An oncologist is called to the emergency department to evaluate a 62-year-old male patient… — USMLE Step 2 CK

An oncologist is called to the emergency department to evaluate a $62$ -year-old male patient who has developed profound lethargy, severe nausea, and diffuse myalgias over the past $5$ days. The patient was diagnosed with metastatic non-small cell lung cancer six months ago and is currently receiving combination immunotherapy with nivolumab and ipilimumab.

Vital signs are as follows: temperature is $37.6^\circ\text{C}$ ( $99.7^\circ\text{F}$ ), blood pressure is $82/50\text{ mmHg}$ , heart rate is $115/\text{min}$ , and respiratory rate is $18/\text{min}$ . Physical examination shows dry mucous membranes, clear lungs to auscultation, and no cutaneous hyperpigmentation.

Laboratory evaluation reveals:
$\text{Sodium}$ : $129\text{ mEq/L}$
$\text{Potassium}$ : $4.1\text{ mEq/L}$
$\text{Glucose}$ : $58\text{ mg/dL}$
$\text{Eosinophils}$ : $8\%$
$\text{Thyroid-stimulating hormone (TSH)}$ : $0.1\text{ \mu U/mL}$ (Normal: $0.5-5.0\text{ \mu U/mL}$ )
$\text{Free T4}$ : $0.4\text{ ng/dL}$ (Normal: $0.9-1.7\text{ ng/dL}$ )

An $8\text{ AM}$ serum cortisol level has been drawn and is pending.

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

A
Administer intravenous levothyroxine and obtain an electrocardiogram
B
Obtain blood and sputum cultures, then administer intravenous cefepime
Administer intravenous hydrocortisone and isotonic normal salineCevap
D
Administer intravenous furosemide and initiate noninvasive positive-pressure ventilation
E
Consult the ethics committee to identify a surrogate decision-maker for palliative care transition

Cevap

Administer intravenous hydrocortisone and isotonic normal saline

The correct answer addresses the patient's acute adrenal crisis caused by immune checkpoint inhibitor-induced hypophysitis. Ipilimumab and nivolumab are notorious for causing immune-related adverse events (irAEs), including inflammation of the pituitary gland. This results in the loss of anterior pituitary hormones, leading to secondary adrenal insufficiency (causing hypotension, hypoglycemia, hyponatremia, and eosinophilia) and secondary hypothyroidism (low TSH and low Free T4). The patient is in hypovolemic and vasodilatory shock due to a lack of cortisol. The absolute rule of endocrine replacement therapy in panhypopituitarism or combined deficiencies is that glucocorticoids (e.g., hydrocortisone) must always be replaced before thyroid hormone. Administering thyroid hormone first increases the basal metabolic rate, accelerating the clearance of any remaining cortisol and precipitating a fatal adrenal crisis. Therefore, immediate administration of intravenous hydrocortisone and isotonic normal saline is the critical next step.

Adım Adım Çözüm

Identify the primary complication of the patient's immunotherapy.

The patient is experiencing immune checkpoint inhibitor-induced hypophysitis.

Nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) frequently cause immune-related adverse events. The combination of severe hypotension, hyponatremia, hypoglycemia, and inappropriately low TSH/Free T4 points directly to inflammation and failure of the anterior pituitary gland.

Analyze the laboratory data to determine the specific endocrine deficits.

The laboratories confirm secondary hypothyroidism and strongly suggest concurrent secondary adrenal insufficiency.

A low Free T4 accompanied by a low TSH indicates central hypothyroidism. Furthermore, the hyponatremia, hypoglycemia, eosinophilia, and hemodynamic instability in this clinical context are classic indicators of an acute adrenal crisis (cortisol deficiency).

Determine the correct sequencing of life-saving hormone replacement therapy.

Glucocorticoids (hydrocortisone) must be administered immediately, prior to any thyroid hormone replacement.

Administering levothyroxine increases the basal metabolic rate, which accelerates the hepatic clearance of the patient's remaining endogenous cortisol. In a state of adrenal insufficiency, this will precipitate or worsen a fatal adrenal crisis.

Anahtar Kavram

Diagnosis and management sequencing of immune checkpoint inhibitor-induced hypophysitis (central hypothyroidism and secondary adrenal insufficiency).

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