EM guidemap - Thyroid storm

Introduction

History of the present illness

Precipitating causes of a thyroid storm

Examination

Diagnostic testing

Medical decision-making

Treatment

Appendix
Introduction

- there is no standard definition of thyroid storm that allows a physician to clearly differentiate it from symptomatic, but not life-threatening, thyrotoxicosis

- thyroid storm is a clinical diagnosis and there is considerable overlap in the serum T4/T3 levels between uncomplicated hyperthyroidism and thyroid storm, and there is no definite evidence of a sudden surge in the serum levels of free T4/T3

- there is no agreed-upon explanation as to what actually precipitates a thyroid storm in a patient with hyperthyroidism, although precipitating conditions or intercurrent illnesses are often present

- thyroid storm is a clinical syndrome mainly characterized by fever + CNS changes (agitation, delirium or a deteriorating mental status) + cardiovascular dysfunction (disproportionate tachycardia or tachyarrythmias +/- CHF)

- one useful method of clinically diagnosing a thyroid storm is to use Burch and Wartofsky's "diagnostic criteriae for thyroid storm"

(see the appendix for further details)

- most patients who develop thyroid storm either have long-standing Graves disease or a toxic mutinodular goitre

- thyroid storm is rarely caused by a single toxic adenoma or a gestational trophoblastic neoplasm

- thyroid storm can rarely present as a variant - apathetic thyroid storm - which is characterized by depression, withdrawal and blunting of affect (suggesting myxedema); and patients with apathetic thyrotoxicosis are usually older females with multinodular goitres, who have blepharoptosis instead of the classic ocular signs; they also have dry, coarse, wrinkled and pigmented skin, proximal muscle wasting, weight loss, and they often also have CHF and atrial fibrillation without disproportionate tachycardia

- the cause of apathetic thyrotoxicosis is unknown and the condition has a high mortality rate

- elderly thyrotoxic patients often lack the ocular signs, tremor, nervousness and heat intolerance commonly associated with hyperkinetic thyrotoxicosis, and they can only present with congestive heart failure, arrhythmias, weight loss, fatigue and mental status changes

- thyroid storm can very rarely manifest itself solely as a worsening of a pre-existing illness eg. CHF becoming unresponsive to treatment, or pre-existing seizures becoming difficult to control - atypical thyrotoxicosis - with no overt signs of classical (hyperkinetic) thyrotoxicosis

History of the present illness

- determine whether there is a previous history of hyperthyroidism

- determine whether the patient stopped taking his anti-thyroid medication

- determine whether the patient inadvertently or intentionally took an overdose of thyroid hormones (factitious hyperthyroidism)

- in patients with no previous history of known thyroid disease => inquire about symptoms suggestive of long-standing (underlying) hyperthyroidism

- inquire about any neck swelling or discomfort secondary to a goiter

- non-specific abdominal pain, nausea or vomiting

- oligomenorrhea/amenorrhea

- excessive fatigue, or inappropriate dyspnea on exertion

- proximal muscle weakness (difficulty climbing stairs secondary to a proximal myopathy)

- eye symptoms (grittiness, photophobia) or a change in their eye appearance (lid retraction with 'staring' eyes) suggests an infiltrative orbitopathy, which is only found in Graves disease

- changes in the skin (moist, silky and decreased wrinkling) or hair (hair thinning or alopecia) or nails (loose friable nails) or fingers (drum-stick clubbing of the fingers)

(thyroid acropachy and dermopathy and vitiligo and periodic paralysis and myasthenia gravis are all unique to Graves disease)

- anginal-type chest pain may occur, which could be secondary to aggravation of underlying coronary artery disease or secondary to coronary artery vasospasm (which disappears when the thyrotoxic state is controlled)

- patients may develop a severely worsening mental status with delirium or frank psychosis, or even stupor progressing to frank coma

- inquire about symptoms suggestive of conditions/diseases that may have precipitated their thyrotoxic crises

Precipitating causes of a thyroid storm

Conditions associated with a rapid rise in thyroid hormone levels

Conditions associated with an acute non-thyroidal illness
Examination

- a disproportionate tachycardia is common

- tachyarrhythmias are common, expecially rapid uncontrolled atrial fibrillation

- wide pulse pressure (with water-hammer pulse)

- systolic hypertension

- moist, hot flushed skin with hyperhydrosis (unless dehydrated)

- fever is typically present (except in apathetic or atypical thyrotoxicosis)

- thyromegaly - either diffuse and symmertical (Graves disease), or lumpy and asymmetrical (multinodular goitre) - is common

- thyroid bruit and thrill is rarely found in Graves disease

- hyperdynamic precordium with loud first heart sound and accentuated pulmonic component of the second heart sound, functional systolic murmur (high-output state)

- tender hepatomegaly and jaundice (jaundice may be a poor prognostic sign)

- hand tremor, hyperkinesis, hyperreflexia, and a delayed relaxation phase of the DTR's

- proximal muscle weakness with wasting (mainly shoulder and pelvic girdle)

- isolated weakness of the bulbar muscles may be a rare variant presentation, mimicing myasthenia gravis (5% of patients with myasthenia gravis have thyrotoxicosis)

- altered mental status (varying from psychic restlessness and wide mood swings => delirium => stupor => coma)

- thyroid dermopathy - localised pretibial myxedema

- thyroid orbitopathy - lid lag, widened palpebral fissure, proptosis, limited extraocular muscle ROM)

- thyroid acropachy - drum-stick fingers with loose friable nails and oncholysis

- hair changes - silky, sparse, waxen hair with patchy alopecia

Diagnostic testing

Serum T4 and TSH

- these tests may not be readily available and treatment should not be delayed if the clinical presentation suggests thyrotoxicosis

- the serum T4 is usually measured by RIA or FTI (free thyroxine index) methodology

- the serum TSH is classically low, except in cases of secondary hyperthyroidism and TSH-producing tumors

- a normal serum FT4 does not exclude the diagnosis because many cases are due to T3 thyrotoxicosis => a FT3 and TSH level should be measured if the serum FT4 level and the clinical picture are discordant, and T3-predominant thyroxicosis is suspected

- a T3/T4 ratio > 20 is virtually diagnostic of Graves disease

Serum glucose, electrolytes and calcium

- non-specific electrolyte changes are common and hypercalcemia occurs (10 - 20%)

- hyperglycemia is not infrequent

CBC

- a non-specific normochromic, normocytic anemia is common

- leukocytosis is a non-specific finding

Liver function tests

- elevated liver enzymes, even in the absence of congestive cardiac failure, are common (~ 75% of cases)

EKG

- signs of cardiac ischemia or pulmonary embolism

Chest X-ray

- signs of CHF or pneumonia or pulmonary embolism

Medical decision-making

- there are many other disease entities that can present with a syndrome of altered mental status + cardiovascular changes + fever - neuroleptic malignant syndrome, serotonin syndrome, anti-cholinergic poisoning, sympathomimetic toxicity, alcohol withdrawal syndromes, encephalopathies - and it is important to carefully consider those possibilities before instituting empirical therapy for a thyroid storm

(see my fever and altered mental status and rigidity guidemap for a more detailed discussion of those entities)

Medical management of thyroid storm is based on the following multi-pronged approach:-

Treatment directed against the thyroid gland

Treatment directed against the peripheral effects of thyroid hormone Treatment of systemic effects Treatment of the precipitating event
Treatment

Treatment directed against the thyroid gland

Inhibition of thyroid hormone synthesis

- propylthiouracil is the drug-of-choice

- the drug is given po, because no parenteral form is available (can be given per NGT or rectally)

- loading dose of propylthiouracil = 600 - 1000 mg, and then 200 - 250 mg every 4 hours

- methimazole is an alternative, but propylthiouracil has the advantage of also blocking peripheral conversion of T4 to T3

- methimazole dose = 20mg every 4 hours (120mg per day)

- contra-indications to these drugs include a history of previous hepatotoxicity or agranulocytosis secondary to the use of thionamides

Inhibition of release of pre-formed thyroid hormone

- iodine preperations po are the drugs-of-choice

- Lugol's solution - 30 drops per day in three-to-four divided doses

or

Saturated solution of potassium iodide (SSKI) - 5 drops every 6 hours

or

Ipodate (orografin) = 1- 3 g per day (ipodate also blocks the peripheral conversion of T4 to T3)

- iodide preperations must be given 1 - 2 hours after the administration of thionamides, because they may increase the production and release of thyroid hormone from the unblocked thyroid gland => aggravation of thyroid storm

- lithium carbonate is only indicated when the patient is allergic to iodine, or if iodine cannot be given because therapy with thionamides is contra-indicated – because lithium is frequently associated with toxic side-effects

- lithium carbonate is given po - 300mg every 6 hours - to obtain a serum level of ~ 1.0 mg/ml

Treatment directed against the peripheral effects of thyroid hormone

Inhibition of peripheral conversion of T4 to T3

- propylthiouracil, ipodate, propanolol, and corticosteroids have this effect

Beta adrenergic blockade

- propanolol is the beta blocker drug-of-choice, because it also blocks the peripheral conversion of T4 to T3

- given po at doses of 40 - 80 mg every 6 hours

- can be given IV at doses of 0.5 - 1.0 mg over 5 minutes q 15 mins if rapid beta blockade is required

- is useful for treating high-output cardiac failure, tachyarrhythmia-induced heart failure and rapid atrial fibrillation

- it also effectively treats many accompanying thyrotoxic symptoms - tremors, diaphoresis, anxiety, heat intolerance and hyperkinesis

- contra-indicated in low-output cardiac failure or asthma

(esmolol can be used if there are relative contra-indications to beta blocker use, because it can be rapidly discontinued if the adverse effects of beta blockade outweigh the benefits)

- alternative beta blockers - such as atenolol or metopropolol - can also be used, but they do not block the peripheral conversion of T4 to T3

- reserpine (2.5mg q 4h) and guanethidine (30mg q 6h) should only be used if there are contra-indications to beta blockade use

- anticoagulants should be used in patients with atrial fibrillation because there is a high incidence of systemic emboli

- digoxin can be used for atrial fibrillation, but larger doses are usually required and toxicity problems are common

- definitive therapy of the atrial fibrillation requires restoration of the euthyroid state

Removal of excess circulating thyroid hormone

- techniques include plasmapheresis, charcoal hemoperfusion and peritoneal dialysis

- reserved for patients who fail to respond to conservative therapy

- may have to be repeated several times, because only ~ 20% of the circulating pool of thyroid hormone is removed each session

Treatment of systemic effects

Treatment of hyperthermia

- acetaminophen is the drug-of-choice

- aspirin is contra-indicated because it displaces thyroid hormone from plasma proteins => increased free T4 levels; and because it uncouples oxidative phosphorylation

- ice packs and cool misting can also be used, although shivering should be avoided

- chlorpromazine (25 - 50 mg IV) can be used to decrease shivering

Glucocorticosteroid therapy

- a  "relative" steroid deficiency exists and steroid administration is always recommended

- drugs include dexamethasone - 2 mg every 6 hours IV, or hydrocortisone - 100 mg q 8h IV

Treat dehydration and nutritional deficits

- most patients require IV hydration and vitamin supplementation, especially thiamine

- fluid deficits of 3 - 5 litres may exist, and hepatic glycogen stores may be depleted requiring use of 5% or 10% glucose solutions

Treatment of precipitating event

- search for and treat any identifiable precipitating causes

- therapy is etiology-dependent

- empiric antibiotic therapy is not recommended in the absence of definite evidence of infection

Appendix

Diagnostic criteriae for thyroid storm
 Temperature

 99 - 100                              5
 100 - 101                           10
 101 - 102                           15
 102 - 103                           20
 103 - 104                           25
 > 104                                 30

 Cardiovascular dysfunction

 Tachycardia

 90 - 110                              5
 110 - 120                           10
 120 - 130                           15
 130 - 140                           20
 > 140                                 25

 Congestive heart failure

 Absent                                0
 Mild CHF                           5
 Moderate CHF                  10
 Severe CHF                      15

 Atrial fibrillation              10
 

  Central nervous system effects

 Absent                                      0
 Mild (agitation)                         10
 Moderate (delirium)                  20
 Severe (seizure, coma)              30

 Gastrointestinal effects

 Absent                                        0
 Moderate (V, D & abd.pain)     10
 Severe (jaundice)                      20 

 Precipitant history

 Negative                                     0
 Positive                                    10

 Likelihood of thyroid storm

 > 45 = Highly suggestive
 25 - 44 = Suggestive 
 < 25 = Unlikely

Causes of thyrotoxicosis
 High uptake thyrotoxicosis
  • Grave's disease
  • Hashitoxicosis
  • Toxic multinodular goitre (Plummer's disease)
  • Solitary toxic thyroid nodule (Goetsch's disease)
  • Gestational trophoblastic neoplasms
  • TSH-producing adenoma
  • Pituatry resistance to thyroid hormone
  Low uptake thyrotoxicosis
  • Subacute thyroiditis
  • Malignant pseudothyroiditis
  • Postpartum thyroiditis
  • Radiation thyroiditis
  • Drug-induced thyroiditis
  • Thyrotoxicosis factitia
  • Iatrogenic thyrotoxicosis
  • Iodine-induced thyrotoxicosis