acd 08 29 143
DESCRIPTION
DFOTRANSCRIPT
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ACD 08/29/2014
Jorge Jo Kamimoto MD, PGY 2 IM
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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
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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)
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• 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
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What’s the diagnosis?
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Ipilimumab induced endocrinopathies
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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
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• 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
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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
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Acute Adrenal insufficiency
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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
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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
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