causes Falsely low Hook effect Heterphile antibody Bromocriptine VS Cabergoline N Engl J Med Oct 6;331(14): Bromocriptine VS Cabergoline N Engl J Med Oct 6;331(14): Presse Med Apr 29;24(16):

15 Bromocriptine vs Cabergoline in PRL secreting macroadenoma J Clin Endocrinol Metab Apr;60(4): J Clin Endocrinol Metab Jun;85(6): When to stop DA? Therapy may be tapered and perhaps discontinued treated with dopamine agonists for at least 2 yr (ENDO SOC), 3 yr (Pituitary Society) Normal serum prolactin No visible tumor remnant on MRI Recurrence rate: 26 69% Predicted by initial PRL and tumor size Increase 18% per mm of tumor size Most likely occur in first year Monitor q 3 month during 1 st year then annually Repeat MRI if PRL above UNL Recurrence after DA discontinuation Recurrence is related to PRL level at Dx and before D/C Pituitary dysfunction at Dx Not related to size, DA dose Not related to longer treatment time J Endocrinol Invest May 31 15

16 Women with Asymptomatic Microadenoma YOUNG WOMEN If pregnancy is desired: DA If pregnancy is not desired: DA or OC Microadenoma rarely grows POSTMENOPAUSAL WOMEN DA may be discontinued Monitoring of tumor size increase periodically Drug induced HyperPRL Discontinue medication for 3 days or substitution of an alternative drug, followed by remeasurement of serum prolactin should not be undertaken without consulting the patient s physician. If drug can t be stopped: perform MRI to differentiate drug induced vs. pituitary/hypothalamic lesion if pretreatment PRL is not available Treatment with DA may cause psychosis relapsed! Not common Use estrogen or testosterone in patients with long term hypogonadism (hypogonadal symptoms or low bone mass) 16