A 56-year-old man with metastatic melanoma is evaluated in the clinic for a 2-week history… — USMLE Step 2 CK

A $56$ -year-old man with metastatic melanoma is evaluated in the clinic for a $2$ -week history of profound fatigue, diffuse muscle weakness, loss of libido, and intermittent dull headaches. Three months ago, he began immunotherapy with a combination of immune checkpoint inhibitors. Blood pressure is $98/62$ mm Hg, and pulse is $92$ /min. Physical examination reveals normal visual fields and no abnormal skin pigmentation. Laboratory studies show:

Laboratory Test	Result	Reference Range
Serum sodium	$132$ mEq/L	$136$ - $145$ mEq/L
Serum potassium	$4.1$ mEq/L	$3.5$ - $5.0$ mEq/L
Thyroid-stimulating hormone (TSH)	$1.1$ mIU/L	$0.4$ - $4.2$ mIU/L
Free thyroxine (T4)	$0.4$ ng/dL	$0.9$ - $1.7$ ng/dL

Which of the following is the most likely underlying mechanism for this patient's current clinical presentation?

Lymphocytic infiltration of the anterior pituitary glandCevap
B
Autoantibody-mediated destruction of thyroid follicular cells
C
Downregulation of peripheral tissue deiodinase enzyme activity
D
Autoimmune destruction of the adrenal cortex
E
Ectopic secretion of antidiuretic hormone by tumor cells

Cevap

Lymphocytic infiltration of the anterior pituitary gland

The correct answer accurately identifies the pathophysiology of hypophysitis. This patient presents with panhypopituitarism—specifically, central hypothyroidism (low Free T4 with inappropriately normal TSH), central adrenal insufficiency (hypotension and hyponatremia with normal potassium), and likely central hypogonadism (loss of libido). The normal potassium is a critical clue: in secondary adrenal insufficiency, ACTH is lost (reducing cortisol), but aldosterone remains intact because it is governed by angiotensin II and serum potassium, distinguishing it from primary adrenal insufficiency. Immune checkpoint inhibitors (such as anti-CTLA-4 and anti-PD-1 agents) commonly cause autoimmune lymphocytic infiltration of the pituitary gland, leading to this precise constellation of findings along with local inflammatory symptoms like headaches.

Adım Adım Çözüm

Analyze the thyroid function tests.

Free T4 is markedly low (

0.4

ng/dL) but TSH is inappropriately normal (

1.1

mIU/L).

This specific pattern confirms secondary (central) hypothyroidism rather than a primary thyroid gland failure, which would exhibit an elevated TSH.

Synthesize the remaining laboratory and clinical findings.

Hyponatremia (

132

mEq/L) and hypotension with normal potassium (

4.1

mEq/L) indicate secondary adrenal insufficiency.

Loss of ACTH causes cortisol deficiency (leading to hypotension and hyponatremia via ADH disinhibition), but preserves aldosterone secretion (which is regulated by the renin-angiotensin-aldosterone system), thereby keeping potassium levels normal.

Integrate the diagnosis with the patient's history.

The combination of multiple anterior pituitary hormone deficiencies (panhypopituitarism) with headaches and recent immune checkpoint inhibitor use points to hypophysitis.

Immune checkpoint inhibitors (e.g., ipilimumab, nivolumab) are known to cause autoimmune lymphocytic infiltration of the pituitary gland, leading to widespread anterior pituitary failure.

Anahtar Kavram

Immune checkpoint inhibitor-induced hypophysitis

Tahmini Süre:1m 45s

Soru

Cevap

Adım Adım Çözüm

Anahtar Kavram

Sık Yapılan Hatalar

Konular

Bu konudan daha fazla soru