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
  • serum calcium:

    low

    More
  • intact PTH level:

    low or undetectable 0 to 10 picograms/mL

    More
  • serum phosphorus:

    elevated

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 diarrhea/steatorrhea, such as celiac disease; use of anticonvulsant therapy such as phenobarbital or diphenylhydantoin; in severe cases, muscle weakness

    Exam

    bone tenderness, pathologic fracture, proximal muscle weakness

    1st investigation
    • serum 25-hydroxyvitamin D:

      usually <20 nanograms/mL (<50 nanomol/L)

      More
    • serum calcium:

      low

      More
    • serum alkaline phosphatase:

      normal or elevated

    Other investigations
    • intact PTH level:

      elevated

    • bone densitometry:

      low

      More
    • x-ray of the pelvic bones or other areas of pain:

      fractures and Looser zone (pseudofracture)

      More

    Hypomagnesemia

    History

    may have history of proton-pump inhibitor use; chronic malnutrition and malabsorption; alcoholism; or celiac disease

    Exam

    usually asymptomatic, but when magnesium is very low, cardiac arrhythmias may occur resulting in irregular heart beat

    1st investigation
    • serum magnesium:

      low

      More
    • serum calcium:

      low

      More
    • ECG:

      cardiac arrhythmias with prolonged PR and QT intervals

    Other investigations
    • intact PTH level:

      variable

    Hyperventilation

    History

    excessive anxiety and worry, panic attack; recent anesthesia; deep or rapid breathing, paresthesias

    Exam

    agitated; tachypnea, tachycardia; signs of hypocalcemia such as Trousseau sign, carpopedal spasm, Chvostek sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilledema could occur in severe cases of hypocalcemia

    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 neurologic symptoms of hypocalcemia, confusion, depression, and gait disturbances; some patients have symptoms related to additional endocrine deficiencies

      Exam

      signs of hypocalcemia, such as carpopedal spasm and seizure; short stature, and cataracts

      1st investigation
      • serum calcium:

        low

        More
      • intact PTH level:

        low or undetectable

        More
      • serum phosphorus:

        elevated

      Other investigations
      • serum 1,25 dihydroxyvitamin D:

        low

      Pseudohypoparathyroidism

      History

      may be asymptomatic (particularly children and adolescents), paresthesias, 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 disease); patients present with hypocalcemic symptoms such as muscle cramps or spasms

      Exam

      signs of hypocalcemia: mainly neuromuscular irritability such as Trousseau sign, carpopedal spasm, Chvostek 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

      a rare occurrence of low PTH in patients with HIV

      Exam

      mainly signs of HIV-related disease

      1st investigation
      • serum calcium:

        low

        More
      • intact PTH:

        typically low

      • serum HIV ELISA:

        positive in HIV infection

        More
      Other investigations

        Hypermagnesemia

        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 >4 mEq/L

        Other investigations

          Hyperphosphatemia

          History

          occurs in patients with renal impairment, hypoparathyroidism, excessive intake of oral or parenteral phosphate, extensive soft tissue injury, and severe hemolysis and tumor lysis syndrome; possible history of kidney stones due to nephrocalcinosis

          Exam

          tetany, seizure in prolonged hyperphosphatemia

          1st investigation
          • serum calcium:

            low

            More
          • intact PTH level:

            variable

          • serum phosphorus:

            elevated >5.5 mg/dL

          Other investigations

            Hypercalciuria

            History

            hx of multiple kidney stones, renal impairment, family history of hypocalcemia with hypercalciuria

            Exam

            signs of renal failure: pallor, skin bruising, lung rales, pericardial rub, edema, poor concentration/memory, myoclonus

            1st investigation
            • serum calcium:

              low

              More
            • intact PTH level:

              variable

            • 24-hour urinary calcium secretion:

              >250 mg/24 hour urine output in patient with regular diet

            Other investigations

              Sepsis

              History

              symptoms of localized infection, nonspecific 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 postpartum period, frailty, recent surgery or invasive procedures, intravenous drug use or breach of skin integrity

              Exam

              tachycardia, tachypnea, hypotension, fever >100.4°F (>38℃) or hypothermia <96.8°F (<36℃), 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 >18 mg/dL (>2 mmol/L) associated with adverse prognosis; even worse prognosis with levels >36 mg/dL (>4 mmol/L)

                More
              • CBC with differential:

                WBC count >12,000/microliter (>12×10⁹/L) (leukocytosis); WBC count <4000/microliter (<4×10⁹/L) (leukopenia); or a normal WBC count with >10% immature forms; low platelets

                More
              • CRP:

                elevated

              • BUN and serum electrolytes:

                serum electrolytes may be deranged; BUN 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 ischemia, 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
              • CBC with differential:

                may show low hematocrit, hypovolemia, neutropenia, thrombocytopenia

                More
              • serum calcium:

                low

                More
              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, edema, poor concentration/memory, myoclonus

                1st investigation
                • BUN and creatinine:

                  elevated

                • urinalysis:

                  hematuria 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 <20 nanograms/mL (<50 nanomol/L)

                  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, hypertriglyceridemia, use of specific medications (e.g., sulphonamides, tetracycline, estrogens, corticosteroids), endoscopic retrograde cholangiopancreatography procedure, HIV/AIDS, systemic lupus erythematosus, and Sjogren 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 sign) and/or the periumbilical area (Cullen sign)

                1st investigation
                • serum lipase:

                  elevated (3 times the upper limit of normal)

                  More
                • serum amylase:

                  elevated (3 times the upper limit of normal)

                  More
                • serum calcium:

                  low

                  More
                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, peripancreatic stranding, calcifications, or fluid collections; confirms or excludes gallstones

                  More
                • MRI/magnetic resonance cholangiopancreatography (MRCP):

                  findings may include stones, tumors, diffuse or segmental enlargement of the pancreas with irregular contour and obliteration of the peripancreatic 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 tumors associated with bone formation are breast cancer and leukemia

                Exam

                signs of bone metastasis, such as pain and pathologic 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 remodeling

                Exam

                signs of hypocalcemia immediately after surgery include Trousseau sign, carpopedal spasm, Chvostek sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilledema could occur in severe cases of hypocalcemia

                1st investigation
                • serum calcium:

                  low

                  More
                • intact PTH level:

                  low

                • serum magnesium:

                  low

                • serum phophorus:

                  low

                Other investigations
                • bone biopsy:

                  extensive bone remineralization (rarely performed in practice)

                Drug-induced hypocalcemia

                History

                proton-pump inhibitor (hypomagnesemia) 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 hypocalcemia such as Trousseau sign, carpopedal spasm, Chvostek sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilledema could occur in severe cases of hypocalcemia

                1st investigation
                • serum calcium:

                  low

                  More
                • serum magnesium:

                  may be low (e.g., proton-pump inhibitors)

                Other investigations
                • serum phosphorus:

                  elevated >5.5 mg/dL

                Multiple transfusions

                History

                recent severe medical/surgical illness necessitating multiple blood transfusions

                Exam

                signs of hypocalcemia such as Trousseau sign, carpopedal spasm, Chvostek sign, seizure disorder, neuromuscular irritability, or muscle cramps; papilledema could occur in severe cases of hypocalcemia

                1st investigation
                • serum calcium:

                  low

                  More
                Other investigations

                  Hypoalbuminemia

                  History

                  history of malnutrition, liver diseases, chronic diarrhea, renal failure, heart failure, leg edema

                  Exam

                  pitting edema, pallor, brittle nails, flaky and dry skin

                  1st investigation
                  • serum albumin:

                    low <3.5 g/dL (<35 g/L)

                  • serum calcium:

                    low

                    More
                  Other investigations

                    Drug interference with assay

                    History

                    history of contrast agent 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 hemochromatosis or Wilson disease

                      Exam

                      signs of hypocalcemia: mainly neuromuscular irritability such as Trousseau sign, carpopedal spasm, Chvostek 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, edema, 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 hybridization (FISH):

                          1 copy of probe per cell confirms 22q11.2 deletion

                        Rhabdomyolysis

                        History

                        recent history of muscle damage relating to exercise, seizures, ischemia, trauma, drug overdose, or medications such as statins

                        Exam

                        localized 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/liter

                        • serum calcium:

                          low

                          More
                        • serum creatinine:

                          elevated

                        • serum potassium:

                          elevated

                        • serum phosphorus:

                          elevated

                        Other investigations

                          Tumor lysis syndrome

                          History

                          recent diagnosis of a malignancy and initiation of chemotherapy and/or radiation therapy; symptoms compatible with malignancy (either solid tumor, lymphoma, or involving blood elements); fever, weight loss

                          Exam

                          depending on malignancy, findings may include lymphadenopathy, altered mental status, abdominal organomegaly, paresthesias, and muscle weakness; symptoms of hypocalcemia such as tetany and positive Chvostek and Trousseau 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 hypocalcemia with hypercalciuria, coincidental detection

                            Exam

                            nonspecific

                            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 hypocalcemia and rickets; bone pain, faltering growth

                            Exam

                            clinical features of hypocalcemia 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 etiology

                            Use of this content is subject to our disclaimer