What is a thyroid storm and how can we recognise it?
A thyroid storm is a rare and life threatening condition caused by an exaggerated metabolic response to thyroid hormones. It is not dose dependent on thyroid hormone levels which means there is no thyroid hormone level cut off to diagnose a thyroid storm. Instead, a thyroid storm is diagnosed clinically based on a few different manifestations which we will cover in this post. It occurs in patients with underlying thyroid disorders which may or may not have yet been diagnosed. Common causes of thyroid disorders include Graves' disease, toxic multi nodular goitre, toxic adenomas and thyroiditis amongst others. When these are poorly controlled and a trigger (such as infection, pregnancy or surgery, amongst others) occurs concurrently, it may precipitate a thyroid storm. Mortality rates in thyroid storms can be extremely high, ranging between 10-30% and occurs due to organ failure (cardiac/renal/multiorgan) or due to shock or hyperthermia. Hence, rapid assessment and treatment institution is key.
How to assess a patient with a possible thyroid storm
Assessing a patient with possible thyroid storm should be done rapidly to allow appropriate siting of a patient for closer monitoring if necessary. Ensure you have screened the ABCs (Airway Breathing and Circulation) and stabilise the patient as required. Subsequently look for the following features in a systematic manner.
Systemic features:
Thermoregulatory: Hyperthermia /Fever
Tremor
Sweating
Oligomenorrhoea/amenorrhoea
Cardiac manifestations:
Marked tachycardia with HR>130
Arrhythmias such as atrial fibrillation (AF)
Heart failure - with congestive hepatopathy/pedal oedema/jaundice
GI manifestations:
Vomiting/diarrhoea
Dehydration, acute kidney injury (AKI)
Abdominal pain
Neurological manifestations:
Restlessness, agitation, delirium/coma
Psychosis
Any evidence of precipitating factors
Thyroid/non thyroidal surgery
Infections (even minor infections)
Iodine load (from an angiogram, a contrasted CT scan or even Radioiodine 131-I treatment) - due to the Jod-Basedow effect
Trauma
Pregnancy (esp during labour/delivery)
Sudden withdrawal of Anti-Thyroid Drugs (ATDs)
In general, if 3 or more categories are affected, the patient has features concerning for a thyroid storm or at least an impending thyroid storm and would benefit from closer monitoring in a high dependency unit or ICU setting.
Further investigations that would be important to consider:
Baseline vitals and parameters (heart rate, temperature, respiratory rate, oxygen saturations)
Blood tests:
fT4 (free T4), TSH (Thyroid Stimulating Hormone), fT3 (free T3)
Note that T3 may be low in view of ongoing non-thyroidal illness. However, if fT4 and fT3 are high, then these can be trended daily/every few days during the initial period to monitor response to treatment
Urea, creatinine and electrolytes (sodium, potassium, magnesium, calcium)
Random cortisol
To screen for concurrent adrenal insufficiency. An 8am or a random cortisol is fine as well. A lowish cortisol would raise suspicion for adrenal insufficiency as someone who is tachycardic, agitated and hyperthermic should have an elevated cortisol level. If so, empiric IV hydrocortisone should be commenced
Blood glucose levels - watch for hyperglycaemia
Liver enzymes may be deranged due to multiple reasons
Congestive hepatopathy from thyrocardiac disease
Hepatocyte free radical damage from the hypermetabolic state
ATD-related liver toxicity
Other bedside tests:
Pregnancy test
ECG
Chest XR and urine microscopy to screen for infection
Thyroid scoring systems
While there are a few thyroid scoring systems such as the Burch Wartofsky scoring and the Japanese Thyroid Association Criteria, neither is perfect for diagnosing a thyroid storm. The Burch Wartofsky scoring is more sensitive but less specific and may over diagnose thyroid storms. The Japanese Thyroid Association Criteria is more specific and has a slight tendency towards under diagnosis. In any case, these scoring systems can be misleading and should only be used in 2 situations. Firstly, to provide further evidence to support a high suspicion clinical diagnosis or secondly, to rule out a diagnosis when the scores are extremely low.
In the second scenario, always consider the situation of an apathetic thyroid storm which can occur rarely in elderly patients. These patients can present with extreme weakness, emotional apathy, confusion and may not mount high temperatures.
In conclusion, neither of these scoring systems are particularly useful and while it is important to know of them, they may not be as useful in clinical practice.
Immediate treatment of the patient in thyroid storm
As mentioned earlier, rapid assessment and appropriate siting of the patient is essential. Some pointers for general treatment measures are as follows:
Think about the patient's disposition: HD or ICU?
Treat precipitating cause if possible (Does the patient need antibiotics?)
Nurse the patient at 45 degrees reclining, at rest
Cooling blankets to bring down the temperature
Occasionally patients may require mild sedation if they are very agitated
Fluid replacement should be considered if there is no evidence of cardiac failure
Electrolyte replacement
General treatment principles for treating the thyroid storm:
Treatment directed against the thyroid gland
Inhibition of new thyroid hormone synthesis with high dose thionamides
Inhibition of thyroid hormone release with inorganic iodine
Treatment directed against peripheral effects of thyroid hormone
Beta-adrenergic blockade (possibly the most important)
Inhibition of T4 to T3 conversion by PTU, steroids, propranolol
Physical removal of excess circulating thyroid hormone (considered in extreme cases - plasmapheresis)
Treatment directed against systemic decompensation
Treatment of hyperthermia
Correction of dehydration and nutritional deficit
High dose glucocorticoids
Management of heart failure, haemodynamic instability
Treatment directed against the precipitating cause
Definitive treatment
Consider surgery or radio-iodine treatment once the thyroid hormone levels are better controlled
Important factors to consider before instituting treatment:
Does the patient need to be nil by mouth (NBM) for any reason (e.g. perforated bowel) – consider IV/per rectal meds (if there is a surgical cause, discuss with the surgeons whether oral/rectal meds can be allowed)
Does the patient have a history of asthma? If so, you will have to avoid non-selective beta-blockers that can trigger an asthma attack. Instead, consider a calcium channel blocker such as diltiazem, or a careful trial of B1-selective agents such as esmolol
Is the patient hypotensive? Or has the patient had uncontrolled thyrotoxicosis for a long time with evidence of thyrocardiac disease and impending heart failure? If so, observe caution with beta-blockade use, consider short-acting beta-blockade such as esmolol infusions that can be titrated from minute to minute and bring down the heart rate gradually over 24-48 hours.
If urgent surgery is required, weigh the pros and cons of proceeding with surgery in this patient with thyroid storm. If possible, delay the surgery until you can reduce T3 levels and achieve adequate beta-blockade.
Medications:
Thionamides
Mechanism: Inhibits organification of iodine and coupling of iodotyrosine residues. In addition, high doses of PTU inhibit the conversion of T4 to T3
Examples: Propylthiouracil (PTU) and Carbimazole/Methimazole/Thiamazole
Dosing in thyroid storm:
PTU: PO or NG - Loading dose of 600mg followed by maintenance dose 200mg q4h
If a per rectal dose is necessary due to NBM restrictions, use the same loading dose of 600mg of tablets crushed, suspended in 90ml sterile water, given via an indwelling catheter, spigotted for 2hrs followed by similarly prepared maintenance dose of 200mg q4h
Carbimazole: PO or NG - 20mg q4h or 30mg q6-8h
This can be prepared in special cases for IV administration by taking 500mg of methimazole powder reconstituted in 50ml of normal saline (10mg/mL solution) which must then be filtered through a 0.22mm filter. The solution can then be administered as a slow intravenous push over 2 minutes followed by a saline flush.
In general, PTU is preferred due to the additional effects it has on blocking T4 to T3 conversion, however if there are grossly deranged hepatic enzymes (AST and ALT) then carbimazole may be considered instead.
Iodine
Mechanism: inhibits release of of T4 and T3 from the thyroid gland and can temporarily inhibit hormone synthesis
Examples: Lugol's iodine and Sodium iodide
Dosing in thyroid storm: *Caution to ONLY START at least 1 hour AFTER thionamides have been administered.
Lugol's iodine: PO/NG - 10 drops (i.e. 65mg) TDS
Sodium iodide: IV 1g q12h
Beta-blockade
Mechanism: cardiac rate control
Examples: Esmolol, Propranolol
Dosing in thyroid storm:
Esmolol: IV - Loading dose: 250-500mcg/kg followed by maintenance dose: 50-100mcg/kg/min (preferred in the acute setting, especially if there is concern for thyrocardiac disease and possible heart failure as the dose can be titrated on a minute to minute basis depending on the Haem-dynamic response
Propranolol has the additional benefit of inhibiting T4 to T3 conversion at high doses: PO/NG 60-80mg q4h
Glucocorticoids
Mechanism: Treats relative adrenal insufficiency, reduces vasomotor instability and inhibits T4 to T3 conversion
Examples: Hydrocortisone and dexamethasone
Dosing in thyroid storm:
Hydrocortisone IV 100mg Q8H
Final thoughts
I have not included the drug dosing for alternative second line agents here such as lithium when thionamides cannot be used or diltiazem in the case of an asthmatic patient who cannot tolerate beta blockade. If you'd like to know more about these agents, drop me a comment and I can feature a separate post at a later date.
Once you have instituted the above management, expect improvement in parameters within 24 to 48 hours. Other considerations include plasmapheresis, need for dialysis and emergent thyroidectomy if the patient continues to deteriorate. As the patient gradually improves, Lugol's iodine can slowly be tapered down and off. ATDs and beta blockade can be slowly tailed down and target heart rate can be kept at 60-80bpm eventually. IV hydrocortisone can be reduced once the patient is clinically better and their HPA axis should be assessed to ensure there is no concurrent adrenal insufficiency if there was previous suspicion before stopping glucocorticoid treatment.
The patient should be counselled to pursue definitive treatment to prevent another episode of a thyroid storm - either in the form of thyroidectomy or radioactive iodine treatment though neither should be pursued without adequate control of thyroid status and sufficient beta blockade.
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