Clinical Chemistry practice questions.

Answer: A — Gluconeogenesis

Gluconeogenesis builds new glucose, mainly in the liver. Glycogenolysis breaks down stored glycogen; glycolysis breaks glucose down to pyruvate.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Hepatic gluconeogenesis

Overnight fasting relies on hepatic glycogenolysis; prolonged fasting relies on gluconeogenesis. Lipolysis supplies glycerol (a gluconeogenic substrate) and fatty acids, but fatty acids themselves cannot be converted to glucose. Muscle lacks glucose-6-phosphatase, so its glycogen cannot release free glucose.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Beta cells

Beta cells secrete insulin (with C-peptide in equal amounts). Alpha cells secrete glucagon; delta cells secrete somatostatin; acinar cells are exocrine.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Sodium fluoride/potassium oxalate (grey top)

Fluoride inhibits enolase and slows glycolysis. In unseparated whole blood at room temperature, glucose falls by roughly 5-7% per hour.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — 126 mg/dL (7.0 mmol/L) or higher

Diabetes: FPG 126 mg/dL or higher, 2-h OGTT glucose 200 mg/dL or higher, HbA1c 6.5% or higher, or random glucose 200 mg/dL or higher with classic symptoms. Without symptoms, an abnormal result should be confirmed.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: B — Impaired fasting glucose (prediabetes)

Prediabetes: FPG 100-125 mg/dL, 2-h OGTT 140-199 mg/dL, or HbA1c 5.7-6.4%.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: B — 75 g, sample at 2 hours

The OGTT assesses glucose tolerance: 75 g anhydrous glucose with plasma glucose at 2 hours. 50 g (1-h) and 100 g (3-h) loads are used in two-step screening for gestational diabetes.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: C — 2-3 months

HbA1c reflects the lifespan of red cells (about 8-12 weeks), weighted towards the most recent month. Fructosamine (glycated serum proteins) reflects about 2-3 weeks.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: A — Shortened red cell survival gives less time for glycation

Any condition that shortens red cell lifespan (hemolysis, blood loss, recent transfusion) falsely lowers HbA1c. Fructosamine or glucose monitoring may be more reliable.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: B — Exogenous (injected) insulin

C-peptide is released with endogenous insulin. Injected insulin contains no C-peptide and suppresses the patient's own secretion. Insulinoma and sulfonylureas raise both insulin and C-peptide.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Type 1 diabetes

Autoimmune destruction of beta cells in type 1 diabetes leaves little endogenous insulin, so C-peptide is low. Autoantibodies (GAD65, IA-2, ZnT8, insulin) support the diagnosis.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: D — Acetoacetate

Nitroprusside reacts strongly with acetoacetate, weakly with acetone, and not at all with beta-hydroxybutyrate, which is the predominant ketone in DKA. Blood beta-hydroxybutyrate is preferred for diagnosis and monitoring.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: A — High anion gap metabolic acidosis

Ketoacids (beta-hydroxybutyrate and acetoacetate) are unmeasured anions, so the anion gap rises. Breathing becomes deep and fast (Kussmaul) to lower pCO2.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Potassium

Total body potassium is depleted in DKA even if serum K is normal or high. Insulin drives potassium into cells, so serum K can fall quickly; it is monitored and replaced.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: C — 180 mg/dL

About 180 mg/dL (10 mmol/L) is the renal threshold. Glucosuria with normal blood glucose suggests renal glycosuria (a tubular reabsorption defect, e.g., SGLT2) or SGLT2 inhibitor use.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — 24-28 weeks of pregnancy

Screening at 24-28 weeks uses a 75 g OGTT (one-step) or a 50 g screen followed by a 100 g OGTT (two-step).

Reference: ADA Standards of Care in Diabetes (2025)

Answer: A — Urine albumin-to-creatinine ratio (UACR)

A UACR of 30-300 mg/g (moderately increased albuminuria) is an early marker of diabetic kidney disease. It should be confirmed in 2 of 3 samples over 3-6 months.

Reference: ADA Standards of Care in Diabetes (2025)

Answer: B — Chylomicrons

Chylomicrons carry dietary triglyceride from the intestine (apoB-48). VLDL carries triglyceride made in the liver (apoB-100).

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — LDL

LDL is about 50% cholesterol (free and esterified) and delivers it to tissues; raised LDL is a causal risk factor for atherosclerotic cardiovascular disease. HDL carries cholesterol back to the liver (reverse cholesterol transport).

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — ApoA-I

ApoA-I is the major HDL protein and activates LCAT. ApoB-100 is on VLDL, IDL and LDL; apoB-48 on chylomicrons; apo(a) defines Lp(a).

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — VLDL

Alpha band = HDL, pre-beta = VLDL, beta = LDL; chylomicrons stay at the origin. IDL gives a 'broad beta' band.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: B — 120 mg/dL

LDL = TC - HDL - TG/5 = 200 - 50 - 30 = 120 mg/dL (all in mg/dL). The equation is not valid when triglycerides are 400 mg/dL or higher; use direct LDL or another method.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Triglycerides

Triglycerides rise for several hours after a fatty meal (chylomicrons). Total and HDL cholesterol change little, which is why non-fasting lipid profiles are acceptable for most people.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Familial hypercholesterolemia

FH is usually caused by LDL receptor mutations (less often APOB or PCSK9). It gives very high LDL with normal triglycerides, tendon xanthomas, and early corneal arcus.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Increased chylomicrons

Chylomicrons float and form a creamy top layer. A turbid infranatant would suggest increased VLDL as well.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: B — A sterol that is the precursor of steroid hormones and bile acids

Cholesterol has the four-ring steroid nucleus but is not a hormone. It is the precursor of cortisol, aldosterone, sex hormones, vitamin D and bile acids.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Lipoprotein(a)

Lp(a) levels are largely inherited and stable through life, so one measurement in adulthood is often enough.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Albumin

Albumin makes up about 55-60% of plasma protein. It maintains oncotic pressure and transports bilirubin, calcium, hormones and many drugs.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Albumin, alpha-1, alpha-2, beta, gamma

Albumin is the most negatively charged and moves furthest towards the anode; gamma globulins move least.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: B — Alpha-1 antitrypsin

Alpha-1 antitrypsin forms most of the alpha-1 band; a flat alpha-1 band suggests AAT deficiency. Haptoglobin and alpha-2 macroglobulin are in alpha-2; transferrin is in beta.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: C — Nephrotic syndrome

Small proteins such as albumin are lost in urine, while large alpha-2 macroglobulin is retained and rises. Lipids also rise.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: D — Cirrhosis of the liver

Polyclonal IgA rises in cirrhosis and fills the gap between the beta and gamma bands. Albumin is usually low.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: A — A monoclonal gammopathy such as multiple myeloma

A sharp band is a monoclonal protein; a broad diffuse increase is polyclonal (chronic inflammation, infection, liver disease). Immunofixation identifies the heavy and light chain type.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: B — Free monoclonal immunoglobulin light chains

Classically they precipitate at 40-60 C and redissolve near 100 C. Today they are detected by urine immunofixation and serum free light chain assays.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Prealbumin (transthyretin)

Albumin's half-life is about 20 days, so it responds slowly. Both are negative acute-phase proteins and fall in inflammation.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Pseudohyponatremia from the electrolyte exclusion effect

Very high protein or lipid reduces the water fraction of plasma. Indirect ISE (with a dilution step) then under-reads sodium. Direct ISE, as in blood gas analyzers, gives the true value.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Water soluble and can appear in urine

Bilirubin is conjugated with glucuronic acid by UGT1A1 in the liver, making it water soluble. Unconjugated bilirubin is carried bound to albumin and does not appear in urine.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Gilbert syndrome

Gilbert syndrome is common and benign, caused by reduced UGT1A1 activity. Dubin-Johnson and Rotor syndromes cause conjugated hyperbilirubinemia.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Bilirubin is destroyed by light

Bilirubin is photosensitive. Protect samples from light (foil or amber tubes) and analyze promptly.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Raised unconjugated bilirubin, no bilirubin in urine, increased urine urobilinogen

Excess bilirubin is produced, so more urobilinogen forms in the gut and appears in urine. Unconjugated bilirubin is not filtered, so urine bilirubin is negative.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: A — Complete biliary obstruction (post-hepatic jaundice)

Bile cannot reach the gut, so no urobilinogen forms and stools are pale. Conjugated bilirubin backs up into blood and urine. Gallstones and pancreatic head tumors are common causes.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: B — Acute hepatocellular injury, e.g., viral or drug-induced hepatitis

A hepatocellular pattern has aminotransferases raised more than ALP. A cholestatic pattern has ALP (with GGT) raised more than aminotransferases.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: C — Alcohol-related liver disease

Alcohol depletes pyridoxal phosphate, which affects ALT more than AST, and damages mitochondria (which contain AST). Viral hepatitis and early fatty liver usually have ALT higher than AST.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — GGT

GGT rises with hepatobiliary ALP but not with bone ALP. High ALP with normal GGT suggests bone (Paget disease, healing fracture, osteomalacia, growth in children).

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Paget disease of bone

Paget disease causes high bone turnover with very high ALP. Osteoporosis alone usually has normal ALP and calcium.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — EDTA or heparin tube, placed on ice and analyzed within about 30 minutes

Ammonia rises in vitro as red cells and amino acids break down. Avoid hemolysis, prolonged tourniquet use and smoking before collection.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — The urea cycle

The liver converts ammonia to urea. In liver failure ammonia accumulates and contributes to hepatic encephalopathy. Glutamine (from tissues) and alanine (from muscle) carry ammonia to the liver.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Primary biliary cholangitis

AMA (M2) is present in about 95% of primary biliary cholangitis (formerly primary biliary cirrhosis). Autoimmune hepatitis is linked to ANA and anti-smooth muscle antibodies.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Prothrombin time (PT/INR)

Clotting factors, especially factor VII, have short half-lives, so PT changes within hours to days. Albumin's long half-life makes it a slow marker.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Cardiac troponin (I or T), ideally high-sensitivity

MI is diagnosed by a rise and/or fall of cardiac troponin with at least one value above the 99th percentile, plus clinical evidence of ischemia. CK-MB is less sensitive and less specific.

Reference: Fourth Universal Definition of Myocardial Infarction (2018)

Answer: C — CK-MB

Troponin stays raised for 7-14 days, so a new rise is harder to see. CK-MB falls within 48-72 hours, though serial troponin is now also used.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Heart failure

Natriuretic peptides are released from ventricles under wall stress. A normal result makes heart failure unlikely in a breathless patient.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Rhabdomyolysis

Skeletal muscle damage releases CK (mostly CK-MM), AST, ALT, LDH and myoglobin. Myoglobinuria gives dark urine and can cause acute kidney injury.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Creatine kinase (CK)

CK is found in skeletal muscle, heart and brain, not liver. Raised CK with mildly raised AST/ALT points to muscle as the source.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Lipase

Lipase is more pancreas-specific than amylase and stays raised longer. Diagnosis needs two of three: typical pain, lipase or amylase more than 3 times the upper limit, or imaging findings.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Macroamylasemia

Amylase bound to immunoglobulin forms a large complex that cannot be filtered by the kidney, so serum amylase stays high and urine amylase is low. It is benign.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Fecal elastase-1

Low fecal elastase-1 indicates reduced pancreatic enzyme output. Serum lipase and amylase are often normal in chronic pancreatitis.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Potassium and LDH

Red cells contain much more potassium, LDH and AST than plasma. Hemolysed samples should be recollected for these tests.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — 90 mL/min/1.73 m2 or higher

KDIGO categories: G1 90 or higher, G2 60-89, G3a 45-59, G3b 30-44, G4 15-29, G5 below 15. CKD needs abnormalities lasting more than 3 months.

Reference: KDIGO Clinical Practice Guideline for CKD (2024)

Answer: D — Creatinine production is low because it comes from muscle

Creatinine comes from muscle creatine. Low muscle mass gives a low creatinine even when GFR is reduced. Cystatin C does not depend on muscle mass.

Reference: KDIGO Clinical Practice Guideline for CKD (2024)

Answer: B — 100 mL/min

Clearance = (U x V) / P. V = 1440 mL / 1440 min = 1 mL/min, so clearance = (100 x 1) / 1.0 = 100 mL/min.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Pre-renal azotemia

In pre-renal states, slow tubular flow increases urea reabsorption, so urea rises more than creatinine. GI bleeding and high protein intake can also raise the ratio.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: C — Liver

The liver converts ammonia from protein breakdown into urea through the urea cycle. Low urea can occur in severe liver disease and low protein intake.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Purines

Raised uric acid occurs in gout, high cell turnover (tumor lysis), kidney disease and some drugs such as thiazides.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Heavy proteinuria, low serum albumin, edema and hyperlipidemia

Proteinuria is above 3.5 g/day in adults; serum total protein and albumin fall. Oval fat bodies and fatty casts may be seen in urine. Hematuria with red cell casts suggests nephritic syndrome.

Reference: Bishop's Clinical Chemistry: Principles, Techniques and Correlations

Answer: B — Calcium oxalate

Calcium oxalate stones are the most common. Struvite stones are linked to urease-producing bacteria such as Proteus.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — 12 mmol/L

AG = Na - (Cl + HCO3) = 140 - 128 = 12 mmol/L. Reference ranges vary by analyzer; low albumin lowers the anion gap.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Severe diarrhea

Diarrhea loses bicarbonate, and chloride rises to replace it, so the anion gap stays normal. Lactate, ketones and toxic alcohol metabolites are unmeasured anions that raise the gap.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — 300 mOsm/kg

Calculated osmolality = 2 x Na + glucose/18 + BUN/2.8 = 280 + 10 + 10 = 300 mOsm/kg.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Toxic alcohol ingestion such as methanol or ethylene glycol

An osmolal gap above about 10 mOsm/kg means an unmeasured osmotically active substance is present. Ethanol, methanol, ethylene glycol and isopropanol are common causes. Measure osmolality by freezing point depression, because vapor pressure methods miss volatile alcohols.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Acute respiratory acidosis

Low pH with high pCO2 is respiratory acidosis. HCO3 has barely risen, which suggests an acute process with little renal compensation.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Appropriate

Expected pCO2 = 1.5 x HCO3 + 8 (plus or minus 2) = 1.5 x 14 + 8 = 29 mmHg. The measured pCO2 matches, so this is a compensated metabolic acidosis.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Metabolic alkalosis

Loss of gastric acid (HCl) raises bicarbonate. The pCO2 rises slightly as compensation. Low chloride and potassium are common.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — High potassium and low calcium

K2-EDTA adds potassium and chelates calcium and magnesium (ALP can also be falsely low). Such a sample must be recollected.

Reference: CLSI GP41: Collection of Diagnostic Venous Blood Specimens

Answer: C — Hyperkalemia

Severe hyperkalemia causes peaked T waves, widened QRS and arrhythmias. Always exclude pseudohyperkalemia (hemolysis, EDTA contamination, delayed separation) first.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — SIADH

In SIADH, inappropriate ADH makes the urine concentrated despite low plasma osmolality. Thyroid and adrenal insufficiency must be excluded first. In primary polydipsia, urine is maximally dilute (below 100 mOsm/kg).

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Primary (psychogenic) polydipsia

In primary polydipsia, excess intake dilutes plasma (sodium low or low-normal). In diabetes insipidus, water loss comes first, so sodium tends to be high-normal or high. A water deprivation test separates them.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Central (cranial) diabetes insipidus

Central DI lacks ADH, so giving desmopressin works. In nephrogenic DI the kidney does not respond to ADH or desmopressin.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — 9.2 mg/dL

Corrected Ca = measured Ca + 0.8 x (4.0 - albumin) = 7.6 + 0.8 x 2.0 = 9.2 mg/dL. Ionized calcium is the most accurate measure when available.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Decreases ionized calcium

In alkalosis, albumin binds more calcium, so ionized calcium falls and tingling or tetany can occur even though total calcium is unchanged.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Primary hyperparathyroidism

Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatients. In malignancy and vitamin D toxicity, PTH is suppressed. Vitamin D toxicity raises both calcium and phosphate.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Magnesium

Low magnesium impairs PTH secretion and action, causing refractory hypocalcemia (and hypokalemia). Common causes are alcohol, diuretics, PPIs and diarrhea.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Primary hypothyroidism

The failing thyroid cannot make enough T4, so the pituitary increases TSH. Hashimoto thyroiditis is the most common cause where iodine intake is adequate.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Primary hyperthyroidism

Excess thyroid hormone suppresses TSH. Graves disease is the most common cause; others include toxic nodular goiter and thyroiditis.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Secondary (central) hypothyroidism

Pituitary or hypothalamic disease fails to raise TSH despite low T4. In this case TSH alone can be misleading, so free T4 is needed.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — TSH

TSH responds sensitively to small changes in thyroid hormone. Free T4 is added when TSH is abnormal or pituitary disease is suspected. TSH is also used in newborn screening for congenital hypothyroidism.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — TSH receptor antibodies (TRAb / TSI)

Graves disease is caused by stimulating antibodies against the TSH receptor. Anti-TPO is typical of Hashimoto thyroiditis, although it can also be positive in Graves disease.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Hashimoto (chronic autoimmune) thyroiditis

Hashimoto thyroiditis is an autoimmune destruction of the thyroid with anti-TPO and often anti-thyroglobulin antibodies.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Non-thyroidal illness (euthyroid sick syndrome)

Severe illness reduces conversion of T4 to T3 and increases reverse T3. Thyroid tests are best repeated after recovery unless thyroid disease is strongly suspected.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Calcitonin

Medullary carcinoma arises from parafollicular C cells, which secrete calcitonin (and CEA). Thyroglobulin is used after treatment of differentiated (papillary or follicular) cancer.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Cortisol

The adrenal cortex makes cortisol, aldosterone and adrenal androgens. ACTH comes from the anterior pituitary; epinephrine from the adrenal medulla; ADH from the posterior pituitary.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Overnight 1 mg dexamethasone suppression test

Recommended first-line tests are the overnight 1 mg dexamethasone suppression test, 24-hour urinary free cortisol, and late-night salivary cortisol. A single random cortisol is not reliable.

Reference: Endocrine Society Clinical Practice Guidelines

Answer: A — An adrenal tumor

Autonomous adrenal cortisol suppresses ACTH. High or normal ACTH points to ACTH-dependent causes: pituitary (Cushing disease) or ectopic ACTH.

Reference: Endocrine Society Clinical Practice Guidelines

Answer: B — ACTH (cosyntropin) stimulation test

A low cortisol response to synthetic ACTH confirms adrenal insufficiency. Low sodium and high potassium support primary disease (Addison) but are not diagnostic.

Reference: Endocrine Society Clinical Practice Guidelines

Answer: C — Primary adrenal insufficiency (Addison disease)

Adrenal gland failure removes cortisol feedback, so ACTH rises; aldosterone loss causes hyponatremia and hyperkalemia. In secondary insufficiency ACTH is low and potassium is usually normal.

Reference: Endocrine Society Clinical Practice Guidelines

Answer: D — Plasma aldosterone-to-renin ratio

Primary aldosteronism gives high aldosterone with suppressed renin. A raised ratio is followed by a confirmatory test (for example, saline infusion).

Reference: Endocrine Society Clinical Practice Guidelines

Answer: A — Plasma free metanephrines (or 24-h urine fractionated metanephrines)

Metanephrines are produced continuously inside tumor cells, which makes them more sensitive than catecholamines or VMA.

Reference: Endocrine Society Clinical Practice Guidelines

Answer: B — Prolactinoma (pituitary adenoma)

Pregnancy, drugs (antipsychotics, metoclopramide) and hypothyroidism must be excluded. A moderately raised prolactin without symptoms may be macroprolactin, which can be checked by PEG precipitation.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Luteinizing hormone (LH)

The mid-cycle LH surge triggers ovulation. A mid-luteal (about day 21 of a 28-day cycle) progesterone is used to confirm that ovulation occurred.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Beta-hCG

hCG is made by the placenta (syncytiotrophoblast). The beta subunit is specific; the alpha subunit is shared with LH, FSH and TSH.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Menopause (primary ovarian failure)

When the ovaries stop responding, loss of estradiol and inhibin feedback raises FSH (and LH).

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — CA 19-9 and pancreatic cancer

CA 19-9: pancreatic; CA-125: ovarian; PSA: prostate; CA 15-3: breast; CEA: colorectal; calcitonin: medullary thyroid; AFP: hepatocellular and germ cell tumors.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Monitor treatment response and detect recurrence

They lack the sensitivity and specificity needed for screening or diagnosis. Trends in the same patient, measured by the same method, are what matter.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Non-seminomatous germ cell tumor

AFP is not produced by pure seminoma, so a raised AFP indicates non-seminomatous elements (for example, yolk sac tumor). Beta-hCG can be raised in both.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Low ceruloplasmin, raised 24-hour urine copper and Kayser-Fleischer rings

ATP7B mutation impairs biliary copper excretion and copper loading onto ceruloplasmin. Total serum copper is usually low (ceruloplasmin-bound copper is low), while free copper and urine copper are high.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: B — Phenylketonuria

PKU is usually caused by phenylalanine hydroxylase deficiency. Early dietary treatment prevents intellectual disability.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Tryptophan

Defective intestinal and renal transport of neutral amino acids, including tryptophan, can cause niacin deficiency with a pellagra-like rash.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: D — Sweat chloride

A sweat chloride of 60 mmol/L or higher supports CF, caused by CFTR mutations. 30-59 mmol/L is intermediate and needs further testing.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: A — Blood culture, citrate, serum, heparin, EDTA, fluoride

This order reduces additive carryover, for example EDTA contaminating a chemistry tube (falsely high potassium, low calcium).

Reference: CLSI GP41: Collection of Diagnostic Venous Blood Specimens

Answer: B — Potassium falsely high

Cold inhibits the red cell Na/K pump, so potassium leaks out of cells. Glucose falls with time unless a fluoride tube is used.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics

Answer: C — Total protein and calcium

Hemoconcentration raises proteins and protein-bound substances (calcium, lipids, enzymes). Fist clenching can also raise potassium.

Reference: CLSI GP41: Collection of Diagnostic Venous Blood Specimens

Answer: D — It can interfere with photometric assays and indirect ISE sodium; high-speed centrifugation or ultracentrifugation can clear it

Lipemia scatters light and displaces plasma water. Clearing the sample or using alternative methods reduces the error.

Reference: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics