2026 VERSION COMSAE Phase 1 Form
115 Practice Exam Questions with
Answers and Detailed Rationales
Question 1
A 24-year-old woman presents with fatigue, weight loss, heat
intolerance, and palpitations. Examination reveals a diffusely
enlarged thyroid and bilateral exophthalmos. Laboratory
studies show elevated free T4 and suppressed TSH. Which
mechanism best explains the patient's thyroid enlargement?
A. Increased TSH secretion from a pituitary adenoma
B. Activating mutation of the TSH receptor
C. Autoantibodies that stimulate the TSH receptor
D. Destruction of thyroid follicular cells by cytotoxic T cells
Answer: C. Autoantibodies that stimulate the TSH receptor
Rationale: Graves disease results from IgG autoantibodies
that bind and activate the TSH receptor, stimulating thyroid
hormone synthesis and diffuse thyroid growth. The same
autoimmune process can activate orbital fibroblasts, causing
exophthalmos. A pituitary adenoma would cause an
inappropriately elevated TSH, while Hashimoto thyroiditis
involves destructive autoimmune mechanisms.
Question 2
,A 67-year-old man with a history of hypertension develops
sudden right-sided weakness and expressive aphasia. MRI
demonstrates an infarction involving the left middle cerebral
artery territory. Which vascular territory is most likely
responsible for the patient's language deficit?
A. Right anterior cerebral artery
B. Left posterior cerebral artery
C. Left middle cerebral artery
D. Right middle cerebral artery
Answer: C. Left middle cerebral artery
Rationale: In most individuals, language function is localized
to the dominant hemisphere, typically the left hemisphere.
The middle cerebral artery supplies Broca and Wernicke
areas, making a dominant MCA infarction capable of
producing aphasia along with contralateral face and upper-
extremity weakness. The anterior cerebral artery primarily
supplies the medial frontal and parietal lobes, especially the
lower extremity.
Question 3
A 32-year-old woman develops fever, hypotension, diffuse
erythematous rash, and multiorgan dysfunction several hours
after retained vaginal packing is discovered. Which bacterial
product is most directly responsible for this presentation?
A. Endotoxin-mediated activation of macrophages
B. Exotoxin A-mediated inhibition of EF-2
,C. Superantigen-mediated massive T-cell activation
D. ADP-ribosylation of inhibitory G proteins
Answer: C. Superantigen-mediated massive T-cell activation
Rationale: Toxic shock syndrome caused by Staphylococcus
aureus is mediated by toxic shock syndrome toxin-1, a
superantigen that cross-links MHC II molecules on antigen-
presenting cells with T-cell receptors. This causes massive
cytokine release, leading to fever, hypotension, rash, and
multiorgan dysfunction. Exotoxin A is associated with
Pseudomonas aeruginosa, whereas ADP-ribosylation of
inhibitory G proteins is characteristic of pertussis toxin.
Question 4
A 45-year-old man with chronic alcohol use presents with
confusion, ophthalmoplegia, and severe gait ataxia. Which
biochemical process is most likely impaired?
A. Conversion of methylmalonyl-CoA to succinyl-CoA
B. Oxidative decarboxylation of α-ketoacids
C. Conversion of homocysteine to methionine
D. Synthesis of tetrahydrofolate from dihydrofolate
Answer: B. Oxidative decarboxylation of α-ketoacids
Rationale: The patient's triad of confusion, ophthalmoplegia,
and ataxia indicates Wernicke encephalopathy caused by
thiamine deficiency. Thiamine pyrophosphate is required for
pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and branched-chain α-ketoacid dehydrogenase. Deficiency
, impairs oxidative decarboxylation of α-ketoacids and can lead
to lactic acidosis.
Question 5
A 59-year-old woman presents with fatigue, constipation, and
muscle weakness. Laboratory studies show potassium of 2.7
mmol/L, metabolic alkalosis, and low renin and aldosterone
levels. Which diagnosis is most likely?
A. Primary hyperaldosteronism
B. Renal artery stenosis
C. Bartter syndrome
D. Laxative-induced hypokalaemia
Answer: D. Laxative-induced hypokalaemia
Rationale: Hypokalaemic metabolic alkalosis with suppressed
renin and aldosterone suggests a non-renal cause of
potassium loss. Chronic laxative use can cause
gastrointestinal potassium loss and volume depletion.
Primary hyperaldosteronism and renovascular hypertension
typically increase aldosterone and renin, respectively, while
Bartter syndrome causes increased renin and aldosterone.
Question 6
A 28-year-old man develops severe epigastric pain radiating
to the back after binge drinking. Serum lipase is markedly
elevated. Which pancreatic enzyme is primarily responsible
for fat necrosis in acute pancreatitis?
115 Practice Exam Questions with
Answers and Detailed Rationales
Question 1
A 24-year-old woman presents with fatigue, weight loss, heat
intolerance, and palpitations. Examination reveals a diffusely
enlarged thyroid and bilateral exophthalmos. Laboratory
studies show elevated free T4 and suppressed TSH. Which
mechanism best explains the patient's thyroid enlargement?
A. Increased TSH secretion from a pituitary adenoma
B. Activating mutation of the TSH receptor
C. Autoantibodies that stimulate the TSH receptor
D. Destruction of thyroid follicular cells by cytotoxic T cells
Answer: C. Autoantibodies that stimulate the TSH receptor
Rationale: Graves disease results from IgG autoantibodies
that bind and activate the TSH receptor, stimulating thyroid
hormone synthesis and diffuse thyroid growth. The same
autoimmune process can activate orbital fibroblasts, causing
exophthalmos. A pituitary adenoma would cause an
inappropriately elevated TSH, while Hashimoto thyroiditis
involves destructive autoimmune mechanisms.
Question 2
,A 67-year-old man with a history of hypertension develops
sudden right-sided weakness and expressive aphasia. MRI
demonstrates an infarction involving the left middle cerebral
artery territory. Which vascular territory is most likely
responsible for the patient's language deficit?
A. Right anterior cerebral artery
B. Left posterior cerebral artery
C. Left middle cerebral artery
D. Right middle cerebral artery
Answer: C. Left middle cerebral artery
Rationale: In most individuals, language function is localized
to the dominant hemisphere, typically the left hemisphere.
The middle cerebral artery supplies Broca and Wernicke
areas, making a dominant MCA infarction capable of
producing aphasia along with contralateral face and upper-
extremity weakness. The anterior cerebral artery primarily
supplies the medial frontal and parietal lobes, especially the
lower extremity.
Question 3
A 32-year-old woman develops fever, hypotension, diffuse
erythematous rash, and multiorgan dysfunction several hours
after retained vaginal packing is discovered. Which bacterial
product is most directly responsible for this presentation?
A. Endotoxin-mediated activation of macrophages
B. Exotoxin A-mediated inhibition of EF-2
,C. Superantigen-mediated massive T-cell activation
D. ADP-ribosylation of inhibitory G proteins
Answer: C. Superantigen-mediated massive T-cell activation
Rationale: Toxic shock syndrome caused by Staphylococcus
aureus is mediated by toxic shock syndrome toxin-1, a
superantigen that cross-links MHC II molecules on antigen-
presenting cells with T-cell receptors. This causes massive
cytokine release, leading to fever, hypotension, rash, and
multiorgan dysfunction. Exotoxin A is associated with
Pseudomonas aeruginosa, whereas ADP-ribosylation of
inhibitory G proteins is characteristic of pertussis toxin.
Question 4
A 45-year-old man with chronic alcohol use presents with
confusion, ophthalmoplegia, and severe gait ataxia. Which
biochemical process is most likely impaired?
A. Conversion of methylmalonyl-CoA to succinyl-CoA
B. Oxidative decarboxylation of α-ketoacids
C. Conversion of homocysteine to methionine
D. Synthesis of tetrahydrofolate from dihydrofolate
Answer: B. Oxidative decarboxylation of α-ketoacids
Rationale: The patient's triad of confusion, ophthalmoplegia,
and ataxia indicates Wernicke encephalopathy caused by
thiamine deficiency. Thiamine pyrophosphate is required for
pyruvate dehydrogenase, α-ketoglutarate dehydrogenase,
and branched-chain α-ketoacid dehydrogenase. Deficiency
, impairs oxidative decarboxylation of α-ketoacids and can lead
to lactic acidosis.
Question 5
A 59-year-old woman presents with fatigue, constipation, and
muscle weakness. Laboratory studies show potassium of 2.7
mmol/L, metabolic alkalosis, and low renin and aldosterone
levels. Which diagnosis is most likely?
A. Primary hyperaldosteronism
B. Renal artery stenosis
C. Bartter syndrome
D. Laxative-induced hypokalaemia
Answer: D. Laxative-induced hypokalaemia
Rationale: Hypokalaemic metabolic alkalosis with suppressed
renin and aldosterone suggests a non-renal cause of
potassium loss. Chronic laxative use can cause
gastrointestinal potassium loss and volume depletion.
Primary hyperaldosteronism and renovascular hypertension
typically increase aldosterone and renin, respectively, while
Bartter syndrome causes increased renin and aldosterone.
Question 6
A 28-year-old man develops severe epigastric pain radiating
to the back after binge drinking. Serum lipase is markedly
elevated. Which pancreatic enzyme is primarily responsible
for fat necrosis in acute pancreatitis?
