Differentials
Common
Iatrogenic postsurgical hypoparathyroidism
History
history of parathyroid surgery or thyroid surgery with inadvertent removal of or trauma to the parathyroid glands
Exam
surgical scar on the neck
1st investigation
Other investigations
Vitamin D deficiency
History
lack of or avoidance of sunshine exposure; nutritional deficiency (patient not consuming dairy products); aches and pains; history of bone fracture; gastric bypass surgery; gastrointestinal diseases that cause chronic diarrhoea/steatorrhoea, such as coeliac disease; use of anticonvulsant therapy such as phenobarbital or diphenylhydantoin; in severe cases, muscle weakness
Exam
bone tenderness, pathological fracture, proximal muscle weakness
1st investigation
Hypomagnesaemia
History
may have history of proton-pump inhibitor use; chronic malnutrition and malabsorption; alcoholism; or coeliac disease
Exam
usually asymptomatic, but when magnesium is very low, cardiac arrhythmias may occur resulting in irregular heart beat
1st investigation
Other investigations
- intact PTH level:
variable
Hyperventilation
History
excessive anxiety and worry, panic attack; recent anaesthesia; deep or rapid breathing, paraesthesias
Exam
agitated; tachypnoea, tachycardia; signs of hypocalcaemia such as Trousseau's sign, carpopedal spasm, Chvostek's sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilloedema could occur in severe cases of hypocalcaemia
1st investigation
- serum calcium:
low
More - serum potassium:
low
- ABG:
low PaCO2
Other investigations
Uncommon
Isolated hypoparathyroidism
History
usually diagnosed in the first decade of life, but may present much later; patients present with neurological symptoms of hypocalcaemia, confusion, depression, and gait disturbances; some patients have symptoms related to additional endocrine deficiencies
Exam
signs of hypocalcaemia, such as carpopedal spasm and seizure; short stature, and cataracts
1st investigation
Other investigations
- serum 1,25 dihydroxyvitamin D:
low
Pseudohypoparathyroidism
History
may be asymptomatic (particularly children and adolescents), paraesthesias, muscular cramping, tetany, carpopedal spasm
Exam
patients usually have short stature, intellectual disability, round facies, and short fourth fingers
1st investigation
- serum calcium:
low
More - intact PTH level:
normal to high
Other investigations
- serum phosphorus:
normal to high
Autoimmune hypoparathyroidism
History
autoimmune disease of parathyroid glands and possibly of thyroid, islets of Langerhans, and adrenals (hyper- or hypothyroidism, type 1 diabetes, and/or Addison's disease); patients present with hypocalcaemic symptoms such as muscle cramps or spasms
Exam
signs of hypocalcaemia: mainly neuromuscular irritability such as Trousseau's sign, carpopedal spasm, Chvostek's sign; chronic mucocutaneous candidiasis may be present in polyglandular syndromes
1st investigation
- serum calcium:
low
More - intact PTH level:
low
Other investigations
- parathyroid antibodies:
may be positive
HIV-related hypoparathyroidism
History
rare occurrence of low PTH in patients with HIV
Exam
mainly signs of HIV-related disease
1st investigation
Other investigations
Hypermagnesaemia
History
occurs in patients with renal dysfunction and/or massive exogenous magnesium intake such as excessive use of magnesium-containing cathartics in the presence of intestinal obstruction
Exam
hypotension refractory to vasopressors and volume expansion, neuromuscular irritability
1st investigation
- serum calcium:
low
More - intact PTH level:
variable
- serum magnesium:
elevated >2 mmol/L (>4 mEq/L)
Other investigations
Hyperphosphataemia
History
occurs in patients with renal impairment, hypoparathyroidism, excessive intake of oral or parenteral phosphate, extensive soft tissue injury, and severe haemolysis and tumour lysis syndrome; possible history of kidney stones due to nephrocalcinosis
Exam
tetany, seizure in prolonged hyperphosphataemia
1st investigation
- serum calcium:
low
More - intact PTH level:
variable
- serum phosphorus:
elevated >1.8 mmol/L (>5.5 mg/dL)
Other investigations
Hypercalciuria
History
history of multiple kidney stones, renal impairment, family history of hypocalcaemia with hypercalciuria
Exam
signs of renal failure: pallor, skin bruising, lung rales, pericardial rub, oedema, poor concentration/memory, myoclonus
1st investigation
- serum calcium:
low
More - intact PTH level:
variable
- 24-hour urinary calcium secretion:
>6.2 mmol (250 mg)/24 hour urine output in patient with regular diet
Other investigations
Sepsis
History
symptoms of localised infection, non-specific symptoms include fever or shivering, dizziness, nausea and vomiting, muscle pain, feeling confused or disoriented; may be history of risk factors: for example, immunosuppression, pregnancy or postnatal period, frailty, recent surgery or invasive procedures, intravenous drug use or breach of skin integrity
Exam
tachycardia, tachypnoea, hypotension, fever >38℃ (>100.4°F) or hypothermia <36℃ (<96.8°F), prolonged capillary refill, mottled or ashen skin, cyanosis, low oxygen saturation, newly altered mental state, reduced urine output
1st investigation
- blood culture:
may be positive for organism
More - serum lactate:
may be elevated; levels >2 mmol/L (>18 mg/dL) associated with adverse prognosis; even worse prognosis with levels >4 mmol/L (>36 mg/dL)
More - FBC with differential:
WBC count >12×10⁹/L (>12,000/microlitre) (leukocytosis); WBC count <4×10⁹/L (<4000/microlitre) (leukopenia); or a normal WBC count with >10% immature forms; low platelets
More - CRP:
elevated
- blood urea and serum electrolytes:
serum electrolytes may be deranged; blood urea may be elevated
- serum creatinine:
may be elevated
More - LFTs:
may show elevated bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase
More - coagulation studies:
May be abnormal
- ABG:
may be hypoxia, hypercapnia, elevated anion gap, metabolic acidosis
Other investigations
- ECG:
may show evidence of ischaemia, atrial fibrillation, or other arrhythmia; may be normal
More - CXR:
may show consolidation; demonstrates position of central venous catheter and tracheal tube
- urine microscopy and culture:
may be positive for nitrites, protein or blood; elevated leukocyte count; positive culture for organism
- sputum culture:
may be positive for organism
- lumbar puncture:
may be elevated WBC count, presence of organism on microscopy and positive culture
More
Burns
History
contact with hot liquids, flame, heated objects, electrical current, or chemicals
Exam
erythema; injury predominantly to skin and superficial tissues; may be associated injuries (e.g., inhalation injury and trauma)
1st investigation
Other investigations
Renal failure
History
presence of risk factors (e.g., family history of kidney disease, long-term analgesic use, diabetes); fatigue, nausea, pruritus
Exam
pallor, skin bruising, lung rales, pericardial rub, oedema, poor concentration/memory, myoclonus
1st investigation
- urea and creatinine:
elevated
- urinalysis:
haematuria and/or proteinuria
- estimated GFR:
decreased
- serum calcium:
low
More
Other investigations
- intact PTH level:
normal or elevated
- serum 25-hydroxyvitamin D:
25-hydroxyvitamin D level usually <50 nanomol/L (<20 nanograms/mL)
More - serum phosphorus:
elevated
Acute pancreatitis
History
occurs in patients with severe acute illness associated with liver failure and/or renal failure, especially those who require multiple blood transfusions; presence of risk factors: middle-aged women, young-to-middle-aged men, gallstones, high alcohol consumption, hypertriglyceridaemia, use of specific medicines (e.g., sulphonamides, tetracycline, oestrogens, corticosteroids), endoscopic retrograde cholangiopancreatography procedure, HIV/AIDS, systemic lupus erythematosus, and Sjogren's syndrome; nausea, vomiting, anorexia, abdominal pain
Exam
varying degrees of abdominal tenderness, usually worse in the epigastric region; guarding, abdominal distension, and reduced or absent bowel sounds; ecchymoses in the skin of one or both flanks (Grey-Turner's sign) and/or the periumbilical area (Cullen's sign)
1st investigation
Other investigations
- ultrasound abdomen:
fluid around the pancreas; may show biliary duct dilation
More - CT scan of abdomen with oral and intravenous contrast:
may show pancreatic inflammation, peri-pancreatic stranding, calcifications, or fluid collections; confirms or excludes gallstones
More - MRI/magnetic resonance cholangiopancreatography (MRCP):
findings may include stones, tumours, diffuse or segmental enlargement of the pancreas with irregular contour and obliteration of the peri-pancreatic fat, necrosis, or pseudocysts
More
Extensive osteoblastic skeletal metastasis
History
typically occurs in patients with cancers that are prone to extensive osteoblastic cancer metastasis, such as prostate cancer; other tumours associated with bone formation are breast cancer and leukaemia
Exam
signs of bone metastasis, such as pain and pathological bone fracture
1st investigation
- x-ray of affected bone:
signs of increased bone formation
- serum calcium:
low
More - intact PTH level:
elevated
- serum alkaline phosphatase:
elevated
Other investigations
- isotope bone scan:
increased tracer uptake in the affected areas where there are osteoblastic changes
Hungry bone syndrome
History
occurs in patients following parathyroid surgery for hyperparathyroidism or thyroidectomy for thyrotoxicosis; occurs due to rapid increase in bone remodelling
Exam
signs of hypocalcaemia immediately after surgery include Trousseau's sign, carpopedal spasm, Chvostek's sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilloedema could occur in severe cases of hypocalcaemia
1st investigation
- serum calcium:
low
More - intact PTH level:
low
- serum magnesium:
low
- serum phophorus:
low
Other investigations
- bone biopsy:
extensive bone remineralisation (rarely performed in practice)
Drug-induced hypocalcaemia
History
proton-pump inhibitor (hypomagnesaemia) or bisphosphonate use, particularly when given intravenously; denosumab; chemotherapies; glucocorticoids; anticonvulsants; chelating agents such as EDTA (ethylenediaminetetraacetic acid), citrate, foscarnet, and lactate; cinacalcet (usually given to patients with renal failure, to inhibit PTH release); ingestion or infusion of phosphate, resulting in acute increase of plasma phosphate levels
Exam
signs of hypocalcaemia such as Trousseau's sign, carpopedal spasm, Chvostek's sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilloedema could occur in severe cases of hypocalcaemia
1st investigation
- serum calcium:
low
More - serum magnesium:
may be low (e.g., proton-pump inhibitors)
Other investigations
- serum phosphorus:
elevated >1.8 mmol/L (>5.5 mg/dL)
Multiple transfusions
History
recent severe medical/surgical illness necessitating multiple blood transfusions
Exam
signs of hypocalcaemia such as Trousseau's sign, carpopedal spasm, Chvostek's sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilloedema could occur in severe cases of hypocalcaemia
1st investigation
- serum calcium:
low
More
Other investigations
Hypoalbuminaemia
History
history of malnutrition, liver diseases, chronic diarrhoea, renal failure, heart failure, leg oedema
Exam
pitting oedema, pallor, brittle nails, flaky and dry skin
1st investigation
- serum albumin:
low <35 g/L (<3.5 g/dL)
- serum calcium:
low
More
Other investigations
Drug interference with assay
History
history of contrast agent use such as gadolinium-based MRI contrast agents, including gadodiamide and gadoversetamide (these drugs interfere with the colorimetric assay used to measure calcium)
Exam
none
1st investigation
- none:
history of contrast media use is adequate to explain falsely lowered calcium levels when using colorimetric assay to measure calcium
More
Other investigations
Infiltrative hypoparathyroidism
History
chronic condition requiring repeated transfusions; weight loss, malaise, fevers, fatigue; malignancy in another organ; rarely, history suggestive of haemochromatosis or Wilson's disease
Exam
signs of hypocalcaemia: mainly neuromuscular irritability such as Trousseau's sign, carpopedal spasm, Chvostek's sign; specific signs of underlying disease; may have palpable neck mass
1st investigation
- serum calcium:
low
More - intact PTH level:
low
Other investigations
DiGeorge syndrome and other developmental complexes
History
trouble with feeding, attributed partly to cleft lip and palate; speech development delay and learning disorders
Exam
abnormal facial features; cleft lip and palate; signs of heart failure, such as hepatomegaly, oedema, poor feeding, or cardiogenic shock; cyanosis
1st investigation
- serum calcium:
low
More - intact PTH:
low or undetectable
Other investigations
- T-cell count:
low
- fluorescence in situ hybridisation (FISH):
1 copy of probe per cell confirms 22q11.2 deletion
Rhabdomyolysis
History
recent history of muscle damage relating to exercise, seizures, ischaemia, trauma, drug overdose, or medications such as statins
Exam
localised or diffuse muscle fullness and tenderness, low blood pressure, altered mental status if seizures are or have been present; tense muscles may reflect development of a compartment syndrome
1st investigation
- serum creatine kinase:
increased to >5 times normal, or >1000 units/litre
- serum calcium:
low
More - serum creatinine:
elevated
- serum potassium:
elevated
- serum phosphorus:
elevated
Other investigations
Tumour lysis syndrome
History
recent diagnosis of a malignancy and initiation of chemotherapy and/or radiotherapy; symptoms compatible with malignancy (either solid tumour, lymphoma, or involving blood elements); fever, weight loss
Exam
depending on malignancy, findings may include lymphadenopathy, altered mental status, abdominal organomegaly, paraesthesias, and muscle weakness; symptoms of hypocalcaemia such as tetany and positive Chvostek's and Trousseau's signs
1st investigation
- serum uric acid:
elevated
- serum calcium:
low
More - serum potassium:
elevated
- serum phosphorus:
elevated
Other investigations
Constitutively activating calcium sensing receptor (CaSR) abnormalities (mutations or autoimmune activation)
History
mild hypocalcaemia with hypercalciuria, coincidental detection
Exam
nil specific
1st investigation
- serum calcium:
low
More - urine calcium:
excretion low
Other investigations
- intact PTH:
normal
Vitamin D resistance or receptor mutations
History
presentation in early childhood with severe hypocalcaemia and rickets; bone pain, faltering growth
Exam
clinical features of hypocalcaemia and rickets; bony deformities, muscle weakness, carpopedal spasm, tetany
1st investigation
- serum calcium:
low
More - alkaline phosphatase:
elevated
- intact PTH:
elevated
Other investigations
- x-ray:
showing classical rickets
- 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations:
variable dependent upon specific aetiology
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