CONTENTS

• Rapid Reference 🚀
• Diagnosis
  • Epidemiology (including triggers)
  • Recognition of the clinical syndrome
  • Catalog of potential findings
  • Investigations
  • Definition & differential
• Treatment
  • Treatment of cause
  • Supportive care
  • Hormonal manipulations
    • Stress dose steroid
    • IV levothyroxine (T4)
    • Liothyronine (T3)
  • Followup
• Podcast
• Questions & discussion
• Pitfalls

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rapid reference

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basic workup should include:

• Endocrine evaluation:
  • TSH & free T4.
  • Random serum cortisol.
• Infectious workup:
  • Blood cultures.
  • Urinalysis +/- urine culture.
  • Chest X-ray.
• POCUS (patients may have pericardial effusion, cardiomyopathy).

treatment for decompensated hypothyroidism:

• IV dextrose if hypoglycemic.
• Steroid: 100 mg IV hydrocortisone q8hr (alternative: 60 mg IV methylprednisolone daily).
• IV levothyroxine (T4): Loading dose ~250 mcg IV.
• Antibiotics: consider empiric therapy if sepsis is possible.
• Liothyronine (T3): consider in the sickest patients. 📖

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epidemiology

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Decompensated hypothyroidism is generally caused by a combination of severe hypothyroidism plus a triggering event. Unfortunately, this may be the initial presentation of hypothyroidism. 

triggering event

• Thyroid supplementation nonadherence.
• Medications:
  • Sedatives.
  • Opioids.
  • Diuretics.
  • Beta-blockers.
  • Amiodarone.
  • Antipsychotics.
  • Lithium.
  • Checkpoint inhibitors, tyrosine kinase inhibitors.
• Infection.
• Surgery, trauma, burns.
• MI or heart failure.
• Cerebrovascular accident (CVA).
• GI bleed.
• Some iodinated contrast dyes may cause transient thyroid suppression.
• Physical stress (including cold exposure).

epidemiology

• Patients are typically female and elderly.
• The majority of cases occur during the winter.

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recognition of the clinical syndrome

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core features that may help suggest decompensated hypothyroidism:

• (1) Altered mental status:
  • Usually not frankly comatose, most patients have hypoactive delirium.
  • Rarely, may see an activated form known as “myxedema madness.”
• (2) Presence of one of the following two cardinal features:
  • Hypothermia (may be severe).
  • Bradycardia.

may also see:

• Features of precipitating event.
• Hypoglycemia.
• Hyponatremia.
• Hypoventilation.
• Reduced bowel & bladder motility.

clues to the diagnosis of hypothyroidism:

• Any history of prior thyroid disease (either hyper- or hypothyroid).
• Thyroidectomy scar or goiter.
• Myxedema:
  • Non-pitting edema of hands, ankles, face.
  • Hoarseness, macroglossia.
• Hair loss, loss of outer third of the eyebrows.
• Cold intolerance.

Myoedema may be a sign of myopathy due to hypothyroidism. When stimulated, the muscle tissue contracts locally (video above).

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catalog of potential findings

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cardiovascular

• Bradycardia
• Pericardial effusion.
• Cardiogenic shock (late finding)
  • Hypothyroid patients often have diastolic hypertension. When the diastolic blood pressure starts falling, this may be a poor sign.
  • Shock may result from some combination of bradycardia, pericardial effusion, impaired contractility, and/or peripheral vasoconstriction.
  • Hypothyroidism can cause vasopressor-refractory shock (which will start responding to therapy once thyroid replacement is administered).
• Torsades de Pointes can occur.

neurologic

• Delirium or coma is a core feature.
• Seizures can occur, including status epilepticus (potentially exacerbated by hyponatremia).

pulmonary

• Hypoventilation may result from central reduction in respiratory drive, as well as from muscular weakness.
• Pleural effusions may promote hypoxemia.
• Edema of the tongue can complicate intubation.

hematologic

• Acquired von Willebrand syndrome may occur, due to reduced synthesis of von Willebrand's factor. Additionally, factors V, VII, VIII, IX, and X may be reduced.(31424777)
  • May be treated with desmopressin (DDAVP).(7750191)
• Anemia is common.

renal

• Hyponatremia usually results from excessive levels of antidiuretic hormone (ADH).
• Acute kidney injury may result from hypoperfusion and possibly also from rhabdomyolysis.
• Reduced bladder motility may cause urinary retention.

gastrointestinal

• Ileus may cause nausea and vomiting.
• Hypothyroidism may lead to megacolon.
• Ascites can occur, but isn't common.
• Gastrointestinal bleeding may occur as a result of coagulopathy (see above).

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investigations

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thyroid labs

• Check: TSH, free T4, and random serum cortisol.
• Findings in decompensated hypothyroidism:
  • TSH will generally be markedly elevated (although this may not occur with central hypothyroidism due to pituitary insufficiency).
  • Free T4 should be decreased.
• The extent of laboratory abnormalities doesn't differentiate compensated vs. decompensated hypothyroidism.
  • Labs will show hypothyroidism, but labs cannot diagnose decompensated hypothyroidism.
  • A wide range of labs are seen in decompensated hypothyroidism, possibly because this may itself suppress hypothalamic function (thereby reducing the TSH level).
  • Decompensated hypothyroidism is a clinical diagnosis based on clinical features in the context of hypothyroidism.

other lab abnormalities which may be seen in hypothyroidism:

• Elevated creatinine kinase (CK).
• Leukopenia can occur.

EKG findings

• Rhythm abnormalities: Sinus bradycardia (most often), conduction blocks.
• QTc may be prolonged, potentially leading to Torsades de Pointes.
• Low voltage complexes.

evaluation for triggers

• Infectious evaluation (CXR, Blood cultures, urinalysis).
• Head CT scan.
• Lumbar puncture (decompensated hypothyroidism may cause a slight increase in protein level due to increased vascular permeability).

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definition & differential

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operational definition of decompensated hypothyroidism?

• “Myxedema Coma” is a misleading term:
  • i) Most patients aren't truly comatose (but they are generally delirious).
  • ii) Most patients don't have myxedema.
  • The construct of “myxedema coma” sets clinicians up for diagnostic failure.
• Decompensated hypothyroidism may be conceptualized as hypothyroidism causing organ failure.
  • The first organ to fail is generally the brain. Thus, a clinical hallmark of decompensated hypothyroidism is delirium.

differential diagnostic considerations include

• Adrenal crisis.
• Septic shock.
• Meningitis.
• Hypothermia of other etiology. 📖
• Hypoglycemia due to another etiology.
• Cerebrovascular accident.
• Drug intoxication (e.g. carbon monoxide, clonidine, beta-blocker or calcium channel blocker).
• Malnutrition.

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treatment of cause

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The trigger of decompensated hypothyroidism should be aggressively investigated and treated. This most often may involve…

sepsis

• Consider empiric therapy for sepsis.
• Decompensated hypothyroidism can mask may features of sepsis (including fever and leukocytosis).

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supportive care

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hypothermia management

• Provide supportive care as described in the hypothermia chapter: 📖.

hypoglycemia

• May require IV dextrose; follow serial glucose levels.
• Hypoglycemic should improve somewhat with steroid administration.

hyponatremia

• Severe hyponatremia may be a contributory factor towards seizure and delirium. This should be treated as described in the hyponatremia chapter: 📖.
• Mild hyponatremia will resolve with thyroid supplementation.

respiratory support

• Intubation and mechanical ventilation may be required due to coma.
• Macroglossia may make intubation more challenging.

cardiovascular support

• Tamponade may rarely require drainage. However, these patients tend to bleed and pericardial effusions will improve over time following treatment with thyroid hormone. Therefore, if it's possible to avoid pericardiocentesis, this may be wise. (28255471)
• Patients may be volume depleted, so titrated fluid resuscitation may be helpful.
• Shock may be pressor-refractory until thyroid hormone is administered.

hematologic support

• For hemorrhage, consider addition of desmopressin 0.3 mcg/kg IV.(7750191) von Willebrand syndrome won't cause alteration in standard coagulation labs, so empiric therapy may be needed.

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hormonal manipulations

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stress dose steroid

• Rationale: Hypothyroidism may associate with adrenal insufficiency, either due to pituitary disease or as a multifocal autoimmune disorder.
  • Giving thyroid hormone without steroid can precipitate adrenal crisis.
• Hydrocortisone 100 mg IV q8hr is the standard therapy here.
• Hydrocortisone should be given prior to thyroid hormone administration (although this is could be less important for levothyroxine, which takes hours to work).
• Patients may be weaned off steroid fairly rapidly, once they are hemodynamically stable and improving.

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IV levothyroxine (T4) = backbone therapy

• 1st day: Loading dose of 200-400 micrograms IV push.(25266247)
  • Consider using the lower end of the dose range in patients who are elderly, have low body weight, or a history of coronary artery disease or arrhythmia. Lower doses should also be used in patients who are being treated with liothyronine (more on this below).
  • This dose repletes the peripheral hormone pool.
• Safe to give empirically (e.g. if there is a delay in labs returning).
  • T4 is the inactive form of thyroid hormone, so this won't cause any immediate effects.
  • The normal amount of circulating T4 is ~1000 mcg. So, if the patient doesn't actually have hypothyroidism, giving 200-400 mcg of levothyroxine won't have much effect.
• Subsequently, the maintenance dose is 1.2 micrograms/kg IV daily.(25266247) Or, simply 100 mcg IV daily for most patients.
• Oral thyroid replacement shouldn't be used in decompensated hypothyroidism, because GI absorption may be erratic in this situation.

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liothyronine (T3) = adjunctive therapy

basics

• T3 is the activated form of thyroid hormone.
• Normally the body converts T4 into T3, but this conversion can be impaired in decompensated hypothyroidism. Therefore, T3 could be beneficial in combination with T4 to jump-start recovery. However, any more aggressive treatment strategy could carry an increased risk of arrhythmia.
• Old, retrospective, small studies have correlated the administration of huge doses of liothyronine (>75 mcg/day) with mortality.(10646654) This isn't necessarily surprising since it's a high dose of liothyronine and that was utilized in the sickest patients. 

American Thyroid Association Taskforce 2014 recommendations

• Indications?
  • Liothyronine isn't necessarily mandatory, but it may be given as adjunctive therapy in combination with thyroxine. It's probably sensible to reserve liothyronine for more severe situations (e.g. intubated or shocky patients).(25266247)
• Dose?
  • The loading dose is 5-20 micrograms IV, followed by a maintenance dose of 2.5-10 micrograms IV q8hr.(25266247) Use the lower end of the dose range in smaller or older patients and patients with a history of coronary disease or arrhythmia.(25266247)
  • Discontinue once recovering (e.g. improved consciousness) or if T3 levels become elevated.
• If you don't have IV liothyronine, oral liothyronine 💊 may be used instead. The oral bioavailability is ~95%, although absorption may well be lower in severe, chronic hypothyroidism.

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followup

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check thyroid hormones every 1-2 days (TSH, free T4, T3).

• If TSH fails to decrease, the patient may require higher dosing of thyroid hormone.
  • However, TSH typically falls at a rate of ~50% per week.
• High T3 suggests excess administration of liothyronine.
• Avoid drawing labs shortly after administering exogenous T3.
• Free T4 should normalize within four days of starting therapy.(31424777)
• By this point endocrinology should be involved, so discuss the results with them.

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podcast

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Mostly diagnostic problems:
  • Failure to consider decompensated hypothyroidism in a patient with altered mental status.
  • Satisfaction of search: after finding decompensated hypothyroidism, don't forget to look for a cause (e.g. sepsis).
• Avoid any potentially sedating medications, as these patients may have very tenuous mental status.

Guide to emoji hyperlinks

• = Link to online calculator.
• = Link to Medscape monograph about a drug.
• = Link to IBCC section about a drug.
• = Link to IBCC section covering that topic.
• = Link to FOAMed site with related information.
• = Link to supplemental media.