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| There are three types of hyperparathyroidism and should be differentiated between each other. Hyperparathyroidism should be differeniated from other causes of hypercalcemia.
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| Causes of hypercalcemia include:
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| *Parathyroid related
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| **Primary hyperparathyroidism
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| ***Typical primary hyperparathyroidism
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| ***Familial hypocalciuric hypercalcemia
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| **Secondary hyperparathyroidism
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| **Tertiary hyperparathyroidism
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| *Non-parathyroid related
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| **Malignancy
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| ***Para-neoplastic syndrome: Parathyroid hormone related peptide
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| ***Hypercalcemia due to bone destruction
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| **Medication induced
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| ***Thiazide diuretics
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| ***Lithium
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| **Nutritional
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| ***Milk alkali syndrome
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| ***Vitamin D toxicity
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| **Granulomatous disease
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| ***Sarcoidosis
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| **Surgical
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| ***Immobilization
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| == Differential diagnosis == | | =Codes= |
| {| class="wikitable"
| | <div style="text-align: center;">'''Corrected total calcium = measured total calcium + 0.8 (4.0 − serum albumin)''' </div> |
| ! colspan="6" |Differential diagnosis fo hyperparathyroidism on the basis of hypercalcemia
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| |-
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| ! colspan="2" |Disorder
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| !Mechanism of hypercalcemia
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| !Clinical features
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| !Laboratory findings
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| !Imaging & diagnostic modalities
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| |-
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| | rowspan="3" |Hyperparathyroidism
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| |Primary hyperparathyroidism
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| |Increase in [[secretion]] of [[parathyroid hormone]] (PTH) from a primary process in [[parathyroid gland]]. Parathyroid hormone causes increase in serum calcium.
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| * Usually asymptomatic
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| * Hypercalcemia detected on routine biochemical panel
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| * ↑ PTH
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| * ↑ Calcium
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| * ''↓/N Phosphate''
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| * N/↑ calcitriol
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| | rowspan="3" |Findings of bone resorption:
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| * X-ray
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| * DXA
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| Preoperative localization of hyperfunctioning parathyroid gland:
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| * Non-Invasive
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| ** Tc-99m sestamibi scintigraphy
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| ** Neck ultrasound
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| ** 4D-CT
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| ** SPET(P-SPECT)
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| ** PET
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| ** MRI
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| * Invasive:
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| ** Super sensitive venous sampling
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| ** Selective arteriography
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| ** Angiography
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| Predicting post-operative success:
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| * Intraoperative parathyroid hormone monitoring
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| |-
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| |Secondary hyperparathyroidism
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| |Increase in [[secretion]] of [[parathyroid hormone]] (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium.
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| * May present with history of:
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| ** Chronic renal failure
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| ** Vitamin D deficiency
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| * '''↑''' PTH
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| * '''''↓/'''N'' Calcium
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| * ''↑ Phosphate''
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| |-
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| |Tertiary hyperparathyroidism
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| |Continuous elevation of [[parathyroid hormone]] (PTH) even after successful treatment of the secondary cause of elevated parathyroid hormone. Parathyroid hormone causes increase in serum calcium.
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| * Usually present with history of:
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| ** Kidney transplant
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| * Usually hyperplasia of all four parathyroid glands
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| * '''↑''' PTH
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| * '''''↑''''' Calcium
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| * ''↑ Phosphate''
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| |-
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| | rowspan="4" |Malignancy
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| |Humoral hypercalcemia of malignancy
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| |Tumor cells secretes parathyroid hormone related protein (PTHrP) which has similar action as parathyroid hormone.
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| * Most common cause of malignancy related hypercalcemia.
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| * Usually present in solid tumors
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| * '''↑''' PTHrP
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| * '''''↑''''' Calcium
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| * '''↓'''/N P''hosphate''
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| * N/↑ Calcitriol
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| * Chest X-ray
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| * CT scan
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| * MRI
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| |-
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| |Osteolytic tumors
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| |Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metastasis can cause bone resorption causing hypercalcemia.
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| * Most commonly present in multiple myeloma and breast cancer.
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| * '''''↓''''' PTH
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| * '''↑''' Calcium
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| * DXA
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| * X-ray
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| * Mammography
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| * Ultrasound
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| * ESR
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| |-
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| |Production of calcitirol
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| |Some tumors has ectopic activity of 1-alpha-hydroxylase leading to increased production of calcitriol. Calcitriol is active form of vitamin D and causes hypercalcemia.
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| * Most commonly present in lymphomas and in some ovarian germ cell tumors.
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| * '''↑''' Calcium
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| * ↑ Calcitriol
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| * CT scan
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| * MRI
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| |-
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| |Ectopic parathyroid hormone
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| |Some tumors leads to ectopic production of parathyroid hormone.
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| * In rare instances, small cell carcinoma of lung may produce hypercalcemia by this process.
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| * ↑ PTH
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| * ↑ Calcium
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| * ''↓/N Phosphate''
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| * N/↑ Calcitriol
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| * Chest X-ray
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| * CT scan
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| * MRI
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| |-
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| | rowspan="2" |Medication induced
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| |Lithium
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| |Lithium lowers urinary calcium and causes hypercalcemia. Lithium has been reported to cause an increase in parathyroid hormones and enlargement if parathyroid gland after weeks to months of therapy.
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| * History of mood disorder
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| * ↑ PTH
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| * ↑ Calcium
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| * Lithium levels
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| |-
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| |Thiazide diuretics
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| |Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia
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| * History of cardiac disorder
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| * Rarely causes hypercalcemia
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| | <div style="width: 70%;"> |
| * ↑ Calcium
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| | --
| | <br style="clear:left" /> |
| |-
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| | rowspan="2" |Nutritional
| | ==References== |
| |Milk-alkali syndrome
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| |Hypercalcemia is be caused by high intake of calcium carbonate
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| * History of
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| ** High milk intake
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| ** Excess calcium intake for treating:
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| *** Osteoporosis
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| *** Dyspepsia
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| * May lead to metabolic alkalosis and renal insufficiency.
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| * ↑ Calcium
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| |Renal function test
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| |-
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| |Vitamin D toxicity
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| |Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia.
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| * History of:
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| ** Excess intake vitamin D
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| ** Excess milk fortified with vitamin D
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| ** Topical application of vitamin D analogue analogue calcipotriol
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| * '''↑''' Calcium
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| * ↑ Vitamin D (calcidiol and/or calcitriol)
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| | --
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| |-
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| |Granulomatous disease
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| |Sarcoidosis
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| |Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages.
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| * History of:
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| ** Cough
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| ** Dyspnea
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| ** Chest pain
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| ** Tiredness or weakness
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| ** Fever
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| ** Weight loss
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| * '''↑''' Calcium
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| * ↑ Calcitriol
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| * ↑ ACE levels
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| |Chest X-ray
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| |}
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| | | | | | | | | | | | | | | Hypercalcemia |
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| | | | | | | | Related to Parathyroid gland | | | | | | | | | | | | Unrelated to parathyroid gland | | |
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| | | Primary hyperparathyroidism | | | Secondary hyperparathyroidism | | | Tertiary hyperparathyroidism | | | | | | | | | |
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| Typical primary hyperparathyroidism | | Familial hypocalciuric hypercalcemia | | | | | | | | | | | | | | | | | | | |
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| | | | | | Malignancy | | | | | | Medication induced | | | | Nutritional | | | | | Granulomatous disease | | | Surgical | |
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| | | | Para-neoplastic syndrome: Parathyroid hormone related peptide | | Metaplasia: Hypercalcemia due to bone destruction | | Thiazide diuretics | | Lithium | | Milk alkali syndrome | | Vitamin D toxicity | | Sarcoidosis | | | Immobilization | |
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Codes
Corrected total calcium = measured total calcium + 0.8 (4.0 − serum albumin)