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Laboratory test results 

Laboratory test results
Chapter:
Laboratory test results
Author(s):

Huw Llewelyn

, Hock Aun Ang

, Keir Lewis

, and Anees Al-Abdullah

DOI:
10.1093/med/9780199679867.003.0011
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Microscopic haematuria

This is detected on routine urine dipstick testing. Initial investigations (other tests in bold below): MSU, FBC.

Main differential diagnoses and typical outline evidence, etc.

Menstruation

  • Suggested by: history of current, recent or imminent periods, and no urinary symptoms.

  • Confirmed by: dipstick –ve on repeating in mid-cycle.

  • Finalized by the predictable outcome of management, e.g. reassurance.

Urinary tract infection

  • Suggested by: fever, frequency, or dysuria; ↑ nitrites, ↑ leucocytes on dipstick.

  • Confirmed by: MSU microscopy and culture, response to antibiotics. US scan for possible anatomical abnormality.

  • Finalized by the predictable outcome of management, e.g. increased fluid intake, cranberry juice, and regular bladder emptying. Provisional 1st line antibiotic pending MSU result, e.g. trimethoprim, cefalexin for 3d; 2nd line, e.g. ciprofloxacin bd for 5d.

Recent urethral trauma

  • Suggested by: recent urethral catheterization.

  • Confirmed by: history, no infection in MSU.

  • Finalized by the predictable outcome of management, e.g. explanation, reassurance.

Bleeding diathesis

  • Suggested by: bruising, anticoagulant therapy.

  • Confirmed by: abnormal platelet and clotting screen.

  • Finalized by the predictable outcome of management, e.g. treatment of underlying cause, replacement treatment e.g. vitamin K, platelet transfusion.

Kidney calculus

  • Suggested by: excruciating pain that fluctuates in the back below ribs, cloudy dark urine with a foul smell, recurrent dysuria, gout, persistent x3 microscopic haematuria.

  • Confirmed by: renal ultrasound, intravenous urography (IVU), cystoscopy by urologist.

  • Finalized by the predictable outcome of management, e.g. immediate analgesia, e.g. diclofenac IM or suppository, or pethidine IM with metoclopramide IM, and antibiotics.

  • Emergency surgery if renal tract obstruction was confirmed on imaging.

Glomerulonephritis 1° or 2° to SLE, SBE, etc.

  • Suggested by: persistent x3 microscopic haematuria, associated proteinuria, hypertension.

  • Confirmed by: urine microscopy, renal ultrasound, immunoglobulins, complement, ANA, ANCA positive blood cultures/response to antibiotics.

  • Finalized by the predictable outcome of management, e.g. corticosteroids and/or immunosuppression with cyclophosphamide. Plasmapharesis to remove auto-antibodies in rapidly progressive glomerulonephritis.

Nephritis 2° to NSAIDs, etc.

  • Suggested by: persistent x3 microscopic haematuria, taking NSAIDs or other suspicious drug.

  • Confirmed by: urine microscopy, renal ultrasound, improvement on stopping suspected drug, IVU, etc.

  • Finalized by the predictable outcome of management, e.g. eliminate possible causes; treat infection with antibiotics, treat renal failure.

Tumour of kidney

  • Suggested by: flank pain and abdominal mass, dark urine, weight loss, varicocoele (forms blockage of testicular vein), persistent x3 microscopic haematuria.

  • Confirmed by: renal ultrasound, IVU, then cystoscopy by urologist.

  • Finalized by the predictable outcome of management, e.g. treat infection. Stenting, surgical resection, radio- or chemotherapy as single or combined treatments.

Asymptomatic proteinuria

Total protein excretion is usually <50mg/24h, of which albumin alone is normally <30mg/24h. Abnormal proteinuria is regarded as >150mg/24h. Initial investigations (other tests in bold below): urine dipstick ± MSU, FBC, U&E.

Main differential diagnoses and typical outline evidence, etc.

Postural or orthostatic proteinuria

  • Suggested by: specimen from ambulant person <40y.

  • Confirmed by: protein testing –ve on early morning urine specimen.

  • Finalized by the predictable outcome of management, e.g. explanation to patient and reassurance.

Non-specific febrile illness

  • Suggested by: known febrile illness.

  • Confirmed by: normal when illness resolved.

  • Finalized by the predictable outcome of management, e.g. no change when temperature is back to normal.

Urinary tract infection

  • Suggested by: strong urge to pass urine, dysuria, increased frequency and fever; ↑nitrites, ↑leucocytes on dipstick.

  • Confirmed by: MSU microscopy and culture, response to antibiotics. US scan for possible anatomical abnormality.

  • Finalized by the predictable outcome of management, e.g. increased fluid intake, cranberry juice, and regular bladder emptying. Provisional 1st line antibiotic pending MSU result, e.g. trimethoprim, cefalexin for 3d. 2nd line, e.g. ciprofloxacin bd for 5d.

Glomerulonephritis 1° or 2° to SLE, etc.

  • Suggested by: proteinuria >1g/24h, persistent x3 microscopic haematuria, hypertension.

  • Confirmed by: urine microscopy, renal ultrasound, immunoglobulins, complement, ANA, ANCA, etc.

  • Finalized by the predictable outcome of management, e.g. corticosteroids and/or immunosuppression with cyclophosphamide. Plasmapharesis to remove auto-antibodies in rapidly progressive glomerulonephritis.

Nephritis 2° to NSAIDs, etc.

  • Suggested by: proteinuria >1g/24h, taking NSAIDs or other suspicious drug.

  • Confirmed by: urine microscopy, renal ultrasound, improvement on stopping suspected drug, IVU, etc.

  • Finalized by the predictable outcome of management, e.g. elimination of causes; treatment of renal failure.

Nephrotic syndrome due to minimal change glomerulonephritis, diabetes mellitus, etc.

  • Suggested by: frothy urine, oedema of legs, and swelling around the eyes, reduced quantity of urine, high blood pressure, and blood in urine.

  • Confirmed by: proteinuria >3g/24h. Serum albumin low (<30g/L), and elevated total cholesterol and ↑triglycerides.

  • Finalized by the predictable outcome of management, e.g. treat specific disease. Monitor U&E, BP, fluid balance, and weight. Lifestyle advice: no smoking, exercise, and low-fat diet. Restricted salt and normal protein intake, consider diuretics and ACE inhibitors.

Glycosuria

Almost always indicates diabetes and blood sugar has to be tested, but consider other possibilities. Initial investigations (other tests in bold below): urine dipstick ±MSU, FBC, fasting glucose, U&E.

Main differential diagnoses and typical outline evidence, etc.

Diabetes mellitus

  • Suggested by: fatigue or other unexplained symptoms, thirst, polydipsia, polyuria.

  • Confirmed by: fasting blood glucose ≥7.0mmol/L OR random or 2h glucose tolerance test (GTT) glucose ≥11.1mmol/L once only with symptoms or on two occasions if no symptoms OR HbA1c ≥6.5% (48mmol/mol).

  • Finalized by the predictable outcome of management, e.g. lifestyle advice—stop smoking, exercise, and weight reduction. Dietary advice, ↓saturated fat, ↓glucose, and ↑carbohydrate. When dietary measures are not enough in type 2 diabetes, oral treatment, e.g. metformin or sulphonylurea. Insulin for all type 1 diabetics, and if ↑HbA1c despite oral treatment in type 2 diabetics.

Renal glycosuria

  • Suggested by: patient well or renal disease or pregnant.

  • Confirmed by: glycosuria when blood sugar shown to be normal on glucose tolerance test.

  • Finalized by the predictable outcome of management, e.g. explanation and reassurance.

Raised urine or serum bilirubin

Initial investigations (other tests in bold below): US scan of liver.

Main differential diagnoses and typical outline evidence, etc.

Hepatocellular jaundice (due to hepatitis or very severe liver failure) (see Laboratory test results Hepatocellular jaundice, p.[link])

  • Suggested by: jaundice with dark stools and dark urine. Also ↑urine urobilinogen (you can check this immediately).

  • Confirmed by:serum bilirubin and ↑urine urobilinogen. Highly abnormal LFT. Normal bile ducts but abnormal liver parenchyma on US scan.

  • Finalized by the predictable outcome of management, e.g. treatment of the cause.

Obstructive jaundice due to intrahepatic causes (drugs, hepatitis, etc.) or extrahepatic (stones, tumours, etc.) (see Laboratory test results Obstructive jaundice, p.[link])

  • Suggested by: jaundice with pale stools and dark urine. Also NO ↑ urine urobilinogen.

  • Confirmed by: ↑plasma bilirubin but ↑↑alkaline phosphatase, otherwise slightly abnormal LFT. Dilated bile ducts on US scan.

  • Finalized by the predictable outcome of management, e.g. treatment of the cause.

Hepatocellular jaundice

  • Suggested by: jaundice with dark or normal stools and dark urine.

  • Confirmed by: ↑serum bilirubin and ↑ urine urobilinogen. Highly abnormal LFT. Normal bile ducts on US scan.

Main differential diagnoses and typical outline evidence, etc.

Acute (viral) hepatitis A

  • Suggested by: flu-like illness, pruritis, loss of appetite, jaundice, and tender hepatomegaly.

  • Confirmed by: presence of hepatitis A IgM antibody suggests acute infection.

  • Finalized by the predictable outcome of management, e.g. supportive care, rest, nutritious diet, and no alcohol. General hygiene. Liver transplantation for fulminant hepatic failure. Immunize contacts with hepatitis A vaccine.

Acute hepatitis B

  • Suggested by: history of IV drug use, transfusion, needle punctures, tattoos, tender hepatomegaly.

  • Confirmed by: presence of HBsAg in serum.

  • Finalized by the predictable outcome of management, e.g. conservative advice—no alcohol. Chronic despite antiviral treatment: pegylated interferon alfa, entecavir, or tenofovir disoproxil fumarate. Immunize sexual contacts.

Acute hepatitis C

  • Suggested by: history of transfusion or other blood products. Tender hepatomegaly.

  • Confirmed by: presence of anti-HCV antibody and antigen.

  • Finalized by the predictable outcome of management, e.g. combination of ribavirin + pegylated interferon alfa for moderate and severe chronic hepatitis (response depends on ethnic group, age, viral load, and HCV genotype).

Alcoholic hepatitis

  • Suggested by: history of drinking, presence of spider naevi, and other signs of chronic liver disease.

  • Confirmed by: raised GGT, raised ALT, liver biopsy.

  • Finalized by the predictable outcome of management, e.g. stop alcohol, treatment of alcohol withdrawal, high dose vitamin B, steroids in severe disease if no infection.

Drug-induced hepatitis, e.g. paracetamol (dose-dependent), halothane (dose-independent)

  • Suggested by: drug history, recent surgery.

  • Confirmed by: improvement after stopping the offending drug.

  • Finalized by the predictable outcome of management, e.g. stop causative agent, conservative treatment.

1° hepatoma

  • Suggested by: weight loss, abdominal pain, heaviness feeling in right upper abdomen, excessive alcohol intake, right upper quadrant (RUQ) mass.

  • Confirmed by: US scan/CT liver, liver biopsy,alpha-fetoprotein.

  • Finalized by the predictable outcome of management, e.g. resection for solitary tumour <3cm diameter. Liver transplantation, chemotherapy, percutaneous ablation, tumour embolizations.

Right heart failure (due to pulmonary hypertension, COPD, tricuspid incompetence, worsened by anaemia, infection

  • Suggested by: shortness of breath, fatigue, tachycardia, rapid weight gain, ↑JVP, hepatomegaly, ankle oedema.

  • Confirmed by: CXR, ECG, echocardiogram, radionuclide ventriculography.

  • Finalized by the predictable outcome of management, e.g. diuretics, β-blockers, and digoxin. Treatment of cause. Lifestyle advice on weight reduction, diet, and smoking cessation.

Obstructive jaundice

  • Suggested by: jaundice with pale stools and dark urine.

  • Confirmed by:urine and serum bilirubin but NO ↑urobilinogen in urine. ↑↑alkaline phosphatase, otherwise slightly abnormal LFT. Dilated bile ducts on US liver scan.

Main differential diagnoses and typical outline evidence, etc.

Common bile duct stones

  • Suggested by: pain in RUQ ± Murphy’s sign.

  • Confirmed by: US scan liver/biliary ducts.

  • Finalized by the predictable outcome of management, e.g. analgesics, anti-emetics, and antibiotics. Emergency or elective cholecystectomy.

Cancer of head of pancreas

  • Suggested by: progressive painless jaundice, itching, dappetite and weight loss, development of diabetes mellitus, palpable gallbladder (Courvoisier’s law).

  • Confirmed by: CT pancreas, ERCP or MRCP.

  • Finalized by the predictable outcome of management, e.g. relief of symptoms caused by jaundice with an endoscopic or percutaneous stent insertion. Pain control with opiates. Surgery if patient fit with no metastases and tumour is <3cm.

Sclerosing cholangitis

  • Suggested by: progressive fatigue, pruritus, dark urine, right upper abdominal pain, and jaundice.

  • Confirmed by:serum alkaline phosphatase, no gallstones on US scan, normal anti-mitochondrial antibodies, ERCP (beading of the intra- and extra-hepatic biliary ducts).

  • Finalized by the predictable outcome of management, e.g. colestyramine for pruritus. Ursodeoxycholic acid to improve LFT and jaundice. Antibiotics for infection, endoscopic stenting for strictures, yearly follow-up, and liver transplantation for end-stage disease.

1° biliary cirrhosis

  • Suggested by: scratch marks, non-tender hepatomegaly ± splenomegaly, xanthelasmata, and xanthomas, arthralgia.

  • Confirmed by: +ve anti-mitochondrial antibody, ↑↑serum IgM, liver biopsy.

  • Finalized by the predictable outcome of management, e.g. colestyramine for pruritus. Codeine for diarrhoea. Vitamins D and K if clotting abnormal. Ursodeoxycholic acid to improve LFT, jaundice, and spironolactone if ascites.

Drug-induced e.g. oral contraceptive pill, phenothiazines, anabolic steroids, erythromycin

  • Suggested by: drug history.

  • Confirmed by: symptoms recede when offending drug is discontinued.

  • Finalized by the predictable outcome of management, e.g. improvement after the discontinuation of the causative agent.

Pregnancy (last trimester)

  • Suggested by: jaundice during pregnancy and severe itching.

  • Confirmed by: resolution following delivery.

  • Finalized by the predictable outcome of management, e.g. explanation and reassurance.

Alcoholic hepatitis/cirrhosis

  • Suggested by: history of drinking, presence of spider naevi, and other signs of chronic liver disease.

  • Confirmed by: liver biopsy.

  • Finalized by the predictable outcome of management, e.g. stop alcohol. Treat withdrawal symptoms. High dose vitamin B, thiamine, and steroid in severe disease if no infection.

Dubin–Johnson syndrome (decreased excretion of conjugated bilirubin)

  • Suggested by: intermittent jaundice and associated pain in the right hypochondrium. No hepatomegaly.

  • Confirmed by: normal alkaline phosphatase, normal LFT. ↑urinary bilirubin. Pigment granules on liver biopsy.

Hypernatraemia

Initial investigations (other tests in bold below): repeat U&E, blood glucose, urine and simultaneous serum osmolality.

Main differential diagnoses and typical outline evidence, etc.

Hypertonic plasma with hypervolaemia (e.g. excess IV saline) or hypovolaemia (e.g. diabetic polyuria or diabetes insipidus)

  • Suggested by: little hypotonic fluid orally or intravenously and thirsty, high volume of urine with low sodium content (e.g. in diabetic polyuria).

  • Confirmed by: ↑plasma osmolality and urine osmolality higher (unless diabetes insipidus).

  • Finalized by the predictable outcome of management, e.g. replace fluids. Avoid rapid changes. Give water orally or IV in the form of 5% glucose. Monitor serum electrolytes regularly.

Diabetes inspidus with hypovolaemia

  • Suggested by: drinking excessively and passing large volumes of urine (polydipsia and polyuria). Thirsty.

  • Confirmed by: ↑plasma osmolality and ↓urine osmolality.

  • Finalized by the predictable outcome of management, e.g. replace fluids. Avoid rapid changes. The aim is to reduce sodium at a rate of <10mmol/L per day. Normal saline may be used initially if serum sodium was >170mmol/L. Desmopressin 100–200 micrograms tds orally IM might be used.

Primary aldosteronism due to adrenal hyperplasia or Conn’s sydrome with adrenal tumour

  • Suggested by: normal fluid intake, ↑BP. ↓serum potassium, metabolic alkalosis.

  • Confirmed by:plasma renin activity and ↑aldosterone levels. CT or MRI scan appearance.

  • Finalized by the predictable outcome of management, e.g. spironolactone, amiloride, or eplerenone for cases of bilateral adrenal hyperplasia. Adrenalectomy for aldosterone-producing adenoma.

Hyponatraemia

Also usually indicates hypotonicity—low plasma osmolality. Initial investigations (other tests in bold below): U&E, blood glucose, urine and simultaneous serum osmolality.

Main differential diagnoses and typical outline evidence, etc.

Hypotonic with hypovolaemia due to excess renal or non-renal loss (excessive diuretic therapy, history of renal tubular disease, diarrhoea, vomit, fistula, burns, small bowel obstruction, blood loss)

  • Suggested by:serum sodium and ↓osmolality. Loss of skin turgor, tachycardia, ↓BP. History of possible cause.

  • Confirmed by: response to removal or treating of cause.

  • Finalized by the predictable outcome of management, e.g. treat the cause. If symptomatic, saline water. In chronic conditions, fluid restriction. Avoid rapid changes, e.g. maximum change of sodium of 12–15mmol/L/d.

Hypotonic with normovolaemia, including pseudohyponatraemia (severe hypothyroidism or glucocorticoid deficiency). Symptoms of severe diabetes mellitus

  • Suggested by:serum sodium and ↓osmolality. Normal skin turgor, normal pulse and BP.

  • Confirmed by: response to treating cause, balancing fluid intake. Blood glucose of >20mmol/L in pseudohyponatraemia.

  • Finalized by the predictable outcome of management, e.g. treatment of the cause, e.g. hypothyroidism, Addison’s disease, or diabetes mellitus.

Hypotonic with hypervolaemia (water overload, cardiac failure, cirrhosis, renal failure, nephrotic syndrome, inappropriate antidiuretic hormone (ADH) secretion)

  • Suggested by:serum sodium and ↓osmolality. Oedema, basal lung crackles.

  • Confirmed by: response to treating cause, reducing fluid intake.

  • Finalized by the predictable outcome of management, e.g. treatment of the underlying condition.

Syndrome of inappropriate ADH secretion (malignancy, CNS disorders, chest infections, metabolic problems, drugs)

  • Suggested by: serum sodium usually <120mmol/L. Confusion, progressing to coma, mild oedema.

  • Confirmed by: urine osmolality > serum osmolality despite ↓serum osmolality (<270mmol/L). Urine sodium >20mmol/L.

  • Finalized by the predictable outcome of management, e.g. fluid restriction. Treat the underlying cause. If not possible, demeclocycline for long-term control.

Hyperkalaemia

Initial investigations (other tests in bold below): U&E, blood glucose.

Main differential diagnoses and typical outline evidence, etc.

Drug effect: potassium administration or other drug effect

  • Suggested by: potassium supplements, blood transfusion, ACE inhibitor, spironolactone, amiloride, triamterene, etc.

  • Confirmed by: normal potassium when drug reduced or stopped.

  • Finalized by the predictable outcome of management, e.g. stop suspect drug.

Metabolic acidosis, renal failure, diabetic ketoacidosis

  • Suggested by: usually obvious illness and severe metabolic disturbance, ↓pH and ↓plasma HCO3.

  • Confirmed by: response to treatment of metabolic disturbance.

  • Finalized by the predictable outcome of management, e.g. if K+ >6.5 and not falling, calcium gluconate IV, glucose + insulin, Calcium Resonium®. Treatment of cause.

Addison’s disease

  • Suggested by: fatigue, ↓BP, pigmented buccal mucosa, and palmar creases, ↓Na+, ↑K+.

  • Confirmed by: ↓random and 9a.m cortisol, ↑ACTH, and poor response to Synacthen® stimulation. Response to hydrocortisone IV and normal saline.

  • Finalized by the predictable outcome of management, e.g. hydrocortisone, e.g. 10–20mg mane and 5–10mg evening. Fludrocortisone, e.g. 50–100 micrograms daily.

Recent blood transfusion

  • Suggested by: history.

  • Confirmed by: fall of potassium after few hours.

  • Finalized by the predictable outcome of management, e.g. monitor potassium. If K+ >6.5 and not falling, calcium gluconate IV, glucose + insulin, Calcium Resonium®.

Spurious result due to haemolysis in specimen bottle

  • Suggested by: laboratory reporting haemolysis in specimen bottle.

  • Confirmed by: normal potassium when repeated with no delay in delivery to lab.

  • Finalized by the predictable outcome of management, e.g. repeat potassium.

Hypokalaemia

Initial investigations (other tests in bold below): U&E, plasma glucose.

Main differential diagnoses and typical outline evidence, etc.

Diuretic therapy

  • Suggested by: taking thiazide or loop diuretic (fondness of liquorice or Pernod drink).

  • Confirmed by: normal potassium after stopping diuretic.

  • Finalized by the predictable outcome of management, e.g. stop suspected cause ± oral potassium supplements.

β-agonist treatment

  • Suggested by: taking high doses of β-agonist, usually in nebulizer for acute asthmatic attack in hospital.

  • Confirmed by: normal potassium after stopping drug.

  • Finalized by the predictable outcome of management, e.g. stop β-agonist.

Vomiting e.g. pyloric stenosis

  • Suggested by: history of severe vomiting with poor fluid intake.

  • Confirmed by: normal potassium without subsequent need for replacement when cause of vomiting treated.

  • Finalized by the predictable outcome of management, e.g. depending on severity, replacement of fluids and electrolytes, correction of acid–base imbalance, and dealing with specific underlying causes.

Chronic diarrhoea, purgative abuse, intestinal fistula, villous adenoma of rectum

  • Suggested by: history of severe diarrhoea or mucous loss.

  • Confirmed by: normal potassium without need for further replacement when cause treated subsequently.

  • Finalized by the predictable outcome of management, e.g. oral potassium supplements if not dehydrated, potassium IV with IV fluid replacement, treatment of cause.

1° hyperaldos- teronism due to adrenal hyperplasia or Conn’s syndrome with adrenal tumour

  • Suggested by: normal fluid intake, ↑BP, ↓serum potassium.

  • Confirmed by:plasma renin activity and ↑aldosterone. CT or MRI scan appearance.

  • Finalized by the predictable outcome of management, e.g. spironolactone, amiloride, or eplerenone for bilateral adrenal hyperplasia. Adrenalectomy for ‘Conn’s syndrome’ (aldosterone-producing adenoma).

Renal tubular defect (in recovery phase from renal failure, pyelonephritis, associated myeloma, heavy metal poisoning, congenital renal tubular defects)

  • Suggested by: hypokalaemia and history of possible cause.

  • Confirmed by: test for renal concentrating ability.

  • Finalized by the predictable outcome of management, e.g. treatment of underlying cause. If serum K+ <3mmol/L, potassium PO or IV not exceeding 20mmol/L/h. Serum U&E and ECG monitoring during treatment.

Hypercalcaemia

Present when specimen taken without a venous cuff, and calcium result was corrected for albumin concentration. Initial investigations (other tests in bold below): U&E, calcium, alkaline phosphatase.

Main differential diagnoses and typical outline evidence, etc.

Severe hypercalcaemia

  • Confirmed by: calcium >3.5 mmol/L.

  • Finalized by the predictable outcome of management, e.g. saline infusion + furosemide to maintain fluid balance and prevent overload. Correct hypokalaemia and hypomagnesaemia. If calcium remains high, pamidronate disodium over 2–3d.

Thiazide diuretics

  • Suggested by: mild hypercalcaemia, drug history, normal phosphate and alkaline phosphatase.

  • Confirmed by: normal calcium when drug stopped.

  • Finalized by the predictable outcome of management, e.g. stop thiazide.

Bone metastases from breast, bronchus, kidney, thyroid, ovary, colon

  • Suggested by: normal phosphate and ↑alkaline phosphatase.

  • Confirmed by: 2°s on bone scan.

  • Finalized by the predictable outcome of management, e.g. pamidronate to lower calcium over 2–3d. Appropriate treatment of neoplastic process.

Thyrotoxicosis

  • Suggested by: weight loss with good appetite, tremor, palpitation and agitation, goitre, mild ↑calcium.

  • Confirmed by:T4 or ↑T3 and ↓↓TSH. Normal phosphate and alkaline phosphatase. Response to treatment of thyrotoxicosis.

  • Finalized by the predictable outcome of management, e.g. propranolol 40–80mg 8mg hourly to control symptoms (avoid in asthmatics). Carbimazole, e.g. 40mg reduced to 10 ± 5mg for 18mo according to test results. Written warning about agranulocytosis.

1° (or tertiary) hyperparathyroidism

  • Suggested by: fatigue, constipation, depression, impaired memory, renal colic and kidney stones, stomach ulcer, ↑BP, pancreatitis, low phosphate, and ↑alkaline phosphatase.

  • Confirmed by:plasma parathyroid levels with ↑calcium.

  • Finalized by the predictable outcome of management, e.g. correct very high calcium. Surgical removal of parathyroid adenoma.

Myeloma

  • Suggested by: low back pain, polyuria and polydypsia, spinal fracture, normal serum phosphate and alkaline phosphatase.

  • Confirmed by: paraprotein with immunoparesis on electrophoresis, hypercalcaemia, ↓Hb, Bence–Jones protein in urine, spinal X-ray showing fracture with an osteolytic lesion.

  • Finalized by the predictable outcome of management, e.g. correct very high calcium. Analgesics for bone pain. Oral bisphosphonate to keep calcium down. Local radiotherapy in progressive disease. Prompt treatment of infections. Transfusions for anaemia. Chemotherapy using melphalan or cyclophosphamide in conjunction with steroids. More aggressive treatment for fitter patients.

Sarcoidosis

  • Suggested by: cough, weight loss, night sweats, shortness of breath, erythema nodosum, ↑phosphate and alkaline phosphatase. Bilateral hilar shadows on CXR.

  • Confirmed by: lung function tests, Kveim test, biopsy from a granuloma, ↑vitamin D levels and ↑ACE levels.

  • Finalized by the predictable outcome of management, e.g. correct very high calcium. Long-term prednisolone to control calcium. If severe cases, methylprednisolone IV or immunosuppression, e.g. methotrexate and cyclophosphamide.

Vitamin D excess

  • Suggested by: drug history and ↑phosphate.

  • Confirmed by: normal calcium when drug stopped.

  • Finalized by the predictable outcome of management, e.g. stop suspected drug.

Ectopic parathyroid hormone due to lung cancer usually

  • Suggested by: ↓phosphate and ↑alkaline phosphatase.

  • Confirmed by: ↑plasma parathyroid levels with high calcium presence of underlying neoplasm.

  • Finalized by the predictable outcome of management, e.g. correct very high calcium. Surgical resection of cancer in appropriate cases.

Hypocalcaemia

Present when specimen taken without a venous cuff and corrected for albumin concentration. Investigations in bold below:

Main differential diagnoses and typical outline evidence, etc.

Vitamin D deficiency—due to dietary deficiency or 1,25 (OH)2D abnormality

  • Suggested by: diet history, ↓phosphate, and ↑alkaline phosphatase.

  • Confirmed by:1, 25(OH)2 vitamin D, normal calcium after adequate treatment with vitamin D.

  • Finalized by the predictable outcome of management, e.g. calcium + vitamin D, 1–2 tablets daily.

Hypoparathyroidism (transient or permanent after thyroid surgery, autoimmune disease, radiations)

  • Suggested by: neck surgery, ↑phosphate.

  • Confirmed by:parathyroid hormone or normal in presence of ↓calcium.

  • Finalized by the predictable outcome of management, e.g. alfacalcidol with careful monitoring of calcium levels.

Chronic renal failure

  • Suggested by:phosphate, ↑creatinine, ↑alkaline phosphatase, ↓Hb.

  • Confirmed by: improvement with control of renal failure and phosphate levels.

  • Finalized by the predictable outcome of management, e.g. stop nephrotoxic drugs, relieve obstruction; prompt treatment of infections, treat ↑BP with ACE inhibitors or angiotensin receptor blockers (ARBs); hyperlipidaemia with statins. Restriction of fluids and furosemide for oedema. Erythropoietin for severe anaemia. Alfacalcidol for renal bone disease. Dialysis.

Pseudohypo-parathyroidism

  • Suggested by: short stature, obesity, round face, short metacarpals, ↑phosphate.

  • Confirmed by:plasma parathyroid levels with ↓or normal calcium.

  • Finalized by the predictable outcome of management, e.g. alfacalcidol with careful monitoring of calcium levels.

Pancreatitis

  • Suggested by: abdominal pain and tenderness, ↓phosphate, normal alkaline phosphatase.

  • Confirmed by: ↑↑serum amylase and US scan of abdomen.

  • Finalized by the predictable outcome of management, e.g. nil by mouth, nasogastric (NG) tube, saline infusion to correct dehydration, strong analgesics (e.g. pethidine IM), regular monitoring.

Fluid overload

  • Suggested by: history and ↓phosphate and normal alkaline phosphatase.

  • Confirmed by: normalization with correction of fluid balance.

  • Finalized by the predictable outcome of management, e.g. reduced fluid intake to allow correction use of diuretics.

Rhabdomyolysis

  • Suggested by: severe muscle pains, weakness, dark or cola-coloured urine, racing heart, history of extreme muscle activity, ↑phosphate.

  • Confirmed by: ↑↑CPK,creatinine, ↑urinary myoglobin, CT and MRI scans of the muscles and muscle biopsy.

  • Finalized by the predictable outcome of management, e.g. correct electrolyte disturbances, e.g. hyperkalaemia. Rehydration to maintain a urine output of 300mL/h until myoglobinuria disappears. Sodium bicarbonate IV ± dialysis.

Raised alkaline phosphatase

Investigations in bold below.

Main differential diagnoses and typical outline evidence, etc.

Paget’s disease

  • Suggested by: deformity of skull or tibia typically, ↑alkaline phosphatase.

  • Confirmed by: bone deformity, especially on skull and tibia X-ray and ↑urinary hydroxyproline.

  • Finalized by the predictable outcome of management, e.g. analgesics for bone pain. If not enough, try alendronic acid.

Vitamin D deficiency due to dietary deficiency

  • Suggested by: diet history, ↓phosphate and ↑alkaline phosphatase.

  • Confirmed by:1,25 (OH)2 vitamin D level, and normal calcium after oral vitamin D and calcium supplement.

  • Finalized by the predictable outcome of management, e.g. dietary treatment and calcium supplement with vitamin D.

Bone metastases from breast, bronchus, kidney, thyroid, ovary, colon

  • Suggested by: normal phosphate, ↑calcium and ↑alkaline phosphatase.

  • Confirmed by: 2°s on bone scan.

  • Finalized by the predictable outcome of management, e.g. appropriate management of malignancy.

1° or tertiary hyperparathyroidism

  • Suggested by: ↓phosphate and ↑alkaline phosphatase after years of 2° hyperparathyroidism.

  • Confirmed by:plasma parathyroid levels with ↑calcium.

  • Finalized by the predictable outcome of management, e.g. correct very high calcium. Surgical removal of parathyroid adenoma.

Cholestasis

  • Suggested by: jaundice with pale stools and dark urine. Bilirubin (i.e. conjugated and thus soluble) in urine.

  • Confirmed by:urine and serum bilirubin but NO ↑urobilinogen in urine. ↑↑alkaline phosphatase, otherwise slightly abnormal LFT.

  • Finalized by the predictable outcome of management, e.g. colestyramine for pruritus. Treat infections. Relieve obstruction by stenting or surgery.

Raised serum urea and creatinine

Investigations in bold below.

Main differential diagnoses and typical outline evidence, etc.

High protein load due to gastrointestinal (GI) bleed, catabolism, sepsis, etc.

  • Suggested by:blood urea and normal creatinine or urea/creatinine ratio strongly in favour of urea.

  • Confirmed by: recovery when catabolism or GI bleeding stops.

  • Finalized by the predictable outcome of management, e.g. IV line—IV fluids and then blood transfusion, regular monitoring. Reduce acidity, e.g. with PPI.

Pre-renal failure due to hypovolaemia (due to low fluid intake, or high fluid loss of any cause)

  • Suggested by: ↑blood urea and ↑creatinine. History of fluid imbalance with fluid loss exceeding intake. Urea/creatinine ratio in favour of urea.

  • Confirmed by: improvement (↓creatinine) with restoration of fluid volume.

  • Finalized by the predictable outcome of management, e.g. correction of fluid and electrolyte imbalance. Antibiotics for infection. Stop nephrotoxic drugs. Rehydration orally, via NG tube or IV infusion. Monitor urine output ± central venous pressure (CVP) monitoring.

Chronic renal failure due to pyelonephrititis, glomerulonephrititis, interstitial nephritis, diabetes mellitus, renovascular disease, analgesic nephropathy, hypertension, etc.

  • Suggested by:blood urea and ↑creatinine and not rising rapidly over days. dcalcium, iphosphate, ↓Hb, small renal size on US scan.

  • Confirmed by: renal biopsy appearance.

  • Finalized by the predictable outcome of management, e.g. treat infections, stop nephrotoxic drugs, relieve obstruction: treat ↑BP with ACE inhibitors or ARBs, and hyperlipidaemia with statins. Restriction of fluids and furosemide for oedema. Calcium carbonate for hyperphosphatemia. Erythropoietin for severe anaemia. Alfacalcidol for renal bone disease. Dialysis.

Acute tubular necrosis, severe hypotension, nephrotoxins (NSAIDs, aminoglycosides, amphotericin B, etc.)

  • Suggested by: ↑blood urea and ↑creatinine and rising rapidly over days. Hb normal. Recent acute illness with hypotension and oliguria (fall in urine output <1mL/kg/h). US scan: normal kidney size and no obstructive uropathy.

  • Confirmed by: no improvement when normovolaemic and renal biopsy.

  • Finalized by the predictable outcome of management, e.g. eliminate any causes. Maintain fluid balance with careful monitoring of output and input + insensible loss (± CVP). Temporary dialysis.

Obstructive renal failure

  • Suggested by: ↑blood urea and ↑creatinine and rising. Hb normal. ↓urine output.

  • Confirmed by: US scan showing dilatation of renal calyces or ureters.

  • Finalized by the predictable outcome of management, e.g. catheterization for acute retention of urine. Ureteric stenting or nephrostomy.

Low haemoglobin

Investigations in bold below.

Main differential diagnoses and typical outline evidence, etc.

Microcytic anaemia (see Laboratory test results Microcytic anaemia, p.[link])

  • Suggested by: history of blood loss or familial microcytic anaemias (especially in Mediterranean origin).

  • Confirmed by: ↓Hb and ↓MCV.

Macrocytic anaemia (see Laboratory test results Macrocytic anaemia, p.[link])

  • Suggested by: sore tongue, diarrhoea. Family history of pernicious anaemia (PA), medication or alcohol.

  • Confirmed by: ↓Hb and ↑MCV.

Normocytic anaemia (see Laboratory test results Normocytic anaemia, p.[link])

  • Suggested by: history of chronic intercurrent illness, e.g. pancytopaenia, chronic renal failure.

  • Confirmed by:↓Hb and MCV normal.

Microcytic anaemia

Usually accompanied by low mean corpuscular Hb concentration. Investigations in bold below.

Main differential diagnoses and typical outline evidence, etc.

Iron deficiency anaemia

  • Suggested by: history of blood loss (e.g. history of heavy periods, passing blood rectally), or poor diet.

  • Confirmed by:serum iron, ↓ferritin, and ↑total iron binding capacity.

  • Finalized by the predictable outcome of management, e.g. treat the cause. Iron replacement therapy.

Thalassaemia: α, β, intermedia, and variants

  • Suggested by: persistent mild anaemia, failure to thrive, family history, Mediterranean origin. Hepatosplenomegaly, ↓↓MCV for degree of anaemia.

  • Confirmed by: blood film: target and nucleated cells. Hb electrophoresis shows ↑HbF or ↑HbA2, ↑serum iron and iron binding capacity.

  • Finalized by the predictable outcome of management, e.g. regular blood transfusions to keep Hb above 9g/dL. Iron-chelating agents, e.g. desferrioxamine infusion 8–10h per day. Splenectomy when increased frequency of transfusions; treat complications such as 2° diabetes mellitus. Bone marrow transplantation.

Sideroblastic anaemia rarely congenital or acquired due to alcohol lead poisoning, etc.

  • Suggested by: history of chronic intercurrent illness, e.g. chronic renal failure.

  • Confirmed by:serum iron, ↑ferritin, and total iron binding capacity normal.

  • Finalized by the predictable outcome of management, e.g. elimination of the cause. Pyridoxine. Blood transfusion in severe anaemia.

Macrocytic anaemia

Investigations in bold below.

B12 deficiency: pernicious anaemia, intestinal malabsorption

  • Suggested by: associated autoimmune disease, e.g. primary hypothyroidism, vitiligo, etc. ↓Hb, ↓WCC, and ↓platelets.

  • Confirmed by:serum B12 (± ↓folate too due to anorexia) + pernicious anaemia diagnosed in absence of general malabsorption.

  • Finalized by the predictable outcome of management, e.g. treat any malabsorption. In pernicious anaemia, hydroxocobalamin 1mg IM every 3–4mo after loading doses (e.g. 6x 1mg IM over 2wk).

Folate deficiency

  • Suggested by: poor diet, pregnancy, lactation, general malabsorption.

  • Confirmed by:folate but serum B12 normal.

  • Finalized by the predictable outcome of management, e.g. eliminate cause + folic acid, e.g. 5mg daily for 4mo. Correct any B12 deficiency before starting folic acid.

Antifolate drugs

  • Suggested by: phenytoin typically, barbiturates and similar, methotrexate and similar.

  • Confirmed by: response to high dose folic acid treatment or stopping drug (serum folate may be normal).

  • Finalized by the predictable outcome of management, e.g. stopping antifolate drug.

Alcohol abuse

  • Suggested by: history of abuse and poor diet.

  • Confirmed by: response to abstinence (serum folate may be normal).

  • Finalized by the predictable outcome of management, e.g. stop alcohol; treat withdrawal symptoms—high dose vitamin B.

Hepatitis and liver disease

  • Suggested by: abnormal liver enzymes.

  • Confirmed by: normal (or ↑) serum B12 and poor response to folic acid.

  • Finalized by the predictable outcome of management, e.g. conservative treatment. Advise no alcohol. If chronic, trial of interferon alfa or antiviral treatment.

Hypothyroidism

  • Suggested by:FT4 and ↑TSH.

  • Confirmed by: normal B12 and response to treatment with thyroxine.

  • Finalized by the predictable outcome of management, e.g. levothyroxine replacement, e.g. 25–50 micrograms per day and adjust, based on TSH.

Haemolysis

  • Suggested by: urobilinogen in urine.

  • Confirmed by: ↑reticulocytes on blood film, dhaptoglobin.

  • Finalized by the predictable outcome of management, e.g. avoid precipitating factors. Blood transfusion if anaemia is severe. Treatment depends on cause, e.g. steroid and immunosuppressants in autoimmune haemolytic anaemia.

Myelodysplasia

  • Suggested by: hepato- or splenomegaly.

  • Confirmed by: bone marrow examination, normal B12 and folate, pancytopenia in later stages.

  • Finalized by the predictable outcome of management, e.g. intensive combination or single-agent chemotherapy. Frequent transfusion of RBC and platelets. Stem cell transfusions if young patient.

Normocytic anaemia

Investigations in bold below.

Anaemia of chronic disease (e.g. rheumatoid arthritis, hypogonadism, etc.)

  • Suggested by: associated chronic disease.

  • Confirmed by: iron, B12 normal. ↓folate or normal. Normal or ↑ferritin from inflammation.

  • Finalized by the predictable outcome of management, e.g. treatment of underlying cause.

Chronic renal failure

  • Suggested by: high creatinine and urea.

  • Confirmed by: response to erythropoietin treatment only.

  • Finalized by the predictable outcome of management, e.g. erythropoietin.

‘Anaemia of pregnancy’

  • Suggested by: pregnant state.

  • Confirmed by: persistence despite folic acid and iron supplements, resolution after birth.

  • Finalized by the predictable outcome of management, e.g. explanation, reassurance.

Hypothyroidism

  • Suggested by:FT4 and ↑TSH.

  • Confirmed by: normal B12 and response to treatment with thyroxine.

  • Finalized by the predictable outcome of management, e.g. thyroxine replacement, e.g. 25–50 micrograms levothyroxine per day and adjust based on TSH.

Haemolysis (e.g. due to reticulosis)

  • Suggested by: urobilinogen in urine.

  • Confirmed by: ↑reticulocytes on blood film.

  • Finalized by the predictable outcome of management, e.g. avoid precipitating factors. Blood transfusion if severe haemolysis. Treat infection depending on the cause, e.g. steroids, immunosuppressants, splenectomy, anticoagulation, and stem cell transplantation.

Bone marrow failure

  • Suggested by: pancytopaenia.

  • Confirmed by: bone marrow examination.

  • Finalized by the predictable outcome of management, e.g. blood cell transfusion to support blood count. Immunosuppression (e.g. ciclosporin) may be effective but not curative. Allogeneic marrow transplantation for younger patients who are severely affected.

Very high ESR, CRP, or plasma viscosity

An ESR or CRP or plasma viscosity which is just above normal is non-specific as it is associated with any cause of inflammation, including infection—but an ESR near 100 or above is a good lead. Initial investigations (other tests in bold below): FBC.

Severe bacterial infection, e.g. osteomyelitis empyema, peritonitis

  • Suggested by: high fever, ↑leucocytes.

  • Confirmed by: positive bacterial culture from blood and/or site of infection and response to antibiotics and/or surgical drainage.

  • Finalized by the predictable outcome of management, e.g. antibiotics according to culture and sensitivity. Clearance of pus.

Giant cell arteritis

  • Suggested by: localized headache, especially over temple, late loss of vision ± muscle pain and stiffness in shoulder area.

  • Confirmed by: vessel wall inflammation on biopsy.

  • Finalized by the predictable outcome of management, e.g. prednisolone 40–60mg per day and reduce the dose gradually after a week. Bisphosphonates as a prophylaxis for osteoporosis.

Bacterial endocarditis

  • Suggested by: fever, changing heart murmurs, nail splinter haemorrhages.

  • Confirmed by: bacterial growth from several blood cultures, echocardiogram may show vegetations.

  • Finalized by the predictable outcome of management, e.g. aggressive antibiotic treatment, e.g. benzylpenicillin 1.2g/4h IV + gentamicin 1mg/kg/8h IV for 4wk. Addition of flucloxacillin 2g qds IV in acute causes. Surgical treatment, e.g. if unstable infected prosthetic valve.

Myeloma

  • Suggested by: bone pain or fractures. Bence–Jones protein in urine and monoclonal protein band on electrophoresis.

  • Confirmed by: myeloma cells on bone marrow examination.

  • Finalized by the predictable outcome of management, e.g. treat severe hypercalcaemia (see Laboratory test results Hypercalcaemia, p.[link]). Analgesics for bone pain. Bisphosphonates to reduce fracture rates. Local radiotherapy in rapidly progressive disease. Prompt treatment of infection. Transfusions for anaemia, chemotherapy using melphalan or cyclophosphamide in conjunction with steroids. More aggressive treatment for fitter patients.

Prostatic carcinoma

  • Suggested by: bone pain, few urinary symptoms.

  • Confirmed by: sclerotic changes in pelvic bones X-ray and ↑prostatic-specific antigen (PSA) and prostatic biopsy.

  • Finalized by the predictable outcome of management, e.g. for localized disease, radical prostatectomy or radiotherapy with hormonal therapy. For metastatic disease, hormonal therapy.