A 33-year-old woman presents to the physician because of abdominal discomfort, weakness, and fever. She has had a significant weight loss of 15 kg (33.1 lb) over the past 2 months. She has no history of medical illness and is not on any medications. Her pulse is 96/min, the blood pressure is 167/92 mm Hg, the respiratory rate is 20/min, and the temperature is 37.7°C (99.8°F). Her weight is 67 kg (147.71 lb), height is 160 cm (5 ft 3 in), and BMI is 26.17 kg/m2. Abdominal examination shows purple striae and a vaguely palpable mass in the left upper quadrant of the abdomen, which does not move with respirations. She has coarse facial hair and a buffalo hump along with central obesity. Her extremities have poor muscle bulk, and muscle weakness is noted on examination. An ultrasound of the abdomen demonstrates an adrenal mass with para-aortic lymphadenopathy. Which of the following is the most likely laboratory profile in this patient?

Impaired glucose tolerance, elevated serum cortisol, elevated 24-h urinary free cortisol, and low plasma ACTH

Impaired glucose tolerance, elevated serum cortisol, elevated 24-h urinary free cortisol, and high plasma ACTH

Normal glucose tolerance, elevated serum cortisol, normal 24-h urinary free cortisol, and normal plasma adrenocorticotropic hormone (ACTH)

Impaired glucose tolerance, reduced serum cortisol, normal 24-h urinary free cortisol, and low plasma ACTH

Impaired glucose tolerance, elevated serum cortisol, normal 24-h urinary free cortisol, and normal plasma ACTH

A 69-year-old woman is brought to the emergency department because of fatigue and lethargy for 5 days. She has also had weakness and nausea for the last 3 days. She has sarcoidosis, major depressive disorder, and hypertension. She had a stroke 5 years ago. Current medications include aspirin, nifedipine, prednisolone, fluoxetine, and rosuvastatin, but she has not taken any of her medications for 7 days due to international travel. Her temperature is 36.1°C (96.9°F), pulse is 95/min, and blood pressure is 85/65 mm Hg. She is lethargic but oriented. Examination shows no other abnormalities. Her hemoglobin concentration is 13.4 g/dL and leukocyte count is 9,600/mm3. Both serum cortisol and ACTH levels are decreased. This patient is most likely to have which of the following additional laboratory abnormalities?

Normal anion gap metabolic acidosis

A 27-year-old woman presents to her primary care physician because of headaches that she has had over the last three weeks. She has not had any significant past medical history though she does recall that various types of cancer run in her family. She has also noticed that she has been gaining some weight, and her feet no longer fit into her favorite shoes. On presentation, her temperature is 98.6°F (37°C), blood pressure is 159/92 mmHg, pulse is 75/min, and respirations are 16/min. Physical exam reveals 1+ edema in her lower extremities bilaterally. She is placed on captopril and presents to the emergency department two weeks later after a minor motor vehicle accident. She is cleared of any serious injuries, and as part of her workup, labs are drawn with the following results: BUN: 47 mg/dL Creatinine: 1.4 mg/dL Which of the following findings would most likely also be seen in this patient?

String-of-beads appearance on angiography

Atherosclerotic plaques blocking blood flow

Mass present in adrenal medulla

A 45-year-old woman presents to her physician with a four-month history of headache. Her headache is nonfocal but persistent throughout the day without any obvious trigger. She was told that it was a migraine but has never responded to sumatriptan, oxygen, or antiemetics. She takes amlodipine for hypertension. She does not smoke. She denies any recent weight loss or constitutional symptoms. Her temperature is 98°F (36.7°C), blood pressure is 180/100 mmHg, pulse is 70/min, and respirations are 15/min. She is obese with posterior cervical fat pads and central abdominal girth. Her neurological exam is unremarkable. In her initial laboratory workup, her fasting blood glucose level is 200 mg/dL. The following additional lab work is obtained and is as follows: Serum: Na+: 142 mEq/L Cl-: 102 mEq/L K+: 4.1 mEq/L HCO3-: 24 mEq/L BUN: 20 mg/dL Glucose: 135 mg/dL Creatinine: 1.3 mg/dL Ca2+: 10.0 mg/dL AST: 8 U/L ALT: 8 U/L 24-hour urinary cortisol: 500 µg (reference range < 300 µg) Serum cortisol: 25 µg/mL (reference range 5-23 µg/dL) 24-hour low dose dexamethasone suppression test: Not responsive High dose dexamethasone suppression test: Responsive Adrenocorticotropin-releasing hormone (ACTH): 20 pg/mL (5-15 pg/mL) Imaging reveals a 0.5 cm calcified pulmonary nodule in the right middle lobe that has been present for 5 years but an otherwise unremarkable pituitary gland, mediastinum, and adrenal glands. What is the best next step in management?

Inferior petrosal sinus sampling

CT-guided biopsy of the pulmonary nodule

Repeat high dose dexamethasone suppression test

A 63-year-old woman presents to your outpatient clinic complaining of headaches, blurred vision, and fatigue. She has a blood pressure of 171/91 mm Hg and heart rate of 84/min. Physical examination is unremarkable. Her lab results include K+ of 3.1mEq/L and a serum pH of 7.51. Of the following, which is the most likely diagnosis for this patient?

Primary hyperaldosteronism (Conn’s syndrome)

Adrenal cortical diseases for USMLE Step 2 CK: High-Yield Pathology Lessons

Adrenal Cortex - Anatomy & Steroidogenesis

Adrenal Gland Anatomy: Cortex, Medulla, and Zones

Cortex Layers (superficial to deep): Zona Glomerulosa, Fasciculata, Reticularis.
📌 Mnemonic: Go Find Rex (GFR) - Makes Sweet Sex (Salt, Sugar, Sex).
- Glomerulosa → Salt (Aldosterone)
- Fasciculata → Sugar (Cortisol)
- Reticularis → Sex (Androgens)

⭐ The rate-limiting enzyme for steroidogenesis is cholesterol desmolase, which converts cholesterol to pregnenolone. It is stimulated by ACTH.

Cushing Syndrome - Cortisol Overload

Pathophysiology: Excess cortisol from any cause. Cushing disease is specifically due to a pituitary adenoma.
Etiology:
- Exogenous: Most common cause; iatrogenic steroids.
- Endogenous:
  - ACTH-dependent: Cushing disease (~70%), ectopic ACTH (e.g., small cell lung cancer).
  - ACTH-independent: Adrenal adenoma, carcinoma, or hyperplasia.

Cushing's Syndrome: Clinical Features Diagram

Clinical Features: Central obesity, moon facies, buffalo hump, purple striae, hypertension, hyperglycemia, osteoporosis, immunosuppression.
Diagnosis Flowchart:

⭐ Exam Favorite: In ACTH-dependent Cushing's, a high-dose dexamethasone test differentiates causes. Cortisol suppression suggests a pituitary adenoma (Cushing's disease), whereas a lack of suppression points to an ectopic source like small cell lung cancer.

Hyperaldosteronism - The Salt & Pressure Show

Primary (Conn's Syndrome): Caused by adrenal adenoma or hyperplasia.
Secondary: Driven by high renin (e.g., renal artery stenosis, diuretics).
Clinical Picture: Hypertension, hypokalemia (muscle weakness, paresthesias), and metabolic alkalosis.
Diagnosis:
- Primary: ↑ Aldosterone, ↓ Renin. High aldosterone-to-renin ratio.
- Secondary: ↑ Aldosterone, ↑ Renin.

⭐ Despite ↑Na+ reabsorption, significant hypernatremia and edema are rare due to the 'aldosterone escape' mechanism (pressure natriuresis).

Adrenal Insufficiency - Powering Down

Primary (Addison's Disease): Adrenal gland destruction (autoimmune, TB). Results in ↓ Cortisol, ↓ Aldosterone, but ↑ ACTH.
- Presents with hypotension, hyperkalemia, metabolic acidosis, and skin/mucosal hyperpigmentation.
Secondary/Tertiary: Pituitary/hypothalamic failure (e.g., chronic steroid use). Causes ↓ Cortisol, ↓ ACTH, but normal Aldosterone.
- No hyperpigmentation or significant electrolyte shifts.
Acute Adrenal Crisis: Life-threatening shock from stressors (infection, surgery). Requires immediate fluid and steroid resuscitation.

⭐ Waterhouse-Friderichsen Syndrome: Acute, massive hemorrhagic adrenalitis, classically due to Neisseria meningitidis septicemia, leading to adrenal crisis.

Hyperpigmentation of gums and buccal mucosa in Addison's

Adrenocortical Neoplasms - Lumps & Bumps

Adrenocortical Adenoma:
- Benign, well-circumscribed tumor. Most are non-functional incidentalomas.
- Functional types can cause Cushing's syndrome (cortisol) or Conn's syndrome (aldosterone).
Adrenocortical Carcinoma:
- Rare, aggressive malignancy; often large (>5 cm) with necrosis & hemorrhage.
- Frequently functional, causing rapid virilization or Cushing's.
- Associated with Li-Fraumeni syndrome (TP53 mutation).

⭐ Most adrenal "incidentalomas" (asymptomatic masses) are benign, non-functioning adenomas.

High‑Yield Points - ⚡ Biggest Takeaways

Cushing's syndrome is most commonly due to exogenous steroids. Use the dexamethasone suppression test for endogenous causes.

Addison's disease (primary adrenal insufficiency) presents with hypotension, hyperpigmentation, and hyperkalemia; often autoimmune.

Conn's syndrome (primary hyperaldosteronism) causes hypertension, hypokalemia, and low plasma renin, typically from an adenoma.

21-hydroxylase deficiency is the most common Congenital Adrenal Hyperplasia (CAH), causing virilization and salt wasting.

Waterhouse-Friderichsen syndrome is acute adrenal hemorrhage from sepsis (classically meningococcemia), causing shock.

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