Ver el código de «Thyroid storm»

==Background==
*Mortality 
**Without treatment: 80-100% 
**With treatment: 10-30%<ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
*Difference between severe thyrotoxicosis and thyroid storm is clinical diagnosis<ref>Nayak B1, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006 Dec;35(4):663-86, vii.</ref>
**Must empirically treat before laboratory confirmation
**Death caused by multi-organ dysfunction, [[congestive heart failure]], respiratory failure, [[dysrhythmias]], [[DIC]], hypoxic brain injury, or [[sepsis]] <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>

===Precipitants===
*Long-standing untreated [[hyperthyroidism]] 
*[[Infection]]
*[[Trauma]]
*Recent thyroid manipulation (physical or surgical)
*[[Burns]]
*Surgery (non-thyroid)
*[[DKA]] 
*Withdrawal of thyroid medication 
*[[Lithium]] withdrawal
*Iodine load (contrast media or [[amiodarone]]<ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>)
*[[MI]] 
*[[CVA]] 
*[[PE]]
*[[Interferon-α]] treatment
*Recent [[delivery|parturition]]
*[[Molar pregnancy]]
*[[Hypoglycemia]]
*[[Hyperemesis gravidarum]] <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
*Toxemia of pregnancy <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>

{{Thyroid gen background}}

==Clinical Features==
[[File:PMC5384127 TJO-47-94-g6.png|thumb|Bilateral infiltrative thyroid-associated exophthalmos]]
[[File:PMC3742527 OL-06-01-0144-g00.png|thumb|Enlarged and homogeneous thyroid.]]
[[File:PMC3371544 IJD-57-247-g002.png|thumb|"Plummer's nail" demonstrating onycholysis (separation of the nail from the nail bed). Abnormal nail findings occurs in about 5% of hyperthyroid patients.]]
{{Thyrotoxicosis clinical features}}

===Complications===
*Cardiovascular collapse<ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
**[[Congestive heart failure]]
**[[Hypotension]]
**Cardiac [[dysrhythmias]]
*[[Hypovolemia]], [[hypotension]]
**Due to nausea, [[vomiting]], [[diarrhea]]
*[[Hepatic failure]] with cholestatic jaundice <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
**Rare but carries poor prognosis

===Apathetic Hyperthyroidism===
*Strikingly different rare form, dominated by depressed mental status, cardiac complications<ref>Parker KI et al. A case of apathetic thyroid storm with resultant hyperthyroidism-induced hypercalcemia. Am J Med Sci. 2013 Oct;346(4):338-40.</ref>
*Treatment with antithyroid therapy is still mainstay
*More common in elderly patients <ref>Poudel RR et al. Apathetic thyrotoxicosis presenting with diabetes mellitus. J Community Hosp Intern Med Perspect. 2014 4(5).</ref>

==Differential Diagnosis==
{{Widened Pulse Pressure DDX}}

==Evaluation==
===Workup===
*TSH
**Low or undetectable
*Free T3/T4
**Elevated
*Chemistry
**[[hypercalcemia|Calcium]] may be elevated
**[[Hyperglycemia]] often present <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
*CBC
**May have [[thrombocytopenia]]
**[[Leukocytosis]] common <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
*[[LFTs]]
**Mild elevation in AST, ALT, LDH, bilirubin, ALP may be seen <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's emergency medicine: Concepts and clinical practice (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>
*Cortisol level (rule-out concurrent adrenal insufficiency) 
*[[ECG]] 
*Rule out infection: 
**[[CXR]]
**[[Blood culture]]
**[[UA]]
**Consider [[lumbar puncture]] after CTH

===Diagnosis===
[[File:thyroid studies.JPG|px200]]

===Burch & Wartofsky Diagnostic Criteria===
{| class="wikitable"
| align="center" style="background:#f0f0f0;"|'''Category'''
| align="center" style="background:#f0f0f0;"|'''Points'''
|-
!colspan="6"|Thermoregulatory dysfunction (°F)
|-
|Tmax= 99-99.9||5
|-
|Tmax= 100-100.9||10
|-
|Tmax= 101-101.9||15
|-
|Tmax= 102-102.9||20
|-
|Tmax= 103-103.9||25
|-
|Tmax= 104||30
|-
!colspan="6"|Central nervous system effects
|-
| Mild (Agitation)||10
|-
| Moderate (delirium, psychosis, extreme lethargy)||20
|-
| Severe (seizure, coma)||30
|-
!colspan="6"|Gastrointestinal-hepatic dysfunction
|-
| Moderate ([[diarrhea]], [[nausea and vomiting]], [[abdominal pain]]) 
| 10
|-
| Severe (unexplained [[jaundice]]) 
| 20
|-
!colspan="6"|Cardiovascular dysfunction (tachycardia)
|-
|HR= 99-109 
| 5
|-
|HR= 110-119 
| 10
|-
|HR= 120-129 
| 15
|-
|HR= 130-139 
| 20
|-
|HR= 140 
| 25
|-
!colspan="6"|[[Congestive Heart Failure]]
|-
| Mild (pedal edema) 
| 5
|-
| Moderate (bibasilar rales) 
| 10
|-
| Severe ([[pulmonary edema]], [[A. fib]]) 
| 15
|-
!colspan="6"|Precipitant history
|-
| Negative 
| 0
|-
| Positive 
| 10
|}

'''Scoring'''<ref>Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993 Jun;22(2):263-77</ref>
*>45 = Highly suggestive of thyroid storm 
*25-44 = Suggestive of impending storm 
*<25 = Unlikely to represent storm

==Management<ref>Bahn chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21(6):593-646.</ref>==
''Identify precipitant (i.e. med noncompliance, [[DKA]], infection).''
'''''When in doubt of diagnosis, the EP should treat given the high mortality rate, as a few doses of anti-thyroid medication are unlikely to harm euthyroid patient<ref>LoPresti J. A New Look at Thyroid Emergencies Part II: Handling Thyroid Storm. http://epmonthly.com/article/a-new-look-at-thyroid-emergencies-part-ii-handling-thyroid-storm/.</ref>'''''
===Supportive care===
#'''[[Fever]]'''
#*Do not aggressively cool as this can lead to vasoconstriction<ref>Chiha, Maguy, Shanika Samarasinghe, and Adam S Kabaker. 2013. Thyroid storm: an updated review. Journal of intensive care medicine, no. 3. http://www.ncbi.nlm.nih.gov/pubmed/23920160.</ref>
#*Careful cooling measures (ice packs & cooling blankets)
#*[[Acetaminophen]] ('''avoid aspirin or NSAIDS''' because they displace thyroid hormone from TBG)
#'''[[Dehydration]]/[[hypoglycemia]]'''
#*D5NS (most patients have depleted glycogen stores) 
#*Crackles in lungs are likely [[high output heart failure]], NOT fluid overload
#Cardiac decompensation ([[CHF]], [[A-fib]]) 
#*Rate control, inotropes, diuretics as needed (short acting always better)
#Agitation
#*[[Benzodiazepines]] are the preferred agent

===Treat Increased Adrenergic Tone===
*[[Propranolol]] PO 60-80 mg q4hr (if can tolerate PO, no PR form)
:''or''
*[[Propranolol]] IV 1-2mg over 10 min; if tolerates then 1-2mg boluses q15 minutes until HR <100<ref>http://emcrit.org/podcasts/thyroid-storm/ EMCrit - Thryoid Storm (149)</ref>
**Followed by drip at dose required for heart rate control (3-5mg/hr) 
**Relative contraindications are same as for other medical conditions (e.g. [[CHF]], [[Reactive Airway Disease]], see alternative therapies)
**In addition to decreasing peripheral conversion, propranolol will improve tremor, hyperpyrexia, and agitation
**Unlike other beta-blockers, propranolol also partially blocks conversion of T4 to T3
:''or''
*[[Esmolol]] 250-500mcg/kg loading dose, then 50-100mcg/kg/min<ref>Brunette DD, Rothong C. Emergency department management of thyrotoxic crisis with esmolol. Am J Emerg Med. 1991;9(3):232-4.</ref>
**B1 selective so can be used with active CHF, asthma, etc
**Does not have T4 to T3 blocking properties of propranolol
:''or''
*Reserpine 2.5 - 5 mg IM q4h
**Option for patients in whom beta-blockers are contraindicated <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders in Rosen's Emergency Medicine (9th ed.). Philadelphia, PA: Elsevier/Saunders.</ref>

===Block New Hormone Synthesis<ref>Doses based on American Association of Clinical Endocrinologists recommendations</ref>===
''Thionamides are the main class of medications which prevent new hormone synthesis by inhibiting the iodination of tyrosine residues by thyroid peroxidase (TPO) enzymes. Propylthiouracil (PTU) is prefered over methimazole because it will also bock T4→T3 conversion''
#'''[[PTU]]''' 500-1000mg PO or NG followed by 250mg q4hr 
#*May provide PR, but PO or NG are preferred routes (IV formulations not available in US)
#*PTU recommended in the first trimester of pregnancy with transition to methimazole afterwards<ref>Kobaly K, Mandel SJ. Hyperthyroidism and Pregnancy. Endocrinol Metab Clin North Am. 2019 Sep;48(3):533-545. doi: 10.1016/j.ecl.2019.05.002. Epub 2019 Jun 17. PMID: 31345521.</ref>
#*Note black box warning of hepatotoxicity so check LFTs prior
#*Avoid in patients with significant liver disease; use methimazole instead
#*Theoretically first line and offers advantage over methimazole
#**PTU has earlier onset of action and capacity to inhibit peripheral conversion of T4 to T3
#**However, no significant difference in mortality between PTU and methimazole<ref>Isozaki O et al. Treatment and management of thyroid storm: analysis of the nationwide surveys: The taskforce committee of the Japan Thyroid Association and Japan Endocrine Society for the establishment of diagnostic criteria and nationwide surveys for thyroid storm. Clin Endocrinol (Oxf).  2016; 84(6):912-8 (ISSN: 1365-2265).</ref>
#'''[[Methimazole]]''' 20-25mg q4hr (80 - 100 mg daily in divided doses)
#*Longer acting than PTU
#*IV formulations may be available in Europe
#*Should be avoided in first trimester of pregnancy (freely crosses placenta, birth defects)<ref>Kobaly K, Mandel SJ. Hyperthyroidism and Pregnancy. Endocrinol Metab Clin North Am. 2019 Sep;48(3):533-545. doi: 10.1016/j.ecl.2019.05.002. Epub 2019 Jun 17. PMID: 31345521.</ref>
#*Available in IV formulations outside America, but use supported by case reports only <ref>Thiessen, M. (2018). Thyroid and Adrenal Disorders. Rosen's Emergency Medicine (9th ed). Philadelphia, PA: Elsevier/Saunders.</ref>
#'''[[Potassium iodide]] (SSKI)'''
#*Give 1hr after PTU or methimazole to prevent increased hormone production (Jod-Basedow effect)<ref name="chiha">Chiha M. et al Thyroid storm: an updated review. J Intensive Care Med. 2015 Mar;30(3):131-40. </ref>
#*Block hormone release: (Wolff-Chaikoff effect) only after hormone synthesis is inhibited. Iodine concentration leads to transient decrease of T3/T4 
#*5 drops (0.25 mL or 250mg) orally every 6 hours
#*Avoid potassium iodide if patient is on amiodarone
#*Can substitute radiocontrast dyes (Iopanoic acid, ipodate and iopanoate), PO Lugol solution, '''OR''' IV sodium iodide <ref>Weingart, Scott. EMCRIT Thyroid Storm Show Notes. http://emcrit.org/podcasts/thyroid-storm/ </ref>
#[[Lithium]] carbonate<ref>Carroll R, Matfin G. Endocrine and metabolic emergencies: thyroid storm. Ther Adv Endocrinol Metab. 2010 Jun; 1(3): 139–145. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475282/ Full Text]</ref>
#*Consider if iodine allergic
#*'''Lithium carbonate''' 300mg PO q8hr
#*Lithium inhibits thyroid hormone release from the gland and reduces iodination of tyrosine residues, but its use is complicated by the toxicity that can ensue
#*Treatment of choice for iodine-induced hyperthyroidism as the result of contrast load or amiodarone
#Lugol’s Solution 8 drops PO q 6 ''(alternative iodine source)''
#Sodium Iodide 0.5mg IV Q 12 hours ''(alternative iodine source)''
#Cholestyramine 1-4g BID PO
#*Inhibits enterohepatic circulation of thyroid hormone by binding to conjugated products and promote excretion

===Adrenal Insufficiency Treatment===
''Often there may be associated [[adrenal insufficiency]] (also blocks T4>T3)''
*[[Hydrocortisone]] 300mg IV bolus, followed by 100mg TID for several days '''OR'''
*[[Dexamethasone]] 4mg IV q6hr
*Note that corticosteroids also inhibit conversion of T4 to T3 and block release of hormone from thyroid gland

===[[Plasmapheresis]]<ref>Muller C et al. Role of plasma exchange in the thyroid storm. Ther Apher Dial. 2011 Dec;15(6):522-31.</ref>===
*For recalcitrant thyroid storm, with remaining cardiac and neurologic symptoms
*Especially in the case of fulminant liver failure, in which anti-thyroid drugs are contraindicated<ref>Garg N et al. CALMING THE ST'''OR'''M - ROLE OF PLASMAPHERESIS IN THYROTOXIC CRISES. The Endocrine Society's 95th Annual Meeting and Expo, June 15–18, 2013 - San Francisco.</ref>
*Repeat sessions until TFTs normalize
*Removes cytokines, auto-antibodies, thyroid hormones, thyroid hormone bound proteins

===Antibiotics===
*Second most common etiology of thyroid storm (after medication noncompliance) is infection <ref>Akamizu T, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid 2012; 22:661. </ref>
*Low threshold to start broad spectrum antibiotics

===Additional Interventions===
*Consider L-Carnitine (1 g PO q 12h) - blocks T3 & T4 entry into cell nuclei peripherally <ref>Salvatore Benvenga, et al. Effects of carnitine on thyroid hormone action PMID: 15591013 DOI: 10.1196/annals.1320.015 </ref>
*Consider Cholestyramine (4g PO q 6h) - decreases GI hormone recycling

==Disposition==
*Admission to ICU

==See Also==
*[[Hyperthyroidism]]

==External Links==
*[https://www.youtube.com/watch?v=LWOByFjjemc Thyroid Storm YouTube Video]
*[http://emcrit.org/podcasts/thyroid-storm/ EMCrit - Thryoid Storm (149)]

==References==
<references/>

[[Category:Endocrinology]]