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 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)

A 32-year-old woman comes to the physician because of weight gain, generalized weakness, and irregular menstrual cycles for the past 16 months. She began having symptoms of insomnia and depression 10 months ago. More recently, she has been having difficulties rising from a chair. She has a 2-year history of hypertension. Current medications include citalopram and hydrochlorothiazide. She is 168 cm (5 ft 6 in) tall and weighs 100 kg (220 lb). BMI is 36 kg/m2. Her pulse is 92/min, respirations are 18/min, and blood pressure is 134/76 mm Hg. She appears tired and has a full, plethoric face and central obesity. Examination of the skin shows violaceous linear striations on her lower abdomen. Two midnight serum cortisol studies show measurements of 288 μg/L and 253 μg/L (N < 90); a 24-hour urinary cortisol measurement was 395 μg (N < 300). Upon follow-up laboratory examination, the patient's serum ACTH levels were also elevated at 136 pg/mL (N = 7–50). Which of the following is the most appropriate next step in evaluation?

High-dose dexamethasone suppression test

Measure ACTH levels in inferior petrosal sinuses

CT scan of the abdomen with contrast

A 47-year-old woman complains of weight gain and irregular menses for the past 2 years. She has gained 13 kg (28.6 lb) and feels that most of the weight gain is in her abdomen and face. She has type 2 diabetes and hypertension for 1 year, and they are difficult to control with medications. Vital signs include a temperature of 36.9°C (98.4°F), blood pressure of 160/100 mm Hg, and pulse of 95/min. The patient's late-night salivary cortisol is elevated. Morning plasma ACTH is high. Brain magnetic resonance imaging shows a 2 cm pituitary adenoma. Which of the following is the optimal therapy for this patient?

Transsphenoidal pituitary adenomectomy

A 48-year-old woman presents to her primary care physician with the complaints of persistent fatigue, dizziness, and weight loss for the past 3 months. She has hypothyroidism for 15 years and takes thyroxine replacement. Her blood pressure is 90/60 mm Hg in a supine position and 65/40 mm Hg while sitting, temperature is 36.8°C (98.2°F) and pulse is 75/min. On physical examination, there is a mild increase in thyroid size, with a rubbery consistency. Her skin shows diffuse hyperpigmentation, more pronounced in the oral mucosa and palmar creases. The morning serum cortisol test is found to be 3 µg/dL. Which of the following is the best next step in this case?

Adrenocorticotropic hormone (ACTH) stimulation test

Serum adrenocorticotropic hormone (ACTH)

A 35-year-old male is brought to the emergency room after he was found to have a blood pressure of 180/100 mm Hg during a routine health check-up with his family physician. Past medical history is insignificant and both of his parents are healthy. He currently does not take any medication. The patient's blood pressure normalizes before the emergency department physician can evaluate him. During the physical examination, his blood pressure is 148/80 mm Hg, heart rate is 65/min, temperature is 36.8°C (98.2°F), and respirations are 14/min. He has a round face, centripetal obesity, and striae on the skin with atrophy over the abdomen and thighs. On visual field examination, he is found to have loss of vision in the lateral visual fields bilaterally. You order a low dose dexamethasone suppression test, which is positive, and you proceed to measure ACTH and obtain a high-dose dexamethasone suppression test. If this is a pituitary gland disorder, which of the following lab abnormalities is most likely present in this patient?

Before test: ACTH high, after test: cortisol suppression

Before test: ACTH low, after test: cortisol elevation

Before test: ACTH high, after test: aldosterone suppression

Before test: ACTH low, after test: aldosterone normalizes

Before test: ACTH high, after test: cortisol elevation

Adrenal disorders for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Adrenal Gland - The Stress Factory

Adrenal gland layers: capsule, cortex (3 zones), and medulla

Cortex (Outer): GFR → Salt, Sugar, Sex (📌 Goes Faster with Rush)
- Zona Glomerulosa: Aldosterone (Salt)
- Zona Fasciculata: Cortisol (Sugar)
- Zona Reticularis: Androgens (Sex)
Medulla (Inner): Catecholamines (Epinephrine, Norepinephrine)
Cushing's Syndrome: ↑ Cortisol. Moon facies, buffalo hump, central obesity, purple striae. Dexamethasone suppression test.
Addison's Disease: ↓ Cortisol & Aldosterone. Hyperpigmentation, hypotension, hyperkalemia.

⭐ Addisonian Crisis: Hypotensive shock. Treat with IV fluids & high-dose hydrocortisone immediately, before lab results.
Pheochromocytoma: Tumor of medulla. Spells of 5 P's: Pressure (↑BP), Pain (headache), Perspiration, Palpitations, Pallor.

Cushing's Syndrome - Cortisol Chaos

Pathophysiology: Chronic excess of glucocorticoids (cortisol).
Etiology:
- Iatrogenic: Most common cause (exogenous steroids).
- Endogenous:
  - Cushing's Disease: Pituitary adenoma (↑ACTH) - 70%.
  - Ectopic ACTH: Small cell lung cancer, carcinoid (↑ACTH).
  - Adrenal: Adenoma, carcinoma (↓ACTH).
Clinical Features: 📌 CUSHINGOID
- Cataracts, Ulcers, Striae/Skin thinning, Hypertension/Hirsutism, Immunosuppression, Necrosis (avascular), Glucose elevation, Osteoporosis/Obesity (central), Irritability, Depression.
- Moon facies, buffalo hump, proximal muscle weakness.

⭐ Nelson's Syndrome: Development of a large pituitary adenoma with hyperpigmentation (due to ↑MSH) following bilateral adrenalectomy for Cushing's disease.

Adrenal Insufficiency - Powering Down

Etiology: Primary (Addison's disease; autoimmune), Secondary (↓ACTH), Tertiary (↓CRH).
Presentation: Weakness, fatigue, orthostatic hypotension, N/V, weight loss.
- Hyperpigmentation (skin, mucosa) & hyperkalemia are specific to Primary due to ↑POMC/MSH & ↓aldosterone.
Labs: ↓Na, ↑K, hypoglycemia. Non-anion gap metabolic acidosis.

Oral hyperpigmentation in adrenal insufficiency

⭐ Adrenal (Hemorrhagic) Infarction (Waterhouse-Friderichsen Syndrome): A catastrophic complication of sepsis, classically with Neisseria meningitidis. Presents with sudden circulatory collapse, shock, and DIC.

Conn & Pheo - Salty & Speedy

Conn Syndrome (Primary Aldosteronism): Adrenal adenoma/hyperplasia → ↑ Aldosterone. Causes resistant HTN, hypokalemia, & metabolic alkalosis.
- Dx: Aldosterone:Renin ratio > 20 with low renin. Confirm with saline suppression test.
- Tx: Surgery for unilateral adenoma; spironolactone/eplerenone for bilateral hyperplasia.
Pheochromocytoma: Catecholamine-secreting tumor of the adrenal medulla.
- 📌 5 P's: episodic Pressure (HTN), Pain (headache), Perspiration, Palpitations, Pallor.
- Dx: ↑ 24-hr urine & plasma metanephrines.

⭐ Pre-op for pheochromocytoma requires α-blockade (e.g., phenoxybenzamine) before β-blockade to prevent hypertensive crisis from unopposed α-receptor stimulation.

High‑Yield Points - ⚡ Biggest Takeaways

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