Hypercalcemia differential diagnosis: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
Line 8: Line 8:


==Differential Diagnosis==
==Differential Diagnosis==
(In alphabetical order)
Different causes of hypecalcemia should be differentiated from each other. Common causes of hypercalcemia to be differentiaetd include:
* Abnormal [[parathyroid gland]] function
*'''Parathyroid related'''
* [[Acromegaly]]
**Hyperparathyroidism
* [[Osteoporosis|Acute osteoporosis]]
***Primary hyperparathyroidism
* [[Acute renal failure]]
***Secondary hyperparathyroidism
* [[Addison's disease]]
***Tertiary hyperparathyroidism
* [[Adrenal insufficiency]]
**[[Familial hypocalciuric hypercalcemia]]
* After [[kidney transplant]]
*'''Non-parathyroid related'''
* [[Aluminum]] intoxication
**[[Malignancy]]
* [[Aspirin]] (in large amounts)
***Humoral [[hypercalcemia]] of [[malignancy]]
* Autonomous [[hyperparathyroidism]] (post long-term [[renal failure]])
***[[Osteolytic metasteses|Osteolytic tumors]]
* [[Bartter's Syndrome]]
***Production of [[calcitriol]] by [[Tumor|tumors]]
* [[Berylliosis]]
***[[Ectopia|Ectopic]] [[parathyroid hormone]] production
* Bone [[fracture]]
**[[Medication-induced]]
* [[Breast cancer]]
***[[Thiazide diuretics]]
* [[Bronchial carcinoma]]
***[[Lithium]]  
* [[Carcinoma]]
**[[Nutritional]]
* [[Chronic renal failure]]
***[[Milk-alkali syndrome]]
* [[Coccidioidomycosis]]
***[[Hypervitaminosis D|Vitamin D toxicity]]
* [[Cushing's syndrome]]
**[[Granulomatous]] disease
* [[Dehydration]]
***[[Sarcoidosis]]
* [[Drugs]]
**Surgical
* Familial hypocalcuric hypercalcemia
***Immobization
* Familial isolated [[hyperparathyroidism]] ({{OMIM|146200}})
 
* [[Gitelman syndrome]]
 
* Granulomatous diseases with [[tuberculosis]]
<br>
* [[Hematologic]] [[malignancy]] ([[multiple myeloma]], [[lymphoma]], [[leukemia]])
 
* [[Hepatocellular carcinoma]]
{|
* [[Histoplasmosis]]
! colspan="9" style="background: #4479BA; text-align: center;" |{{fontcolor|#FFF|Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia}}
* [[Hodgkin's Lymphoma]]
|-
* [[Hyperparathyroidism]] (in the preceding oliguric-anuric phase)
! colspan="2" rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Disorder}}
* [[Hyperthyroidism]]
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Mechanism of hypercalcemia}}
* [[Hypervitaminosis D]] (vitamin D intoxication)
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Clinical features}}
* [[Idiopathic]] hypercalcemia (in infants)
! colspan="4" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Laboratory findings}}
* Immobilization
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Imaging & diagnostic modalities}}
* Isolated or multinodal adenoma
|-
* [[Kidney cancer]]
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|PTH}}
* [[Leprosy]]
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Calcium}}
* [[Leukemia]]
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Phosphate}}
* [[Lithium]]  
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Other findings}}
* [[Lymphoma]]
|-
* [[Malignancy]]
! rowspan="3" style="background: #DCDCDC; text-align: center;" |'''Hyperparathyroidism'''
* [[Medullary sponge kidney]]
! style="background: #DCDCDC; text-align: center;" |Primary hyperparathyroidism
* [[Milk-alkali syndrome]]
| style="background: #F5F5F5;" |Increase in [[secretion]] of [[parathyroid hormone]] ([[PTH]]) from a primary process in [[parathyroid gland]]. [[Parathyroid hormone]] causes increase in [[serum]] [[calcium]].
* [[Multiple endocrine neoplasia]] (MEN)
| style="background: #F5F5F5;" |
* [[Multiple myeloma]]
* Usually asymptomatic
* [[Oral candidiasis]]
* [[Hypercalcemia]] detected on routine biochemical  panel
* [[Osteomalacia]]
| style="background: #F5F5F5; text-align: center;" |↑
* [[Ovarian cancer]]
| style="background: #F5F5F5; text-align: center;" |↑
* [[Paget's disease]]
| style="background: #F5F5F5; text-align: center;" |↓/Normal
* [[Paraplegia]]
| style="background: #F5F5F5; text-align: center;" |Normal/↑ calcitriol
* Parathyroid [[carcinoma]] ({{ICD10|C|75|0|c|73}})
| rowspan="3" style="background: #F5F5F5;" |Findings of bone resorption:
* [[Parathyroid]] hyperplasia
* [[X-ray]]
* [[Pheochromocytoma]]
* [[Dual energy X-ray absorptiometry]] ([[DXA]])
* [[Plasma cell]] [[granuloma]]
Preoperative localization of hyperfunctioning [[parathyroid gland]]:
* [[Polycythemia]]
* Non-Invasive
* [[Primary hyperparathyroidism]]
** [[Tc-99m sestamibi scintigraphy]]
* Primary Parathyroid [[hyperplasia]]
** Neck [[ultrasound]]
* Rebound hypercalcemia after [[rhabdomyolysis]]
** 4D-CT
* [[Renal failure]]
** [[SPECT]](P-SPECT)
* [[Sarcoidosis]]
** [[Positron emission tomography|PET]]
* Secretion of [[prostaglandin]]s
** [[MRI]]
* Severe [[secondary hyperparathyroidism]]
* Invasive:
* [[Silicone]]-induced [[granuloma]]
** Super sensitive [[venous]] sampling
* [[Sjogren's syndrome]]
** Selective [[arteriography]]
* Solid tumor with humoral mediation of hypercalcemia (e.g. [[lung cancer|lung]] or [[renal cell carcinoma|kidney cancer]], [[pheochromocytoma]])
** [[Angiogram|Angiography]]
* Solid tumor with metastasis (e.g. [[breast cancer]])
Predicting post-operative success:
* Solitary parathyroid [[adenoma]]
* [[Intraoperative parathyroid hormone]] monitoring
* [[Thiazide]] [[diuretic]]s
|-
* [[Total parenteral nutrition]]
! style="background: #DCDCDC; text-align: center;" |Secondary hyperparathyroidism
* [[Tuberculosis]]
| style="background: #F5F5F5;" |Increase in [[secretion]] of [[parathyroid hormone]] ([[PTH]]) from a secondary process. [[Parathyroid hormone]] causes increase in [[serum]] [[calcium]] after long periods.
* [[Vasoactive intestinal polypeptide-producing tumor]] ([[VIPoma]])
| style="background: #F5F5F5;" |
* [[Vitamin A]] intoxication
* May present with history of:
* [[Vitamin D]] intoxication
** [[Chronic renal failure]]
* [[Vitamin D]] [[metabolic disorders]]
** [[Vitamin D deficiency]]
* [[William's syndrome]]
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" |↓/Normal
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" | --
|-
! style="background: #DCDCDC; text-align: center;" |Tertiary hyperparathyroidism
| style="background: #F5F5F5;" |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: #F5F5F5;" |
* Usually present with history of [[kidney transplant]]
* Usually [[hyperplasia]] of all four [[parathyroid glands]]
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" | --
|-
! colspan="2" style="background: #DCDCDC; text-align: center;" |[[Familial hypocalciuric hypercalcemia]]
| style="background: #F5F5F5;" |This is a [[genetic disorder]] caused my [[mutation]] in [[calcium-sensing receptor]] gene.
| style="background: #F5F5F5;" |
* A benign condition
* Does not require treatment
| style="background: #F5F5F5; text-align: center;" |Normal/↑
| style="background: #F5F5F5; text-align: center;" |Normal/↑
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5;" |
* Urinary calcium/creatinine clearance ratio
|-
! rowspan="4" style="background: #DCDCDC; 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><ref name="pmid15673803">{{cite journal| author=Stewart AF| title=Clinical practice. Hypercalcemia associated with cancer. | journal=N Engl J Med | year= 2005 | volume= 352 | issue= 4 | pages= 373-9 | pmid=15673803 | doi=10.1056/NEJMcp042806 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15673803  }} </ref>
! style="background: #DCDCDC; 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><ref name="pmid7085851">{{cite journal| author=Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE et al.| title=Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity. | journal=J Clin Endocrinol Metab | year= 1982 | volume= 55 | issue= 2 | pages= 219-27 | pmid=7085851 | doi=10.1210/jcem-55-2-219 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7085851  }} </ref>
| style="background: #F5F5F5;" |[[Tumor]] cells secretes [[parathyroid hormone-related protein]] ([[PTHrP]]) which has similar action as [[parathyroid hormone]].
| style="background: #F5F5F5;" |
* Most common cause of [[malignancy]] related [[hypercalcemia]]
* Usually present with [[solid tumors]]
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" |↓/Normal
| style="background: #F5F5F5; text-align: center;" |↑ [[PTHrP]]


Hypercalcemia must be differentiated from other causes of diabetes insipidus.
Normal/↑ calcitriol
{| class="wikitable"
| style="background: #F5F5F5;" |
!Type of DI
* [[Chest X-rays|Chest X-ray]]
!Subclass
* [[CT scan]]
!Disease
* [[MRI]]
!Defining signs and symptoms
|-
!Lab/Imaging findings
! style="background: #DCDCDC; text-align: center;" |Osteolytic tumors<ref name="pmid15084698">{{cite journal| author=Roodman GD| title=Mechanisms of bone metastasis. | journal=N Engl J Med | year= 2004 | volume= 350 | issue= 16 | pages= 1655-64 | pmid=15084698 | doi=10.1056/NEJMra030831 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15084698  }} </ref><ref name="pmid8833902">{{cite journal| author=Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF et al.| title=Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. | journal=J Clin Invest | year= 1996 | volume= 98 | issue= 7 | pages= 1544-9 | pmid=8833902 | doi=10.1172/JCI118947 | pmc=507586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8833902  }} </ref>
| style="background: #F5F5F5;" |[[Multiple myeloma]] produces [[osteolysis]] of [[bones]] causing [[hypercalcemia]]. [[Osteolytic metasteses]] can cause [[bone resorption]] causing [[hypercalcemia]].
| style="background: #F5F5F5;" |
* Commonly present in [[multiple myeloma]] and [[breast cancer]]
| style="background: #F5F5F5; text-align: center;" |↓
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5;" |
* [[DXA]]
* [[X-ray]]
* [[Mammography]]
* [[Ultrasound]]
* [[ESR]]
* [[Serum protein electrophoresis]]
|-
! style="background: #DCDCDC; text-align: center;" |Production of calcitirol<ref name="pmid7944070">{{cite journal| author=Seymour JF, Gagel RF, Hagemeister FB, Dimopoulos MA, Cabanillas F| title=Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin lymphoma. | journal=Ann Intern Med | year= 1994 | volume= 121 | issue= 9 | pages= 633-40 | pmid=7944070 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7944070  }} </ref>
| style="background: #F5F5F5;" |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: #F5F5F5;" |
* Commonly present in [[lymphomas]] and in some [[Ovarian cancer|ovarian germ cell tumors]]
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" |↑ [[Calcitriol]]
| style="background: #F5F5F5;" |
* [[CT scan]]
* [[MRI]]
|-
! style="background: #DCDCDC; 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: #F5F5F5;" |Some tumors leads to [[Ectopia|ectopic]] production of [[parathyroid hormone]].
| style="background: #F5F5F5;" |
* In rare instances, [[small cell carcinoma of lung]] may produce [[hypercalcemia]] by this process
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" |↓/Normal
| style="background: #F5F5F5; text-align: center;" |Normal/↑ [[calcitriol]]
| style="background: #F5F5F5;" |
* [[Chest X-rays|Chest X-ray]]
* [[CT scan]]
* [[MRI]]
|-
! rowspan="2" style="background: #DCDCDC; text-align: center;" |'''Medication induced'''
! style="background: #DCDCDC; 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: #F5F5F5;" |[[Lithium]] lowers [[Urinary System|urinary]] [[calcium]] and causes [[hypercalcemia]]. [[Lithium]] has been reported to cause an increase in [[parathyroid hormone]] and enlargement if [[parathyroid gland]] after weeks to months of therapy.
| style="background: #F5F5F5;" |
* History of [[mood disorder]]
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5;" |
* [[Lithium]] levels
|-
! style="background: #DCDCDC; text-align: center;" |Thiazide diuretics<ref name="pmid26751196">{{cite journal| author=Griebeler ML, Kearns AE, Ryu E, Thapa P, Hathcock MA, Melton LJ et al.| title=Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 3 | pages= 1166-73 | pmid=26751196 | doi=10.1210/jc.2015-3964 | pmc=4803175 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26751196  }}</ref>
| style="background: #F5F5F5;" |[[Thiazide diuretics]] lowers [[urinary]] [[calcium]] [[excretion]] and causes [[hypercalcemia]].
| style="background: #F5F5F5;" |
* History of [[cardiac]] disorder
* Rarely causes [[hypercalcemia]]
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5;" | --
|-
|-
| rowspan="5" |Central
! rowspan="2" style="background: #DCDCDC; text-align: center;" |'''Nutritional'''
| rowspan="3" |Acquired
! style="background: #DCDCDC; text-align: center;" |Milk-alkali syndrome
|[[Histiocytosis]]
| style="background: #F5F5F5;" |[[Hypercalcemia]] is be caused by high intake of [[calcium carbonate]].
|
| style="background: #F5F5F5;" |
* Bone lysis and [[Bone fracture|fracture]]
* History of
* Purulent [[otitis media]]
** High milk intake
* [[Diabetes insipidus]] and delayed puberty
** Excess calcium intake for treating:
* [[Maxillary]], [[mandibular]], and [[gingival]] disease
*** [[Osteoporosis]]
* [[Rash]] and [[Erythematous|maculoerythematous]] skin lesions
*** [[Dyspepsia]]
* Scaly, [[erythematous]] scalp patches
* May lead to [[metabolic alkalosis]] and [[renal insufficiency]].
* [[Lung]] involvement
| style="background: #F5F5F5; text-align: center;" | --
* [[GI bleeding]]
| style="background: #F5F5F5; text-align: center;" |↑
* [[Lymphadenopathy|Lymph node enlargement]]<ref name="pmid1340034">{{cite journal| author=Ghosh KN, Bhattacharya A| title=Gonotrophic nature of Phlebotomus argentipes (Diptera: Psychodidae) in the laboratory. | journal=Rev Inst Med Trop Sao Paulo | year= 1992 | volume= 34 | issue= 2 | pages= 181-2 | pmid=1340034 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1340034  }} </ref>
| style="background: #F5F5F5; text-align: center;" | --
|
| style="background: #F5F5F5; text-align: center;" |↓ [[calcitriol]]
* CD1a and CD45 +
| style="background: #F5F5F5;" |
* Interleukin-17 (ILITA)
* [[Renal function tests]]
[[Image:Langerhans Skull X ray.jpg|center|300px|thumb|Skull x-ray of a patient with Langerhan's histiocytosis showing lytic lesions - Case courtesy of Dr Hani Salam, Radiopaedia.org, rID: 9459]]
|-
|-
|[[Craniopharyngioma]]
! style="background: #DCDCDC; text-align: center;" |Vitamin D toxicity<ref name="pmid81205272">{{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><ref name="pmid13135472">{{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><ref name="pmid8620732">{{cite journal| author=Sharma OP| title=Vitamin D, calcium, and sarcoidosis. | journal=Chest | year= 1996 | volume= 109 | issue= 2 | pages= 535-9 | pmid=8620732 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8620732  }}</ref>
|
| style="background: #F5F5F5;" |Excess [[vitamin D]] causes increased [[absorption]] of [[calcium]] from [[intestine]] causing [[hypercalcemia]].
* [[Headache]]
| style="background: #F5F5F5;" |
* [[Endocrine disorders|Endocrine dysfunction]]
* History of:
** [[Diabetes insipidus]]
** Excess intake [[vitamin D]]
** [[Hypothyroidism]]  
** 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>
** [[Adrenal failure]]
** Topical application of vitamin D 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>
** [[Diabetes insipidus]] (e.g., excessive fluid intake and urination)
| style="background: #F5F5F5; text-align: center;" | --
** Growth failure and [[delayed puberty]]
| style="background: #F5F5F5; text-align: center;" |↑
|
| style="background: #F5F5F5; text-align: center;" | --
* [[Suprasellar]] calcified cyst on [[MRI]]
| style="background: #F5F5F5; text-align: center;" |↑ [[Vitamin D]] ([[calcidiol]] and/or [[calcitriol]])
[[Image:Craniopharyngioma-papillary-1.jpg|center|300px|thumb|Brain MRI showing suprasellar mass consistent with the diagnosis of craniopharyngioma - Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 16812]]
| style="background: #F5F5F5;" | --
|-
|-
|[[Sarcoidosis]]
! style="background: #DCDCDC; text-align: center;" |'''Granulomatous disease'''
|
! style="background: #DCDCDC; 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>
* Systemic complaints
| style="background: #F5F5F5;" |[[Hypercalcemia]] is causes by endogeous production of [[calcitriol]] by disease-activated [[Macrophage|macrophages]].
| style="background: #F5F5F5;" |
* History of:
** [[Cough]]
** [[Dyspnea]]
** [[Chest pain]]
** [[Tiredness]] or [[weakness]]
** [[Fever]]
** [[Fever]]
** [[Anorexia]]
** [[Weight loss]]
** [[Arthralgias]]
| style="background: #F5F5F5; text-align: center;" | --
* Pulmonary complaints
| style="background: #F5F5F5; text-align: center;" |↑
** [[Dyspnea on exertion]]
| style="background: #F5F5F5; text-align: center;" | --
** [[Cough]]
| style="background: #F5F5F5; text-align: center;" |↑ [[Calcitriol]]
** Chest pain,  
 
** [[Hemoptysis]] (rare)
↑ [[ACE]] levels
* [[Diabetes mellitus]]
| style="background: #F5F5F5;" |
|
* [[Chest X-ray]]
* [[Hypercalcemia]]  
* [[Biopsy]]
* [[Hypercalciuria]] ([[Granulomas|noncaseating granulomas]])
|}
* Elevated [[alkaline phosphatase]]
 
* [[Serum amyloid A]] (SAA)
==DIfferentiating Hyperparathyroidism from other diseases==
* [[Angiotensin-converting enzyme|ACE]] levels may be elevated
 
[[Image:Neurosarcoidosis.jpg|center|300px|thumb|Contrast-enhanced patches in a patient previously diagnosed with lung sarcoidosis - Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 10930]]
<small>
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center"
 
|+
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Disease}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Gene}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Chromosome}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differentiating Features}}
! colspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Components of MEN}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diagnosis}}
|-
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Parathyroid}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pitutary}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pancreas}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[von Hippel-Lindau syndrome]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Von Hippel–Lindau tumor suppressor
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |3p25.3
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Angiomatosis, 
* Hemangioblastomas,
* Pheochromocytoma, 
* Renal cell carcinoma,
* Pancreatic cysts (pancreatic serous cystadenoma)
* Endolymphatic sac tumor,
* Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women)
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | +
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Clinical diagnosis
* In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Carney complex]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | PRKAR1A
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | 17q23-q24
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Myxomas of the heart
* Hyperpigmentation of the skin (lentiginosis)
* Endocrine (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease)
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Clinical diagnosis
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Neurofibromatosis type 1]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |RAS
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Scoliosis]]  
* Learning disabilities
* [[Vision]] disorders
* Cutaneous [[lesion]]s
* [[Epilepsy]].
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |'''<u>Prenatal</u>'''
* Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus.
'''<u>Postnatal</u>'''
Cardinal Clinical Features" are required for positive diagnosis.
* Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals.
* Two or more neurofibromas of any type or 1 plexiform neurofibroma
* Freckling in the axillary (Crowe sign) or inguinal regions
* Optic glioma
* Two or more Lisch nodules (pigmented iris hamartomas)
* A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis.
|-
|-
| rowspan="2" |Congenital
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Li-Fraumeni syndrome]]
|[[Hydrocephalus]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |TP53
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17
* Cognitive deterioration
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Early onset of diverse amount of [[cancer]]s such as
* [[Headaches]]
* [[Sarcoma]]  
* [[Neck pain]]
* [[Cancer]]s of 
* [[Blurred vision]]
** [[Breast]]
* [[Unsteady gait]]
** [[Brain]]  
* [[Incontinence]] such as [[polyuria]]
** [[Adrenal gland]]s
|Dilated [[ventricles]] on [[Computed tomography|CT]] and [[Magnetic resonance imaging|MRI]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
[[Image:Obstructive-hydrocephalus.jpg|center|300px|thumb|Obstructive hydrocephalus showing dilated lateral ventricles - Case courtesy of Dr Paul Simkin, Radiopaedia.org, rID: 30453]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''<u>Criteria</u>'''
* Sarcoma at a young age (below 45)
* A first-degree relative diagnosed with any cancer at a young age (below 45)
* A first or second degree relative with any cancer diagnosed before age 60.
|-
|-
|[[Wolfram syndrome|Wolfram Syndrome]] (DIDMOAD)
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Gardner's syndrome]]
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | APC
* [[Diabetes insipidus|Diabetes Insipidus]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | 5q21
* [[Diabetes mellitus|Diabetes Mellitus]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Optic atrophy|Optic Atrophy]]
* Multiple polyps in the colon 
* [[Deafness]]
* Osteomas of the skull
|
* Thyroid cancer,
* Negative [[islet cell]] antibodies
* Epidermoid cysts,
* [[Optic atrophy]] on [[electroretinogram]]
* Fibromas
* [[Deafness]] on [[audiogram]]
* Desmoid tumors
* [[Atrophy]] of brain stem on [[Magnetic resonance imaging|MRI]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Clinical diagnosis
* Colonoscopy
|-
|-
| rowspan="5" |[[Nephrogenic diabetes insipidus|Nephrogenic]]
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Multiple endocrine neoplasia type 2]]
| rowspan="5" |[[Acquired disorder|Acquired]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |''RET''
|Drug-induced ([[demeclocycline]], [[lithium]])
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Polyuria]]
* [[Medullary thyroid carcinoma]] (MTC)
* [[Polydipsia]]
* [[Pheochromocytoma]]  
* [[Nocturia]]
* Primary [[hyperparathyroidism]]
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | +
* [[Urine osmolality]] <100 mmol/
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Arginine vasopressin]] level >4.6 pmol/
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* Little or no response to administration of  exogenous [[arginine vasopressin]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Hypercalcemia]]
* [[Hypophosphatemia]],
* Elevated [[parathyroid hormone]],
* Elevated [[norepinephrine]]
'''<u>Criteria</u>'''
Two or more specific endocrine tumors
* [[Medullary thyroid carcinoma]]
* [[Pheochromocytoma]]
* [[Parathyroid]] hyperplasia
|-
|-
|[[Hypercalcemia]]
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Cowden syndrome]]
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |PTEN
* [[Polyuria]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Polydipsia]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Hamartomas
* [[Gastrointestinal]] disturbances
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Bone fracture|Pathological fractures]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
* [[Confusion]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Palpitations]] and [[cardiac arrhythmias]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
|
* ''PTEN'' mutation probability risk calculator
* Ca levels greater than 11 meq/L
|-
|-
|[[Hypokalemia]]
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Acromegaly]]/[[gigantism]]
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Polyuria]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Hyporeflexia]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Palpitations]] and [[cardiac arrhythmias]]
* Enlargement of the [[hand]]s, [[feet]], [[nose]], [[lip]]s and [[ear]]s, and a general thickening of the [[skin]]
|
* [[Hypertrichosis]]
* K levels less than 3meq/L on CBC
* [[Hyperpigmentation]]  
* [[Hyperhidrosis]]  
* [[Carpal tunnel syndrome]].
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* An elevated concentration of serum [[Growth hormone|growth hormone (GH)]] and [[Insulin-like growth factor|insulin-like growth factor 1(IGF-1)]] levels is diagnostic of acromegaly.
|-
|-
|[[Multiple myeloma]]
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pituitary adenoma]]
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* Pathologic [[bone fractures]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Bleeding]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Hypercalcemia]] leading to [[polyuria]]
* [[Visual field defect]]s classically [[bitemporal hemianopsia]]
* [[Infection]]
* Increased [[intracranial pressure]]
* [[Hyperviscosity]]
* [[Migraine]]  
* [[Anemia]]
* [[Lateral rectus]] palsy
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[IgG]] or [[IgA]] spike on [[serum protein electrophoresis]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki>
* [[Monoclonal antibody|Monoclonal M spike]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* Disordered [[plasma cell]] proliferation on [[bone marrow biopsy]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
[[Image:Multiple-myeloma-skeletal-survey.jpg|center|300px|thumb|Skeletal survey in a patient with multiple myeloma showing multiple lytic lesions - Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org, rID: 7682]]
:*Elevated serum level of  [[prolactin]]
:*Elevated or decreased serum level of  [[adrenocorticotropic hormone]] (ACTH)
:*Elevated or decreased serum level of  [[growth hormone]] (GH)
:*Elevated or decreased serum level of  [[thyroid-stimulating hormone]] (TSH)
:*Elevated or decreased serum level of  [[follicle-stimulating hormone]] (FSH)
:*Elevated or decreased serum level of  [[luteinizing hormone]] (LH)
|-
|-
|[[Sickle-cell disease|Sickle cell disease]]
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Hyperparathyroidism]]
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Chronic pain]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Anemia]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* [[Aplastic crisis]]
* [[Kidney stone]]s
* Splenic sequestration
* [[Hypercalcemia]],
* [[Infection]]
* [[Constipation]]
* [[Isosthenuria]] presenting with [[polyuria]]
* [[Peptic ulcer]]s
|
* [[Depression]]
* [[Hemoglobin]] level is 5-9 g/dL
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki>
* [[Hematocrit]] is decreased to 17-29%
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
* [[Peripheral blood smear|Peripheral blood smears]] demonstrate [[Target cell|target cells]], elongated cells, and characteristic sickle erythrocytes
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
* MRI can demonstrate [[avascular necrosis]] of the [[femoral]] and [[humeral]] heads
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
[[Image:Sickle cells.jpg|center|300px|thumb|Blood film showing the sickle cells - By Dr Graham Beards - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18421017]]
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level is diagnostic of primary hyperparathyroidism.
* Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum [[parathyroid hormone]] level and low to normal serum [[calcium]].
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level in post [[Kidney transplantation|renal transplant]] patients is diagnostic of tertiary hyperparathyoidism.
|-
|-
| colspan="2" |Primary polydipsia
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pheochromocytoma]]/[[paraganglioma]]
|[[Psychogenic]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
|
''VHL''
* [[Polyuria]]
''RET''
* [[Polydipsia]]
''NF1''  
* [[Nocturia]]
''SDHB'' 
|
''SDHD''
* Dry mucus membrane
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
* History of [[psychiatric disorders]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Characterized by
* Episodic [[hypertension]]
* [[Palpitation]]s
* [[Anxiety]]
* [[Diaphoresis]]
* [[Weight loss]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection.
|-
|-
| colspan="3" |Gestational diabetes insipidus
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Adrenocortical carcinoma]]
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Polyuria]]  
*p53
* [[Polydipsia]]
*Retinoblastoma h19
* [[Nocturia]]
*Insulin-like growth factor II (IGF-II)
* [[Pregnancy]]
*p57<sup>kip2</sup>
|
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17p, 13q 
* Dry mucus membranes
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Pregnancy]]
* [[Cushing syndrome]] ([[cortisol]] hypersecretion)
* [[Conn syndrome]] ([[aldosterone]] hypersecretion)
* [[virilization]] ([[testosterone]] hypersecretion)
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Increased serum glucose
* Increased urine cortisol
* Serum androstenedione and dehydroepiandrosterone
* Low serum potassium
* Low plasma renin activity
* High serum aldosterone.
* Excess serum estrogen.
|-
|-
| colspan="3" |[[Diabetes mellitus]]
| colspan="8" style="padding: 5px 5px; background: #F5F5F5;" |<small>Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013<ref name="pmid23917672">{{cite journal| author=Toledo SP, Lourenço DM, Toledo RA| title=A differential diagnosis of inherited endocrine tumors and their tumor counterparts. | journal=Clinics (Sao Paulo) | year= 2013 | volume= 68 | issue= 7 | pages= 1039-56 | pmid=23917672 | doi=10.6061/clinics/2013(07)24 | pmc=PMC3715026 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23917672  }} </ref> </small>
|
* [[Polyuria]]
* [[Polydipsia]]
* [[Nocturia]]
* [[Weight gain (patient information)|Weight gain]]
|
* Elevated blood sugar levels >126
* Elevated [[HbA1c]] > 6.5
|}
|}
</small>


==References==
==References==

Revision as of 13:27, 3 July 2018

Hypercalcemia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Hypercalcemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Hypercalcemia On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Hypercalcemia

All Images
X-rays
Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Hypercalcemia

CDC on Hypercalcemia

Hypercalcemia in the news

Blogs on Hypercalcemia

Directions to Hospitals Treating Hypercalcemia

Risk calculators and risk factors for Hypercalcemia

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

Please help WikiDoc by adding content here. It's easy! Click here to learn about editing.

Overview

Differential Diagnosis

Different causes of hypecalcemia should be differentiated from each other. Common causes of hypercalcemia to be differentiaetd 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:

Preoperative localization of hyperfunctioning parathyroid gland:

Predicting post-operative success:

Secondary hyperparathyroidism Increase in secretion of parathyroid hormone (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium after long periods. ↑ ↓/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. ↑ ↑ ↑ --
Familial hypocalciuric hypercalcemia This is a genetic disorder caused my mutation in calcium-sensing receptor gene.
  • A benign condition
  • Does not require treatment
 Normal/↑ Normal/↑ -- --
  • Urinary calcium/creatinine clearance ratio
Malignancy[1][2] Humoral hypercalcemia of malignancy[3][4][5][6] Tumor cells secretes parathyroid hormone-related protein (PTHrP) which has similar action as parathyroid hormone. -- ↑ ↓/Normal ↑ PTHrP

Normal/↑ calcitriol

Osteolytic tumors[7][8] Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metasteses can cause bone resorption causing hypercalcemia. ↓ ↑ -- --
Production of calcitirol[9] 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. -- ↑ -- ↑ Calcitriol
Ectopic parathyroid hormone[10] Some tumors leads to ectopic production of parathyroid hormone. ↑ ↑ ↓/Normal Normal/↑ calcitriol
Medication induced Lithium[11] Lithium lowers urinary calcium and causes hypercalcemia. Lithium has been reported to cause an increase in parathyroid hormone and enlargement if parathyroid gland after weeks to months of therapy. ↑ ↑ -- --
Thiazide diuretics[12] Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia. -- ↑ -- -- --
Nutritional Milk-alkali syndrome Hypercalcemia is be caused by high intake of calcium carbonate. -- ↑ -- ↓ calcitriol
Vitamin D toxicity[13][14][15] Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia. -- ↑ -- ↑ Vitamin D (calcidiol and/or calcitriol) --
Granulomatous disease Sarcoidosis[18] Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages. -- ↑ -- ↑ Calcitriol

↑ ACE levels

DIfferentiating Hyperparathyroidism from other diseases

Disease Gene Chromosome Differentiating Features Components of MEN Diagnosis
Parathyroid Pitutary Pancreas
von Hippel-Lindau syndrome Von Hippel–Lindau tumor suppressor 3p25.3
  • Angiomatosis, 
  • Hemangioblastomas,
  • Pheochromocytoma, 
  • Renal cell carcinoma,
  • Pancreatic cysts (pancreatic serous cystadenoma)
  • Endolymphatic sac tumor,
  • Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women)
 - - +
  • Clinical diagnosis
  • In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations.
Carney complex  PRKAR1A 17q23-q24
  • Myxomas of the heart
  • Hyperpigmentation of the skin (lentiginosis)
  • Endocrine (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease)
 - - -
  • Clinical diagnosis
Neurofibromatosis type 1 RAS 17 - - - Prenatal
  • Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus.

Postnatal Cardinal Clinical Features" are required for positive diagnosis.

  • Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals.
  • Two or more neurofibromas of any type or 1 plexiform neurofibroma
  • Freckling in the axillary (Crowe sign) or inguinal regions
  • Optic glioma
  • Two or more Lisch nodules (pigmented iris hamartomas)
  • A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis.
Li-Fraumeni syndrome TP53 17 Early onset of diverse amount of cancers such as - - -

Criteria

  • Sarcoma at a young age (below 45)
  • A first-degree relative diagnosed with any cancer at a young age (below 45)
  • A first or second degree relative with any cancer diagnosed before age 60.
Gardner's syndrome APC  5q21
  • Multiple polyps in the colon 
  • Osteomas of the skull
  • Thyroid cancer,
  • Epidermoid cysts,
  • Fibromas
  • Desmoid tumors
 - - -
  • Clinical diagnosis
  • Colonoscopy
Multiple endocrine neoplasia type 2 RET - + - -

Criteria Two or more specific endocrine tumors

Cowden syndrome PTEN -  Hamartomas - - -
  • PTEN mutation probability risk calculator
Acromegaly/gigantism - - - + -
Pituitary adenoma - - - + -
Hyperparathyroidism - - - + - -
  • An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyroidism.
  • Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum parathyroid hormone level and low to normal serum calcium.
  • An elevated concentration of serum calcium with elevated parathyroid hormone level in post renal transplant patients is diagnostic of tertiary hyperparathyoidism.
Pheochromocytoma/paraganglioma

VHL RET NF1   SDHB  SDHD

- Characterized by - - -
  • Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection.
Adrenocortical carcinoma
  • p53
  • Retinoblastoma h19
  • Insulin-like growth factor II (IGF-II)
  • p57kip2
 17p, 13q  - - -
  • Increased serum glucose
  • Increased urine cortisol
  • Serum androstenedione and dehydroepiandrosterone
  • Low serum potassium
  • Low plasma renin activity
  • High serum aldosterone.
  • Excess serum estrogen.
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013[19]

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. ↑ Stewart AF (2005). "Clinical practice. Hypercalcemia associated with cancer". N Engl J Med. 352 (4): 373–9. doi:10.1056/NEJMcp042806. PMID 15673803.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE; et al. (1982). "Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity". J Clin Endocrinol Metab. 55 (2): 219–27. doi:10.1210/jcem-55-2-219. PMID 7085851.
  7. ↑ Roodman GD (2004). "Mechanisms of bone metastasis". N Engl J Med. 350 (16): 1655–64. doi:10.1056/NEJMra030831. PMID 15084698.
  8. ↑ Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF; et al. (1996). "Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis". J Clin Invest. 98 (7): 1544–9. doi:10.1172/JCI118947. PMC 507586. PMID 8833902.
  9. ↑ Seymour JF, Gagel RF, Hagemeister FB, Dimopoulos MA, Cabanillas F (1994). "Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin lymphoma". Ann Intern Med. 121 (9): 633–40. PMID 7944070.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ Griebeler ML, Kearns AE, Ryu E, Thapa P, Hathcock MA, Melton LJ; et al. (2016). "Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades". J Clin Endocrinol Metab. 101 (3): 1166–73. doi:10.1210/jc.2015-3964. PMC 4803175. PMID 26751196.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ Sharma OP (1996). "Vitamin D, calcium, and sarcoidosis". Chest. 109 (2): 535–9. PMID 8620732.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ Toledo SP, Lourenço DM, Toledo RA (2013). "A differential diagnosis of inherited endocrine tumors and their tumor counterparts". Clinics (Sao Paulo). 68 (7): 1039–56. doi:10.6061/clinics/2013(07)24. PMC 3715026. PMID 23917672.

Template:WS Template:WH

Retrieved from "https://www.wikidoc.org/index.php?title=Hypercalcemia_differential_diagnosis&oldid=1480656"