Peri-op Pituitary / Diabetes Insipidus/ Apoplexy Dr. Stan Van Uum, MD, PhD, FRCPC

10 th Annual Canadian Endocrine Update 3 rd Canadian Endocrine Review Course Peri-op Pituitary / Diabetes Insipidus/ Apoplexy Dr. Stan Van Uum, MD, PhD, FRCPC

10 th Annual Canadian Endocrine Update Dr. Stan Van Uum perceives no conflict of interest with this presentation but has worked with or consulted for: Novartis Genzyme Abbott Pfizer Janssen Lilly

Pituitary Case A 53 year old man is referred to you for evaluation of a pituitary mass. This mass was discovered when his neurologist ordered a CT scan of his head because of headaches. Goal: Develop approach for pre-, peri- and post-operative endocrine assessment

Goal preoperative assesment Assess for functional adenoma, particular acromegaly, Cushing Asses for pituitary hormone insufficiencies Cause of prolactin elevation (pregnancy, drugs, primary hypothyroidism, stalk, prolactinoma).. Assess for mass effects review imaging

Preoperative Lab Laboratory 8-9 AM, fasting Parameter Cor$sol TSH Free T4 Free T3 LH FSH Testosterone/Estradiol Prolac$n IGF- 1 electrolytes Reference Range 119-618 nmol/l 0.27-4.2 miu/l 10-24 pmol/l 3-6.5 pmol/l 1.5-9.0 IU/L 1.0-18.0 IU/L 2-18 μg/l 115-307 μg/l Pereira & Bevan Pituitary 2008,11:347-51

HPA axis - preoperative Pituitary Baseline cortisol: ideally 8-9 AM. < 100 nmol/l = adrenal insufficiency >450 nmol/l = AI highly unlikely? Stimulation test? Insulin tolerance test (peak >500,Δ>200 nmol/l) Glucagon stimulation test Short synacthen test Pereira & Bevan Pituitary 2008,11:347-51

Epidemiology Anterior Pituitary Insufficiency in Patients with Pituitary Adenoma Majority of patients with non-functioning macroadenomas has some degree of pituitary insufficiency Growth Hormone (GH) 85% Gonadal deficiency (LH,FSH) 75% Corticotroph (ACTH) 38% Thyrotroph deficiencies (TSH) 32% Dekker et al, (J Clin Endocrinol Metab 93: 3717 3726, 2008) Van Uum 2009

Diabetes Insipidus (DI) - preop Rare at presentation, more common in: Craniopharyngeoma Hypothalamic pathology Na + > 142 mmol/l Osmolality > 300 mosmol/kg Urine output > 3L/day, Osmolality < 300 Stimulation test usually NOT needed Pituitary May emerge after steroid replacement ( unmask ) Pereira & Bevan Pituitary 2008,11:347-51

Early Postopera3ve Period Stress glucocor$coid coverage Water Balance: Diabetes Insipidus SIADH Neurosurgical General neurological func$on CSF leak meningi$s Ausiello et al Pituitary 2008, 11:391-401

Risk for adrenal insufficiency Extent surgery involvement stalk or hypothalamus? DI 4-fold increase for AI risk Many variations in protocols between centres: - Most centres hydrocortisone stress dose (50-100 mg IV) - Tapered over 2-3 days. - If using Dexamethasone: allows post-op cortisol measurement (day 2-3) and DC if normal - Others, treat for several weeks and reassess. Ausiello et al Pituitary 2008, 11:391-401

Immediate testing for AI ACTH test not useful ITT not useful Can Day 1 early morning cortisol predict normal ITT on day 8? 1. 28 patients, cortisol >340 nmol/l normal ITT 2. 71 patients, cortisol > 400 nmol/l, 77% positive predictive value for excluding AI One option: A: cortisol 100-250 replacement B: cortisol 250-450 stress dosing only. Ausiello et al Pituitary 2008, 11:391-401

Testing for other pituitary hormones Thyroid: T4 one and 4 weeks postop Prolactinoma: early normal PRL may indicate remission Gonadal axis: usually assessed later: gonadal function can be suppressed by stress of surgery and steroid administration Growth hormone: later, IGF-1 at least >3 months. Ausiello et al Pituitary 2008, 11:391-401

Pituitary function post surgery for pituitary adenomas A. If 1 axis dysfunc$on: 48% some improvement B. One study: A. 13% improved pituitary func$on B. 40% worsening pituitary func$on C. If pre- op growth hormone deficiency: recovery in 3.6% D. In apoplexy recovery is unlikely Ausiello et al Pituitary 2008, 11:391-401

Disorders of water balance plasma osmolality (BP, nausea, hypoglycaemia, morphine, ethanol, nicotine) AVP Binds to vasopressin V2 receptor (renal collec$ng tubular cell) aquaporin-2 channels water resorption interstitial osmolaility (urea reabsorption Schreckinger et al Clin Neurol Neurusurg 2013, 114, 121-6

? Diabetes insipidus? You get called at 22.00 re a patient post pit surgery: 1. Na 144 mmol/l 2. Na 144 mmol/l, urine output >350 mmol/hr x3 hr 3. Na 144 mmol/l, previous Na 139 mmol/l 4. Patient thirsty, urine output >250 mmol/l over 4 hours 5. Na 148 mmol/l 6. Urine output 500 ml over last hour 7. Urine specific gravity < 1.005

Frequency of DI post transsphenoidal pituitary surgery Surgery type Microscopic Endoscopic Incident DI 1.6-45.6% 2.5-15% Permanent DI 0-8.8% 0-7.1 % Heterogeneity +++ Criteria vary between authors, considered to be diagnos$c are: Urine output > 30 ml/kg/day 2.5-18 L/day Urine output >250-500 ml/hour for 2-3 consecu$ve hours Urine osmolity <300 and serum > 300 mosm/kg Na >140-145 mequiv/l

Factors affecting risk for DI Pituitary Pa$ent related: more in younger, male pa$ents Surgery related: higher risk < 48 hours, with Intra- opera$ve CSF leak: risk for transient & permanent DI Manipula$on stalk Disease related: higher risk with: craniopharyngeomas (up to 50%) Rathke s cleh cyst Cushing s disease more likely transient DI Hypothalamic disease Microadenoma (more likely transient DI -?manipula$on?) No increased risk with reopera$on

How to monitor postop for DI Intensive care unit (neuro obs unit) Strict recording of all inputs and outputs Serum electrolytes and osmolality daily If pa$ent shows polyuria (defini$on) serial measurement of serum and urine osmolality Urine specific gravity Serum sodium Daily body weight

Medical options for DI Synthe$c AVP (desmopressin, DDAVP, Minrin - prolonged half life) Dose: Oral 100-800 mcg daily (2-3 doses per day) Parenteral 2-4 mcg daily (in 1-2 doses) Intra- nasal 10-40 mcg daily (in 2 doses) avoid if intranasal packing was placed during surgery Sublingual 60-240 mcg 2-3 /day Plasma t½ 3 hours, pharmacological effects last up to 10 hours. More likely used in women, prior pit surgery, polyuria, Na +, higher hydrocornsone stress dose, - do not correlate with later Nme points. Less DI with increased hospital and surgeon case load.

Treatment options for DI Pa$ent awake: Ad lib oral fluid intake, close monitoring IV fluids if impaired thirst or altered mental status In early post- op phase: DDAVP only as needed, as most likely transient Aher DDAVP use, urine osmo results very difficult to interpret Avoid hyponatremia (generally occurs in up to 25% of pa$ents, peak $me is 7 days post- op) Pa$ent instruc$on re DI symptoms ad discharge. Symptoms hyponatremia: headache, dizzyness, nausea, vomi$ng and if severe, altered mental status, seizures (cave AI).

? Diabetes insipidus? You get called at 22.00 re a patient post pit surgery: 1. Na 144 mmol/l 2. Na 144 mmol/l, urine output >350 mmol/hr x3 hr 3. In addition fluid balance +1000mL vs -1000mL 4. Na 144 mmol/l, previous Na 139 mmol/l 5. Na 144 mmol/l High risk (surgery, disease)

? Diabetes insipidus? You get called re a patient post pit surgery: 1. Patient thirsty, urine >250 mmol/hr for 4 hours 2. Difference: Nasal packing in place? 3. Difference: Fluid balance? 4. Na 148 mmol/l 5. Urine output 500 ml over last hour 6. Need to add lytes, urine osmo, fluid balance 7. Urine specific gravity < 1.005

Individual complete assessment required for DI post pit surgery 1. Comple3on of findings: o volume dilute urine (>250/hr x 3 hours, with s.g. <1.005 o serum osmolality (>300) and Na (>145, or rising) o thirst (par$cularly craving cold fluids) o Fluid balance o History (risk factors) 2. Assess for confounders: o Volumes administered during surgery o Thirst due to dry mouth (nasal packing) o Pre- op fluid reten$on in acromegaly o Development DM (lower Na) o Diure$c use

Triphasic response : Occurs in 1-3% Second phase due to AVP release from degeneranon of injured magnocellular neurons