Milk-alkali syndrome differential diagnosis: Difference between revisions

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{{Milk-alkali syndrome}}
{{Milk-alkali syndrome}}
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Milk-alkali syndrome must be differentiated from other causes of hypercalcaemia
 
{|
! colspan="9" style="background: #4479BA; text-align: center;" |{{fontcolor|#FFF|Differential diagnosis of hyperparathyroidism on the basis of hypercalcemia}}
|-
! colspan="2" rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Disorder}}
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Mechanism of hypercalcemia}}
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Clinical features}}
! colspan="4" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Laboratory findings}}
! rowspan="2" style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Imaging & diagnostic modalities}}
|-
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|PTH}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Calcium}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Phosphate}}
! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Other findings}}
|-
! rowspan="3" style="background: #DCDCDC; text-align: center;" |'''Hyperparathyroidism'''
! style="background: #DCDCDC; text-align: center;" |Primary hyperparathyroidism
| style="background: #F5F5F5;" |Increase in [[secretion]] of [[parathyroid hormone]] ([[PTH]]) from a primary process in [[parathyroid gland]]. [[Parathyroid hormone]] causes increase in [[serum]] [[calcium]].
| style="background: #F5F5F5;" |
* Usually asymptomatic
* [[Hypercalcemia]] detected on routine biochemical  panel
| 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
| rowspan="3" style="background: #F5F5F5;" |Findings of bone resorption:
* [[X-ray]]
* [[Dual energy X-ray absorptiometry]] ([[DXA]])
Preoperative localization of hyperfunctioning [[parathyroid gland]]:
* Non-Invasive
** [[Tc-99m sestamibi scintigraphy]]
** Neck [[ultrasound]]
** 4D-CT
** [[SPECT]](P-SPECT)
** [[Positron emission tomography|PET]]
** [[MRI]]
* Invasive:
** Super sensitive [[venous]] sampling
** Selective [[arteriography]]
** [[Angiogram|Angiography]]
Predicting post-operative success:
* [[Intraoperative parathyroid hormone]] monitoring
|-
! style="background: #DCDCDC; text-align: center;" |Secondary hyperparathyroidism
| style="background: #F5F5F5;" |Increase in [[secretion]] of [[parathyroid hormone]] ([[PTH]]) from a secondary process. [[Parathyroid hormone]] causes increase in [[serum]] [[calcium]] after long periods.
| style="background: #F5F5F5;" |
* May present with history of:
** [[Chronic renal failure]]
** [[Vitamin D deficiency]]
| 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>
! 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>
| 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]]
 
Normal/↑ calcitriol
| style="background: #F5F5F5;" |
* [[Chest X-rays|Chest X-ray]]
* [[CT scan]]
* [[MRI]]
|-
! style="background: #DCDCDC; text-align: center;" |Osteolytic tumors
| 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
| 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
| 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="2" style="background: #DCDCDC; text-align: center;" |'''Nutritional'''
! style="background: #DCDCDC; text-align: center;" |Milk-alkali syndrome
| style="background: #F5F5F5;" |[[Hypercalcemia]] is be caused by high intake of [[calcium carbonate]].
| style="background: #F5F5F5;" |
* History of
** High milk intake
** Excess calcium intake for treating:
*** [[Osteoporosis]]
*** [[Dyspepsia]]
* May lead to [[metabolic alkalosis]] and [[renal insufficiency]].
| 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;" |
* [[Renal function tests]]
|-
! style="background: #DCDCDC; text-align: center;" |Vitamin D toxicity
| style="background: #F5F5F5;" |Excess [[vitamin D]] causes increased [[absorption]] of [[calcium]] from [[intestine]] causing [[hypercalcemia]].
| style="background: #F5F5F5;" |
* 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 [[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: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" |↑
| style="background: #F5F5F5; text-align: center;" | --
| style="background: #F5F5F5; text-align: center;" |↑ [[Vitamin D]] ([[calcidiol]] and/or [[calcitriol]])
| style="background: #F5F5F5;" | --
|-
! 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>
| 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]]
** [[Weight loss]]
| 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]]
 
↑ [[ACE]] levels
| style="background: #F5F5F5;" |
* [[Chest X-ray]]
* [[Biopsy]]
|}
 
==References==
==References==
{{reflist|2}}
{{reflist|2}}

Revision as of 02:08, 6 October 2017

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Milk-alkali syndrome must be differentiated from other causes of hypercalcaemia

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] Humoral hypercalcemia of malignancy[2][3][4] Tumor cells secretes parathyroid hormone-related protein (PTHrP) which has similar action as parathyroid hormone. -- ↑ ↓/Normal ↑ PTHrP

Normal/↑ calcitriol

Osteolytic tumors Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metasteses can cause bone resorption causing hypercalcemia. ↓ ↑ -- --
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. -- ↑ -- ↑ Calcitriol
Ectopic parathyroid hormone[5] Some tumors leads to ectopic production of parathyroid hormone. ↑ ↑ ↓/Normal Normal/↑ calcitriol
Medication induced Lithium[6] 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 Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia. -- ↑ -- -- --
Nutritional Milk-alkali syndrome Hypercalcemia is be caused by high intake of calcium carbonate. -- ↑ -- --
Vitamin D toxicity Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia. -- ↑ -- ↑ Vitamin D (calcidiol and/or calcitriol) --
Granulomatous disease Sarcoidosis[9] Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages. -- ↑ -- ↑ Calcitriol

↑ ACE levels

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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