2026 VERSION COMSAE Phase 1 Form
113 Practice Exam Questions with
Verified Answers & Detailed Rationales
Question 1
A 24-year-old woman presents with fatigue, weight loss, heat
intolerance, and palpitations. Examination shows a diffusely
enlarged thyroid and bilateral exophthalmos. Laboratory
studies reveal elevated free T4 and suppressed TSH. Which
mechanism most directly explains her thyroid enlargement?
A. TSH-secreting pituitary adenoma
B. Activating mutation of the TSH receptor
C. Thyroid-stimulating immunoglobulins activating the TSH
receptor
D. Increased hypothalamic TRH secretion
Answer: C
Thyroid-stimulating immunoglobulins are autoantibodies that
bind and activate the TSH receptor, producing diffuse thyroid
hyperplasia and excessive thyroid hormone synthesis in
Graves disease. TSH is suppressed because of negative
feedback from elevated T3 and T4. Exophthalmos results from
autoimmune activation of orbital fibroblasts rather than
direct thyroid hormone excess.
,Question 2
A 67-year-old man develops sudden right-sided weakness and
expressive aphasia. Imaging demonstrates an infarct involving
the dominant inferior frontal gyrus. Which artery is most
likely occluded?
A. Anterior cerebral artery
B. Posterior cerebral artery
C. Superior division of the middle cerebral artery
D. Lenticulostriate artery
Answer: C
The dominant inferior frontal gyrus contains Broca area,
which is supplied primarily by the superior division of the
middle cerebral artery. Infarction causes expressive aphasia,
typically with contralateral face and upper-extremity
weakness. Anterior cerebral artery lesions preferentially affect
the lower extremity, while posterior cerebral artery infarction
commonly causes visual deficits.
Question 3
A 5-year-old boy has recurrent respiratory infections, chronic
diarrhea, and failure to thrive. Laboratory testing reveals
markedly decreased levels of all immunoglobulin classes.
Flow cytometry shows absent CD19+ cells. Which process is
defective?
A. T-cell receptor rearrangement
B. Class switching in mature B cells
,C. B-cell maturation due to defective Bruton's tyrosine
kinase
D. Neutrophil oxidative burst
Answer: C
X-linked agammaglobulinemia results from defective Bruton's
tyrosine kinase, which prevents maturation of pre-B cells into
mature B lymphocytes. The patient therefore has profoundly
reduced immunoglobulins and absent or nearly absent
peripheral B cells. Recurrent bacterial and enteroviral
infections are characteristic.
Question 4
A patient with severe dehydration has a serum sodium
concentration of 158 mEq/L. Which renal adaptation most
directly promotes water conservation?
A. Decreased ADH release
B. Increased proximal sodium excretion
C. Increased ADH-mediated insertion of aquaporin-2
channels
D. Decreased medullary interstitial osmolarity
Answer: C
Hypernatremia increases plasma osmolality, stimulating
hypothalamic osmoreceptors and ADH release. ADH binds V2
receptors on collecting duct principal cells, activating cAMP
and promoting insertion of aquaporin-2 channels into the
, apical membrane. This increases water reabsorption and
concentrates urine.
Question 5
A 32-year-old woman develops progressive proximal muscle
weakness and difficulty climbing stairs. Laboratory studies
show elevated creatine kinase. Muscle biopsy demonstrates
perifascicular atrophy. Which antibody is most strongly
associated with this condition?
A. Anti-centromere antibody
B. Anti-topoisomerase I antibody
C. Anti-Mi-2 antibody
D. Anti-mitochondrial antibody
Answer: C
Dermatomyositis causes symmetric proximal muscle
weakness with characteristic cutaneous findings and
perifascicular atrophy on biopsy. Anti-Mi-2 antibodies are
associated with classic dermatomyositis. Anti-centromere
antibodies are associated with limited systemic sclerosis, anti-
topoisomerase I with diffuse systemic sclerosis, and anti-
mitochondrial antibodies with primary biliary cholangitis.
Question 6
A 58-year-old man with hypertension is started on a
medication that decreases angiotensin II production. Several
113 Practice Exam Questions with
Verified Answers & Detailed Rationales
Question 1
A 24-year-old woman presents with fatigue, weight loss, heat
intolerance, and palpitations. Examination shows a diffusely
enlarged thyroid and bilateral exophthalmos. Laboratory
studies reveal elevated free T4 and suppressed TSH. Which
mechanism most directly explains her thyroid enlargement?
A. TSH-secreting pituitary adenoma
B. Activating mutation of the TSH receptor
C. Thyroid-stimulating immunoglobulins activating the TSH
receptor
D. Increased hypothalamic TRH secretion
Answer: C
Thyroid-stimulating immunoglobulins are autoantibodies that
bind and activate the TSH receptor, producing diffuse thyroid
hyperplasia and excessive thyroid hormone synthesis in
Graves disease. TSH is suppressed because of negative
feedback from elevated T3 and T4. Exophthalmos results from
autoimmune activation of orbital fibroblasts rather than
direct thyroid hormone excess.
,Question 2
A 67-year-old man develops sudden right-sided weakness and
expressive aphasia. Imaging demonstrates an infarct involving
the dominant inferior frontal gyrus. Which artery is most
likely occluded?
A. Anterior cerebral artery
B. Posterior cerebral artery
C. Superior division of the middle cerebral artery
D. Lenticulostriate artery
Answer: C
The dominant inferior frontal gyrus contains Broca area,
which is supplied primarily by the superior division of the
middle cerebral artery. Infarction causes expressive aphasia,
typically with contralateral face and upper-extremity
weakness. Anterior cerebral artery lesions preferentially affect
the lower extremity, while posterior cerebral artery infarction
commonly causes visual deficits.
Question 3
A 5-year-old boy has recurrent respiratory infections, chronic
diarrhea, and failure to thrive. Laboratory testing reveals
markedly decreased levels of all immunoglobulin classes.
Flow cytometry shows absent CD19+ cells. Which process is
defective?
A. T-cell receptor rearrangement
B. Class switching in mature B cells
,C. B-cell maturation due to defective Bruton's tyrosine
kinase
D. Neutrophil oxidative burst
Answer: C
X-linked agammaglobulinemia results from defective Bruton's
tyrosine kinase, which prevents maturation of pre-B cells into
mature B lymphocytes. The patient therefore has profoundly
reduced immunoglobulins and absent or nearly absent
peripheral B cells. Recurrent bacterial and enteroviral
infections are characteristic.
Question 4
A patient with severe dehydration has a serum sodium
concentration of 158 mEq/L. Which renal adaptation most
directly promotes water conservation?
A. Decreased ADH release
B. Increased proximal sodium excretion
C. Increased ADH-mediated insertion of aquaporin-2
channels
D. Decreased medullary interstitial osmolarity
Answer: C
Hypernatremia increases plasma osmolality, stimulating
hypothalamic osmoreceptors and ADH release. ADH binds V2
receptors on collecting duct principal cells, activating cAMP
and promoting insertion of aquaporin-2 channels into the
, apical membrane. This increases water reabsorption and
concentrates urine.
Question 5
A 32-year-old woman develops progressive proximal muscle
weakness and difficulty climbing stairs. Laboratory studies
show elevated creatine kinase. Muscle biopsy demonstrates
perifascicular atrophy. Which antibody is most strongly
associated with this condition?
A. Anti-centromere antibody
B. Anti-topoisomerase I antibody
C. Anti-Mi-2 antibody
D. Anti-mitochondrial antibody
Answer: C
Dermatomyositis causes symmetric proximal muscle
weakness with characteristic cutaneous findings and
perifascicular atrophy on biopsy. Anti-Mi-2 antibodies are
associated with classic dermatomyositis. Anti-centromere
antibodies are associated with limited systemic sclerosis, anti-
topoisomerase I with diffuse systemic sclerosis, and anti-
mitochondrial antibodies with primary biliary cholangitis.
Question 6
A 58-year-old man with hypertension is started on a
medication that decreases angiotensin II production. Several
