ACD 08/29/2014

Jorge Jo Kamimoto MD, PGY 2 IM

Simulated Case• 60 yo man w HTN and melanoma is playing pool when

he abruptly slumps forward onto the table and loses consciousness.• Blood sugar 81, has a pulse, breathing, unresponsive• Taken to ED• History: last two weeks has had slght headache and

malaise/fatigue, has had dysuria last 2 days.• No shaking, bowel/bladder incontinence

ER course• Vitals: HR 125, BP 70s/40s, RR 18, T 101.1• Rest of exam pretty unremarkable besides he is still

pretty unresponsive, minimally awakens.• UA shows UTI, 3L NS given w transient increase in BP

then drops again, high dose norepinephrine drip started w some improvement in MAP to around ~65 .• Blood cultures drawn and abx started• Wife has a med list: nifedipine, lisinopril, docusate, vit

D, and Ipilimumab (for his melanoma)

• Still hypotensive in MICU, 2nd pressor started and someone checks a cortisol: <1• Hydrocortisone 50mg q6h started w prompt BP

response• TSH checked next day and very low

What’s the diagnosis?

Ipilimumab induced endocrinopathies

Why??• Ipilimumab is a monoclonal antibody that targets CTLA-4• CTLA-4 is a down regulator of T-Cell activation• Blockage ok CTLA-4 results in increase number of activated

cytotoxic T cells• Proposed mechanisms

• Activated T cells attack antigens shared by tumor and host tissues• Multiple populations of T cells activated with different anti-host and anti-

tumor effects • Depletion of regulator T - Cells

• Includes• Hypopituitarism, Primary hypothyroidism, Primary adrenal insufficiency

• Description of 147 patients on Ipilimumab• Incidence of hypophysitis 11%

• Monitor TFT’s before every cycle • Declining TFT’s, headaches, fatigue should trigger

work up for Ipilimumab induced Hypophysitis including:• MRI – very sensitive, must include comparison to previous

studies• Pituitary function test • Serum sodium

Management• Stop Ipilimumab• Hormone replacement as necessary:• Gonadal , Thyroid, Steroids

• If grade 3-4 endocrinopathies present • Steroid course equivalent to 1-2mg/kg/d of prednisone

tapered over 4 weeks may improve gland function• Overall very poor rates of gland function recovery reported

Acute Adrenal insufficiency

When to suspect adrenal insufficiency?• High index of suspicion• Vague and non specific symptoms• 2 syndromes: Pure cortisol deficiency vs Cortisol and

mineralocorticoid deficiency• Hypotension non responsive to fluids and vasopressors• Precipitating physiological stress• In critically ill first we treat then we diagnose

Diagnosis• Random cortisol• Only helpful if <3µg/dL or more than 20µg/dL in a period of

stress

• Best Test: Cosyntropin (synthetic ACTH) stimulation test• Measure baseline Cortisol and inject 250µg of Cosyntropin • Measure Cortisol at 30m and 60m • Normal response : Cortisol level > 18µg/dL• Critically ill patients: Rise > 9µg/dL• Can also draw baseline ACTH, renin and aldosterone levels

to help differentiate Primary from Secondary/Tertiary