Pituitary Replacement Therapy and Postopera?ve Management

Transcription

1 Pituitary Replacement Therapy and Postopera?ve Management Sarah ReDnger, MD P A C I F I C N E U R O. O R G

2 The Pituitary: The Master Gland

3 Outline Ø Quick Physiology review ØHypofunc?on: Diagnosis and treatment with prac?cal?ps ØPeriopera?ve management of pituitary surgery with common pimalls ØCommon drug Interac?ons between hormone replacement and commonly used neuro drugs ØImmunotherapy-induced Hypophysi?s

4

5 Causes of hypopituitarism Ø NEOPLASTIC Pituitary adenoma Craniopharyngioma Meningioma Cysts (Rathke s, arachnoid) -Germinoma, Glioma, Astrocytoma Paraganglioma, Teratoma, Chordoma, Ependymoma Pituitary Carcinoma Metastases Ø TREATMENT OF DISEASE Surgery Radiotherapy Ø INFECTIOUS Ø VASCULAR Apoplexy Subarachnoid hemorrhage Ø TRAUMATIC (TBI) Ø INFILTRATIVE/INFECTIOUS Ø MEDICATIONS: CTLA-4 Inhibitor, checkpoint inhibitors

6 Pituitary Hypofunc?on With most insults, the hormones tend to fall out in backwards order of importance 1. Growth Hormone 2. Gonadotrophs (LH/FSH) 3. TSH 4. ACTH

7

8 Central Adrenal Insufficiency Cri?cal to diagnose May cause adrenal crisis= death Must be treated first, before replacement of any other hormones

9 Central Adrenal Insufficiency: Diagnosis Signs/Symptoms Salt craving- DRAMATIC Muscle aches Weight loss Nausea(+/- vomi?ng) Impaired memory/ concentra?on Hypotension

10 Central Adrenal Insufficiency: Diagnosis AM Cor?sol (7am to 9am) should be the first line test Random cor?sol levels are not very helpful (diurnal varia?on)

11 Central Adrenal Insufficiency: Diagnosis AM cor?sol >15mcg/dL likely excludes AI AM cor?sol< 3mcg/dL is likely AI 3-15mcg/dL is equivocal requires ACTH s?mula?on test

12 Central Adrenal Insufficiency: Treatment HYDROCORTISONE is preferred to mimic diurnal varia?on 10mg AM 5mg PM 10mg AM 5mg PM 2.5mg evening

13 Central Adrenal Insufficiency: Treatment For pa?ents with difficulty with compliance or intolerable am symptoms use: PREDNISONE 5-7.5mg DEXAMETHASONE mg

14 Central Adrenal Insufficiency: Treatment REMEMBER: Give the lowest possible dose (to avoid CV disease, osteoporosis, diabetes) Educate the pa?ent about sick-day dosing Make sure all pa?ents have emergency ID and an emergency kit!

15

16 Central Hypothyroidism: Diagnosis Signs/symptoms Fa?gue Cold intolerance Weight gain Cons?pa?on Depression Laboratories: FT4 and TSH Low FT4 with a low, normal or slightly elevated TSH indicates Central Hypothyroidism

17 Central Hypothyroidism: Treatment T4 (levothyroxine or brand) aiming for FT4 in the mid to upper half of the reference range. Full replacement is approximately 1.6mcg x pa?ent s weight (kg). (50kg pa?ent would need 50x1.6=80mcg/day) APer T4 is started, use ONLY FT4 to make adjustments TSH will likely look low no maler what!

18

19 Male Central Hypogonadism: Diagnosis: - Measure fas?ng, morning serum testosterone Treatment: Testosterone replacement (injec?on, transdermal) in pa?ent without contraindica?ons Improves muscle mass, libido, sexual func?on, energy, and strength, Bone mineral density (data for fracture risk are not known)

20 Female Central Hypogonadism Diagnosis: -If menstrual irregulari?es check Estradiol, FSH, LH. Exclude other causes of menstrual irregularity including pregnancy. -In postmenopausal women, the absence of high FSH/LH without HRT is enough for dx Treatment - Pre-menopausal: Estrogen and Progesterone un?l natural age of menopause (approx age 51) for bone health -Post-menopausal: Estrogen as needed for symptom relief +/progesterone if pa?ent has a uterus

21

22 Growth Hormone Deficiency: Diagnosis No need to do any tes?ng for GH if pa?ent has three other documented pituitary deficits Consider tes?ng (provoca?ve only) if : the pa?ent has current or history of demonstrable pituitary disease The pa?ent previously required GH during childhood

23 Growth Hormone Deficiency: Treatment for pa)ents who meet criteria only StarTng dose Age< mg/day Age> mg/day Increase by mg/day in week intervals Target is: IGF-1 levels below upper limit of normal without side effects Fluid reten)on arthralgias, myalgias paresthesias, carpal tunnel sx, dyspnea, OSA

24 But wait! There s more! P A C I F I C N E U R O. O R G

25 Posterior Pituitary

26 ADH: An? Diure?c Hormone ADH Present - Collec?ng Duct is permeable to water and a small volume of urine is produced

27 Not enough ADH=Central Diabetes Insipidus

28 Central Diabetes Insipidus Dx: EXCESSIVE URINATION AND THIRST Polyuria >50ml/kg in 24H (3.5L/day in a 70kg person) Spec grav<0.010, U osm<300mosm Absence of solute diuresis (i.e. dips?ck NEGATIVE for glucose) Treatment: Replace ADH= DDAVP (Will discuss more in peri-opera?ve management)

29 Peri-Opera?ve Management

30 Pre-Opera?ve Evalua?on Aoer checking for hypersecre?on.. Check for deficits AM cor?sol TSH, FT4 LH/FSH Estradiol or Total Testosterone IGF-1 Na+ (posterior pit)

31 Pre-Opera?ve Evalua?on Replace hormones as needed -GlucocorTcoids: Hydrocor?sone or Dexamethasone -Thyroid hormone: Mild hypothyroidism should not delay surgery

32 Immediate Postopera?ve Stage WATER BALANCE! It s all about ADH! Classic Tri-phasic Response aoer pituitary surgery is: 1. Diabetes Insipidus: 2. SIADH (Inappropriate ADH): 3. Diabetes Insipidus:

33 Triphasic Response: The rollercoaster Stage 1 (POD#1-3): Axonal Injury: No AVP Stage 2 (POD#5-12): Uncontrolled Release of AVP Stage 3 (POD #12+): Possibly Permanent Axonal Death: No AVP

34 Stage 1: POD #1-3 Check Q6H Na+, Urine Output Diabetes Insipidus 1.Urine Output >300cc/h x 3 hours AND 2. Na>145 AND 3. spec. grav <1.005

35 Post-Opera?ve Diabetes Insipidus: Treatment Ø ICE COLD WATER Ø DDAVP -- PO (100mcg, 200mcg tabs) -- SubQ 0.5-2mcg -- Nasal spray (10mcg) -- Rhinal tube (1-10mcg)

36 Postopera?ve Management: Diabetes Insipidus Make DDAVP orders one?me only. AVOID STANDING ORDERS Do not over treat! Keep cold water by bedside at all?mes and encourage pa?ents to drink to thirst Use DDAVP at night for comfortable sleep

37 Stage 2: SIADH Post-Op Days #5-12 Sxs: Decreased Urina?on Nausea and vomi?ng (hyponatremia) Dx: Rou?ne Post-op Day 7 Na+ Tx: 120<Na+<135 Free water restric?on <1500cc Na+<120 Hospitalize for Na correc?on and/or vasopressin receptor antagonist (conivaptan)

38 Stage 3: Diabetes Insipidus: Post op days 12 onward usually outpa?ent UNDERDOSE don t OVERDOSE Drink to thirst during the day! Op?on: DDAVP at bed?me only Periodically (weekly) skip a dose of DDAVP to assure medica?on is not building up Emergency Iden?fica?on

39 Postopera?ve Management: The other hormones POD#1: AM cor?sol (AT LEAST 12 hours aoer last hydrocor?sone dose and hours aoer dexamethasone dose) POD #7: Na+, T4 (7 day half-life), AM cor?sol if POD#1 was equivocal Testosterone, Estrogen, GH can should be delayed at least 6 weeks

40 Common Drug Interac?ons and Pituitary Replacement PITFALLS NSAIDs, some AEDs poten?ate the effect of DDAVP (possible hyponatremia and seizures) Enzyme-inducing AEDs may increase dexamethasone requirements Enzyme-inducing AEDs increase metabolism of thyroid hormone. Check FT4 6 weeks aoer star?ng AED

41 A word about Immunotherapy.. P A C I F I C N E U R O. O R G

42 Immunotherapy may induce Hypophysi?s (inflamma?on of the pituitary gland) Rela?vely rare with PD-1, PDL-1 Inhibitors (Nivolumab, Pembrolizumab) Very common with CTLA-4 inhibitors 10-15% of pa?ents receiving Ipilimumab Incidence is increasing as clinical recogni?on improves and defini?ons become more precise. Faje, Pituitary, 2016

43 Ipilimumab-induced Hypophysi?s: A Case 41 yo female s/p second course of ipilimumab for recurrent metasta?c melanoma, presented with 4 days of severe headache, fa?gue, dizziness, and nausea associated with PO intake. TSH: FT4: AM Cor?sol: ACTH: LH/FSH Prolac?n: ( uiu/ml) 0.72 ( ng/dl) 2.9 (7-10AM ug/dl ) 7 (6-58 pg/ml) 1.92, ( ng/ml)

44 Ipilimumab-induced Hypophysi?s Diffuse enlargement of the pituitary gland

45 Ipilimumab-induced Hypophysi?s Faje et al. Min et al. Albarel et al. Total Thyroid 17/17 22/25 13/15 52/56 Adrenal 7/14 22/25 11/15 40/54 Gonadal 15/15 15/20 12/14 42/49 GH 1/6 3/7 2/8 6/21 DI 0/17 0/25 0/15 0/57 Resolu?on of pituitary imaging 17/17 11/11 12/12 40/40 Hypopit at dx Hypopit. at follow-up Thyroid 13/17 8/25 2/15 23/57 Adrenal 14/17 22/25 13/15 49/57 Gonadal 13/15 8/25 2/15 23/57 Adapted from Faje, Pituitary, 2016 Faje et al. JCEM, 2014, Min et al., Clin Cancer Res, 2015, Albarel et al., Eur J Endocrin, 2015

46 Ipilimumab-induced Hypophysi?s: Our Pa?ent ØIni?al Treatment: Prednisone: (FIRST, before any other axis replaced!) 40mg with rapid taper to 5mg Levothyroxine: replacement 50mcg ØLong-term Treatment -Prednisone converted to Hydrocor?sone 10/5 AM Cor?sol=3 aoer with-holding HC x 24 hours -Levothyroxine 88mcg -Oral Contracep?ve to maintain bone health

47 Ipilimumab-Induced Hypophysi?s: Take Home Points Pituitary enlargement may be very subtle and is usually transient (3-8 weeks) so do NOT rely on radiographic findings Most common sxs are HEADACHE, fa?gue, and weakness Central hypothyroidism is most common, followed by central adrenal insufficiency, and hypogonadotropic hypogonadism High doses are steroids are NOT needed in the absence of severe hyponatremia or op?c chiasm compression Thyroid and gonadal axes recover more frequently than adrenal

48 Finally.. Call your Endocrinologist! We love to discuss hormones.