A researcher is studying receptors that respond to epinephrine in the body and discovers a particular subset that is expressed in presynaptic adrenergic nerve terminals. She discovers that upon activation, these receptors will lead to decreased sympathetic nervous system activity. She then studies the intracellular second messenger changes that occur when this receptor is activated. She records these changes and begins searching for analogous receptor pathways. Which of the following receptors would cause the most similar set of intracellular second messenger changes?

Dopamine receptors in the brain

Muscarinic cholinoreceptors in the gastrointestinal tract

Growth hormone receptors in the musculoskeletal system

Vasopressin receptors in the kidney

Aldosterone receptors in the kidney

A newborn is brought to the pediatric clinic by his mother because she has noticed a swelling in the belly while dressing her baby. On physical examination, the newborn is found to have a non-tender upper abdominal mass. The clinician also noticed absent irises and undescended testes in this baby. A magnetic resonance image (MRI) scan of the abdomen shows a mass of intra-renal origin. Which 1 of the following genetic disorders is most probably the cause of this neonate’s symptoms and signs?

Amplification of MYCN (N-myc) proto-oncogene

A 49-year-old male presents with a primary complaint of several recent episodes of severe headache, sudden anxiety, and a "racing heart". The patient originally attributed these symptoms to stress at work; however, these episodes are becoming more frequent and severe. Laboratory evaluation during such an episode reveals elevated plasma free metanephrines. Which of the following additional findings in this patient is most likely?

Decreased 24 hour urine vanillylmandelic acid (VMA) levels

A 43-year-old male with a history of thyroid cancer status post total thyroidectomy presents to his primary care physician after repeated bouts of headaches. His headaches are preceded by periods of anxiety, palpitations, and sweating. The patient says he is unable to pinpoint any precipitating factors and instead says the events occur without warning. Of note, the patient's father and uncle also have a history of thyroid cancer. On exam his vitals are: T 36.8 HR 87, BP 135/93, RR 14, and O2 Sat 100% on room air. The patient's TSH is within normal limits, and he reports taking his levothyroxine as prescribed. What is the next best step in diagnosing this patient's chief complaint?

Plasma fractionated metanephrines

Abdominal CT scan with and without IV contrast

High dose dexamethasone suppression test

A 51-year-old African American man with a history of poorly controlled hypertension presents to the emergency room with blurry vision and dyspnea. He reports rapid-onset blurred vision and difficulty breathing 4 hours prior to presentation. He takes lisinopril, hydrochlorothiazide, and spironolactone but has a history of poor medication compliance. He has a 50 pack-year smoking history and drinks 4-6 shots of vodka per day. His temperature is 99.2°F (37.3°C), blood pressure is 195/115 mmHg, pulse is 85/min, and respirations are 20/min. On exam, he is ill-appearing and pale. He is intermittently responsive and oriented to person but not place or time. Fundoscopic examination reveals swelling of the optic disc with blurred margins. A biopsy of this patient’s kidney would most likely reveal which of the following?

Concentrically thickened arteriolar tunica media with abundant nuclei

Calcific deposits in the arterial media without luminal narrowing

Fibrous atheromatous plaques in the arterial intima

Endothelial proliferation and luminal narrowing with a chronic inflammatory infiltrate

A 60-year-old woman comes to the physician because of lower back pain, generalized weakness, and weight loss that has occurred over the past 6 weeks. She also says that her urine has appeared foamy recently. Physical examination shows focal midline tenderness of the lumbar spine and conjunctival pallor. Her temperature is 100.5°F (38°C). A photomicrograph of a bone marrow biopsy specimen is shown. Further evaluation of this patient is most likely to show which of the following findings?

Grouped erythrocytes with stacked-coin appearance

Myeloblasts with needle-shaped cytoplasmic inclusions

Erythrocytes with cytoplasmic hemoglobin inclusions

Neutrophils with hypersegmented nuclear lobes

B-lymphocytes with radial cytoplasmic projections

A 38-year-old woman with type 1 diabetes for 20 years presents with diabetic ketoacidosis. She is treated and recovers. Six months later, she develops progressive fatigue, nausea, and hyperpigmentation. Laboratory studies show morning cortisol 3 μg/dL, ACTH 180 pg/mL, TSH 8.2 mIU/L, free T4 0.6 ng/dL, and positive anti-thyroid peroxidase antibodies. She also has positive 21-hydroxylase antibodies. Her 12-year-old daughter was recently diagnosed with type 1 diabetes. Evaluate the pathologic process and most critical monitoring recommendation for the daughter.

Autoimmune polyglandular syndrome type 2; screen daughter for adrenal antibodies and thyroid function annually

Multiple endocrine neoplasia syndrome; screen for pheochromocytoma and medullary thyroid cancer

Schmidt syndrome with isolated sporatic occurrence; routine diabetes management only for daughter

Autoimmune polyglandular syndrome type 1; screen for mucocutaneous candidiasis and hypoparathyroidism

Secondary endocrine failure from diabetes complications; optimize glycemic control in daughter

Adrenal medullary disorders for USMLE Step 1: High-Yield Pathology Lessons

Adrenal Medulla - Catecholamine HQ

Core Function: Central hub for catecholamine synthesis and secretion (Epinephrine > Norepinephrine). Regulated by preganglionic sympathetic fibers.
Histology: Composed of chromaffin cells, which are modified postganglionic sympathetic neurons derived from the neural crest.
Synthesis Pathway:

⭐ The enzyme converting norepinephrine to epinephrine, PNMT (Phenylethanolamine-N-methyltransferase), is upregulated by high local cortisol levels from the adrenal cortex. This unique vascular connection ensures maximal epinephrine production during stress.

Pheochromocytoma - The Great Masquerader

Tumor of chromaffin cells in the adrenal medulla; secretes catecholamines.
Rule of 10s: 10% extra-adrenal, 10% bilateral, 10% malignant, 10% calcify, 10% in children.
Clinical: Episodic hypertension, headaches, palpitations, and sweating.
- 📌 5 P's: Pressure (HTN), Pain (headache), Perspiration, Palpitations, Pallor.
Diagnosis: ↑ 24-hr urinary metanephrines and vanillylmandelic acid (VMA). Plasma-free metanephrines are also highly sensitive. CT/MRI to localize.
Treatment: Surgical resection is definitive.
- Pre-op: irreversible α-blocker (phenoxybenzamine) followed by β-blockers.

⭐ Exam Favorite: Always administer alpha-blockade before beta-blockade to prevent unopposed alpha-adrenergic receptor stimulation, which can lead to a hypertensive crisis.

Pheochromocytoma: Dx & Rx - Taming the Tumor

Adrenal Pheochromocytoma on T2-weighted MRI

Diagnosis: Rule of 10s 📌
- 10% extra-adrenal, 10% bilateral, 10% malignant.
- Biochemical: ↑ plasma free metanephrines (best sensitivity) or 24-hr urinary fractionated metanephrines & catecholamines.
- Imaging: CT or MRI to localize tumor; MIBG scan for extra-adrenal or metastatic disease.
Treatment: "α then β"

⭐ Giving β-blockers before adequate α-blockade can precipitate a hypertensive crisis due to unopposed α-receptor stimulation.

Neuroblastoma - Childhood Adrenal Foe

Most common extracranial solid tumor of childhood; median age at diagnosis is 1-2 years.
Origin: Arises from neural crest cells of the adrenal medulla (~40%) or sympathetic ganglia.
Clinical Features:
- Presents as a firm, irregular abdominal mass that can cross the midline.
- Opsoclonus-myoclonus-ataxia syndrome ("dancing eyes, dancing feet").
- Periorbital ecchymoses ("raccoon eyes") from orbital metastases.
- Blueberry muffin rash (subcutaneous nodules).
Diagnosis:
- ↑ urinary catecholamine metabolites: vanillylmandelic acid (VMA) and homovanillic acid (HVA).
- Biopsy: Small, round blue cells forming Homer-Wright rosettes.
- Bombesin and neuron-specific enolase (NSE) positive.

Neuroblastoma histopathology with Homer-Wright rosettes

⭐ N-myc gene amplification is a key prognostic marker indicating a poor prognosis. However, spontaneous regression is common in infants < 1 year old.

High‑Yield Points - ⚡ Biggest Takeaways

Pheochromocytoma, a tumor of chromaffin cells, follows the rule of 10s and presents with episodic hypertension, palpitations, and headaches.

Diagnose with elevated urine/plasma metanephrines and VMA.

Pre-operative treatment is crucial: alpha-blockade (e.g., phenoxybenzamine) before beta-blockade.

Associated with MEN 2A/2B, VHL, and NF1.

Neuroblastoma is the most common extracranial solid childhood tumor, often presenting as an abdominal mass.

Look for opsoclonus-myoclonus syndrome and elevated urine HVA/VMA.

N-myc amplification signifies a poor prognosis.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play