Differentials

Common

Primary hyperparathyroidism

History

usually asymptomatic but may have a history of renal stones, long bone pain, constipation, fatigue, abnormal psyche, slow thought, depression

Exam

long bone tenderness, ectopic corneal calcification, palpable neck mass (rare)

1st investigation
  • serum calcium:

    elevated

  • parathyroid hormone:

    elevated or inappropriately normal despite high calcium

    More
  • 24-hour urine calcium:

    elevated

Other investigations
  • bone densitometry:

    T-score <-2.5

Malignancy

History

history of primary malignancy

Exam

non-specific findings

1st investigation
  • serum calcium:

    elevated

  • parathyroid hormone:

    usually low

    More
Other investigations
  • parathyroid hormone-related protein (PTHrP):

    may be elevated

    More

Multiple myeloma

History

weight loss, bone or back pain, family history of myeloma, infections, renal failure, history of monoclonal gammopathy of unknown significance

Exam

non-specific findings

1st investigation
  • serum calcium:

    elevated

  • parathyroid hormone:

    low

  • serum protein electrophoresis:

    monoclonal gammopathy

Other investigations
  • ionised calcium:

    normal or elevated

    More
  • skeletal survey:

    osteopenia, osteolytic lesions, pathological fractures

  • MALDI-TOF (matrix-assisted laser desorption/ionisation-time of flight mass spectrometry):

    monoclonal gammopathy

    More

Uncommon

Familial hypocalciuric hypercalcaemia

History

asymptomatic, family history usually lacking

Exam

non-specific findings

1st investigation
  • serum calcium:

    elevated

  • parathyroid hormone:

    slightly low, normal, or slightly elevated[24][25]

Other investigations
  • urine calcium:

    low

Vitamin D intoxication

History

history of vitamin supplementation

Exam

non-specific findings

1st investigation
  • serum calcium:

    elevated

  • parathyroid hormone:

    normal or suppressed

Other investigations
  • plasma vitamin D (1,25 OH colecalciferol):

    elevated

Lithium

History

history of lithium use

Exam

non-specific findings

1st investigation
  • serum calcium:

    slightly elevated

    More
Other investigations

    Thiazide diuretics

    History

    history of thiazide diuretic use

    Exam

    non-specific findings

    1st investigation
    • serum calcium:

      slightly elevated

      More
    Other investigations

      Chronic renal failure and secondary hyperparathyroidism

      History

      chronic renal failure and dialysis with bone pain

      Exam

      bone tenderness

      1st investigation
      • serum calcium:

        variable

        More
      • parathyroid hormone:

        elevated

        More
      • serum creatinine:

        elevated

      Other investigations
      • urinalysis:

        haematuria and/or proteinuria

      • kidney ultrasound:

        small kidney size; presence of obstruction/hydronephrosis; kidney stones

      Hyperthyroidism

      History

      anxiety, weight loss, normal or increased appetite, sleep disturbance, palpitations, heat intolerance, sweating, eye pain, bone pain

      Exam

      diffuse nontender thyromegaly, tachycardia, fever, exophthalmos, lid lag, hypertension, thinning hair, bone tenderness

      1st investigation
      • serum calcium:

        elevated

      • parathyroid hormone:

        normal or suppressed

      • thyroid stimulating hormone:

        low

        More
      Other investigations

        Hypervitaminosis A

        History

        history of excess vitamin A intake (usually supplementation), bone pain

        Exam

        bone tenderness, mucous membrane dryness (chronic toxicity)

        1st investigation
        • serum calcium:

          elevated

        • parathyroid hormone:

          normal or suppressed

        Other investigations
        • vitamin A:

          elevated

        Milk-alkali syndrome

        History

        excess dietary milk or alkali (e.g., because of dyspepsia), excess calcium supplementation (e.g., in postmenopausal women), bone pain

        Exam

        non-specific findings

        1st investigation
        • serum calcium:

          elevated

        • parathyroid hormone:

          normal or suppressed

        Other investigations

          Sarcoidosis

          History

          age 20-40 years, cough, dyspnoea, chronic fatigue, arthralgia, wheezing, photophobia, painful red eye, blurred vision; may be asymptomatic; family history of sarcoidosis

          Exam

          rhonchi, lymphadenopathy, erythema nodosum, lupus pernio, conjunctival nodules, facial palsy

          1st investigation
          • serum calcium:

            elevated

          • parathyroid hormone:

            normal or suppressed

          Other investigations
          • chest x-ray:

            hilar and/or paratracheal adenopathy with upper lobe predominant, bilateral infiltrates

            More

          Prolonged immobilisation

          History

          history of prolonged immobilisation in adolescent/young adult due to injury/neurological condition

          Exam

          non-specific findings

          1st investigation
          • serum calcium:

            elevated

          • parathyroid hormone:

            nondetectable

          Other investigations

            Paget's disease

            History

            bone pain, affects pelvis in 75% cases, family history of Paget's disease, may be asymptomatic

            Exam

            bone tenderness, bone deformities, limping, increased local temperature, hearing loss

            1st investigation
            • calcium:

              elevated

            • parathyroid hormone:

              nondetectable

            • alkaline phosphatase:

              markedly elevated[26]

            • x-ray:

              lytic changes in early stage; sclerotic picture predominates over osteolytic in later stage

            Other investigations

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