A 42-year-old woman presents to the emergency department with a 2-day history of high feve… — USMLE Step 3

A 42-year-old woman presents to the emergency department with a 2-day history of high fever, chills, and severe sore throat. She was diagnosed with hyperthyroidism due to Graves' disease 4 weeks ago and was started on methimazole and propranolol. Her temperature is $39.2^\circ\text{C}$ ( $102.6^\circ\text{F}$ ), blood pressure is $110/70$ mm Hg, heart rate is $112$ /min, and respiratory rate is $18$ /min. Physical examination reveals marked pharyngeal erythema with tonsillar exudates but no neck asymmetry or airway compromise. Laboratory studies show:

Test	Result
Hemoglobin	$12.4\text{ g/dL}$
Platelets	$210,000/\text{mm}^3$
Leukocytes	$900/\text{mm}^3$
Neutrophils	$15\%$
Lymphocytes	$80\%$
Monocytes	$5\%$

Which of the following is the most appropriate next step in the management of this patient?

Discontinue methimazole, admit to the hospital, and initiate intravenous broad-spectrum antibioticsAnswer
B
Discontinue methimazole, prescribe oral amoxicillin-clavulanate, and arrange 24-hour outpatient follow-up
C
Discontinue methimazole, initiate propylthiouracil, and admit to the hospital for observation
D
Continue methimazole, administer intramuscular penicillin G benzathine, and discharge home
E
Discontinue methimazole, begin intravenous antibiotics, and perform an immediate bone marrow biopsy

Answer

Discontinue methimazole, admit to the hospital, and initiate intravenous broad-spectrum antibiotics

The correct answer identifies the need to stop the offending medication and aggressively treat the resulting immunocompromised state. This patient has developed methimazole-induced agranulocytosis, an idiosyncratic and life-threatening adverse effect of thionamides that most frequently occurs within the first 90 days of therapy. Her absolute neutrophil count (ANC) is

135/\text{mm}^3

(

900/\text{mm}^3 \times 15\%

). An ANC less than

500/\text{mm}^3

in the presence of fever defines febrile neutropenia, a medical emergency. The most appropriate next step in management is the immediate discontinuation of methimazole, hospital admission, and prompt initiation of intravenous broad-spectrum antibiotics (such as cefepime, meropenem, or piperacillin-tazobactam) to provide empiric coverage against typical pathogens, particularly *Pseudomonas aeruginosa*. Once recovered, definitive management of her Graves' disease will likely require radioactive iodine ablation or surgery.

Step-by-Step Solution

Calculate the Absolute Neutrophil Count (ANC).

\text{ANC} = \text{Total Leukocytes} \times \text{Percentage of Neutrophils} = 900 \times 0.15 = 135/\text{mm}^3

To determine the severity of the neutropenia based on the complete blood count with differential.

Identify the clinical syndrome and its etiology.

The patient has febrile neutropenia (

\text{ANC} < 500/\text{mm}^3

with fever

> 38.3^\circ\text{C}

), secondary to methimazole-induced agranulocytosis.

Antithyroid drugs (methimazole, propylthiouracil) carry a known risk of idiosyncratic agranulocytosis, which typically presents with sudden-onset fever and sore throat within the first 90 days of therapy.

Determine the appropriate management setting and interventions.

The offending agent must be stopped immediately. The patient requires inpatient admission and empiric intravenous broad-spectrum antibiotics.

Febrile neutropenia is a life-threatening emergency with a high risk of rapid progression to overwhelming sepsis if not treated aggressively.

Key Concept

Evaluation and management of antithyroid drug-induced agranulocytosis (febrile neutropenia)

Estimated Time:1m 30s

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