Free USMLE Step 2 CK Endocrinology and Diabetes practice questions

This woman has osteomalacia, almost certainly from vitamin D deficiency due to minimal sun exposure and low dietary intake. The classic features are diffuse bone pain and tenderness (elicited by pressing on the sternum or tibias), proximal muscle weakness with a waddling gait, and laboratory evidence of a mineralization defect: low-normal calcium, low phosphate and high alkaline phosphatase. The radiographic finding is diagnostic: Looser zones (pseudofractures), narrow radiolucent bands perpendicular to the cortex, typically at the pubic rami, femoral neck, ribs and lateral scapula. The next tests are 25-hydroxyvitamin D (expected below 20, often below 10 ng/mL) and PTH (expected high), followed by vitamin D and calcium repletion. Osteomalacia is often mislabeled as fibromyalgia or polymyalgia, delaying treatment for years.

A. Fibromyalgia causes widespread pain with tender points, but strength, gait, laboratory values and radiographs are normal; low phosphate, high alkaline phosphatase and pseudofractures exclude it. B. Polymyalgia rheumatica occurs after age 50 with shoulder and hip girdle stiffness and a high ESR or CRP; her ESR is normal and bone tenderness is not a feature. D. Polymyositis causes proximal weakness with an elevated creatine kinase and no bone pain; her CK is normal. E. Primary osteoporosis is painless until a fracture occurs and has normal calcium, phosphate and alkaline phosphatase; it does not cause Looser zones.

The Whipple triad is met: neuroglycopenic and adrenergic symptoms, a documented plasma glucose of 36 mg/dL, and relief with glucose. The critical sample shows inappropriately high insulin with low beta-hydroxybutyrate, confirming insulin-mediated hypoglycemia (insulin suppresses ketogenesis). The decisive finding is a suppressed C-peptide and proinsulin. Endogenous insulin is cleaved from proinsulin with equimolar C-peptide, whereas pharmaceutical insulin contains no C-peptide and suppresses the patient's own beta cells. High insulin with low C-peptide therefore indicates injected insulin, that is, factitious (or malicious) hypoglycemia. A healthcare worker with access to insulin and a family member with diabetes is a classic setting.

The next steps are a nonjudgmental conversation, consideration of factitious disorder and psychiatric referral, and, if she denies it, consideration of whether someone else could be administering insulin.

A. Insulinoma raises insulin, C-peptide and proinsulin together; a suppressed C-peptide excludes endogenous hyperinsulinism. C. A sulfonylurea such as glipizide also stimulates endogenous secretion and raises C-peptide and proinsulin, and the drug screen is negative. D. Adrenal insufficiency causes non-insulin-mediated hypoglycemia with suppressed insulin and elevated ketones. E. A big IGF-2-secreting tumor activates the insulin receptor while suppressing insulin, C-peptide and ketones; measured insulin would be low, not high.

This man has azoospermia with a low-volume, acidic, fructose-negative ejaculate, normal-size testes, normal gonadotropins and testosterone, and nonpalpable vasa deferentia. Normal testes with a normal FSH indicate intact spermatogenesis, so the azoospermia is obstructive. The seminal vesicles, which arise with the vas from the mesonephric duct, normally supply most of the alkaline, fructose-rich ejaculate; when they are absent or hypoplastic, only the small, acidic prostatic fraction remains. This pattern is congenital bilateral absence of the vas deferens, which is a genital form of cystic fibrosis: most affected men carry CFTR mutations, often without lung disease, although sinus disease is common. Both he and his wife should have CFTR testing and genetic counseling before sperm retrieval with in vitro fertilization and intracytoplasmic sperm injection, and renal ultrasound is advised because unilateral renal agenesis can accompany vasal agenesis.

A. Klinefelter syndrome causes small, firm testes (often less than 4 mL), high FSH and LH, and low testosterone, typically with a normal ejaculate volume. B. Retrograde ejaculation produces a low-volume ejaculate, but sperm would appear in the postejaculatory urine, and the vasa would be palpable. D. Kallmann syndrome is hypogonadotropic hypogonadism with anosmia and delayed puberty; his gonadotropins, testosterone, and virilization are normal. E. Exogenous androgens suppress LH and FSH and shrink the testes, and he denies any use.

A suppressed TSH with a normal free T4 is often labeled subclinical hyperthyroidism, but that label applies only when T3 is also normal. This woman has an elevated total T3 and clear clinical thyrotoxicosis (tachycardia, tremor, weight loss with good appetite, heat intolerance), so she has overt T3 toxicosis. Autonomous thyroid tissue, especially a toxic adenoma or toxic multinodular goiter, and early Graves disease preferentially secrete T3, so T3 can rise before free T4 does. The solitary palpable nodule with the rest of the gland impalpable in a woman in her 60s strongly suggests a toxic adenoma, which a radioiodine scan would show as a single hot nodule with suppression of the remaining gland. This is why guidelines advise measuring T3 whenever TSH is low and free T4 is normal.

The distinction matters: overt hyperthyroidism, including T3 toxicosis, warrants beta-blockade now and definitive treatment (radioiodine or surgery for a toxic adenoma), whereas true subclinical disease is often just repeated in 6 to 12 weeks and treated selectively.

B. Subclinical hyperthyroidism requires normal free T4 and normal T3 and usually produces few symptoms. C. Nonthyroidal illness lowers T3 rather than raising it, and she is not acutely ill. D. A euthyroid state is excluded by the suppressed TSH, high T3, and symptoms. E. "Central hyperthyroidism" (a TSH-secreting adenoma) presents with high thyroid hormone and a nonsuppressed TSH; her TSH is undetectable, which places the problem in the thyroid.

This patient has euglycemic diabetic ketoacidosis associated with an SGLT2 inhibitor: an anion-gap metabolic acidosis (gap 22, bicarbonate 11 mEq/L, pH 7.18) with markedly elevated beta-hydroxybutyrate but a glucose below 250 mg/dL. Empagliflozin was continued up to the day before surgery instead of being held for 3 days, and postoperative fasting and surgical stress lowered insulin and raised counterregulatory hormones. SGLT2 inhibitors keep glucose modest by urinary glucose loss while promoting lipolysis and ketogenesis, so the near-normal glucose falsely reassures. Normal lactate makes lactic acidosis unlikely, and the mild port-site tenderness without fever or guarding does not suggest a surgical complication.

Treatment follows DKA principles with one modification. Ketoacidosis resolves only when insulin suppresses lipolysis and ketogenesis, so a continuous IV insulin infusion is required even though glucose is not very high. Because the glucose is already below 250 mg/dL, dextrose-containing fluids (5% to 10%) are given from the start so that enough insulin can be infused without causing hypoglycemia. Fluids and potassium are managed as in other DKA, ketones and the anion gap are followed, and the SGLT2 inhibitor is not restarted until he is eating normally and the acidosis has resolved, if at all.

A. Correction insulin given only for hyperglycemia would rarely be triggered at this glucose and would leave ketogenesis unchecked. B. Bicarbonate is not indicated at a pH above 7.0 and does not stop ketone production. D. Withholding insulin until glucose rises misreads the disorder; the problem is ketoacidosis, not hyperglycemia, and the glucose may never exceed 250 mg/dL. E. An anastomotic leak would cause fever, peritonitis and a lactic or septic picture; this acidosis is ketotic, with normal lactate, so surgery is not indicated.

Hypercalcemia with a suppressed PTH, a high-normal phosphate, a normal 25-hydroxyvitamin D, and an elevated 1,25-dihydroxyvitamin D points to unregulated calcitriol production. Activated macrophages in granulomas express 1-alpha-hydroxylase that is not controlled by PTH or calcium, so they convert 25-hydroxyvitamin D to calcitriol, which increases intestinal calcium absorption and bone resorption. Her hilar adenopathy, cough, and noncaseating granulomas with negative cultures establish sarcoidosis, and sun exposure (more vitamin D substrate) often unmasks it. Her calcium is above 12 mg/dL with polyuria and a rise in creatinine, so it needs treatment beyond hydration. Glucocorticoids are the treatment of choice: they inhibit macrophage 1-alpha-hydroxylase and lower calcitriol, and calcium usually falls within 3 to 5 days. A moderate prednisone dose is given and tapered by response. She should also avoid vitamin D supplements and excess sun exposure, keep calcium intake moderate, and be monitored for nephrocalcinosis. Hydroxychloroquine or ketoconazole are alternatives when glucocorticoids cannot be used.

B. Cinacalcet lowers PTH secretion from parathyroid tissue; her PTH is already suppressed, so it has no target here.

C. Thiazides reduce urinary calcium excretion and would raise her serum calcium further.

D. Ergocalciferol supplies more substrate for granuloma calcitriol production and would worsen the hypercalcemia.

E. Calcitonin lowers calcium for only about 48 hours before tachyphylaxis; it is a bridge in severe hypercalcemia, not a means of control.

This older woman from an iodine-deficient region has long-standing nodular goiter and new thyrotoxicosis with atrial fibrillation, a classic setting for toxic multinodular goiter. When the gland is nodular, TSH-receptor antibodies alone cannot define the cause, and the 2016 ATA guideline recommends a radioactive iodine uptake with a thyroid scan. The scan shows patchy areas of increased uptake (autonomous nodules) alternating with suppressed or cold areas in toxic multinodular goiter, a single hot nodule with suppressed background in a toxic adenoma, and diffuse uptake in Graves disease. The scan also maps which nodules are hyperfunctioning, which are rarely malignant and need no biopsy, and which are cold, which should then be evaluated with ultrasound and FNA if they meet size and sonographic criteria. The uptake value guides radioiodine dosing, the usual definitive therapy for toxic multinodular goiter without compressive symptoms.

A. FNA before the scan is the wrong order; biopsy of a hot nodule is unnecessary and its cytology often looks indeterminate. B. CT with iodinated contrast does not determine function, and the iodine load would block radioiodine uptake for weeks, delay definitive therapy, and could worsen her thyrotoxicosis through the Jod-Basedow effect in autonomous nodules. C. TPO antibodies indicate thyroid autoimmunity but are present in both Graves disease and Hashimoto thyroiditis and in many healthy people, so they do not localize the source of hormone. D. Thyroglobulin is useful when uptake is low, to separate thyroiditis from exogenous hormone, but it is elevated in nodular goiter and does not distinguish among overproducing glands.

High fasting glucose in a patient taking evening insulin has three main explanations: the dawn phenomenon (early-morning growth hormone, cortisol and catecholamine surges raising hepatic glucose output), waning insulin before morning, and the Somogyi effect (nocturnal hypoglycemia from excess evening insulin followed by counterregulatory rebound). The treatments are opposite: the first two call for more or later evening basal insulin, whereas the Somogyi effect calls for less. Raising the dose in a patient with nocturnal lows deepens the hypoglycemia.

His clues point toward nocturnal hypoglycemia: night sweats, nightmares and morning headaches, with a predinner NPH dose that peaks at 4 to 10 hours, right in the middle of the night. His HbA1c of 7.3% is also lower than his fasting values would suggest. Before any dose change, overnight glucose must be measured: a 3 AM fingerstick on several nights (or a continuous glucose monitor tracing) separates the patterns. A low 3 AM value means reducing the evening NPH, moving it to bedtime or switching to a basal analog with less nocturnal hypoglycemia; a normal or high value supports the dawn phenomenon or waning insulin.

A. C-peptide measures residual beta-cell function and does not explain the timing of hyperglycemia. B. Repeating HbA1c gives an average and cannot reveal nocturnal lows. C. An OGTT is a diagnostic test for diabetes, which he already has. D. Fructosamine is a 2- to 3-week average of glycemia, useful when HbA1c is unreliable, and also cannot detect nocturnal hypoglycemia.