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USMLE Step 2 CK High-Yield Endocrine Topics
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Endocrine
High Yield USMLE Step 2 CK Notes
Welcome to the Endocrine High-Yield Notes for Step 2 CK.
These are the most commonly tested topics on the exam—ideal for quick review in your last 2 weeks before the exam, when you’re short on time, or when you’re just starting out and want to focus on what is high yield. Created and peer-reviewed by physicians who scored 260+ on Step 2 CK in a Q&A style to reinforce active learning.
How to use this file
- Read the question ➔ cover the answer ➔ self-quiz before revealing.
- Review the NOTES ➔ they include high-yield details you don’t want to miss.
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Table of Contents
Thyroid disorders
1. A 36-year-old woman presents with a 3-month history of fatigue, weight gain, and constipation. Her menstrual periods have become irregular. On exam, her skin is dry, reflexes show a delayed relaxation phase. Vital signs reveal bradycardia. What is the diagnosis?
➔ Hypothyroidism
- Note: Common USMLE scenarios and symptoms:
○ Fatigue, cold intolerance, weight gain, constipation, and bradycardia.
○ Hypothyroidism symptoms plus dementia.
○ Hypothyroidism symptoms plus muscle weakness, atrophy, and hyporeflexia “delayed DTR.”
○ Hypothyroidism symptoms plus menstrual irregularities or miscarriage.
○ Hypothyroidism symptoms plus depression and loss of interest.
○ Hypothyroidism symptoms plus dyslipidemia; ↑cholesterol, LDL, or hypertriglyceridemia.
2. A 58-year-old woman with weight loss, heat intolerance, palpitations, and a large thyroid mass. Next best step in management??
➔ Propranolol — to control acute adrenergic symptoms
- Note: Symptoms of hyperthyroidism: (weight loss, heat intolerance, tachycardia, low BMI, and ↓TSH, ↑T4 ) + neck mass → toxic adenoma “RAIU shows nodular uptake; hot nodule”.
- If the same symptoms + multiple nodules → multinodular goiter, while Graves disease shows diffuse goiter.
- Propranolol “non selective Beta Blocker”: “first line”
○ Blocks β1 receptors → ↓ heart rate, ↓ adrenergic symptoms (e.g., tachycardia, palpitations, diaphoresis)
○ Blocks the conversion of T4 to T3 at the level of tissues. - Other treatments:
○ PTU or methimazole: blocks hormone synthesis. They cause agranulocytosis, and methimazole is teratogenic.
○ Radioactive Iodine: use before surgeries, but it can cause permanent hypothyroidism and worsen eye symptoms in Graves.
○ Steroids: reduce T4 to T3 conversion.
3. A 22-year-old woman with Graves’ disease on propylthiouracil (PTU) for 2 weeks develops fever (38.6°C) and sore throat. What is your next step?
➔ Stop the drug, give broad-spectrum IV antibiotics, and CBC
- Note: Antithyroid Drug-Induced Agranulocytosis “propylthiouracil (PTU) and methimazole (MMI)” leading to infection as sore throat or sepsis.
- Routine WBC monitoring is recommended.
4. A 16-year-old girl with 4 months of fatigue, nervousness, weight loss, blurred vision, lid lag, exophthalmos, tremor, thyroid bruit, and enlarged thyroid. What is the most likely cause?
➔ Thyroid-stimulating antibodies (Graves’ disease)
- Note: Hyperthyroid symptoms: fatigue, heat intolerance, insomnia, tremor, tachycardia, weight loss despite increased appetite, and bone loss if not treated.
- Exophthalmos and lid lag (specific for Graves, not other hyperthyroid causes)
- Diffuse goiter with bruit. increased T3/T4, ↓TSH, and TSH receptor antibodies. Radioactive iodine uptake scan → diffuse uptake.
5. A 57-year-old woman with primary hypothyroidism on levothyroxine has a TSH of 9.5 μU/mL after 8 weeks of treatment. She is currently asymptomatic. Best next step in pharmacotherapy?
➔ Increase the dose of levothyroxine
- Note: Primary hypothyroidism = ↑ TSH, ↓ T4. TSH >5 after starting the treatment means that the dose is too low.
- Goal: TSH 0.5–5.0 μU/mL. Adjust dose every 6–8 weeks based on TSH level, even if the patient is asymptomatic.
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6. A 13-year-old girl presents with a diffusely enlarged thyroid. Vitals are normal. TSH, T3, and T4 are within normal range. Thyroid peroxidase antibodies = very high (1000 IU/mL). Most likely diagnosis?
➔ Hashimoto thyroiditis (Chronic lymphocytic thyroiditis)
- Note: Early phase: normal or transient ↑ T3/T4 (euthyroid or mild thyrotoxicosis), later phase: hypothyroidism (↑ TSH, ↓ T3/T4).
- The thyroid is usually non-tender and diffusely enlarged. Histology: lymphoid aggregates, Hürthle cells. ↑ anti-TPO antibodies, and low radioactive iodine uptake.
- Goiter+ ↓ TSH, ↑ T3/T4, or high radioactive iodine uptake: Graves’ disease.
- Painful, tender thyroid, ↑ ESR/CRP → de Quervain thyroiditis.
7. A 62-year-old woman presents with a nontender, firm, irregular thyroid nodule (2 × 1.2 cm) in the left thyroid lobe. Next best step in diagnosis?
➔ Fine-needle aspiration (FNA) biopsy
- Note: Any thyroid nodule ≥1 cm with suspicious features (irregular, firm, solid) on USG needs FNA
- TSH level and ultrasound usually precede biopsy.
8. A 2-week-old girl had elevated TSH on newborn screening. She is well-appearing. Her mother is on propylthiouracil (PTU) for Graves’ disease. What is the most likely explanation?
➔ Transient congenital hypothyroidism due to placental transfer of maternal antithyroid drug
- Note: Repeat TSH and free T4 levels now to determine if the thyroid function has normalized after drug clearance.
- Neonates appear normal initially due to maternal T4. Delayed treatment of hypothyroidism → irreversible intellectual disability.
- Permanent congenital hypothyroidism is due to thyroid dysgenesis. If not treated, it leads to neurodevelopmental delay, jaundice, constipation, and umbilical hernia.
9. A healthy 52-year-old woman is concerned about thyroid cancer due to a family history (father with papillary thyroid carcinoma). She is asymptomatic with a normal exam.
What is the most appropriate screening test?
➔ Thorough history and physical examination
- Note: Thyroid cancer screening begins with:
○ Neck palpation for nodules or enlargement
○ Check for lymphadenopathy, hoarseness, or other compressive symptoms - If abnormal → proceed to TSH and ultrasound.
- No imaging or blood tests are indicated in asymptomatic patients with a normal exam.
10. A 45-year-old woman presents to the emergency department 2 days after undergoing a total thyroidectomy. She complains of tingling in her fingers and around her mouth, as well as intermittent muscle cramps. What best explains her symptoms?
➔ Hypocalcemia (due to hypoparathyroidism)
- Note: → tingling (perioral, fingers/toes), muscle cramps or spasms, Chvostek’s and Trousseau’s signs, and seizures (in severe cases) → Treatment: IV calcium gluconate
- Recurrent laryngeal nerve injury:
○ Hoarseness of voice (unilateral)
○ Dyspnea or stridor if bilateral
11. A 70-year-old man undergoes emergency CABG for critical left main coronary artery stenosis. On postoperative day 4, Labs show low T3 with normal T4 and TSH. What is the diagnosis?
➔ Euthyroid Sick Syndrome (Low T3 Syndrome)
- Note: Cause: Acute illness → ↓ peripheral conversion of T4 to T3.
- Labs: ↓ T3, normal T4, normal/↓ TSH.
- No treatment; repeat thyroid function tests after recovery.
12. A 26-year-old woman with well-controlled primary hypothyroidism (TSH 2.0 µU/mL) wants to become pregnant. She’s on a stable dose of levothyroxine and is asymptomatic. She asks about managing her thyroid condition during pregnancy.
➔ Increase the levothyroxine dose once pregnancy is confirmed.
- Note: Pregnancy ↑ Estrogen → ↑thyroxine-binding globulin (TBG) → ↓ free thyroid if dose is not increased.
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Diabetes Mellitus
13. A 52-year-old woman with type 2 diabetes and hypertension has LDL = 112 mg/dL, HbA1c = 6.4%. She’s on metformin and lisinopril. What is the next best pharmacologic step?
➔ Start simvastatin
- Note: Diabetes = cardiovascular risk equivalent
- Statins = first-line for LDL lowering in diabetics over 40 years old or LDL > 100.
- Lisinopril: diabetics with proteinuria or HTN >130/80.
14. A 17-year-old girl presents with fatigue, dehydration, tachypnea, hypotension, and recent polyuria/polydipsia. She is underweight with dry mucous membranes and tachycardia. Labs show hyperglycemia. What is the most likely serum abnormality?
➔ Decreased bicarbonate concentration
- Note: Presentation = classic DKA (type 1 diabetes)
○ Symptoms: fatigue, polydipsia, tachypnea, weight loss, tachycardia, low BP, and dehydration.
○ Hyperglycemia but ↓ Insulin → ↑ lipolysis → ↑ ketones = acetoacetate, β-hydroxybutyrate, acetone → High anion gap metabolic acidosis, and ↓ Bicarbonate (used to buffer acid).
○ K⁺ may appear normal/high, but total body stores are low (lost via diuresis). - Treatment:
○ 1st: IV fluids (0.9% saline), 2nd: IV potassium (if K⁺ < 5.3), then: Insulin later to avoid hypokalemia due to intracellular K⁺ shift.
○ Monitor the resolution of DKA by the serum anion gap and serum beta-hydroxybutyrate levels.
15. A 62-year-old woman with type 2 diabetes presents with 2 days of weakness and confusion after stopping all medications. Vitals: HR 128, BP 178/94. Labs: Glucose 950 mg/dL, Na⁺ 128, K⁺ 3.0, HCO₃⁻ 20. She is lethargic and dehydrated.
➔ Hyperosmolar Hyperglycemic State (HHS)
- Note: HHS (T2DM, glucose > 600, AMS, no ketosis, normal HCO₃⁻, low total K, and serum osmolarity >320 mOsm/L).
- Treatment:
○ 1st: IV fluids (0.9% saline), 2nd: IV potassium (if K⁺ < 5.3), then: Insulin later to avoid hypokalemia due to intracellular K⁺ shift.
16. A 15-year-old boy has a BMI of 35 and a strong family history of type 2 diabetes. He eats a high-sugar diet and is mostly sedentary. A1c is 6.3%. What best explains his presentation?
➔ Prediabetes
- Note: A1c 5.7–6.4% indicates prediabetes
- First-line management: structured diet and exercise counseling. No medications unless lifestyle fails or diabetes develops.
- New DM → screen for HTN, and new HTN → screen for DM.
17. A 54-year-old man with type 2 diabetes on glimepiride is found unresponsive with severe hypoglycemia (glucose 15 mg/dL) and no IV access. What is the best immediate management?
➔ Intramuscular (IM) glucagon
- Note: Hypoglycemia symptoms:
○ Autonomic: Sweating, tremor, palpitations, hunger, and anxiety.
○ Neuroglycopenic: Confusion, visual changes, seizures, and coma. - Recurrent hypoglycemia reduces hypoglycemia awareness, increasing the risk for progressively worsening hypoglycemic episodes.
- Unconscious patients cannot give oral glucose due to aspiration risk. No IV access → cannot give IV dextrose. IM glucagon is the choice.
- Patients with type 1 DM and CKD have a high risk of hypoglycemia → Decrease their Insulin dose. Also, decrease the dose before exercise, as it encourages muscle uptake of glucose.
18. A 30-year-old man presents with tremors, palpitations, sweating, and hypoglycemia. Prolonged fasting reveals glucose 40 mg/dL with elevated insulin, C-peptide, and a negative sulfonylurea screen. What is the diagnosis?
➔ Insulinoma (pancreatic beta-cell tumor)
- Note: Key Labs:
○ ↑ Insulin during hypoglycemia (inappropriate), ↑ C-peptide (indicates endogenous insulin production).
○ Negative sulfonylurea screen (rules out exogenous secretagogue use) - Differential Clues:
○ Exogenous insulin: ↑ insulin, ↓ C-peptide
○ Sulfonylurea use: ↑ insulin, ↑ C-peptide, positive sulfonylurea - Next step: Imaging for pancreatic mass (CT/MRI/endoscopic ultrasound).
19. A 28-year-old woman with recently diagnosed type 2 diabetes is asymptomatic and on metformin. HbA1c is 6.1%, and glucose is 135 mg/dL. How can we to prevent diabetes-related morbidity?
➔ Regular screening for diabetic complications
- Note: Annual assessments include:
○ Dilated eye exam (retinopathy)
○ Urine albumin/creatinine ratio + serum creatinine (nephropathy)
○ Foot exam (neuropathy, ulcers) by Monofilament testing, while a visual exam is done at every visit.
○ Weight counselling and smoking cessation.
○ Lipid and blood pressure screening.
Intensive blood glucose control decreases the risk of microvascular complications (eg, retinopathy, nephropathy) but has no effect on macrovascular outcomes (eg, stroke, myocardial infarction) and mortality.
20. An 82-year-old man with long-standing type 2 diabetes has painful tingling in his feet. The exam shows reduced sensation in the midcalves. What is the next pharmacologic step?
➔ Gabapentin
- Note: This is painful diabetic neuropathy in a stocking-glove distributio
- Treatments: gabapentin, pregabalin, TCAs, duloxetine
- TCA, effective for neuropathic pain but considered second line due to its anticholinergic effects, especially in older people.
21. A 54-year-old man with type 2 diabetes, hypertension, and recent ST-elevation MI presents for follow-up. He is on metformin. Labs show HbA1c of 8.2%. Which antidiabetic medication provides cardiovascular benefits in this patient?
➔ SGLT-2 inhibitor (e.g., empagliflozin, canagliflozin)
- Note: Blocks glucose reabsorption in proximal tubules → ↑ urinary glucose loss → decreases blood glucose and pressure.
- Both SGLT-2 inhibitors and GLP-1 receptor agonists ↓ CV mortality & heart failure hospitalizations and promote weight loss.
↑ Risk of UTI and vaginal candidiasis. - Metformin is contraindicated in those with renal insufficiency due to lactic acidosis risk.
22. A full-term newborn girl (4.2 kg) is born to a mother with gestational diabetes. What test is most likely to be abnormal in this infant?
➔ Blood glucose
- Note: Maternal hyperglycemia → fetal hyperglycemia → fetal hyperinsulinemia → ↓ glucose after birth
- Signs: Often asymptomatic; may have jitteriness, lethargy, or seizures if severe
- Management: Early feeding or IV glucose if symptomatic or severely low
Infant of diabetic mother (IDMs) with pregestational DM are at high risk for:
○ Neural tube defects and congenital heart diseases.
IDMs with gestational diabetes are at high risk for:
○ Macrosomia, birth trauma, polycythemia, and HCM
23. A 52-year-old woman with type 1 diabetes mellitus. Fasting glucose is normal, but HbA1c is elevated (8.1%), and random glucose is high (290 mg/dL). What is the most likely explanation for high HbA1c despite normal fasting glucose?
➔ Postprandial hyperglycemia
- Note: Basal long-acting insulin (e.g., glargine) controls fasting glucose, while postprandial level is controlled by rapid-acting insulin (e.g., insulin aspart).
- HbA1c reflects a 3-month average of both fasting and postprandial glucose.
- Normal fasting glucose “between meals” + high HbA1c → suspect postprandial spikes → Add rapid-acting insulin (e.g., insulin aspart) to target post-meal glucose.
24. A 58-year-old man with no known diabetes presents with a painless foot ulcer on the plantar surface, no trauma history, and a negative probe-to-bone test. Which would diagnose the underlying cause of this patient’s foot ulcer?
➔ Hemoglobin A1c (diabetes mellitus)
- Note: Neuropathic ulcer → is common in diabetes mellitus; it is painless on the plantar surface under the metatarsal heads.
- If positive probe-to-bone test → bone biopsy for osteomyelitis.
- Arterial ulcers: in peripheral artery disease, at the tip toes, and associated with pallor and decreased pulse.
- Venous ulcers: around the medial malleolus, associated with venous insufficiency, and have brown skin color.
Adrenal Gland Disorders
25. A 62-year-old chronic smoker with fatigue, weight loss, hyperpigmentation, proximal muscle weakness, hypokalemia, and hyperglycemia. What is the most likely diagnosis?
➔ Paraneoplastic Cushing syndrome due to small-cell lung carcinoma
- Note: Small-cell lung carcinoma or renal cell carcinoma causes ectopic ACTH secretion → ↑ cortisol.
- Old smoker with cough and hemoptysis + symptoms of Cushing syndrome:
○ Hyperglycemia (insulin resistance)
○ Hypokalemia (via mineralocorticoid receptor activation)
○ Proximal muscle weakness and atrophy (catabolic)
○ Hypertension (via volume expansion)
○ Hyperpigmentation (↑ACTH → ↑MSH)
○ Psychiatric symptoms: anxiety, insomnia, or depression. - ACTH from the tumor bypasses feedback regulation → unregulated cortisol by even high-dose dexamethasone suppression test → Chest CT.
- ACTH from a pituitary adenoma can be suppressed by a high-dose dexamethasone suppression test.
Cushing syndrome
See original file for the list of authors. (https://commons.wikimedia.org/wiki/File:Cushing_syndrome_svg_hariadhi_annotated(anotated).png), https://creativecommons.org/licenses/by-sa/4.0/legalcode
26. A 31-year-old woman with weight gain despite diet, proximal muscle weakness, hirsutism, menstrual irregularity, hypertension (160/100 mm Hg), and hyperglycemia. What is the best next step?
➔ Screening for hypercortisolism: (Late-night salivary cortisol/ 24-hour urine free cortisol/ Low-dose dexamethasone suppression test)
- Note: → If 2 tests are abnormal, confirm Cushing syndrome, then check ACTH to classify as ACTH-dependent or independent.
- ACTH-dependent: Pituitary adenoma (Cushing disease), ectopic ACTH
- ACTH-independent: Adrenal adenoma/carcinoma
27. A patient on chronic corticosteroids undergoes emergency appendectomy. Post-op, he becomes confused, hypotensive, and fluids fail to raise his BP. What is the diagnosis?
➔ Acute Adrenal Insufficiency
- Note: Chronic steroid use → adrenal atrophy → can’t meet stress demand→ Adrenal Insufficiency→ post-op hypotension unresponsive to fluids and confusion.
- Diagnosis clue: History of exogenous corticosteroids, treated with IV hydrocortisone.
- Another scenario for Acute Adrenal Insufficiency is meningococcemia.
28. A 29-year-old woman with a history of hypothyroidism complains of fatigue, weight loss, nausea, abdominal pain, generalized weakness, and orthostatic hypotension. Labs show normal CBC with eosinophilia. What is the most likely diagnosis?
➔ Autoimmune Primary Adrenal Insufficiency (Addison’s Disease)
- Note: Common causes of chronic primary adrenal Insufficiency, “less acute”: Autoimmune adrenalitis, TB, and metastasis as melanoma.
- Associated with other autoimmune conditions (e.g., hypothyroidism, vitiligo)
- Triad: hypotension, hyperpigmentation, hyponatremia, hyperkalemia, and eosinophilia = due to lack of cortisol.
- Hyperpigmentation due to ↑ ACTH.
- Treat with glucocorticoids + mineralocorticoids
29. A 32-year-old woman presents with 3 months of mild headaches and generalized weakness. Vitals: BP 150/105 mm Hg, HR 80/min. Labs show hypokalemia and metabolic alkalosis. What is the diagnosis?
➔ Hyperaldosteronism
- Note: Adrenal adenoma (Conn syndrome) or adrenal hyperplasia → ↑ Aldosterone → ↑ Na⁺ reabsorption, ↑ K⁺ & H⁺ secretion→ Hypertension, hypokalemia, metabolic alkalosis.
- Next step: Aldosterone-renin ratio (ARR)→ ↑ Aldosterone, ↓ Renin → confirm with saline suppression or CT abdomen.
- Treated with spironolactone or eplerenone “Aldosterone receptor antagonists”.
- Aldosterone-renin ratio (ARR) showing elevated aldosterone and renin → conditions with RAAS activation, such as renal hypoperfusion or renal artery stenosis.
30. A 10-year-old girl presents with 6 months of hirsutism, acne, and clitoromegaly. She has normal testosterone, ↑ DHEA-S, ↑ 17-ketosteroids, and normal pelvic US. What is the diagnosis?
➔ Adrenal adenoma secreting androgen
- Note: DHEA-S is produced in the adrenal gland, not the ovaries
- Elevated DHEA-S and 17-ketosteroid + virilization + normal pelvic US = adrenal source.
- PCOS and ovarian tumors: normal DHEA-S, and pelvic USG is positive.
31. A 10-day-old girl presents with poor feeding, vomiting, lethargy, dehydration, hypotension, and hyperpigmentation. She has Ambiguous genitalia. What is the diagnosis?
➔ Classic Congenital Adrenal Hyperplasia (21-hydroxylase deficiency)
- Note: ↓ Cortisol → hypoglycemia
- ↓ Aldosterone→ ↓ Sodium ”dehydration, vomiting, and hypotension“ and ↑K.
- ↑ ACTH (leads to skin hyperpigmentation)
- ↑Androgens → Ambiguous genitalia. ↑ 17-hydroxyprogesterone (diagnostic ).
- Treat with hydrocortisone + fludrocortisone
| Enzyme Deficiency | Aldosteron | Cortisol “glucose” | Sex Hormones | BP | K | Labs | Presentation |
|---|---|---|---|---|---|---|---|
| 17α-hydroxylase | ↑ | ↓ | ↓ | ↑ | ↓ | – | XY: ambiguous genitalia. |
| 21-hydroxylase “Most common” | ↓ | ↓ | ↑ | ↓ | ↑ | ↑ 17-hydroxyprogesterone | XX: ambiguous genitalia. |
| 11β-hydroxylase | ↓ aldosterone | ↓ | ↑ | ↑ | ↓ | ↑ 11-deoxycorticosterone | XX: virilization |
Congenital adrenal hyperplasia
Endocrine doctor (https://commons.wikimedia.org/wiki/File:Adrenal_steroid_hormone_synthesis.png), https://creativecommons.org/licenses/by-sa/4.0/legalcode
32. A 32-year-old woman with hirsutism and irregular menses was found to have elevated 17α-hydroxyprogesterone. After 6 months of prednisolone, her menses normalized and hirsutism improved. Repeat 17-OHP dropped. What is the diagnosis?
➔ Nonclassical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency
- Note: Nonclassical CAH = partial 21-hydroxylase deficiency→ ↑Androgens → oligomenorrhea and hirsutism in females, while precocious puberty in males. ↑17α-hydroxyprogesterone.
- Prednisolone suppresses ACTH from the pituitary → ↓ Androgens → improved hirsutism, regular menses
- ↓ 17α-hydroxyprogesterone confirms hormonal control.
33. A 42-year-old woman with episodic headache, sweating, palpitations (classic triad), and resistant hypertension. Adrenal mass on MRI consistent with pheochromocytoma. What is the next best step?
➔ Administer phenoxybenzamine followed by β-blockers
- Note: Key to pheochromocytoma is the episodic presentation of headache, sweating, and palpitations.
- Pheochromocytoma is diagnosed by elevated urine catecholamines and metanephrines → abdominal imaging.
- Irreversible α-blocker, blocks α1 receptors → vasodilation → prevents intraoperative hypertensive crisis caused by catecholamine surge during tumor manipulation.
- We give α1 receptor blockers first to avoid unopposed α-vasoconstriction (which can worsen hypertension).
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Ca & PTH & Vit D
34. A young man has high calcium, low phosphate, and subperiosteal bone resorption. What is the most likely etiology?
➔ Primary hyperparathyroidism
- Note: Caused by parathyroid adenoma or hyperplasia. PTH increases calcium, decreases phosphate, and leads to bone breakdown → Subperiosteal bone resorption and bone cysts may be seen on X-ray
- The resulting hypercalcemia causes kidney stones and abdominal pain due to constipation. “Stones, bones, groans, and psychiatric overtones”.
- The best next step after either hypo- or hypercalcemia is measuring PTH after repeating testing and albumin level.
35. A patient with chronic kidney disease has bone pain and elevated alkaline phosphatase. What condition best explains these findings?
➔ Secondary hyperparathyroidism
- Note: CKD leads to phosphate retention and low calcium in addition of decreased vitamin D activation → triggering high PTH.
- Labs: low calcium, high phosphate, high PTH, and ALP.
36. An elderly smoker has hypercalcemia with suppressed PTH. What is the most likely etiology?
➔ PTHrP secretion from lung squamous cell carcinoma
- Note: Labs show high calcium, low phosphate, and low PTH.
- Renal cell carcinoma can also produce PTHrP.
- Bone metastasis increases Ca by osteolysis. Lymphoma increases Ca by activating Vitamin D.
37. An African American patient presents with a dry cough, hypercalcemia, and suppressed PTH. What is the most likely explanation for this presentation?
➔ Sarcoidosis (hypervitaminosis D)
- Note: Granulomas activate vitamin D → increases calcium absorption. Labs: high calcium, low PTH, elevated 1,25(OH)₂ vitamin D.
- Noncaseating granulomas on biopsy. Treated with steroids.
38. An alcoholic has persistent low calcium and potassium despite replacement. What is the most likely etiology?
➔ Hypomagnesemia
- Note: Low magnesium impairs PTH release and action → secondary hypocalcemia. Also causes renal potassium wasting.
- Must correct magnesium to normalize calcium and potassium.
39. A child has bowed legs, craniotabes, and costochondral thickening. What condition best explains these findings?
➔ Rickets (vitamin D deficiency)
- Note: Defective mineralization of osteoid in growing bones.
- Other signs include rachitic rosary, frontal bossing, and widened growth plates.
- Causes of Vitamin D deficiency are: vegan diet, malabsorption syndromes, decreased sun exposure, CKD, and anticonvulsants.
- In adults, it causes osteomalacia; bone pain, weakness, and difficulty walking.
Rickets
Edward Mellanby, Medical Research Council London (https://commons.wikimedia.org/wiki/File:E._Mellanby,_Experimental_rickets._Wellcome_L0000954.jpg), https://creativecommons.org/licenses/by/4.0/legalcode
40. A 42-year-old woman presents with 1 month of paresthesia and fatigue. She has hypocalcemia (Ca²⁺ 7.1 mg/dL), hyperphosphatemia (6 mg/dL), normal albumin, and a positive Chvostek sign. What is the cause of the symptoms?
➔ Primary hypoparathyroidism
- Note: High phosphate and low calcium increase excitability: perioral tingling, Positive Chvostek sign, and Trousseau sign.
- No history of thyroid surgery → likely autoimmune etiology.
- Other causes of acute hypocalcemia are pancreatitis, sepsis, tumor lysis syndrome, alkalosis, and blood transfusion.
41. A 57-year-old woman with metastatic breast cancer (recent radiation for bone mets) is brought in comatose after 3 days of increasing lethargy and dehydration. No focal neurologic deficits. What best explains these findings?
➔ Hypercalcemic Crisis
- Note: Malignancy-associated hypercalcemia due to bone lysis from metastasis→ ↑ Calcium, short QT, possible nephrogenic DI → Lethargy, coma, and dehydration.
- Treatment:
○ 1st step: IV normal saline (volume repletion)
○ Then: Bisphosphonates ± calcitonin - Avoid confusion with: Tumor lysis syndrome (hypocalcemia).
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ADH Disorders
42. An elderly patient presents with cough, hemoptysis, and hyponatremia. What is the most likely etiology?
➔ Small cell lung carcinoma
- Note: Produces ectopic ADH → SIADH. Leads to dilutional hyponatremia with low serum osmolality and inappropriately concentrated urine.
- Labs: low serum Na, low serum osmolality, high urine Na, and osmolality.
- Common after CNS or lung pathology: infection/hemorrhage/tumors.
- Treat with fluid restriction or vasopressin antagonists, such as conivaptan.
43. A man with head trauma develops polyuria and hypernatremia. What is the diagnosis?
➔ Central diabetes insipidus
- Note: Deficiency of ADH due to hypothalamic or pituitary injury. Labs show high serum osmolality, low urine osmolality.
- Treat with desmopressin (DDAVP).
44. A bipolar patient on lithium presents with polyuria and dilute urine. What is the most likely etiology?
➔ Nephrogenic diabetes insipidus
- Note: Kidneys are resistant to ADH. Labs show high serum osmolality, low urine osmolality.
- Does not respond to desmopressin. Treat with thiazide.
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Endocrine Tumors
45. A man presents with coarse facial features, diabetes, and large hands. IGF-1 is elevated. What is the most likely explanation for this presentation?
➔ Acromegaly
- Note: GH-secreting pituitary adenoma. IGF-1 promotes the growth effects of GH. Produced mainly in the liver. Responsible for bone and tissue growth.
- Can also have carpal tunnel syndrome, arthritis, sleep apnea, and colon cancer.
- Measure IGF-1 as a screening. Confirm with an oral glucose suppression test. GH does not suppress in acromegaly.
- Cardiomyopathy is the leading cause of mortality.
46. A woman presents with episodic flushing, diarrhea, and a right-sided heart murmur. What condition best explains these findings?
➔ Carcinoid syndrome
- Note: Caused by serotonin-secreting neuroendocrine tumor, often from small intestine.
- Symptoms appear only after liver metastasis. Right-sided heart lesions occur due to serotonin in systemic circulation.
- The next step is Urine 5-HIAA. Treated with Octreotide.
47. A 37-year-old woman presents with amenorrhea, galactorrhea, and vaginal dryness. Her pregnancy test is negative, and labs show a serum prolactin level of 150 ng/mL on repeat testing. TSH and renal function are normal. MRI reveals a 6-mm pituitary lesion. What is the diagnosis?
➔ Symptomatic microprolactinoma
- Note: Start dopamine agonist: Cabergoline or Bromocriptine→ Inhibits prolactin secretion, reduces tumor size. Surgery is reserved for: Medication failure.
- Other causes of hyperprolactinemia are hypothyroidism, antipsychotics, and pregnancy.
48. A 57-year-old man presents with profuse watery diarrhea, facial flushing, fatigue, and weight loss. Labs reveal metabolic acidosis, hypokalemia, and stool potassium is elevated. CT abdomen shows a pancreatic mass. What is the diagnosis?
➔ VIPoma
- Note: Caused by excess VIP secretion from a pancreatic neuroendocrine tumor→ Watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). Labs: ↓ K⁺, ↓ pH
- Management: fluids, octreotide, tumor resection.
49. A patient presents with new DM, necrolytic skin rash, and depression. What is the most likely diagnosis?
➔ Glucagonoma
- Note: Pancreatic α-cell tumor. Causes hyperglycemia, weight loss, and necrolytic migratory erythema. Diagnose with elevated glucagon levels.
- New DM in a thin old man is classic!
50. A 51-year-old man has had a painless neck mass for 10 days. He has a family history of thyroid cancer. Exam reveals a 2-cm thyroid nodule + cervical lymphadenopathy
➔ Medullary Thyroid Carcinoma (MTC)
- Note: Cell origin: Parafollicular C cells, which secrete Calcitonin.
- Associated with: MEN 2A & 2B (RET proto-oncogene mutations)
- Spread: Lymphatic + hematogenous
- Family history of early-onset thyroid cancer is a key.
- Screen for pheochromocytoma + hyperparathyroidism
51. A man presents with recurrent peptic ulcers and kidney stones. What is the most likely etiology?
➔ MEN 1 (Multiple Endocrine Neoplasia type 1)
- Note: Involves the 3 Ps — Parathyroid adenomas, Pancreatic tumors (e.g., gastrinomas causing Zollinger-Ellison syndrome), and Pituitary adenomas (e.g., prolactinomas).
- Caused by a mutation in the MEN1 (menin) gene.
52. A woman has episodic hypertension and a thyroid mass. What is the diagnosis?
➔ MEN 2A
- Note: Characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia. Associated with the RET proto-oncogene mutation. Prophylactic thyroidectomy is recommended.
- MEN 2B includes medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas (on lips, tongue). No parathyroid involvement. Also caused by a RET mutation. Features include long limbs, joint laxity, and a high-arched palate.
Miscellaneous
53. A 34-year-old woman presents 6 weeks postpartum with fatigue, poor appetite, weight loss, hypotension, and inability to lactate. She had a massive postpartum hemorrhage during delivery, requiring blood transfusion. What is the likely diagnosis?
➔ Sheehan syndrome (Postpartum pituitary infarction)
- Note: Ischemic necrosis of the pituitary due to postpartum hemorrhage
- Common USMLE scenarios:
○ A woman with lactation failure (↓ prolactin)
○ A woman with adrenal insufficiency symptoms(↓ ACTH, ↓cortisol)
○ A woman with Central hypothyroidism (↓ TSH) - Management: Hormone replacement therapy (eg, glucocorticoids, levothyroxine)
54. A 16-year-old healthy girl started a strict vegan diet 2 months ago (no dairy or animal products). BMI is 18. No medications or supplements. What is the most appropriate supplement?
➔ A. Calcium
- Note: Also, Vitamin B12, Iron, Zinc, and Omega-3 fatty acids.
🏁 Final Thoughts
You made it to the end—well done! These high-yield notes are designed to save you time and keep you focused on what actually matters for Step 2 CK. Review these vignettes regularly—steady practice beats cramming.
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Disclaimer
Version 1.0 August 2025. No part of this document may be reproduced or distributed without written permission. For personal study only. Medical information herein is for educational purposes and does not constitute clinical advice. Always confirm with current guidelines and your institution’s policies.
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