Hyperthyroidism, Emergency Medicine

Basics

Description

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 hyperthyroidism
- Thyrotoxicosis
- Thyroid 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 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 T3
  - T3 is much more biologically active than T4 although it has a shorter half-life
Genetics:
- 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 goiter
- Excessive iodine intake (Jod-Basedow disease)
Thyroiditis:
- Postpartum thyroiditis
- Radiation thyroiditis
- Subacute thyroiditis (de Quervain)
- Chronic thyroiditis (Hashimoto/lymphocytic)
Metastatic thyroid cancer
Ectopic thyroid tissue (struma ovarii)
Pituitary adenoma
Drug induced:
- Amiodarone
- Lithium
- α-interferon
- Interleukin-2
- Iodine (radiographic contrast agents)
- Excessive thyroid hormone (factitious thyrotoxicosis)
- Aspirin overdose

Diagnosis

Thyroid storm is a life-threatening condition, which may be precipitated by: �

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:
  - 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
- Symptoms:
  - 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
Thyroid storm involves exaggerated signs and symptoms of thyrotoxicosis:
- Extreme tachycardia/dysrhythmias
- CHF
- Shock
- Disorientation and mental status changes including coma and seizure
- Thromboembolic events

Apathetic hyperthyroidism: �

Owing to multinodular goiter, often have history of nontoxic goiter
Subtle clinical findings that often reflect single-organ system dysfunction:
- CHF
- Refractory atrial fibrillation (AFib)
- Weight loss
- Depression, emotional lability, flat affect
- Tremor
- Hyperactivity

History
Gradual onset of aforementioned signs and symptoms �
Physical Exam

Vital signs:
- Fever
- Tachycardia
- Elevation of systolic blood pressure
- Widened pulse pressure
- Tachypnea/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

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 thyrotoxicosis
- If TSH levels unavailable, clinical suspicion should prompt initiation of therapy

Diagnosis Tests & Interpretation

Lab

Thyroid function tests for:
- Symptoms of hyperthyroidism
- Elderly patient with new-onset CHF
- New AFib/supraventricular tachycardia (SVT)
TSH (usually decreased)
Free T4 (usually elevated):
- 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
Lab studies are often not helpful/nonspecific, get as needed to look for underlying precipitants:
- CBC to rule out anemia
- Chemistry panel:
  - BUN, creatinine may be elevated secondary to dehydration
  - Hypokalemia, hyperglycemia
Liver function tests (increased transaminases)
ABG for hypoxemia and acidosis
Cardiac markers

Imaging
CXR (in CHF or sepsis) �
Diagnostic Procedures/Surgery
EKG: �

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

Stabilization and supportive care �

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

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 choice
  - Decreases hormone synthesis and reduces peripheral conversion of T4
- Methimazole (MMI)
Block hormone release using iodineonly after hormone synthesis is inhibited as above:
- 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
Block peripheral effects of thyroid hormone:
- β-blockade:
  - 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.
- Reserpine, guanethidine
- Albumin solution
- Cholestyramine to reduce enteric reabsorption of thyroid hormone
Dexamethasone/hydrocortisone:
- Prevents peripheral T4 to T3 conversion
Treatment of thyrotoxicosis, secondary thyroiditis:
- β-blockade
- Anti-inflammatory medications
General thyrotoxicosis support:
- Acetaminophen for hyperpyrexia
- Treat CHF with usual methods
- Manage 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.)

Medication

Cholestyramine: 4 g PO QID
Dexamethasone: 2 mg IV q6h (peds: 0.15 mg/kg q6h)
Esmolol: 500 μg/kg IV over 1 min followed by 50 μg/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

First Line

PTU
Propranolol
Iodine therapy (Lugol), 1 hr after PTU

Second Line

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 gravidarum
- Premature labor
- Preeclampsia
- Low birth weight
- Spontaneous abortion
- Stillbirth
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/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
Postpartum thyroiditis:
- 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

Admission Criteria

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

Discharge Criteria
Minimal symptoms that respond well to PO therapy �

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 �RS, Burch �HB, Cooper �DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the ATA and AACE. Endocr Pract. 2011;17(3):456-520.
Klubo-Gwiezdzinska �J, Wartofsky �L. Thyroid emergencies. Med Clin North Am. 2012;96(2):385-403.
Nayak �B, Hodak �SP. Hyperthyroidism. Endocrinol Metab Clin North Am. 2007;36(3):617-656, v.

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)

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