Thyroid Storm

Article Author:
Binod Pokhrel
Article Editor:
Kamal Bhusal
Updated:
6/3/2019 8:09:29 PM
PubMed Link:
Thyroid Storm

Introduction

Thyroid storm, also known as thyrotoxic crisis, is an acute, life-threatening complication of hyperthyroidism. It is an exaggerated presentation of thyrotoxicosis. It comes with sudden multisystem involvement. The mortality associated with thyroid storm is estimated to be 8-25% despite modern advancements in its treatment and supportive measures.[1] Thus, it is very important to recognize it early and start aggressive treatment to reduce the mortality.

Etiology

Superimposed precipitating factors cause thyroid storm in patients with diagnosed or undiagnosed hyperthyroidism. It is more common with Graves’ disease but can occur with other etiologies of hyperthyroidism, for example, toxic multinodular goiter and toxic adenoma of the thyroid.[2]

The precipitating factors are:

  • Abrupt discontinuation of antithyroid medicine
  • Thyroid surgery
  • Non-thyroid surgery
  • Trauma
  • Acute illness like infections, diabetic ketoacidosis, acute myocardial infarction, cardiovascular accident, cardiac failure, drug reaction
  • Parturition
  • Recent use of Iodinated contrast medium
  • Radioiodine therapy (rare)

Epidemiology

It is a rare presentation of hyperthyroidism. Thyroid storm accounts for about 1% to 2% of admissions for hyperthyroidism. As per the Japanese National Survey, the incidence of thyroid storm was 0.2 per 100,000 population per year, about 0.22% of all thyrotoxicosis patients and 5.4% of hospitalized thyrotoxicosis patients. The average age of people with thyroid storm was 42 to 43 years, which was similar to people with thyrotoxicosis without thyroid storm. The male to female ratio for incidence of thyroid storm was about 1:3, similar to thyrotoxicosis without storm group.[3]

Pathophysiology

The pathophysiological basis for precipitation of thyroid storm in patients with thyrotoxicosis is not clear. But, a precipitating factor, as mentioned above, is always required to cause thyroid storm. Several hypotheses have been purposed. One hypothesis suggests the incidence of thyroid storm is due to the rapid increase in thyroid hormone levels, rather than the absolute hormone level that occurs during thyroid surgery, following radioactive iodine treatment, after sudden discontinuation of the antithyroid drug, or after administration of the large dose of iodine in contrast studies. The hyperactivity of sympathetic nervous system with increased response to catecholamine along with an increased cellular response to thyroid hormone during acute stress or infections, causing cytokines release and altered immunological disturbances, are other possible mechanisms of thyroid storm. Most studies have failed to relate higher thyroid hormone level as a cause of thyroid storm, except for the study by Brooks and others, reported higher free thyroid hormone among the patients with thyroid storm.[4] In other words, the degree of thyroid hormone level is not directly related to higher incidence of thyroid storm.[2]

History and Physical

Presentation of thyroid storm is an exaggerated manifestation of hyperthyroidism, with the presence of an acute precipitating factor. Fever, cardiovascular involvement (including tachycardia, heart failure, arrhythmia), central nervous system (CNS) manifestations, and gastrointestinal symptoms are common. Fever of 104 F to 106 F with diaphoresis is a key presenting feature. Cardiovascular manifestations include tachycardia more than 140 HR/minute, heart failure with pulmonary edema and peripheral edema, hypotension, arrhythmia, and death from cardiac arrest. CNS involvement includes agitation, delirium, anxiety, psychosis, or coma. Gastrointestinal (GI) symptoms include nausea, vomiting, diarrhea, abdominal pain, intestinal obstruction, and acute hepatic failure.[5] A Japanese study found the CNS involvement to be a poor prognostic factor for increased mortality.[3]

Physical examination findings may include high temperature, tachycardia, orbitopathy, goiter, hand tremors, moist and warm skin, hyperreflexia, systolic hypertension, and jaundice.

Evaluation

The diagnosis of thyroid storm needs clinical suspicion based on the presentation mentioned above in a patient with hyperthyroidism or suspected hyperthyroidism. One should not wait for lab results before starting treatment. Thyroid function tests can be obtained which usually show high FT4/FT3 and low TSH. It is not necessary to have very high level of thyroid hormone to cause thyroid storm. Other lab abnormalities may include hypercalcemia, hyperglycemia (due to inhibition of insulin release and increased glycogenolysis), abnormal LFTs, high or low white blood cell (WBC) count.

Burch-Wartofsky Point Scale (BWPS)[2]

In 1993, the following scoring system for the diagnosis of thyroid storm was introduced:

  • Temperature: 5 points per 1 F above 99 F (maximum 30 points)
  • CNS dysfunction: 10 points for mild (agitation), 20 for moderate (delirium, psychosis or extreme lethargy), and 30 for severe (seizure or coma)
  • Tachycardia: 5 (99-109), 10 (110 -119), 15 (120 -129), 20 (130 -139) and 25 (greater than 140)
  • Presence of atrial fibrillation:10
  • Heart failure: 5 for mild (pedal edema), 10 for moderate (bi-basilar rales), 15 for severe (pulmonary edema)
  • GI dysfunction: 10 for moderate (diarrhea, nausea/vomiting or abdominal pain) and 20 for severe (unexplained jaundice)
  • Presence of Precipitating factor: 10 points 

Diagnosis: Total score of more than 45 is highly suggestive of thyroid storm, 25 to 44 supports the diagnosis, and less than 25 makes the diagnosis unlikely.

The Japanese Thyroid Association (JTA)[3] 

This is a different scoring system based on similar clinical findings. Thyrotoxicosis (elevated FT3 and/or FT4) is a prerequisite, and it requires various combinations of following symptoms:

  • CNS manifestation (restlessness, delirium, psychosis/mental aberration, lethargy/somnolence, coma)
  • Fever (38 C/100.4 F or greater)
  • Tachycardia (130/min or higher)
  • CHF (pulmonary edema, rales, cardiogenic shock, or NYHA class IV)
  • GI/Hepatic Manifestation (Nausea, vomiting, diarrhea, total Bilirubin 3 mg/dl or more

Diagnosis

Definite Thyroid Storm (TS1): Thyrotoxicosis (elevated FT3 and/or FT4) plus

  • At least one CNS manifestation plus one or more other symptoms (fever, tachycardia, CHF, GI/Hepatic) ‘OR’ A combination of at least three features among fever, GI/Hepatic, CHF, or tachycardia

Suspected Thyroid Storm (TS2): Thyrotoxicosis (elevated FT3 and/or FT4) plus

  • A combination of at least two features among tachycardia, CHF, GI/Hepatic, Fever ‘OR’ A patient with h/o thyroid disease, presence of goiter and exophthalmos who meets criteria for TS1 but TFTs not available 

These scoring systems are just guidelines. The actual diagnosis is based on clinical judgment. Based on BWPS scoring system, a score of 45 or more is more sensitive but less specific than JTA scoring systems TS1 or TS2 to detect thyroid storm cases. BWPS score of 25 to 45 may suggest an impending storm.

Treatment / Management

Treatment of thyroid storm consists of supportive measures like intravenous (IV) fluids, oxygen, cooling blankets, acetaminophen, as well as specific measures to treat hyperthyroidism. If any precipitating factors, for example, infection, are present, that needs to be taken care. Patients with thyroid storm must be admitted to the intensive care unit with close cardiac monitoring and ventilatory support if needed.[1][6]

Specific Strategic Steps for Treatment

  1. Therapy to control increased adrenergic tone: Beta-blocker
  2. Therapy to reduce thyroid hormone synthesis: Thionamide
  3. Therapy to reduce release of thyroid hormone: Iodine solution
  4. Therapy to block peripheral conversion of T4 to T3: Iodinated radiocontrast agent, glucocorticoid, PTU, propranolol
  5. Therapy to reduce enterohepatic recycling of thyroid hormone: Bile acid sequestrant

After initial supportive measures, a beta blocker should be started for any case of suspected thyroid storm. Typically, propranolol 40 mg to 80 mg is given every 4 to 6 hours. Then, either a loading dose of propylthiouracil (PTU) 500 mg to 1000 mg followed by 250 mg every 4 hours or Methimazole (MMI) 20 mg every 4 to 6 hours should be given. Propylthiouracil is favored because it has a small but additional effect of blocking the peripheral conversion of T4 to T3. An hour after the administration of propylthiouracil or Methimazole, give five drops of SSKI (super saturated potassium iodide) by mouth every 6 hours. Always administer thionamide before starting iodine solution (SSKI) therapy. [7][8][9] This prevents the eminent increase in thyroid hormone synthesis due to increased iodine load from super saturated potassium iodide. Hydrocortisone 100 mg IV every eight hours (or Dexamethasone 2 mg every 6 hours) should also be started. If available, oral cholestyramine 4 grams four times daily can be started for severe cases. One should look for precipitating factors and treat them accordingly. Use of aspirin should be avoided due to its potential risk of increasing free thyroid hormone levels by interfering with thyroid binding protein.

In the first 24 hours of treatment, propylthiouracil decreases T3 level by 45%, but Methimazole drops T3 level by only 10 % to 15%. Methimazole, whereas, causes more rapid normalization of serum T3 level after few weeks of treatment and it has less hepatotoxicity compared to propylthiouracil. Therefore, after initial stabilization, we should treat with Methimazole (if propylthiouracil was started at the beginning, it should be changed to Methimazole). For patients who cannot take oral antithyroid medicine, liquid preparation (pharmacist may have to compound) can be given as enemas. Sometimes, pharmacists can prepare IV form of antithyroid medicine by dissolving the tablet.[10][11][12]

Esmolol, a short-acting beta blocker, at a loading dose of 250 mcg/kg to 500 mcg/kg followed by 50 mcg/kg to -100 mcg/kg/minute can be given in ICU setting.  For patients with reactive airway disease, cardioselective beta blocker like atenolol or metoprolol should be chosen. If there is a contraindication for the use of beta blocker, diltiazem is an alternative.

If thionamide therapy is contraindicated because of an allergic reaction, thyroidectomy is needed after treatment with a beta blocker, hydrocortisone, cholestyramine, and iodine solution. Plasmapheresis is the last resort if all other measures fail.

Once patients’ clinical conditions improve, the iodine solution should be stopped, glucocorticoids can be tapered and stop, and beta blocker should be adjusted. Thionamide therapy should be titrated, and if propylthiouracil is used initially, it should be switched to Methimazole. Patients should be recommended for a definitive treatment with radioiodine (RAI) therapy or thyroidectomy.

Enhancing Healthcare Team Outcomes

Thyroid storm is a rare life-threatening medical emergency which is difficult to diagnose. Thus, a multidisciplinary team that includes an intensivist, cardiologist, endocrinologist, internist, emergency department physician and infectious disease expert is recommended. These patients are best managed in the ICU and monitored by ICU nurses.

Treatment of thyroid storm consists of supportive measures like intravenous (IV) fluids, oxygen, cooling blankets, acetaminophen, as well as specific measures to treat hyperthyroidism. If any precipitating factors, for example, infection, are present, that needs to be taken care of first. Patients with thyroid storm must be admitted to the intensive care unit with close cardiac monitoring and ventilatory support if needed.[1][6] 

The outlook for patients with thyroid storm is guarded and depends on patient age, number of organs involved, comorbidity, need for mechanical ventilation, renal failure and response to treatment.[13][14]


References

[1] 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis., Ross DS,Burch HB,Cooper DS,Greenlee MC,Laurberg P,Maia AL,Rivkees SA,Samuels M,Sosa JA,Stan MN,Walter MA,, Thyroid : official journal of the American Thyroid Association, 2016 Oct     [PubMed PMID: 27521067]
[2] Life-threatening thyrotoxicosis. Thyroid storm., Burch HB,Wartofsky L,, Endocrinology and metabolism clinics of North America, 1993 Jun     [PubMed PMID: 8325286]
[3] Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys., Akamizu T,Satoh T,Isozaki O,Suzuki A,Wakino S,Iburi T,Tsuboi K,Monden T,Kouki T,Otani H,Teramukai S,Uehara R,Nakamura Y,Nagai M,Mori M,, Thyroid : official journal of the American Thyroid Association, 2012 Jul     [PubMed PMID: 22690898]
[4] Free thyroxine concentrations in thyroid storm., Brooks MH,Waldstein SS,, Annals of internal medicine, 1980 Nov     [PubMed PMID: 7212477]
[5] Clinical features and hospital outcomes in thyroid storm: a retrospective cohort study., Angell TE,Lechner MG,Nguyen CT,Salvato VL,Nicoloff JT,LoPresti JS,, The Journal of clinical endocrinology and metabolism, 2015 Feb     [PubMed PMID: 25343237]
[6] Thyroid emergencies., Sarlis NJ,Gourgiotis L,, Reviews in endocrine & metabolic disorders, 2003 May     [PubMed PMID: 12766540]
[7] Neiva J,Fernandes G,Carvalho D,Ferreira B,Duarte R,Araújo R, Thyroid storm and myxoedema: two reversible causes of acute heart failure. Acute medicine. 2018;     [PubMed PMID: 30882107]
[8] Goodier CG, Endocrine Emergencies in Obstetrics. Clinical obstetrics and gynecology. 2019 Mar 13;     [PubMed PMID: 30882392]
[9] Jacobi J, Management of Endocrine Emergencies in the ICU. Journal of pharmacy practice. 2019 Mar 10;     [PubMed PMID: 30852927]
[10] Ba JH,Wu BQ,Wang YH,Shi YF, Therapeutic plasma exchange and continuous renal replacement therapy for severe hyperthyroidism and multi-organ failure: A case report. World journal of clinical cases. 2019 Feb 26;     [PubMed PMID: 30842962]
[11] Kalpakam H,Dhooria S,Agarwal R,Mukherjee S,Sehgal IS, A rare complication of bedside tracheotomy: Thyroid crisis. Lung India : official organ of Indian Chest Society. 2019 Jan-Feb;     [PubMed PMID: 30604713]
[12] Andrade Luz I,Pereira T,Catorze N, Thyroid storm: a case of haemodynamic failure promptly reversed by aggressive medical therapy with antithyroid agents and steroid pulse. BMJ case reports. 2018 Dec 14;     [PubMed PMID: 30567262]
[13] Wyble AJ,Moore SC,Yates SG, Weathering the storm: A case of thyroid storm refractory to conventional treatment benefiting from therapeutic plasma exchange. Journal of clinical apheresis. 2018 Dec;     [PubMed PMID: 30321468]
[14] Simsir IY,Ozdemir M,Duman S,Erdogan M,Donmez A,Ozgen AG, Therapeutic plasmapheresis in thyrotoxic patients. Endocrine. 2018 Oct;     [PubMed PMID: 29968224]