Differentials

Common

Central diabetes insipidus

History

polyuria; history of trauma, neoplasm, or neurosurgery; history of phenytoin and/or ethanol ingestion

Exam

may have signs of head trauma, pituitary surgery, and/or severe hypernatraemia (hyperthermia, delirium, seizures, and coma)

1st investigation
  • serum sodium:

    may be elevated

  • serum osmolality:

    normal or elevated

  • urine osmolality:

    <300 mmol/kg (300 mOsm/kg)

    More
  • 24 hour urine collection:

    >50 ml/kg/24 hours

Other investigations
  • water deprivation test:

    urine osmolality < serum osmolality following dehydration

    More
  • AVP (desmopressin) stimulation test:

    >50% increase in urine osmolality following desmopressin

    More
  • MRI brain:

    may show pituitary or parapituitary mass, congenital abnormalities, abnormal pituitary stalk; evidence of trauma or previous surgery

    More

Nephrogenic diabetes insipidus

History

family history of nephrogenic diabetes insipidus; history of underlying kidney disorder (e.g., sickle cell disease, polycystic disease, and obstructive uropathy); lithium, colchicine, gentamicin, rifampin (rifampicin), or propoxyphene (dextropropoxyphene) use; patient may be pregnant in second or third trimester[14]

Exam

signs of volume depletion may be present: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, and hypotension

1st investigation
  • serum sodium:

    may be elevated

    More
  • serum osmolality:

    normal or elevated

  • urine osmolality:

    <300 mmol/kg (300 mOsm/kg)

    More
  • 24 hour urine collection:

    >50 ml/kg/24 hours

Other investigations
  • water deprivation test:

    urine osmolality < serum osmolality following dehydration

    More
  • AVP (desmopressin) stimulation test:

    no or <50% increase in urine osmolality following desmopressin

    More

Hyperosmolar hyperglycaemic state (HHS)

History

older patient with known type 2 diabetes mellitus, weight loss, lethargy, visual disturbances, altered mental status common

Exam

signs of severe volume depletion (dry mucous membranes, poor skin turgor, drowsiness), blurred vision; stupor/coma[12]

1st investigation
  • plasma glucose:

    >33.3 mmol/L (600 mg/dL)

    More
  • serum osmolality:

    >320 mmol/kg (320 mOsm/kg)

    More
Other investigations
  • serum urea and creatinine:

    elevated

    More
  • serum potassium:

    usually elevated; decreased in severe cases

    More

Post-obstructive diuresis

History

most commonly after relief of bilateral obstruction or obstruction of a solitary kidney, especially after relief of urinary retention (e.g., as may occur with benign prostatic hypertrophy, prostatitis, prostate cancer, nephrolithiasis, bladder tumours, urethral strictures)

Exam

signs of volume depletion may be present: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, hypotension, decreased urine output

1st investigation
  • none:

    diagnosis is clinical

Other investigations

    Severe diarrhoea

    History

    passage of frequent loose stools, may be colicky abdominal pain, dizziness, weight loss, lethargy, thirst; hx of tropical sprue, pancreatitis, lactose intolerance, or bowel surgery may be present (suggesting carbohydrate malabsorption); may be history of contact with infected people, food, or fluids suggesting viral gastroenteritis

    Exam

    abdominal discomfort; signs of volume depletion: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, hypotension, decreased urine output

    1st investigation
    • stool culture:

      may be positive for E coli, Campylobacter, Shigella, Salmonella or Yersinia

      More
    • CBC:

      may show increased haematocrit, anaemia or leukocytosis

      More
    Other investigations
    • faecal leukocytes:

      positive or negative

      More
    • faecal pH:

      variable

      More
    • faecal reducing substance/sugar:

      positive or negative

      More
    • serum potassium:

      hypokalaemia may be present

    • urine osmolality:

      hypertonic urine

      More

    Vomiting

    History

    abdominal pain; may be a history of binge eating and vomiting consistent with a diagnosis of bulimia

    Exam

    abdominal discomfort; signs of volume depletion may be present: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, and hypotension

    1st investigation
    • basic metabolic panel:

      may show decreased potassium and chloride

      More
    Other investigations
    • urine osmolality:

      hypertonic urine

      More
    • ABG:

      metabolic alkalosis may occur

      More

    Limited access to water

    History

    may affect infants, disabled people, people with impaired mental status, postoperative patients, intubated patients

    Exam

    signs of volume depletion: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, hypotension, decreased urine output

    1st investigation
    • none:

      diagnosis is clinical but supportive tests necessary to exclude associated electrolyte abnormalities

    Other investigations
    • metabolic panel:

      may show hypokalaemia and/or renal impairment

    Uncommon

    Primary hypodipsia

    History

    lack of thirst, history of hypothalamic brain tumour, vascular occlusion in the brain, or granulomatous disease (e.g., sarcoidosis)

    Exam

    signs of volume depletion: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, hypotension, decreased urine output; signs of underlying abnormality may be present

    1st investigation
    • serum sodium:

      elevated

      More
    Other investigations
    • serum urea and creatinine:

      elevated

    • serum osmolality:

      markedly elevated

      More
    • urine osmolality:

      markedly elevated

    Cushing syndrome

    History

    weight gain, skin changes (purple stretch marks, easily bruised, other signs of skin thinning); difficulty climbing stairs, getting out of a low chair, and raising arms; menstrual irregularities, amenorrhoea, infertility, and decreased libido in women; men may be impotent or have decreased libido; depression, cognitive dysfunction, and emotional lability; poor wound healing; headaches; polyuria and nocturia; visual problems, galactorrhoea

    Exam

    moon face, facial plethora, supraclavicular and/or dorsicocervical fat pads, truncal obesity, purple striae, proximal muscle weakness, hirsutism, growth retardation (children), hypertension; signs of hypervolaemia: irritating cough, dyspnoea, jugular vein distention, and crepitations on auscultation

    1st investigation
    • 24-hour urinary free cortisol:

      >50 micrograms/24 hour

      More
    • low-dose (or overnight) dexamethasone suppression test:

      unsuppressed level at 8 a.m.

      More
    • late night serum or salivary cortisol levels:

      abnormally high levels

      More
    Other investigations
    • serum glucose:

      may be elevated

      More

    Primary aldosteronism

    History

    family history of primary aldosteronism or early onset hypertension and/or stroke; age ≥20 years; nocturia, polyuria, muscle weakness, paraesthesias, muscle cramps, palpitations, lethargy, mood disturbance (irritability, anxiety, depression), difficulty concentrating

    Exam

    hypertension, proximal muscle weakness may be present; signs of hypervolaemia: irritating cough, dyspnoea, jugular vein distention, and crepitations on auscultation

    1st investigation
    • serum sodium:

      normal or elevated

      More
    • serum potassium:

      normal or decreased

      More
    • plasma aldosterone concentration (PAC):

      high

      More
    • plasma renin activity (PRA):

      low (usually <1 nanogram/mL/hour)

      More
    • aldosterone-to-renin ratio (ARR):

      increased: ratio is alternatively >55 for aldosterone in picomol/L and direct active renin concentration in mU/L; ratio >20 for plasma aldosterone in nanograms/100 decilitre and plasma renin activity in nanograms/mL/hour

      More
    Other investigations
    • aldosterone suppression test:

      urine aldosterone excretion >12 microgram/24 hours during adequate sodium loading (24-hour urine sodium excretion >200 mEq)

      More
    • CT or MRI of adrenal glands:

      may be normal or may reveal typical hypodense unilateral macroadenoma (>1 cm) in a young patient

      More

    Laxative and bowel cleansing agent use

    History

    laxative use such as lactulose, glycerin, or sorbitol (may be from charcoal-sorbitol in drug-overdose treatment, sorbitol as a sugar replacement in diet foods/drinks and diet aids); loose stools

    Exam

    abdominal distension and tenderness

    1st investigation
    • none:

      diagnosis is clinical but supportive tests necessary to exclude associated electrolyte abnormalities

    Other investigations
    • serum potassium:

      hypokalaemia may be present

    • urine osmolality:

      hypertonic urine

      More

    Enteric fistulae

    History

    history of Crohn's disease; recurrent urinary tract infections and pneumaturia (enterovesical fistulae), passage of gas or faeces through the vagina (enterovaginal fistulae), bowel contents draining to the surface of the skin (enterocutaneous fistulae), feculent vomiting (cologastric fistulae)

    Exam

    presence of bubbles in the urine (pneumaturia); passage of faeces through the vagina; bowel contents draining to surface of skin; feculent vomiting

    1st investigation
    • none:

      diagnosis is clinical

    Other investigations

      Diuretics

      History

      loop diuretic (e.g., furosemide and torsemide) or osmotic diuretic (e.g., intravenous mannitol) use, especially in older or intubated patients; may have hypertension or pulmonary, peripheral, or cerebral oedema

      Exam

      signs of volume depletion may be present: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, hypotension, decreased urine output

      1st investigation
      • none:

        diagnosis is clinical but additional tests may be indicated to exclude associated abnormalities or support diagnosis

      Other investigations
      • serum potassium:

        hypokalaemia may be present

      • urine osmolality:

        isotonic urine

        More

      Heat exposure

      History

      exposure to high environmental temperatures

      Exam

      evidence of profuse sweating; signs of volume depletion may be present: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, and hypotension

      1st investigation
      • none:

        diagnosis is clinical but supportive tests necessary to exclude associated electrolyte abnormalities

      Other investigations
      • serum potassium:

        hypokalaemia may be present

      • urine osmolality:

        hypertonic urine

        More

      Exercise

      History

      recent exercise

      Exam

      evidence of profuse sweating

      1st investigation
      • none:

        diagnosis is clinical but supportive tests necessary to exclude associated electrolyte abnormalities

      Other investigations
      • basic metabolic panel:

        hypokalaemia may be present

      • urine osmolality:

        hypertonic urine

        More

      Fever

      History

      febrile illness

      Exam

      temperature ≥38°C (≥100.4°F); additional signs depend on related illness

      1st investigation
      • none:

        diagnosis is clinical and further tests usually determined by underlying illness

      Other investigations

        Severe burns

        History

        history of burns

        Exam

        extensive skin loss and ulcerations

        1st investigation
        • none:

          diagnosis is clinical but supportive tests necessary to exclude associated abnormalities

        Other investigations
        • FBC:

          low Hct, neutropenia, thrombocytopenia

          More
        • metabolic panel:

          high levels of urea, creatinine, glucose; hypokalaemia

        • urine osmolality:

          hypertonic urine

          More

        Inadequate breastfeeding of infants

        History

        history of inadequate breastfeeding without supplementation in an infant

        Exam

        signs of volume depletion: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, and hypotension; signs of severe hypernatraemia may be present: hyperthermia, delirium, seizures, and coma

        1st investigation
        • none:

          diagnosis is clinical but additional tests may be indicated to exclude associated abnormalities

        Other investigations
        • serum potassium:

          hypokalaemia may be present

        • ABG:

          metabolic acidosis

        Salt ingestion

        History

        history of replacing sugar with salt in infant formula (accidental or intentional), history of ingesting highly concentrated emetic agent or gargle (e.g., Epsom salts)

        Exam

        signs of hypervolaemia: peripheral oedema, hypertension, irritating cough, dyspnoea, jugular vein distention, and crepitations on auscultation

        1st investigation
        • serum sodium:

          elevated, may be >170 mmol/L (170 mEq/L)

          More
        Other investigations

          High-protein diet

          History

          history of high-protein diet or high-protein tube feeds

          Exam

          signs of volume depletion may be present: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, hypotension, decreased urine output

          1st investigation
          • none:

            diagnosis is clinical

          Other investigations

            Use of intravenous sodium chloride

            History

            current hospital admission (especially in the intensive care unit); more commonly history of hypertonic sodium chloride administration (e.g., for irrigation of hydatid cysts), isotonic sodium chloride administration in a patient who has diabetic ketoacidosis (DKA) with an osmotic diuresis may also result in hypernatraemia[18]

            Exam

            signs of hypervolaemia may be present: weight gain, hypertension, irritating cough, dyspnoea, jugular vein distention, and crepitations on auscultation

            1st investigation
            • serum sodium:

              elevated, may be >170 mmol/L (170 mEq/L)

              More
            Other investigations

              Use of intravenous sodium bicarbonate

              History

              current hospital admission (especially in the intensive care unit), history of severe metabolic acidosis

              Exam

              signs of hypervolaemia may be present: weight gain, hypertension, irritating cough, dyspnoea, jugular vein distention, and crepitations on auscultation

              1st investigation
              • serum sodium:

                elevated, may be >170 mmol/L (170 mEq/L)

                More
              Other investigations

                Enteral feeding

                History

                high-protein diet, limited access to water

                Exam

                signs of volume depletion may be present: altered mental status, poor skin turgor, dry mucous membranes, sunken eyes, irritability, hypotension, decreased urine output

                1st investigation
                • none:

                  diagnosis is clinical

                Other investigations

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