Hyperparathyroidism differential diagnosis: Difference between revisions

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==Overview==
 
==Differentiating hyperparathyroidism from other diseases==
 
There are three types of hyperparathyroidism and should be differentiated between each other.
Hyperparathyroidism should be differeniated from other causes of hypercalcemia. Causes of hypercalcemia include:
*Parathyroid related
**Hyperparathyroidism
***Primary hyperparathyroidism
***Secondary hyperparathyroidism
***Tertiary hyperparathyroidism
**Familial hypocalciuric hypercalcemia
*Non-parathyroid related
**Malignancy
***Humoral hypercalcemia of malignancy
***Osteolytic tumors
***Production of calcitriol by tumors
***Ectopic parathyroid hormone production
**Medication induced
***Thiazide diuretics
***Lithium
**Nutritional
***Milk alkali syndrome
***Vitamin D toxicity
**Granulomatous disease
***Sarcoidosis
**Surgical
***Immobilization
 
{|
! colspan="6" style="background: #4479BA; text-align: center;" |{{fontcolor|#FFF||Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia}}
|-
! colspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Disorder}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Mechanism of hypercalcemia}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Clinical features}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Laboratory findings}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Imaging & diagnostic modalities}}
|-
| rowspan="3" style="background: #F0FFFF; text-align: center;" |'''Hyperparathyroidism'''
| style="background: #F0FFFF; text-align: center;" |Primary hyperparathyroidism
| style="background: #DCDCDC;" |Increase in [[secretion]] of [[parathyroid hormone]] (PTH) from a primary process in [[parathyroid gland]]. Parathyroid hormone causes increase in serum calcium.
| style="background: #DCDCDC;" |
* Usually asymptomatic
* Hypercalcemia detected on routine biochemical panel
| style="background: #DCDCDC;" |
* ↑ PTH
* ↑ Calcium
* ''↓/N Phosphate''
* N/↑ calcitriol
| rowspan="3" style="background: #DCDCDC;" |Findings of bone resorption:
* X-ray
* DXA
Preoperative localization of hyperfunctioning parathyroid gland:
* Non-Invasive
** Tc-99m sestamibi scintigraphy
** Neck ultrasound
** 4D-CT
** SPET(P-SPECT)
** PET
** MRI
* Invasive:
** Super sensitive venous sampling
** Selective arteriography
** Angiography
Predicting post-operative success:
* Intraoperative parathyroid hormone monitoring
|-
| style="background: #F0FFFF; text-align: center;" |Secondary hyperparathyroidism
| style="background: #DCDCDC;" |Increase in [[secretion]] of [[parathyroid hormone]] (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium.
| style="background: #DCDCDC;" |
* May present with history of:
** Chronic renal failure
** Vitamin D deficiency
| style="background: #DCDCDC;" |
* '''↑''' PTH
* '''''↓/'''N'' Calcium
* ''↑ Phosphate''
|-
| style="background: #F0FFFF; text-align: center;" |Tertiary hyperparathyroidism
| style="background: #DCDCDC;" |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.
| style="background: #DCDCDC;" |
* Usually present with history of:
** Kidney transplant
* Usually hyperplasia of all four parathyroid glands
| style="background: #DCDCDC;" |
* '''↑''' PTH
* '''''↑''''' Calcium
* ''↑ Phosphate''
|-
| colspan="2" style="background: #F0FFFF; text-align: center;" |Familial hypocalciuric hypercalcemia
| style="background: #DCDCDC;"
* This is a genetic disorder caused my mutation in calcium-sensing receptor gene.
| style="background: #DCDCDC;"
* This is a benign condition and does not require treatment.
| style="background: #DCDCDC;"
* N'''/↑''' PTH
* N/'''''↑''''' Calcium
| style="background: #DCDCDC;"
* Calcium/creatinine clearance ratio
|-
| rowspan="4" style="background: #F0FFFF; text-align: center;" |'''Malignancy'''
| style="background: #F0FFFF; text-align: center;" |Humoral hypercalcemia of malignancy
| style="background: #DCDCDC;" |Tumor cells secretes parathyroid hormone related protein (PTHrP) which has similar action as parathyroid hormone.
| style="background: #DCDCDC;" |
* Most common cause of malignancy related hypercalcemia.
* Usually present in solid tumors
| style="background: #DCDCDC;" |
* '''↑''' PTHrP
* '''''↑''''' Calcium
* '''↓'''/N P''hosphate''
* N/↑ Calcitriol
| style="background: #DCDCDC;" |
* Chest X-ray
* CT scan
* MRI
|-
| style="background: #F0FFFF; text-align: center;" |Osteolytic tumors
| style="background: #DCDCDC;" |Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metastasis can cause bone resorption causing hypercalcemia.
| style="background: #DCDCDC;" |
* Most commonly present in multiple myeloma and breast cancer.
| style="background: #DCDCDC;" |
* '''''↓''''' PTH
* '''↑''' Calcium
| style="background: #DCDCDC;" |
* DXA
* X-ray
* Mammography
* Ultrasound
* ESR
* Serum protein electrophoresis
|-
| style="background: #F0FFFF; text-align: center;" |Production of calcitirol
| style="background: #DCDCDC;" |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.
| style="background: #DCDCDC;" |
* Most commonly present in lymphomas and in some ovarian germ cell tumors.
| style="background: #DCDCDC;" |
* '''↑''' Calcium
* ↑ Calcitriol
| style="background: #DCDCDC;" |
* CT scan
* MRI
|-
| style="background: #F0FFFF; text-align: center;" |Ectopic parathyroid hormone
| style="background: #DCDCDC;" |Some tumors leads to ectopic production of parathyroid hormone.
| style="background: #DCDCDC;" |
* In rare instances, small cell carcinoma of lung may produce hypercalcemia by this process.
| style="background: #DCDCDC;" |
* ↑ PTH
* ↑ Calcium
* ''↓/N Phosphate''
* N/↑ Calcitriol
| style="background: #DCDCDC;" |
* Chest X-ray
* CT scan
* MRI
|-
| rowspan="2" style="background: #F0FFFF; text-align: center;" |'''Medication induced'''
| style="background: #F0FFFF; text-align: center;" |Lithium
| style="background: #DCDCDC;" |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.
| style="background: #DCDCDC;" |
* History of mood disorder
| style="background: #DCDCDC;" |
* ↑ PTH
* ↑ Calcium
| style="background: #DCDCDC;" |
* Lithium levels
|-
| style="background: #F0FFFF; text-align: center;" |Thiazide diuretics
| style="background: #DCDCDC;" |Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia
| style="background: #DCDCDC;" |
* History of cardiac disorder
* Rarely causes hypercalcemia
| style="background: #DCDCDC;" |
* ↑ Calcium
| style="background: #DCDCDC;" | --
|-
| rowspan="2" style="background: #F0FFFF; text-align: center;" |'''Nutritional'''
| style="background: #F0FFFF; text-align: center;" |Milk-alkali syndrome
| style="background: #DCDCDC;" |Hypercalcemia is be caused by high intake of calcium carbonate
| style="background: #DCDCDC;" |
* History of
** High milk intake
** Excess calcium intake for treating:
*** Osteoporosis
*** Dyspepsia
* May lead to metabolic alkalosis and renal insufficiency.
| style="background: #DCDCDC;" |
* ↑ Calcium
| style="background: #DCDCDC;" |
* Renal function test
|-
| style="background: #F0FFFF; text-align: center;" |Vitamin D toxicity
| style="background: #DCDCDC;" |Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia.
| style="background: #DCDCDC;" |
* History of:
** Excess intake vitamin D
** Excess milk fortified with vitamin D
** Topical application of vitamin D analogue analogue calcipotriol
| style="background: #DCDCDC;" |
* '''↑''' Calcium
* ↑ Vitamin D (calcidiol and/or calcitriol)
| style="background: #DCDCDC;" | --
|-
| style="background: #F0FFFF; text-align: center;" |'''Granulomatous disease'''
| style="background: #F0FFFF; text-align: center;" |Sarcoidosis
| style="background: #DCDCDC;" |Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages.
| style="background: #DCDCDC;" |
* History of:
** Cough
** Dyspnea
** Chest pain
** Tiredness or weakness
** Fever
** Weight loss
| style="background: #DCDCDC;" |
* '''↑''' Calcium
* ↑ Calcitriol
* ↑ ACE levels
| style="background: #DCDCDC;" |
* Chest X-ray
* Biopsy
|}


==References==
==References==

Revision as of 18:41, 8 September 2017

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Template:CMB;Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[1]

Overview

Differentiating hyperparathyroidism from other diseases

There are three types of hyperparathyroidism and should be differentiated between each other. Hyperparathyroidism should be differeniated from other causes of hypercalcemia. Causes of hypercalcemia include:

  • Parathyroid related
    • Hyperparathyroidism
      • Primary hyperparathyroidism
      • Secondary hyperparathyroidism
      • Tertiary hyperparathyroidism
    • Familial hypocalciuric hypercalcemia
  • Non-parathyroid related
    • Malignancy
      • Humoral hypercalcemia of malignancy
      • Osteolytic tumors
      • Production of calcitriol by tumors
      • Ectopic parathyroid hormone production
    • Medication induced
      • Thiazide diuretics
      • Lithium
    • Nutritional
      • Milk alkali syndrome
      • Vitamin D toxicity
    • Granulomatous disease
      • Sarcoidosis
    • Surgical
      • Immobilization
Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia
Disorder Mechanism of hypercalcemia Clinical features Laboratory findings Imaging & diagnostic modalities
Hyperparathyroidism Primary hyperparathyroidism Increase in secretion of parathyroid hormone (PTH) from a primary process in parathyroid gland. Parathyroid hormone causes increase in serum calcium.
  • Usually asymptomatic
  • Hypercalcemia detected on routine biochemical panel
  • ↑ PTH
  • ↑ Calcium
  • ↓/N Phosphate
  • N/↑ calcitriol
 Findings of bone resorption:
  • X-ray
  • DXA

Preoperative localization of hyperfunctioning parathyroid gland:

  • Non-Invasive
    • Tc-99m sestamibi scintigraphy
    • Neck ultrasound
    • 4D-CT
    • SPET(P-SPECT)
    • PET
    • MRI
  • Invasive:
    • Super sensitive venous sampling
    • Selective arteriography
    • Angiography

Predicting post-operative success:

  • Intraoperative parathyroid hormone monitoring
Secondary hyperparathyroidism Increase in secretion of parathyroid hormone (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium.
  • May present with history of:
    • Chronic renal failure
    • Vitamin D deficiency
  • ↑ PTH
  • ↓/N Calcium
  • ↑ Phosphate
Tertiary hyperparathyroidism 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.
  • Usually present with history of:
    • Kidney transplant
  • Usually hyperplasia of all four parathyroid glands
  • ↑ PTH
  • ↑ Calcium
  • ↑ Phosphate
Familial hypocalciuric hypercalcemia style="background: #DCDCDC;"
  • This is a genetic disorder caused my mutation in calcium-sensing receptor gene.
 style="background: #DCDCDC;"
  • This is a benign condition and does not require treatment.
 style="background: #DCDCDC;"
  • N/↑ PTH
  • N/↑ Calcium
 style="background: #DCDCDC;"
  • Calcium/creatinine clearance ratio
Malignancy Humoral hypercalcemia of malignancy Tumor cells secretes parathyroid hormone related protein (PTHrP) which has similar action as parathyroid hormone.
  • Most common cause of malignancy related hypercalcemia.
  • Usually present in solid tumors
  • ↑ PTHrP
  • ↑ Calcium
  • ↓/N Phosphate
  • N/↑ Calcitriol
  • Chest X-ray
  • CT scan
  • MRI
Osteolytic tumors Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metastasis can cause bone resorption causing hypercalcemia.
  • Most commonly present in multiple myeloma and breast cancer.
  • ↓ PTH
  • ↑ Calcium
  • DXA
  • X-ray
  • Mammography
  • Ultrasound
  • ESR
  • Serum protein electrophoresis
Production of calcitirol 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.
  • Most commonly present in lymphomas and in some ovarian germ cell tumors.
  • ↑ Calcium
  • ↑ Calcitriol
  • CT scan
  • MRI
Ectopic parathyroid hormone Some tumors leads to ectopic production of parathyroid hormone.
  • In rare instances, small cell carcinoma of lung may produce hypercalcemia by this process.
  • ↑ PTH
  • ↑ Calcium
  • ↓/N Phosphate
  • N/↑ Calcitriol
  • Chest X-ray
  • CT scan
  • MRI
Medication induced Lithium 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.
  • History of mood disorder
  • ↑ PTH
  • ↑ Calcium
  • Lithium levels
Thiazide diuretics Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia
  • History of cardiac disorder
  • Rarely causes hypercalcemia
  • ↑ Calcium
 --
Nutritional Milk-alkali syndrome Hypercalcemia is be caused by high intake of calcium carbonate
  • History of
    • High milk intake
    • Excess calcium intake for treating:
      • Osteoporosis
      • Dyspepsia
  • May lead to metabolic alkalosis and renal insufficiency.
  • ↑ Calcium
  • Renal function test
Vitamin D toxicity Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia.
  • History of:
    • Excess intake vitamin D
    • Excess milk fortified with vitamin D
    • Topical application of vitamin D analogue analogue calcipotriol
  • ↑ Calcium
  • ↑ Vitamin D (calcidiol and/or calcitriol)
 --
Granulomatous disease Sarcoidosis Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages.
  • History of:
    • Cough
    • Dyspnea
    • Chest pain
    • Tiredness or weakness
    • Fever
    • Weight loss
  • ↑ Calcium
  • ↑ Calcitriol
  • ↑ ACE levels
  • Chest X-ray
  • Biopsy

References

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