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

[Outline]

• DESCRIPTION
• ETIOLOGY

ALERT

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

Geriatric Considerations

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

[Outline]

• INFORMATION
• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

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 iodine only 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

Pregnancy Considerations

• 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

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

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

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• 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

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

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

[Outline]

• ICD9
• ICD10

• 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.

See Also (Topic, Algorithm, Electronic Media Element)

Hypothyroidism

Rita K. Cydulka

Christopher S. Campbell