Hyperparathyroidism differential diagnosis: Difference between revisions

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{| class="wikitable"
{| class="wikitable"
! colspan="6" style="background: #4479BA; text-align: center;" |{{fontcolor|#FFF||Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia}}
! colspan="9" 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}}
! colspan="2" rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Disorder}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Mechanism of hypercalcemia}}
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Mechanism of hypercalcemia}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Clinical features}}
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Clinical features}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Laboratory findings}}
! colspan="4" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Laboratory findings}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Imaging & diagnostic modalities}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Imaging & diagnostic modalities}}
|-
!PTH
!Calcium
!Phosphate
!Other findings
!
|-
|-
| rowspan="3" style="background: #F0FFFF; text-align: center;" |'''Hyperparathyroidism'''
| rowspan="3" style="background: #F0FFFF; text-align: center;" |'''Hyperparathyroidism'''
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* Hypercalcemia detected on routine biochemical  panel
* Hypercalcemia detected on routine biochemical  panel
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* ↑ PTH
* ↑  
* ↑ Calcium
|↑  
* ''↓''/Normal phosphate
|''↓''/Normal  
* Normal/↑ calcitriol
|Normal/↑ calcitriol
| rowspan="3" style="background: #DCDCDC;" |Findings of bone resorption:
| rowspan="3" style="background: #DCDCDC;" |Findings of bone resorption:
* X-ray
* X-ray
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** Vitamin D deficiency
** Vitamin D deficiency
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* '''↑''' PTH
* '''↑'''  
* '''↓/'''Normal calcium
|'''↓/'''Normal  
* ''↑ Phosphate''
|''↑''
|
|-
|-
| style="background: #F0FFFF; text-align: center;" |Tertiary hyperparathyroidism
| style="background: #F0FFFF; text-align: center;" |Tertiary hyperparathyroidism
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* Usually hyperplasia of all four parathyroid glands
* Usually hyperplasia of all four parathyroid glands
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* '''↑''' PTH
* '''↑'''  
* '''''↑''''' Calcium
|'''''↑'''''  
* ''↑ Phosphate''
|''↑''  
|
|-
|-
| colspan="2" style="background: #F0FFFF; text-align: center;" |Familial hypocalciuric hypercalcemia
| colspan="2" style="background: #F0FFFF; text-align: center;" |Familial hypocalciuric hypercalcemia
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* This is a benign condition and does not require treatment.
* This is a benign condition and does not require treatment.
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* Normal'''/↑''' PTH
* Normal'''/↑'''
* Normal/'''''↑''''' calcium
|Normal/'''''↑'''''
|
|
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* Calcium/creatinine clearance ratio
* Calcium/creatinine clearance ratio
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* Usually present in solid tumors
* Usually present in solid tumors
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* '''↑''' PTHrP
*  
* '''''↑''''' Calcium
|'''''↑'''''  
* '''↓'''/Normal p''hosphate''
|'''↓'''/Normal  
* Normal/↑ calcitriol
|'''↑''' PTHrP
 
Normal/↑ calcitriol
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* Chest X-ray
* Chest X-ray
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* Most commonly present in multiple myeloma and breast cancer.
* Most commonly present in multiple myeloma and breast cancer.
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* '''''↓''''' PTH
* '''''↓'''''  
* '''↑''' Calcium
|'''↑'''  
|
|
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* DXA
* DXA
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* Most commonly present in lymphomas and in some ovarian germ cell tumors.
* Most commonly present in lymphomas and in some ovarian germ cell tumors.
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* '''↑''' Calcium
* Calcium
* ↑ Calcitriol
*
|'''↑'''  
|
|↑ Calcitriol
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* CT scan
* CT scan
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* ''↓''/Normal phosphate
* ''↓''/Normal phosphate
* N/↑ Calcitriol
* N/↑ Calcitriol
|
|
|
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* Chest X-ray
* Chest X-ray
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* ↑ PTH
* ↑ PTH
* ↑ Calcium
* ↑ Calcium
|
|
|
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* Lithium levels
* Lithium levels
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| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* ↑ Calcium
* ↑ Calcium
|
|
|
| style="background: #DCDCDC;" | --
| style="background: #DCDCDC;" | --
|-
|-
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| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* ↑ Calcium
* ↑ Calcium
|
|
|
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* Renal function test
* Renal function test
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* '''↑''' Calcium
* '''↑''' Calcium
* ↑ Vitamin D (calcidiol and/or calcitriol)
* ↑ Vitamin D (calcidiol and/or calcitriol)
|
|
|
| style="background: #DCDCDC;" | --
| style="background: #DCDCDC;" | --
|-
|-
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* ↑ Calcitriol
* ↑ Calcitriol
* ↑ ACE levels
* ↑ ACE levels
|
|
|
| style="background: #DCDCDC;" |
| style="background: #DCDCDC;" |
* Chest X-ray
* Chest X-ray

Revision as of 16:39, 12 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

There are three types of hyperparathyroidism (primary, secondary, and tertiary) and should be differentiated between each other. Hyperparathyroidism should be differentiated from other causes of hypercalcemia. Causes of hypercalcemia other than hyperparathyroidism include familial hypocalciuric hypercalcemia, hypercalcemia related to malignancy, medication-induced hypercalcemia, hypercalcemia due to nutritional disorders, and hypercalcemia related to granulomatous diseases.

Differentiating hyperparathyroidism from other diseases

There are three types of hyperparathyroidism (primary, secondary, and tertiary) and should be differentiated between each other. Hyperparathyroidism should be differentiated from other causes of hypercalcemia. Causes of hypercalcemia include:

Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia
Disorder Mechanism of hypercalcemia Clinical features Laboratory findings Imaging & diagnostic modalities
PTH Calcium Phosphate Other findings
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
  • ↑
 ↑ ↓/Normal Normal/↑ 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
  • ↑
 ↓/Normal ↑
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
  • ↑
 ↑ ↑
Familial hypocalciuric hypercalcemia
  • This is a genetic disorder caused my mutation in calcium-sensing receptor gene.
  • This is a benign condition and does not require treatment.
  • Normal/↑
 Normal/↑
  • Calcium/creatinine clearance ratio
Malignancy[1] Humoral hypercalcemia of malignancy[2][3][4] 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
↑ ↓/Normal ↑ PTHrP

Normal/↑ 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.
  • ↓
 ↑
  • 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[5] 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
  • ↓/Normal phosphate
  • N/↑ Calcitriol
  • Chest X-ray
  • CT scan
  • MRI
Medication induced Lithium[6] 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[7]
    • Topical application of vitamin D analogue analogue calcipotriol[8]
  • ↑ Calcium
  • ↑ Vitamin D (calcidiol and/or calcitriol)
 --
Granulomatous disease Sarcoidosis[9] 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

  1. ↑ Mirrakhimov AE (2015). "Hypercalcemia of Malignancy: An Update on Pathogenesis and Management". N Am J Med Sci. 7 (11): 483–93. doi:10.4103/1947-2714.170600. PMC 4683803. PMID 26713296.
  2. ↑ Ratcliffe WA, Hutchesson AC, Bundred NJ, Ratcliffe JG (1992). "Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia". Lancet. 339 (8786): 164–7. doi:10.1016/0140-6736(92)90220-W. PMID 1346019.
  3. ↑ Ikeda K, Ohno H, Hane M, Yokoi H, Okada M, Honma T, Yamada A, Tatsumi Y, Tanaka T, Saitoh T (1994). "Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma". J. Clin. Endocrinol. Metab. 79 (5): 1322–7. doi:10.1210/jcem.79.5.7962324. PMID 7962324.
  4. ↑ Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocaña A, Stewart AF (2003). "Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers". J. Clin. Endocrinol. Metab. 88 (4): 1603–9. doi:10.1210/jc.2002-020773. PMID 12679445.
  5. ↑ VanHouten JN, Yu N, Rimm D, Dotto J, Arnold A, Wysolmerski JJ, Udelsman R (2006). "Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene". J. Clin. Endocrinol. Metab. 91 (2): 580–3. doi:10.1210/jc.2005-2095. PMID 16263810.
  6. ↑ Mallette LE, Khouri K, Zengotita H, Hollis BW, Malini S (1989). "Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume". J. Clin. Endocrinol. Metab. 68 (3): 654–60. doi:10.1210/jcem-68-3-654. PMID 2918061.
  7. ↑ Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, Seely EW (1992). "Hypervitaminosis D associated with drinking milk". N. Engl. J. Med. 326 (18): 1173–7. doi:10.1056/NEJM199204303261801. PMID 1313547.
  8. ↑ Hoeck HC, Laurberg G, Laurberg P (1994). "Hypercalcaemic crisis after excessive topical use of a vitamin D derivative". J. Intern. Med. 235 (3): 281–2. PMID 8120527.
  9. ↑ Dusso AS, Kamimura S, Gallieni M, Zhong M, Negrea L, Shapiro S, Slatopolsky E (1997). "gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses". J. Clin. Endocrinol. Metab. 82 (7): 2222–32. doi:10.1210/jcem.82.7.4074. PMID 9215298.
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