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Hyperthyroidism, Emergency Medicine

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Hyperthyroidism, Emergency Medicine

Basics

Description

Gradual onset of aforementioned signs and symptoms пїЅ

Minimal symptoms that respond well to PO therapy пїЅ

  • Excessive thyroid hormone production results in a continuum of disease caused by both the direct physiologic effect of thyroid hormones as well as increased catecholamine sensitivity:Subclinical or mild hyperthyroidismThyrotoxicosisThyroid storm or thyrotoxic crisis with life-threatening manifestations:1-2% of patients with hyperthyroidism
  • Regulation of thyroid hormone:Thyrotropin-releasing hormone (TRH) from hypothalamus acts on the anterior pituitaryThyroid stimulating hormone (TSH) released by anterior pituitary gland and results in increased T3 and T4 from the thyroid gland:Most of circulating hormone is T4, which is peripherally converted to T3T3 is much more biologically active than T4 although it has a shorter half-life
  • Genetics:Interplay between genetics and environmentGraves disease is associated with HLA-B8 and HLA-DR3Autosomal dominant inheritance seen in some families with nontoxic goiter
  • Subclinical or mild hyperthyroidism
  • Thyrotoxicosis
  • Thyroid storm or thyrotoxic crisis with life-threatening manifestations:1-2% of patients with hyperthyroidism
  • 1-2% of patients with hyperthyroidism
  • Thyrotropin-releasing hormone (TRH) from hypothalamus acts on the anterior pituitary
  • Thyroid stimulating hormone (TSH) released by anterior pituitary gland and results in increased T3 and T4 from the thyroid gland:Most of circulating hormone is T4, which is peripherally converted to T3T3 is much more biologically active than T4 although it has a shorter half-life
  • Most of circulating hormone is T4, which is peripherally converted to T3
  • T3 is much more biologically active than T4 although it has a shorter half-life
  • Interplay between genetics and environment
  • Graves disease is associated with HLA-B8 and HLA-DR3
  • Autosomal dominant inheritance seen in some families with nontoxic goiter

Etiology

  • Primary hyperthyroidism:Toxic diffuse goiter (Graves disease)Toxic multinodular (Plummer disease) or uninodular goiterExcessive iodine intake (Jod-Basedow disease)
  • Thyroiditis:Postpartum thyroiditisRadiation thyroiditisSubacute thyroiditis (de Quervain)Chronic thyroiditis (Hashimoto/lymphocytic)
  • Metastatic thyroid cancer
  • Ectopic thyroid tissue (struma ovarii)
  • Pituitary adenoma
  • Drug induced:AmiodaroneLithiumО±-interferonInterleukin-2Iodine (radiographic contrast agents)Excessive thyroid hormone (factitious thyrotoxicosis)Aspirin overdose
  • Toxic diffuse goiter (Graves disease)
  • Toxic multinodular (Plummer disease) or uninodular goiter
  • Excessive iodine intake (Jod-Basedow disease)
  • Postpartum thyroiditis
  • Radiation thyroiditis
  • Subacute thyroiditis (de Quervain)
  • Chronic thyroiditis (Hashimoto/lymphocytic)
  • Amiodarone
  • Lithium
  • О±-interferon
  • Interleukin-2
  • Iodine (radiographic contrast agents)
  • Excessive thyroid hormone (factitious thyrotoxicosis)
  • Aspirin overdose

Diagnosis

  • Infection
  • Trauma
  • Diabetic ketoacidosis
  • Organophosphate intoxication
  • Cytotoxic chemotherapy
  • Myocardial infarction
  • Cerebrovascular accident
  • Surgery
  • Abrupt withdrawal of antithyroid medication or acute ingestion of thyroid medication

Signs and Symptoms

  • Signs and symptoms reflect end-organ responsiveness to thyroid hormone:Signs:FeverTachycardia, wide pulse pressureDiaphoresis/sweatingCongestive heart failure (CHF)ShockTremorDisorientation/psychosisGoiter/thyromegalyThyrotoxic stare/exophthalmos/lid lagHyperreflexiaPretibial myxedemaSymptoms:Weight loss despite increased appetiteDysphagia or dyspnea secondary to obstruction by a goiterRash/pruritus/hyperhidrosisPalpitations/chest painDiarrhea and vomitingMyalgias and weaknessNervousness/anxietyMenstrual irregularitiesHeat intoleranceInsomnia and fatigue
  • Thyroid storm involves exaggerated signs and symptoms of thyrotoxicosis:Extreme tachycardia/dysrhythmiasCHFShockDisorientation and mental status changes including coma and seizureThromboembolic events
  • Signs:FeverTachycardia, wide pulse pressureDiaphoresis/sweatingCongestive heart failure (CHF)ShockTremorDisorientation/psychosisGoiter/thyromegalyThyrotoxic stare/exophthalmos/lid lagHyperreflexiaPretibial myxedema
  • Symptoms:Weight loss despite increased appetiteDysphagia or dyspnea secondary to obstruction by a goiterRash/pruritus/hyperhidrosisPalpitations/chest painDiarrhea and vomitingMyalgias and weaknessNervousness/anxietyMenstrual irregularitiesHeat intoleranceInsomnia and fatigue
  • Fever
  • Tachycardia, wide pulse pressure
  • Diaphoresis/sweating
  • Congestive heart failure (CHF)
  • Shock
  • Tremor
  • Disorientation/psychosis
  • Goiter/thyromegaly
  • Thyrotoxic stare/exophthalmos/lid lag
  • Hyperreflexia
  • Pretibial myxedema
  • Weight loss despite increased appetite
  • Dysphagia or dyspnea secondary to obstruction by a goiter
  • Rash/pruritus/hyperhidrosis
  • Palpitations/chest pain
  • Diarrhea and vomiting
  • Myalgias and weakness
  • Nervousness/anxiety
  • Menstrual irregularities
  • Heat intolerance
  • Insomnia and fatigue
  • Extreme tachycardia/dysrhythmias
  • CHF
  • Shock
  • Disorientation and mental status changes including coma and seizure
  • Thromboembolic events
  • Owing to multinodular goiter, often have history of nontoxic goiter
  • Subtle clinical findings that often reflect single-organ system dysfunction:CHFRefractory atrial fibrillation (AFib)Weight lossDepression, emotional lability, flat affectTremorHyperactivity
  • CHF
  • Refractory atrial fibrillation (AFib)
  • Weight loss
  • Depression, emotional lability, flat affect
  • Tremor
  • Hyperactivity
  • Vital signs:FeverTachycardiaElevation of systolic blood pressureWidened pulse pressureTachypnea/hypoxia
  • Alopecia
  • Exophthalmos or lid lag
  • Thyromegaly or goiter, thyroid bruit
  • Fine, thin, diaphoretic skin
  • Irregularly irregular heartbeat
  • Lung rales (CHF)
  • Right upper quadrant tenderness/jaundice
  • Muscular atrophy/weakness
  • Tremor
  • Mental status changes/coma
  • Fever
  • Tachycardia
  • Elevation of systolic blood pressure
  • Widened pulse pressure
  • Tachypnea/hypoxia

Essential Workup

  • Find underlying cause/precipitating factors.
  • Plasma TSH is the initial ED test of choice:Normal level usually rules out hyperthyroidism:TSH may be low with normal T4. Get T3 level to rule out T3 thyrotoxicosisIf TSH levels unavailable, clinical suspicion should prompt initiation of therapy
  • Normal level usually rules out hyperthyroidism:TSH may be low with normal T4. Get T3 level to rule out T3 thyrotoxicosis
  • If TSH levels unavailable, clinical suspicion should prompt initiation of therapy
  • TSH may be low with normal T4. Get T3 level to rule out T3 thyrotoxicosis

Diagnosis Tests & Interpretation

  • Thyroid function tests for:Symptoms of hyperthyroidismElderly patient with new-onset CHFNew AFib/supraventricular tachycardia (SVT)
  • TSH (usually decreased)
  • Free T4 (usually elevated):If free T4 is unavailable, total T4 and resin T3 uptake5% will have T3 thyrotoxicosis, if low TSH with normal T4, send T3 to rule out
  • Lab studies are often not helpful/nonspecific, get as needed to look for underlying precipitants:CBC to rule out anemiaChemistry panel:BUN, creatinine may be elevated secondary to dehydrationHypokalemia, hyperglycemia
  • Liver function tests (increased transaminases)
  • ABG for hypoxemia and acidosis
  • Cardiac markers
  • Symptoms of hyperthyroidism
  • Elderly patient with new-onset CHF
  • New AFib/supraventricular tachycardia (SVT)
  • If free T4 is unavailable, total T4 and resin T3 uptake
  • 5% will have T3 thyrotoxicosis, if low TSH with normal T4, send T3 to rule out
  • CBC to rule out anemia
  • Chemistry panel:BUN, creatinine may be elevated secondary to dehydrationHypokalemia, hyperglycemia
  • BUN, creatinine may be elevated secondary to dehydration
  • Hypokalemia, hyperglycemia
  • Most commonly sinus tachycardia
  • Rule out MI as precipitant of thyroid storm
  • New-onset AFib

Differential Diagnosis

  • Pheochromocytoma
  • Sepsis
  • Sympathomimetic ingestion
  • Psychosis
  • Heat stroke
  • Delirium tremens
  • Malignant hyperthermia
  • Neuroleptic malignant syndrome
  • Hypothalamic stroke
  • Hypothyroidism (may mimic apathetic hyperthyroidism)
  • Factitious thyrotoxicosis

Treatment

Pre-Hospital

Initial Stabilization/Therapy

  • Airway, breathing, and circulation management
  • Cardiac monitor
  • Supplemental oxygen
  • IV fluids
  • Initiate cooling measures:Acetaminophen for fever:Avoid aspirin (displaces thyroid hormone from thyroglobulin, elevates free T4)Cooling blanket
  • Acetaminophen for fever:Avoid aspirin (displaces thyroid hormone from thyroglobulin, elevates free T4)
  • Cooling blanket
  • Avoid aspirin (displaces thyroid hormone from thyroglobulin, elevates free T4)

Ed Treatment/Procedures

  • Identify and treat the precipitating event
  • For thyroid storm, initiate treatment sequence outlined below based on clinical suspicion
  • Inhibit hormone synthesis using thioamides:Propylthiouracil (PTU):Drug of choiceDecreases hormone synthesis and reduces peripheral conversion of T4Methimazole (MMI)
  • Block hormone release using iodineonly after hormone synthesis is inhibited as above:Oral Lugol solution (saturated potassium iodide solution), orIopanoic acid (Telepaque)Give iodine at least 1 hr after thioamides to prevent increased hormone productionConsider lithium in patient allergic to iodine
  • Block peripheral effects of thyroid hormone:β-blockade:Propranolol is first line as it also inhibits T4 conversion to T3Esmolol, β-1 selective so may be used in patient with active CHF, asthma, etc.Reserpine, guanethidineAlbumin solutionCholestyramine to reduce enteric reabsorption of thyroid hormone
  • Dexamethasone/hydrocortisone:Prevents peripheral T4 to T3 conversion
  • Treatment of thyrotoxicosis, secondary thyroiditis:β-blockadeAnti-inflammatory medications
  • General thyrotoxicosis support:Acetaminophen for hyperpyrexiaTreat CHF with usual methodsManage dehydration with 10% dextrose solution (D 10) to restore depleted hepatic glycogen
  • Identify and treat associated and underlying conditions (infection, ketoacidosis, pulmonary thromboembolism, stroke, etc.)
  • Propylthiouracil (PTU):Drug of choiceDecreases hormone synthesis and reduces peripheral conversion of T4
  • Methimazole (MMI)
  • Drug of choice
  • Decreases hormone synthesis and reduces peripheral conversion of T4
  • Oral Lugol solution (saturated potassium iodide solution), or
  • Iopanoic acid (Telepaque)
  • Give iodine at least 1 hr after thioamides to prevent increased hormone production
  • Consider lithium in patient allergic to iodine
  • β-blockade:Propranolol is first line as it also inhibits T4 conversion to T3Esmolol, β-1 selective so may be used in patient with active CHF, asthma, etc.
  • Reserpine, guanethidine
  • Albumin solution
  • Cholestyramine to reduce enteric reabsorption of thyroid hormone
  • Propranolol is first line as it also inhibits T4 conversion to T3
  • Esmolol, β-1 selective so may be used in patient with active CHF, asthma, etc.
  • Prevents peripheral T4 to T3 conversion
  • β-blockade
  • Anti-inflammatory medications
  • Acetaminophen for hyperpyrexia
  • Treat CHF with usual methods
  • Manage dehydration with 10% dextrose solution (D 10) to restore depleted hepatic glycogen

Medication

  • Cholestyramine: 4 g PO QID
  • Dexamethasone: 2 mg IV q6h (peds: 0.15 mg/kg q6h)
  • Esmolol: 500 Ојg/kg IV over 1 min followed by 50 Ојg/kg/min IV; titrate to effect
  • Guanethidine: 30-40 mg PO q6h for 1-3 days
  • Hydrocortisone: 100 mg IV initially, followed by 100 mg IV q8h for first 24-36 hr
  • Iopanoic acid: 1 g IV q8h for first 24 hr, then 500 mg IV BID
  • Lithium carbonate: 300 mg PO QID (peds: 15-60 mg/kg/d div. TID-QID)
  • Lugol solution: 5 drops (250 mg) PO q6h
  • MMI: 60-80 mg/d PO (peds: 0.4 mg/kg) (peds: 0.2 mg/kg/d) in 3 div. doses
  • Propranolol: 0.5-1 mg IV + subsequent 2-3 mg doses over 10-15 min q several hours, or 60-80 mg PO q4h
  • PTU: 100-150 mg PO q8h initially then 200-250 mg PO q4h (peds: 5-7 mg/kg/d in 3 div. doses)
  • Reserpine: 1-5 mg IM, then 0.07-0.3 mg/kg in the 1st 24 hr
  • PTU
  • Propranolol
  • Iodine therapy (Lugol), 1 hr after PTU
  • MMI
  • Esmolol
  • Lithium (only with iodine allergy)
  • Guanethidine (for patients with bronchospasm), reserpine
  • Physiologic changes associated with pregnancy may resemble many symptoms of hyperthyroidism
  • Poorly controlled hyperthyroidism during pregnancy may result in:Hyperemesis gravidarumPremature laborPreeclampsiaLow birth weightSpontaneous abortionStillbirth
  • Thyroid storm often precipitated by stressors including infection, labor, birth
  • Treatment:Initial stabilization as in the nonpregnant patient (ABCs, supportive measures)PTU considered safer than MMI. Both cross the placenta. PTU should be ≤ 200 mg/dayPropranolol may be safely usedRadioactive iodine absolutely contraindicated when pregnant or nursingThyroidectomy is the only other option if unable to tolerate PTU while pregnant
  • Postpartum thyroiditis:5-10% of patients within 6 mo of deliveryMay require antithyroid medications50% affected become euthyroid within 1 yrTransient hypothyroidism may follow
  • Hyperemesis gravidarum
  • Premature labor
  • Preeclampsia
  • Low birth weight
  • Spontaneous abortion
  • Stillbirth
  • Initial stabilization as in the nonpregnant patient (ABCs, supportive measures)
  • PTU considered safer than MMI. Both cross the placenta. PTU should be ≤ 200 mg/day
  • Propranolol may be safely used
  • Radioactive iodine absolutely contraindicated when pregnant or nursing
  • Thyroidectomy is the only other option if unable to tolerate PTU while pregnant
  • 5-10% of patients within 6 mo of delivery
  • May require antithyroid medications
  • 50% affected become euthyroid within 1 yr
  • Transient hypothyroidism may follow

Follow-Up

Disposition

  • Thyroid storm
  • Requiring IV medications to control heart rate
  • Significantly symptomatic or unstable patients

Follow-Up Recommendations

  • Should have PCP follow-up within a few weeks depending on symptoms
  • May benefit from endocrinology referral

Pearls and Pitfalls

  • Thyroid storm can be fatal. Diagnosis requires a high level of suspicion and treatment often needs to be started presumptively
  • Radioactive iodine is never a treatment option in the pregnant patient with hyperthyroidism
  • Never give iodine before blocking hormone synthesis with PTU or MMI in thyroid storm

Additional Reading

  • Bahn пїЅRS, Burch пїЅHB, Cooper пїЅDS, et al. Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the ATA and AACE. Endocr Pract. 2011;17(3):456-520.
  • Klubo-Gwiezdzinska пїЅJ, Wartofsky пїЅL. Thyroid emergencies. Med Clin North Am. 2012;96(2):385-403.
  • Nayak пїЅB, Hodak пїЅSP. Hyperthyroidism. Endocrinol Metab Clin North Am. 2007;36(3):617-656, v.

See Also (Topic, Algorithm, Electronic Media Element)

Codes

ICD9

  • 242.20 Toxic multinodular goiter without mention of thyrotoxic crisis or storm
  • 242.90 Thyrotoxicosis without mention of goiter or other cause, and without mention of thyrotoxic crisis or storm
  • 242.91 Thyrotoxicosis without mention of goiter or other cause, with mention of thyrotoxic crisis or storm
  • 242.10 Toxic uninodular goiter without mention of thyrotoxic crisis or storm
  • 242.11 Toxic uninodular goiter with mention of thyrotoxic crisis or storm
  • 242.1 Toxic uninodular goiter
  • 242.21 Toxic multinodular goiter with mention of thyrotoxic crisis or storm
  • 242.2 Toxic multinodular goiter
  • 242.9 Thyrotoxicosis without mention of goiter or other cause
  • 245.1 Subacute thyroiditis

ICD10

  • E05.01 Thyrotoxicosis w diffuse goiter w thyrotoxic crisis or storm
  • E05.20 Thyrotxcosis w toxic multinod goiter w/o thyrotoxic crisis
  • E05.90 Thyrotoxicosis, unspecified without thyrotoxic crisis or storm
  • E05.10 Thyrotxcosis w toxic sing thyroid nodule w/o thyrotxc crisis
  • E05.00 Thyrotoxicosis w diffuse goiter w/o thyrotoxic crisis
  • E05.0 Thyrotoxicosis with diffuse goiter
  • E05.11 Thyrotxcosis w toxic single thyroid nodule w thyrotxc crisis
  • E05.1 Thyrotoxicosis with toxic single thyroid nodule
  • E05.21 Thyrotxcosis w toxic multinodular goiter w thyrotoxic crisis
  • E05.2 Thyrotoxicosis with toxic multinodular goiter
  • E05.91 Thyrotoxicosis, unspecified with thyrotoxic crisis or storm
  • E05.9 Thyrotoxicosis, unspecified
  • E05 Thyrotoxicosis [hyperthyroidism]
  • E06.3 Autoimmune thyroiditis

SNOMED

  • 34486009 hyperthyroidism (disorder)
  • 90739004 thyrotoxicosis (disorder)
  • 29028009 Thyrotoxic crisis (disorder)
  • 353295004 Graves disease (disorder)
  • 237501007 Thyrotoxicosis due to acute thyroiditis (disorder)
  • 26389007 toxic multinodular goiter (disorder)
  • 27538003 Hyperthyroidism with Hashimoto disease (disorder)
  • 30985009 Toxic nodular goiter with thyrotoxic storm (disorder)
  • 73869005 toxic uninodular goiter (disorder)