A 47-year-old woman comes to the physician because of fatigue, difficulty falling asleep, and night sweats for the past 6 months. Over the past year, her menstrual cycle has become irregular and her last menstrual period was 2 months ago. She quit smoking 2 years ago. Pelvic exam shows vulvovaginal atrophy. A pregnancy test is negative. Which of the following changes is most likely to occur in this patient's condition?
Q72
An 18-year-old female presents to the clinic complaining of acute abdominal pain for the past couple of hours. The pain is concentrated at the right lower quadrant (RLQ) with no clear precipitating factor and is worse with movement. Acetaminophen seems to help a little but she is concerned as the pain has occurred monthly for the past 3 months. She denies any headache, chest pain, weight changes, diarrhea, nausea/vomiting, fever, or sexual activity. The patient reports a regular menstruation cycle with her last period being 2 weeks ago. A physical examination demonstrates a RLQ that is tender to palpation with a negative psoas sign. A urine beta-hCG test is negative. An ultrasound of the abdomen is unremarkable. What is the main function of the hormone that is primarily responsible for this patient’s symptoms?
Q73
An investigator is studying gastric secretions in human volunteers. Measurements of gastric activity are recorded after electrical stimulation of the vagus nerve. Which of the following sets of changes is most likely to occur after vagus nerve stimulation?
$$$ Somatostatin secretion %%% Gastrin secretion %%% Gastric pH $$$
Q74
A 20-year-old woman reports to student health complaining of 5 days of viral symptoms including sneezing and a runny nose. She started coughing 2 days ago and is seeking cough medication. She additionally mentions that she developed a fever 2 days ago, but this has resolved. On exam, her temperature is 99.0°F (37.2°C), blood pressure is 118/76 mmHg, pulse is 86/min, and respirations are 12/min. Changes in the activity of warm-sensitive neurons in which part of her hypothalamus likely contributed to the development and resolution of her fever?
Q75
You are conducting a lab experiment on skeletal muscle tissue to examine force in different settings. The skeletal muscle tissue is hanging down from a hook. The experiment has 3 different phases. In the first phase, you compress the muscle tissue upwards, making it shorter. In the second phase, you attach a weight of 2.3 kg (5 lb) to its lower vertical end. In the third phase, you do not manipulate the muscle length at all. At the end of the study, you see that the tension is higher in the second phase than in the first one. What is the mechanism underlying this result?
Q76
A 56-year-old woman visits her family physician accompanied by her son. She has recently immigrated to Canada and does not speak English. Her son tells the physician that he is worried that his mother gets a lot of sugar in her diet and does not often monitor her glucose levels. Her previous lab work shows a HbA1c value of 8.7%. On examination, her blood pressure is 130/87 mm Hg and weight is 102 kg (224.9 lb). Which of the following is the correct location of where the glucose transport is most likely affected in this patient?
Q77
A 15-year-old boy is undergoing the bodily changes associated with puberty. He is concerned that he easily develops a foul skin odor, even with mild exercise. Which of the following glandular structures is the causative agent for this foul skin odor?
Q78
Three days after admission to the intensive care unit for septic shock and bacteremia from a urinary tract infection, a 34-year-old woman has persistent hypotension. Her blood cultures were positive for Escherichia coli, for which she has been receiving appropriate antibiotics since admission. She has no history of serious illness. She does not use illicit drugs. Current medications include norepinephrine, ceftriaxone, and acetaminophen. She appears well. Her temperature is 37.5°C (99.5°F), heart rate 96/min, and blood pressure is 85/55 mm Hg. Examination of the back shows costovertebral tenderness bilaterally. Examination of the thyroid gland shows no abnormalities. Laboratory studies show:
Hospital day 1 Hospital day 3
Leukocyte count 18,500/mm3 10,300/mm3
Hemoglobin 14.1 g/dL 13.4 g/dL
Serum
Creatinine 1.4 mg/dL 0.9 mg/dL
Fasting glucose 95 mg/dL 100 mg/dL
TSH 1.8 μU/mL
T3, free 0.1 ng/dL (N: 0.3–0.7 ng/dL)
T4, free 0.9 ng/dL (N: 0.5–1.8 ng/dL)
Repeat blood cultures are negative. An x-ray of the chest shows no abnormalities. Which of the following is the most likely underlying mechanism of this patient's laboratory abnormalities?
Q79
A previously healthy 39-year-old woman comes to the physician because of a slowly enlarging, painless neck mass that she first noticed 3 months ago. During this period, she has also experienced intermittent palpitations, hair loss, and a weight loss of 4.5 kg (10 lb). There is no personal or family history of serious illness. She appears anxious and fidgety. Her temperature is 37.1°C (98.8°F), pulse is 101/min and irregular, respirations are 16/min, and blood pressure is 140/90 mm Hg. Physical examination shows a firm, nontender left anterior cervical nodule that moves with swallowing. Laboratory studies show:
TSH 0.4 μU/mL
T4 13.2 μg/dL
T3 196 ng/dL
Ultrasonography confirms the presence of a 3-cm solid left thyroid nodule. A thyroid 123I radionuclide scintigraphy scan shows increased uptake in a nodule in the left lobe of the thyroid gland with suppression of the remainder of the thyroid tissue. Which of the following is the most likely underlying mechanism of this patient's condition?
Q80
A 28-year-old man presents to his primary care physician for a general checkup. The patient is a healthy young man with no significant past medical history. He is a MD/PhD student and lives in New York City. He exercises frequently and is doing very well in school. He is currently sexually active with multiple female partners and does not use protection. His temperature is 98.9°F (37.2°C), blood pressure is 147/98 mmHg, pulse is 90/min, respirations are 14/min, and oxygen saturation is 99% on room air. Physical exam is notable for a very muscular young man. The patient has comedonal acne and palpable breast tissue. Testicular exam reveals small and symmetrical testicles. Which of the following laboratory changes is most likely to be found in this patient?
Cardiovascular US Medical PG Practice Questions and MCQs
Question 71: A 47-year-old woman comes to the physician because of fatigue, difficulty falling asleep, and night sweats for the past 6 months. Over the past year, her menstrual cycle has become irregular and her last menstrual period was 2 months ago. She quit smoking 2 years ago. Pelvic exam shows vulvovaginal atrophy. A pregnancy test is negative. Which of the following changes is most likely to occur in this patient's condition?
A. Decreased gonadotropin-releasing hormone
B. Increased inhibin B
C. Decreased luteinizing hormone
D. Increased estrogen
E. Increased follicle-stimulating hormone (Correct Answer)
Explanation: ***Increased follicle-stimulating hormone***
- The patient's symptoms (fatigue, insomnia, night sweats, irregular menses, 2 months amenorrhea, vulvovaginal atrophy) at age 47 are classic for **menopause**.
- During menopause, declining **ovarian function** leads to decreased estrogen and inhibin, which in turn causes the pituitary to release more **FSH** and LH via a feedback loop.
*Decreased gonadotropin-releasing hormone*
- **GnRH** levels are typically increased in menopause due to the lack of negative feedback from ovarian hormones, stimulating the pituitary.
- A decrease in GnRH would reduce pituitary gonadotropin secretion, which is contrary to what is observed in menopause.
*Increased inhibin B*
- **Inhibin B** is produced by ovarian granulosa cells and typically **decreases** significantly during the menopausal transition due to the reduced number of ovarian follicles.
- Decreased inhibin B contributes to the rise in FSH levels during menopause.
*Decreased luteinizing hormone*
- In menopause, both **LH** and FSH levels are **elevated** due to the loss of negative feedback from declining ovarian hormones like estrogen and inhibin.
- While FSH rises earlier and more dramatically, LH also increases.
*Increased estrogen*
- In menopause, the ovaries produce **significantly less estrogen**, leading to the classic symptoms like hot flashes and vaginal atrophy.
- The decline in estrogen is a primary hormonal change driving the menopausal transition.
Question 72: An 18-year-old female presents to the clinic complaining of acute abdominal pain for the past couple of hours. The pain is concentrated at the right lower quadrant (RLQ) with no clear precipitating factor and is worse with movement. Acetaminophen seems to help a little but she is concerned as the pain has occurred monthly for the past 3 months. She denies any headache, chest pain, weight changes, diarrhea, nausea/vomiting, fever, or sexual activity. The patient reports a regular menstruation cycle with her last period being 2 weeks ago. A physical examination demonstrates a RLQ that is tender to palpation with a negative psoas sign. A urine beta-hCG test is negative. An ultrasound of the abdomen is unremarkable. What is the main function of the hormone that is primarily responsible for this patient’s symptoms?
A. Inhibition of the anterior pituitary to decrease secretion of FSH and LH
B. Increases the activity of aromatase to synthesize 17-beta-estradiol
C. Increases the activity of cholesterol desmolase to synthesize progesterone (Correct Answer)
D. Induction of pulsatile release of follicle stimulating hormone (FSH) and luteinizing hormone (LH)
E. Inhibition of the hypothalamus to decrease secretion of gonadotrophin releasing hormone (GnRH)
Explanation: ***Increases the activity of cholesterol desmolase to synthesize progesterone***
- The patient's symptoms of recurrent unilateral lower abdominal pain corresponding with her menstrual cycle (2 weeks after her last period, consistent with mid-cycle), negative beta-hCG, and unremarkable ultrasound are highly suggestive of **mittelschmerz** (ovulation pain).
- **Luteinizing hormone (LH)** surge is the primary trigger for ovulation. LH acts on ovarian theca and luteal cells to increase the activity of **cholesterol desmolase (CYP11A1/P450scc)**, the rate-limiting enzyme that converts cholesterol to pregnenolone, the precursor for all steroid hormones including **progesterone**.
- The mid-cycle LH surge triggers ovulation and subsequent formation of the corpus luteum, which produces progesterone. This steroidogenic action of LH is the most relevant to the ovulation process causing her symptoms.
*Inhibition of the anterior pituitary to decrease secretion of FSH and LH*
- This describes the **negative feedback** mechanism exerted by **estrogen** and **progesterone** on the anterior pituitary, not the primary function of LH.
- While important for menstrual cycle regulation, this mechanism does not trigger ovulation or directly cause mittelschmerz.
*Increases the activity of aromatase to synthesize 17-beta-estradiol*
- This is the primary function of **FSH (follicle-stimulating hormone)** on **granulosa cells** within the ovarian follicle.
- FSH stimulates **aromatase**, which converts androgens (produced by theca cells under LH stimulation) into **estrogen**, primarily **17-beta-estradiol**.
- While crucial for follicle maturation, FSH is not the hormone directly responsible for the ovulation event that causes this patient's pain.
*Induction of pulsatile release of follicle stimulating hormone (FSH) and luteinizing hormone (LH)*
- This is the primary function of **gonadotropin-releasing hormone (GnRH)**, secreted by the hypothalamus.
- GnRH's pulsatile release is essential for the menstrual cycle, but GnRH itself is not the direct mediator of ovulation or the associated symptoms.
*Inhibition of the hypothalamus to decrease secretion of gonadotrophin releasing hormone (GnRH)*
- This represents a **negative feedback** mechanism exerted primarily by **estrogen** and **progesterone** on the hypothalamus.
- This feedback loop helps regulate the menstrual cycle but is not the direct mechanism for ovulation or mittelschmerz pain.
Question 73: An investigator is studying gastric secretions in human volunteers. Measurements of gastric activity are recorded after electrical stimulation of the vagus nerve. Which of the following sets of changes is most likely to occur after vagus nerve stimulation?
$$$ Somatostatin secretion %%% Gastrin secretion %%% Gastric pH $$$
A. ↓ ↓ ↓
B. ↑ ↓ ↑
C. ↓ ↑ ↓ (Correct Answer)
D. ↑ ↑ ↑
E. ↑ ↑ ↓
Explanation: ***↓ ↑ ↓***
- Vagal stimulation directly promotes **gastrin release** from G cells, which in turn stimulates **acid secretion**.
- Increased acid secretion **decreases gastric pH** and a lower pH **inhibits somatostatin secretion** in a negative feedback loop.
*↓ ↓ ↓*
- This option incorrectly suggests that vagal stimulation would **decrease gastrin secretion**. Vagal stimulation is a primary stimulant for gastrin release.
- A decrease in gastrin would lead to less acid, resulting in a **higher gastric pH**, not a lower one.
*↑ ↓ ↑*
- This suggests an **increase in somatostatin** and a **decrease in gastrin** which is contrary to the direct effects of vagal stimulation.
- Furthermore, a decreased gastrin would lead to **higher pH**, not lower, unless acid secretion was independently inhibited, which is not the case here.
*↑ ↑ ↑*
- This option correctly indicates an **increase in gastrin secretion** but
incorrectly suggests an **increase in somatostatin** and an **increase in gastric pH**.
- Increased gastrin leads to **increased acid** and thus a **decreased pH**, while high acid levels inhibit somatostatin.
*↑ ↑ ↓*
- This sequence correctly shows an **increase in gastrin** and a **decrease in pH**, but incorrectly suggests an **increase in somatostatin**.
- Somatostatin secretion would be **inhibited** by the increased acid levels resulting from vagal stimulation and gastrin release.
Question 74: A 20-year-old woman reports to student health complaining of 5 days of viral symptoms including sneezing and a runny nose. She started coughing 2 days ago and is seeking cough medication. She additionally mentions that she developed a fever 2 days ago, but this has resolved. On exam, her temperature is 99.0°F (37.2°C), blood pressure is 118/76 mmHg, pulse is 86/min, and respirations are 12/min. Changes in the activity of warm-sensitive neurons in which part of her hypothalamus likely contributed to the development and resolution of her fever?
A. Anterior hypothalamus (Correct Answer)
B. Paraventricular nucleus
C. Suprachiasmatic nucleus
D. Lateral area
E. Posterior hypothalamus
Explanation: ***Anterior hypothalamus***
- The **anterior hypothalamus** contains warm-sensitive neurons that detect increases in body temperature and activate mechanisms for heat dissipation, such as sweating and vasodilation.
- In fever, **prostaglandins** increase the set point in the anterior hypothalamus, causing the body to retain heat and increase heat production until the new set point is reached; resolution of fever involves resetting this set point back to normal.
*Paraventricular nucleus*
- The **paraventricular nucleus** is primarily involved in neuroendocrine functions, stress response, and the regulation of appetite and autonomic nervous system.
- It plays a significant role in releasing hormones like **corticotropin-releasing hormone (CRH)** and **oxytocin**, not direct temperature regulation.
*Suprachiasmatic nucleus*
- The **suprachiasmatic nucleus (SCN)** is the body's main biological clock, regulating **circadian rhythms** including the sleep-wake cycle and daily fluctuations in body temperature.
- While it influences the normal diurnal variation in body temperature, it is not directly responsible for the acute regulation of fever.
*Lateral area*
- The **lateral hypothalamus** primarily functions as the "hunger center," stimulating foraging and feeding behavior.
- Damage to this area can lead to **anorexia** and reduced food intake, not impairments in fever response.
*Posterior hypothalamus*
- The **posterior hypothalamus** is primarily involved in heat conservation and production mechanisms, such as shivering and vasoconstriction, in response to cold.
- It contains cold-sensitive neurons and functions to raise body temperature if it falls below the set point, but it is not where the set point itself is regulated in response to pyrogens.
Question 75: You are conducting a lab experiment on skeletal muscle tissue to examine force in different settings. The skeletal muscle tissue is hanging down from a hook. The experiment has 3 different phases. In the first phase, you compress the muscle tissue upwards, making it shorter. In the second phase, you attach a weight of 2.3 kg (5 lb) to its lower vertical end. In the third phase, you do not manipulate the muscle length at all. At the end of the study, you see that the tension is higher in the second phase than in the first one. What is the mechanism underlying this result?
A. The tension in phase 1 is only active, while in phase 2 it is both active and passive.
B. Shortening the muscle in phase 1 pulls the actin and myosin filaments apart.
C. Lengthening of the muscle in phase 2 increases passive tension. (Correct Answer)
D. There are more actin-myosin cross-bridges attached in phase 2 than in phase 1.
E. Shortening of the muscle in phase 1 uses up ATP stores.
Explanation: ***Lengthening of the muscle in phase 2 increases passive tension.***
- Attaching a weight of 2.3 kg (5 lb) in phase 2 **stretches** the muscle, increasing the **passive tension** generated by elastic components like **titin**.
- This added passive tension, combined with any active tension, results in a **higher total tension** compared to the shortened state in phase 1 where passive tension is minimal.
*The tension in phase 1 is only active, while in phase 2 it is both active and passive.*
- While passive tension is more significant in phase 2 due to stretching, the muscle in phase 1, even when compressed, can still generate some **active tension** if stimulated.
- The key difference contributing to higher tension in phase 2 is the additional **passive component** from stretching, not necessarily the exclusive presence of active tension in one phase.
*Shortening the muscle in phase 1 pulls the actin and myosin filaments apart.*
- Shortening the muscle too much, beyond its optimal resting length, leads to **overlap of actin filaments** and **crumpling of myosin filaments**, reducing the number of available cross-bridge binding sites.
- This **decreases active tension** rather than pulling filaments apart, which would require excessive stretching.
*There are more actin-myofibril cross-bridges attached in phase 2 than in phase 1.*
- Shortening the muscle in phase 1 beyond optimal length **reduces the number of cross-bridges** that can form due to actin filament overlap.
- While lengthening in phase 2 might bring the muscle closer to an **optimal length** for cross-bridge formation (increasing active tension), the primary reason for the higher tension in phase 2 as described is the increase in **passive tension** from stretching, rather than solely increased active cross-bridge formation.
*Shortening of the muscle in phase 1 uses up ATP stores.*
- Muscle contraction, whether shortening or lengthening, requires **ATP hydrolysis** for cross-bridge cycling.
- The act of shortening itself doesn't uniquely "use up" ATP stores more significantly than other contractile actions to explain the observed tension difference; ATP is continuously consumed and regenerated during muscle activity.
Question 76: A 56-year-old woman visits her family physician accompanied by her son. She has recently immigrated to Canada and does not speak English. Her son tells the physician that he is worried that his mother gets a lot of sugar in her diet and does not often monitor her glucose levels. Her previous lab work shows a HbA1c value of 8.7%. On examination, her blood pressure is 130/87 mm Hg and weight is 102 kg (224.9 lb). Which of the following is the correct location of where the glucose transport is most likely affected in this patient?
A. Skeletal muscle (Correct Answer)
B. Red blood cells
C. Pancreas
D. Brain
E. Liver
Explanation: ***Skeletal muscle***
- This patient presents with an HbA1c of 8.7% and obesity, indicative of **Type 2 Diabetes Mellitus**, where **insulin resistance** is a key feature.
- **Skeletal muscle** is a primary site of **glucose uptake** stimulated by insulin and is therefore most significantly affected by insulin resistance.
*Red blood cells*
- **Red blood cells** take up glucose via **insulin-independent** GLUT1 transporters.
- Their glucose transport is generally **not affected** in Type 2 Diabetes, although high glucose levels can lead to glycation of hemoglobin (HbA1c).
*Pancreas*
- The **pancreas** (specifically beta cells) produces insulin, and in Type 2 Diabetes, there can be a **progressive decline in beta cell function** over time.
- However, the initial and primary defect in glucose utilization is **insulin resistance** in peripheral tissues, not impaired glucose transport into pancreatic cells for metabolic regulation.
*Brain*
- The **brain** primarily utilizes glucose for energy via **insulin-independent** GLUT1 and GLUT3 transporters at the blood-brain barrier and neurons, respectively.
- Glucose uptake into the brain is generally **preserved** in Type 2 Diabetes, even in severe insulin resistance.
*Liver*
- The **liver** is involved in both glucose production (gluconeogenesis, glycogenolysis) and uptake (glycogenesis). In Type 2 Diabetes, the liver exhibits **increased glucose output** due to insulin resistance and impaired suppression of endogenous glucose production.
- While **hepatic insulin resistance** is present, the question asks about the primary site where **glucose transport is most likely affected**, and skeletal muscle's role in glucose disposal makes it a more direct answer for impaired glucose transport.
Question 77: A 15-year-old boy is undergoing the bodily changes associated with puberty. He is concerned that he easily develops a foul skin odor, even with mild exercise. Which of the following glandular structures is the causative agent for this foul skin odor?
A. Sebaceous gland
B. Serous gland
C. Apocrine gland (Correct Answer)
D. Mucous gland
E. Eccrine gland
Explanation: ***Apocrine gland***
- **Apocrine glands** become active during puberty and are primarily located in the **axillary** and **genital regions**, secreting a milky, odorless fluid that bacteria on the skin break down, producing a characteristic foul odor.
- The onset of this type of body odor during puberty, exacerbated by exercise, is a hallmark of apocrine gland activity.
*Sebaceous gland*
- **Sebaceous glands** produce **sebum**, an oily substance that lubricates the skin and hair, and its overactivity can contribute to acne.
- While sebaceous glands are associated with puberty, their secretions themselves do not typically produce the characteristic foul body odor, although they can make the skin feel greasy.
*Serous gland*
- **Serous glands** primarily secrete **watery fluids rich in enzymes** or proteins, such as those found in salivary glands (parotid) or the serous membranes (pleura, peritoneum).
- These glands are not typically associated with body odor in the skin.
*Mucous gland*
- **Mucous glands** produce **mucus**, a thick, viscous substance that lubricates and protects surfaces in the respiratory, digestive, and reproductive tracts.
- They are not located in the skin in a way that would cause widespread body odor.
*Eccrine gland*
- **Eccrine glands** are a type of **sweat gland** that are widely distributed over most of the body surface and primarily secrete a **watery sweat** for thermoregulation.
- While their sweat contributes to dampness, their secretions are generally odorless and do not directly cause the foul body odor described in the question, unless mixed with other factors.
Question 78: Three days after admission to the intensive care unit for septic shock and bacteremia from a urinary tract infection, a 34-year-old woman has persistent hypotension. Her blood cultures were positive for Escherichia coli, for which she has been receiving appropriate antibiotics since admission. She has no history of serious illness. She does not use illicit drugs. Current medications include norepinephrine, ceftriaxone, and acetaminophen. She appears well. Her temperature is 37.5°C (99.5°F), heart rate 96/min, and blood pressure is 85/55 mm Hg. Examination of the back shows costovertebral tenderness bilaterally. Examination of the thyroid gland shows no abnormalities. Laboratory studies show:
Hospital day 1 Hospital day 3
Leukocyte count 18,500/mm3 10,300/mm3
Hemoglobin 14.1 g/dL 13.4 g/dL
Serum
Creatinine 1.4 mg/dL 0.9 mg/dL
Fasting glucose 95 mg/dL 100 mg/dL
TSH 1.8 μU/mL
T3, free 0.1 ng/dL (N: 0.3–0.7 ng/dL)
T4, free 0.9 ng/dL (N: 0.5–1.8 ng/dL)
Repeat blood cultures are negative. An x-ray of the chest shows no abnormalities. Which of the following is the most likely underlying mechanism of this patient's laboratory abnormalities?
A. Sick euthyroid syndrome (Correct Answer)
B. Subclinical hypothyroidism
C. Pituitary apoplexy
D. Medication toxicity
E. Fibrous thyroiditis
Explanation: ***Sick euthyroid syndrome***
- The patient's **low free T3** and **normal TSH** in the setting of severe illness (septic shock) are characteristic of **sick euthyroid syndrome**, a common response to acute stress.
- Despite the **abnormal thyroid hormone levels**, this condition typically does not require thyroid hormone replacement as it is an adaptive response to conserve energy during critical illness.
*Subclinical hypothyroidism*
- **Subclinical hypothyroidism** is characterized by an **elevated TSH** with normal free T4 levels, which is not seen here as TSH is normal.
- While it can manifest as fatigue or subtle symptoms, it is less likely given the acute, severe presentation with normal TSH.
*Pituitary apoplexy*
- **Pituitary apoplexy** is a sudden hemorrhage or infarction of the pituitary gland, typically presenting with severe headache, visual disturbances, and signs of hypopituitarism (e.g., adrenal insufficiency, central hypothyroidism).
- The patient's presentation does not include headache or visual changes, and her TSH is normal, making pituitary apoplexy less likely.
*Medication toxicity*
- While some medications (e.g., amiodarone, lithium) can affect thyroid function, these are not among her current medications.
- The thyroid abnormalities are directly tied to her critical illness, rather than a drug side effect.
*Fibrous thyroiditis*
- **Fibrous thyroiditis** (**Riedel's thyroiditis**) is a rare condition involving extensive fibrosis of the thyroid gland, typically presenting as a hard, fixed, painless goiter, and can lead to hypothyroidism.
- The patient's thyroid examination is normal, and the acute onset of her thyroid abnormalities is inconsistent with this chronic fibrosing process.
Question 79: A previously healthy 39-year-old woman comes to the physician because of a slowly enlarging, painless neck mass that she first noticed 3 months ago. During this period, she has also experienced intermittent palpitations, hair loss, and a weight loss of 4.5 kg (10 lb). There is no personal or family history of serious illness. She appears anxious and fidgety. Her temperature is 37.1°C (98.8°F), pulse is 101/min and irregular, respirations are 16/min, and blood pressure is 140/90 mm Hg. Physical examination shows a firm, nontender left anterior cervical nodule that moves with swallowing. Laboratory studies show:
TSH 0.4 μU/mL
T4 13.2 μg/dL
T3 196 ng/dL
Ultrasonography confirms the presence of a 3-cm solid left thyroid nodule. A thyroid 123I radionuclide scintigraphy scan shows increased uptake in a nodule in the left lobe of the thyroid gland with suppression of the remainder of the thyroid tissue. Which of the following is the most likely underlying mechanism of this patient's condition?
A. Gain-of-function mutations of the TSH receptor (Correct Answer)
B. Thyroglobulin antibody production
C. Activation of oncogenes promoting cell division
D. Persistent TSH stimulation and heterogeneous thyroid tissue hyperplasia
E. Thyroid peroxidase autoantibody-mediated destruction of thyroid tissue
Explanation: ***Gain-of-function mutations of the TSH receptor***
- The patient's symptoms (palpitations, weight loss, anxiety, irregular pulse) and lab results (low TSH, high T3/T4) indicate **hyperthyroidism**. The **hot nodule** on scintigraphy with suppressed surrounding tissue points to a **toxic adenoma**.
- **Gain-of-function mutations** in the TSH receptor gene (e.g., *TSHR* gene) cause constitutive activation of the receptor, leading to autonomous thyroid hormone production independent of TSH.
*Thyroglobulin antibody production*
- **Antithyroglobulin antibodies** are typically associated with autoimmune thyroid diseases like **Hashimoto's thyroiditis** (hypothyroidism) or occasionally Graves' disease (hyperthyroidism), but the specific presentation here points to a functional nodule.
- While they can be present in Graves' disease, the scintigraphy showing a **single hot nodule** with suppressed surrounding tissue is not characteristic of Graves' disease, which typically shows diffuse uptake.
*Activation of oncogenes promoting cell division*
- While thyroid nodules can be malignant and involve **oncogene activation** (e.g., *BRAF, RET/PTC*), this mechanism primarily relates to uncontrolled cell growth and **cancer**, not necessarily hyperfunction and excessive hormone production (toxic nodule).
- Malignant nodules are typically "cold" on scintigraphy, meaning they do not take up iodine, unlike the **"hot" nodule** described in this patient.
*Persistent TSH stimulation and heterogeneous thyroid tissue hyperplasia*
- This description is characteristic of a **multinodular goiter** or **diffuse hyperplasia**, often seen in conditions of **chronic TSH stimulation** (e.g., iodine deficiency leading to hypothyroidism and compensatory TSH rise).
- The patient has **suppressed TSH** and a **single hyperfunctioning nodule**, not diffuse hyperplasia or chronic TSH stimulation.
*Thyroid peroxidase autoantibody-mediated destruction of thyroid tissue*
- **Thyroid peroxidase (TPO) antibodies** are involved in **Hashimoto's thyroiditis**, an autoimmune condition leading to gradual **destruction of thyroid tissue** and **hypothyroidism**.
- This patient presents with **hyperthyroidism** and a hyperfunctioning nodule, which is the opposite of the clinical picture seen with TPO antibody-mediated destruction.
Question 80: A 28-year-old man presents to his primary care physician for a general checkup. The patient is a healthy young man with no significant past medical history. He is a MD/PhD student and lives in New York City. He exercises frequently and is doing very well in school. He is currently sexually active with multiple female partners and does not use protection. His temperature is 98.9°F (37.2°C), blood pressure is 147/98 mmHg, pulse is 90/min, respirations are 14/min, and oxygen saturation is 99% on room air. Physical exam is notable for a very muscular young man. The patient has comedonal acne and palpable breast tissue. Testicular exam reveals small and symmetrical testicles. Which of the following laboratory changes is most likely to be found in this patient?
A. Elevated hematocrit
B. Elevated liver enzymes (AST/ALT)
C. Decreased endogenous testosterone
D. Increased estradiol
E. Decreased LH and FSH (Correct Answer)
Explanation: ***Decreased LH and FSH***
- This patient exhibits symptoms (e.g., **comedonal acne**, **palpable breast tissue**, **small and symmetrical testicles**, and **hypertension**) suggestive of **anabolic steroid abuse**. Exogenous anabolic steroids suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to decreased production of **Luteinizing Hormone (LH)** and **Follicle-Stimulating Hormone (FSH)**.
- This is the **most direct and consistent laboratory finding** in anabolic steroid abuse. The suppression of LH and FSH is the primary mechanism that leads to **testicular atrophy** (as seen in this patient) and subsequent suppression of endogenous testosterone production.
- LH and FSH will be **measurably low** in virtually all cases of anabolic steroid abuse, making this the most reliable laboratory marker.
*Decreased endogenous testosterone*
- Anabolic steroid abuse suppresses the HPG axis, leading to decreased **endogenous testosterone production** (due to lack of LH stimulation). However, because patients are administering **exogenous testosterone or testosterone derivatives**, the **total testosterone level** measured in the laboratory may actually be normal, elevated, or vary widely depending on timing of administration and the specific steroid used.
- This makes total testosterone an **unreliable marker** compared to LH/FSH, which will be consistently suppressed. Additionally, distinguishing endogenous from exogenous testosterone requires specialized testing not typically done in routine workup.
*Elevated hematocrit*
- While anabolic steroids stimulate erythropoiesis, leading to **elevated hematocrit** (polycythemia) in many users, this is not as **universally present** or as directly reflective of the HPG axis suppression that causes the testicular atrophy observed clinically.
- Elevated hematocrit increases the risk of **thrombotic events** but is a secondary effect rather than the primary hormonal disruption.
*Elevated liver enzymes (AST/ALT)*
- Oral anabolic steroids, particularly **17-alpha-alkylated compounds**, are **hepatotoxic** and can cause elevated liver enzymes. However, not all anabolic steroids are equally hepatotoxic (injectable forms are less so), and the clinical presentation here more directly points to the **HPG axis suppression** evidenced by testicular atrophy.
- Liver enzyme elevation is **variable** depending on the type and route of steroid administration.
*Increased estradiol*
- Many anabolic steroids are **aromatized to estrogen** (estradiol), which causes **gynecomastia** (as seen in this patient). However, while increased estradiol explains the breast tissue, the **most consistent and diagnostically specific** laboratory finding that explains the testicular atrophy is the suppression of LH and FSH.
- Increased estradiol is a contributing factor to some clinical signs but is not as universally present or as directly related to the testicular findings as LH/FSH suppression.