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BE, a 45-year-old woman, presents with concerns about sudden, intense, and brief episodes of headache, sweating, and a racing heart. The attacks began around 3 weeks ago and last from 2 to 10 minutes. During the attacks, she experiences anxiety and feels her heart skipping beats. Initially, she attributed the attacks to work stress and menopause. However, during her last attack, her blood pressure was measured at 165/110 mm Hg. BE has also experienced weight loss of approximately 8 lbs despite having a good appetite.

Upon physical examination, BE appears thin and pale. Her blood pressure is elevated at 150/100 mm Hg, and her heart rate is increased at 110-120 beats per minute. Considering her symptoms and history, blood levels of normetanephrine and metanephrine were ordered and found to be elevated.

BE is diagnosed with a pheochromocytoma, which is a rare tumor of the adrenal medulla that secretes catecholamines. Imaging studies of the abdomen were conducted to locate the tumor, followed by surgical resection. The tumor was determined to be nonmalignant. Two weeks later, plasma metanephrines were measured again and found to be within the normal range.

The prognosis for nonmalignant pheochromocytomas is favorable, with a 5-year survival rate exceeding 95%.

Q1. Pheochromocytomas secrete norepinephrine (NE) and epinephrine. Select the correct statement regarding the synthesis and degradation of these two biogenic amines:
A. The synthesis of NE and epinephrine involves the hydroxylation of tryptophan to 3,4-dihydroxyphenylalanine (DOPA) by tetrahydrobiopterin-requiring tryptophan hydroxylase.
B. The conversion of DOPA to dopamine requires a pyridoxal phosphate-requiring carboxylase.
C. Vitamin C is necessary for the conversion of NE to epinephrine.
D. Degradation of NE and epinephrine involves methylation by catechol-O-methyltransferase, resulting in the production of normetanephrine and metanephrine, respectively.
E. Oxidative deamination by monoamine oxidase converts normetanephrine and metanephrine to homovanillic acid.

Q2. Which statement about the actions of epinephrine and/or NE is correct?
A. NE acts as both a neurotransmitter and a hormone.
B. The initiation of their actions involves autophosphorylation of specific tyrosine residues in their receptors.
C. Adrenergic receptors, a class of nuclear receptors, mediate their effects.
D. They lead to the activation of glycogen and triacylglycerol synthesis.

Q3. NE, when bound to certain receptors, causes vasoconstriction and an increase in blood pressure. Why might NE be used clinically for the treatment of septic shock?

Case 5: Sun Sensitivity
Patient Presentation: AZ, a 6-year-old boy, is undergoing evaluation for freckle-like areas of hyperpigmentation on his face, neck, forearms, and lower legs.

Focused History: According to AZ's father, the boy has always been sensitive to the sun. Sun exposure leads to erythema (redness) of the skin and photophobia (eye discomfort) in AZ.

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Patient Presentation: BE is a 45-year-old woman who presents with concerns about sudden (paroxysmal), intense, brief episodes of headache, sweating (diaphoresis), and a racing heart (palpitations).
Focused History: BE reports that the attacks started ~3 weeks ago. They last from 2 to 10 minutes, during which time she feels quite anxious. During the attacks, it feels as though her heart is skipping beats (arrhythmia). At first, she thought the attacks were related to recent stress at work and maybe even menopause. The last time it happened, she was in a pharmacy and had her blood pressure taken. She was told it was 165/110 mm Hg. BE notes that she has lost weight (~8 lbs) in this period even though her appetite has been good.
Pertinent Findings: The physical examination was remarkable for BE’s thin, pale appearance. Blood pressure was elevated (150/100 mm Hg), as was the heart rate (110–120 beats/minute). Based on BE’s history, blood levels of normetanephrine and metanephrine were ordered. They were found to be elevated.
Diagnosis: BE has a pheochromocytoma, a rare catecholamine-secreting tumor of the adrenal medulla.
Treatment: Imaging studies of the abdomen were done to locate the tumor. Surgical resection of the tumor was performed. The tumor was found to be nonmalignant. Follow-up measurement of plasma metanephrines was performed 2 weeks later and was in the normal range.
Prognosis: The 5-year survival rate for nonmalignant pheochromocytomas is >95%.
Case-Related Questions: Choose the ONE best answer.
Q1. Pheochromocytomas secrete norepinephrine (NE) and epinephrine. Which of the following statements concerning the synthesis and degradation of these two biogenic amines is correct?
A. The substrate for their synthesis is tryptophan, which is hydroxylated to 3,4-dihydroxyphenylalanine (DOPA) by tetrahydrobiopterin-requiring tryptophan hydroxylase.
B. The conversion of DOPA to dopamine utilizes a pyridoxal phosphate– requiring carboxylase.
C. The conversion of NE to epinephrine requires vitamin C.
D. Degradation involves methylation by catechol-O-methyltransferase and produces normetanephrine from NE and metanephrine from epinephrine.
E. Normetanephrine and metanephrine are oxidatively deaminated to homovanillic acid by monoamine oxidase.
Q2. Which of the following statements concerning the actions of epinephrine and/or NE are correct?
A. NE functions as a neurotransmitter and a hormone.
B. They are initiated by autophosphorylation of select tyrosine residues in their receptors.
C. They are mediated by binding to adrenergic receptors, which are a class of nuclear receptors.
D. They result in the activation of glycogen and triacylglycerol synthesis.
Q3. NE bound to certain receptors causes vasoconstriction and an increase in blood pressure. Why might NE be used clinically in the treatment of septic shock?
Case 5: Sun Sensitivity
Patient Presentation: AZ is a 6-year-old boy who is being evaluated for freckle-like areas of hyperpigmentation on his face, neck, forearms, and lower legs.
Focused History: AZ’s father reports that the boy has always been quite sensitive to the sun. His skin turns red (erythema) and his eyes hurt (photophobia) if he is exposed to the sun for any period of time.