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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.
Causes of hypercalcemia include:
*Parathyroid related
**Primary hyperparathyroidism
***Typical primary hyperparathyroidism
***Familial hypocalciuric hypercalcemia
**Secondary hyperparathyroidism
**Tertiary hyperparathyroidism
*Non-parathyroid related
**Malignancy
***Para-neoplastic syndrome: Parathyroid hormone related peptide
***Hypercalcemia due to bone destruction
**Medication induced
***Thiazide diuretics
***Lithium
**Nutritional
***Milk alkali syndrome
***Vitamin D toxicity
**Granulomatous disease
***Sarcoidosis
**Surgical
***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" 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}}
<div style="width: 70%;">
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Mechanism of hypercalcemia}}
 
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Clinical features}}
<br style="clear:left" />
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Laboratory findings}}
 
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Imaging & diagnostic modalities}}
==References==
|-
| 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''
|-
| rowspan="4"  style="background: #F0FFFF; text-align: center;" |'''Malignancy'''<ref name="pmid26713296">{{cite journal |vauthors=Mirrakhimov AE |title=Hypercalcemia of Malignancy: An Update on Pathogenesis and Management |journal=N Am J Med Sci |volume=7 |issue=11 |pages=483–93 |year=2015 |pmid=26713296 |pmc=4683803 |doi=10.4103/1947-2714.170600 |url=}}</ref>
| style="background: #F0FFFF; text-align: center;" |Humoral hypercalcemia of malignancy<ref name="pmid1346019">{{cite journal |vauthors=Ratcliffe WA, Hutchesson AC, Bundred NJ, Ratcliffe JG |title=Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia |journal=Lancet |volume=339 |issue=8786 |pages=164–7 |year=1992 |pmid=1346019 |doi=10.1016/0140-6736(92)90220-W |url=}}</ref><ref name="pmid7962324">{{cite journal |vauthors=Ikeda K, Ohno H, Hane M, Yokoi H, Okada M, Honma T, Yamada A, Tatsumi Y, Tanaka T, Saitoh T |title=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 |journal=J. Clin. Endocrinol. Metab. |volume=79 |issue=5 |pages=1322–7 |year=1994 |pmid=7962324 |doi=10.1210/jcem.79.5.7962324 |url=}}</ref><ref name="pmid12679445">{{cite journal |vauthors=Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocaña A, Stewart AF |title=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 |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue=4 |pages=1603–9 |year=2003 |pmid=12679445 |doi=10.1210/jc.2002-020773 |url=}}</ref>
| 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<ref name="pmid16263810">{{cite journal |vauthors=VanHouten JN, Yu N, Rimm D, Dotto J, Arnold A, Wysolmerski JJ, Udelsman R |title=Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene |journal=J. Clin. Endocrinol. Metab. |volume=91 |issue=2 |pages=580–3 |year=2006 |pmid=16263810 |doi=10.1210/jc.2005-2095 |url=}}</ref>
| 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<ref name="pmid2918061">{{cite journal |vauthors=Mallette LE, Khouri K, Zengotita H, Hollis BW, Malini S |title=Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume |journal=J. Clin. Endocrinol. Metab. |volume=68 |issue=3 |pages=654–60 |year=1989 |pmid=2918061 |doi=10.1210/jcem-68-3-654 |url=}}</ref>
| 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<ref name="pmid1313547">{{cite journal |vauthors=Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, Seely EW |title=Hypervitaminosis D associated with drinking milk |journal=N. Engl. J. Med. |volume=326 |issue=18 |pages=1173–7 |year=1992 |pmid=1313547 |doi=10.1056/NEJM199204303261801 |url=}}</ref>
** Topical application of vitamin D analogue analogue calcipotriol<ref name="pmid8120527">{{cite journal |vauthors=Hoeck HC, Laurberg G, Laurberg P |title=Hypercalcaemic crisis after excessive topical use of a vitamin D derivative |journal=J. Intern. Med. |volume=235 |issue=3 |pages=281–2 |year=1994 |pmid=8120527 |doi= |url=}}</ref>
| 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<ref name="pmid9215298">{{cite journal |vauthors=Dusso AS, Kamimura S, Gallieni M, Zhong M, Negrea L, Shapiro S, Slatopolsky E |title=gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses |journal=J. Clin. Endocrinol. Metab. |volume=82 |issue=7 |pages=2222–32 |year=1997 |pmid=9215298 |doi=10.1210/jcem.82.7.4074 |url=}}</ref>
| 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
|}

Latest revision as of 15:49, 5 March 2018

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypercalcemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Related to Parathyroid gland
 
 
 
 
 
 
 
 
 
 
 
Unrelated to parathyroid gland
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary hyperparathyroidism
 
 
Secondary hyperparathyroidism
 
 
Tertiary hyperparathyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Typical primary hyperparathyroidism
 
Familial hypocalciuric hypercalcemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malignancy
 
 
 
 
 
Medication induced
 
 
 
Nutritional
 
 
 
 
Granulomatous disease
 
 
Surgical
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Para-neoplastic syndrome: Parathyroid hormone related peptide
 
Metaplasia: Hypercalcemia due to bone destruction
 
Thiazide diuretics
 
Lithium
 
Milk alkali syndrome
 
Vitamin D toxicity
 
Sarcoidosis
 
 
Immobilization
 

Codes

Corrected total calcium = measured total calcium + 0.8 (4.0 − serum albumin)



References

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