Parathyroid adenoma differential diagnosis: Difference between revisions

Revision as of 14:03, 29 May 2019

link=https://www.wikidoc.org/index.php/Parathyroid adenoma

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

Majority of parathyroid adenoma are asymptomatic. However, most common presentation of a parathyroid adenoma is hypercalcemia. So, parathyroid adenoma shall be differentiated from other conditions presenting pimarily as hypercalcemia.

Differential Diagnosis

Majority of parathyroid adenoma are asymptomatic.
However, most common presentation of a parathyroid adenoma is hypercalcemia.
So, parathyroid adenoma shall be differentiated from other conditions presenting primarily as hypercalcemia.^[1]
Common conditions presenting as hypercalcemia include:
- Parathyroid adenoma (primary hyperparathyroidism)
- Secondary hyperthyroidism (long term)
- Tertiary hyperparathyroidism
- Familial hypocalceuric hypercalcemia
- Hypercalcemia due to malignancy
  - Humoral hypercalcemia of malignancy
  - Osteolytic tumors
  - Production of calcitriol
  - Ectopic parathyroid gland
- Medication induced
  - Lithium
  - Thiazide diuretics
- Nutritional
  - Milk alkali syndrome
  - Vitamin D toxicity
- Granulomatous disease
  - Sarcoidosis

Differential diagnosis of parathyroid adenoma on the basis of hypercalcemia
Disorder		Mechanism of hypercalcemia	Clinical features	Laboratory findings				Imaging & diagnostic modalities
Disorder		Mechanism of hypercalcemia	Clinical features	PTH	Calcium	Phosphate	Other findings	Imaging & diagnostic modalities
Parathyroid adenoma (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 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) PET MRI Invasive: Super sensitive venous sampling Selective arteriography Angiography Predicting post-operative success: Intraoperative parathyroid hormone monitoring
Secondary hyperparathyroidism (long term)		Increase in secretion of parathyroid hormone (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium after long periods.	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.	A benign condition Does not require treatment	Normal/↑	Normal/↑	--	--	Urinary calcium/creatinine clearance ratio
Malignancy	Humoral hypercalcemia of malignancy	Tumor cells secretes parathyroid hormone-related protein (PTHrP) which has similar action as parathyroid hormone.	Most common cause of malignancy related hypercalcemia Usually present with solid tumors	--	↑	↓/Normal	↑ PTHrP Normal/↑ calcitriol	Chest X-ray CT scan MRI
	Osteolytic tumors	Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metasteses can cause bone resorption causing hypercalcemia.	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.	Commonly present in lymphomas and in some ovarian germ cell tumors	--	↑	--	↑ Calcitriol	CT scan MRI
	Ectopic parathyroid hormone	Some tumors leads to ectopic production of parathyroid hormone.	In rare instances, small cell carcinoma of lung may produce hypercalcemia by this process	↑	↑	↓/Normal	Normal/↑ calcitriol	Chest X-ray CT scan MRI
Medication induced	Lithium	Lithium lowers urinary calcium and causes hypercalcemia. Lithium has been reported to cause an increase in parathyroid hormone and enlargement if parathyroid gland after weeks to months of therapy.	History of mood disorder	↑	↑	--	--	Lithium levels
Medication induced	Thiazide diuretics	Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia.	History of cardiac disorder Rarely causes hypercalcemia	--	↑	--	--	--
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.	--	↑	--	↓ calcitriol	Renal function tests
Nutritional	Vitamin D toxicity	Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia.	History of: Excess intake vitamin D Excess milk fortified with vitamin D Topical application of vitamin D analogue calcipotriol	--	↑	--	↑ Vitamin D (calcidiol and/or calcitriol)	--
Granulomatous disease	Sarcoidosis	Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages.	History of: Cough Dyspnea Chest pain Tiredness or weakness Fever Weight loss	--	↑	--	↑ Calcitriol ↑ ACE levels	Chest X-ray Biopsy

References

↑ Marcocci, Claudio; Cetani, Filomena (2011). "Primary Hyperparathyroidism". New England Journal of Medicine. 365 (25): 2389–2397. doi:10.1056/NEJMcp1106636. ISSN 0028-4793.

[MarcocciCetani2011-1] Marcocci, Claudio; Cetani, Filomena (2011). "Primary Hyperparathyroidism". New England Journal of Medicine. 365 (25): 2389–2397. doi:10.1056/NEJMcp1106636. ISSN 0028-4793.

[1]

@@ Line 4: / Line 4: @@
 ==Overview==
+Majority of parathyroid adenoma are asymptomatic. However, most common presentation of a parathyroid adenoma is [[hypercalcemia]]. So, parathyroid adenoma shall be differentiated from other conditions presenting pimarily as [[hypercalcemia]].
 ==Differential Diagnosis==
+* Majority of parathyroid adenoma are asymptomatic.
+* However, most common presentation of a parathyroid adenoma is [[hypercalcemia]].
+* So, parathyroid adenoma shall be differentiated from other conditions presenting primarily as [[hypercalcemia]].<ref name="MarcocciCetani2011">{{cite journal|last1=Marcocci|first1=Claudio|last2=Cetani|first2=Filomena|title=Primary Hyperparathyroidism|journal=New England Journal of Medicine|volume=365|issue=25|year=2011|pages=2389–2397|issn=0028-4793|doi=10.1056/NEJMcp1106636}}</ref>
+* Common conditions presenting as hypercalcemia include:
+** Parathyroid adenoma ([[primary hyperparathyroidism]])
+** [[Secondary hyperthyroidism]] (long term)
+** Tertiary hyperparathyroidism
+** [[Familial hypocalceuric hypercalcemia]]
+** Hypercalcemia due to malignancy
+*** Humoral hypercalcemia of malignancy
+*** Osteolytic tumors
+*** Production of calcitriol
+*** Ectopic parathyroid gland
+** Medication induced
+*** [[Lithium]]
+*** [[Thiazide diuretics]]
+** Nutritional
+*** Milk alkali syndrome
+*** Vitamin D toxicity
+** Granulomatous disease
+*** [[Sarcoidosis]]
 {|
 ! colspan="9" style="background: #4479BA; text-align: center;" |{{fontcolor|#FFF|Differential diagnosis of parathyroid adenoma on the basis of hypercalcemia}}
@@ Line 21: / Line 42: @@
 ! style="background: #7d7d7d; text-align: center;" |{{fontcolor|#FFF|Other findings}}
 |-
-! colspan="2" style="background: #DCDCDC; text-align: center;" |Primary hyperparathyroidism (Parathyroid adenoma)
+! colspan="2" style="background: #DCDCDC; text-align: center;" |Parathyroid adenoma ([[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;" |
@@ Line 48: / Line 69: @@
 * [[Intraoperative parathyroid hormone]] monitoring
 |-
-! colspan="2" style="background: #DCDCDC; text-align: center;" |Secondary hyperparathyroidism
+! colspan="2" style="background: #DCDCDC; text-align: center;" |[[Secondary hyperparathyroidism]] (long term)
 | 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;" |
@@ Line 59: / Line 80: @@
 | style="background: #F5F5F5; text-align: center;" | --
 |-
-! colspan="2" style="background: #DCDCDC; text-align: center;" |Tertiary hyperparathyroidism
+! colspan="2" 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;" |
@@ Line 81: / Line 102: @@
 * 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>
+! rowspan="4" style="background: #DCDCDC; text-align: center;" |'''Malignancy'''
-! 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: #DCDCDC; text-align: center;" |Humoral hypercalcemia of malignancy
 | style="background: #F5F5F5;" |[[Tumor]] cells secretes [[parathyroid hormone-related protein]] ([[PTHrP]]) which has similar action as [[parathyroid hormone]].
 | style="background: #F5F5F5;" |
@@ Line 98: / Line 119: @@
 * [[MRI]]
 |-
-! 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: #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;" |
@@ Line 114: / Line 135: @@
 * [[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: #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;" |
@@ Line 126: / Line 147: @@
 * [[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: #DCDCDC; text-align: center;" |Ectopic parathyroid hormone
 | style="background: #F5F5F5;" |Some tumors leads to [[Ectopia|ectopic]] production of [[parathyroid hormone]].
 | style="background: #F5F5F5;" |
@@ Line 140: / Line 161: @@
 |-
 ! 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: #DCDCDC; text-align: center;" |Lithium
 | 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;" |
@@ Line 151: / Line 172: @@
 * [[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: #DCDCDC; text-align: center;" |Thiazide diuretics
 | style="background: #F5F5F5;" |[[Thiazide diuretics]] lowers [[urinary]] [[calcium]] [[excretion]] and causes [[hypercalcemia]].
 | style="background: #F5F5F5;" |
@@ Line 179: / Line 200: @@
 * [[Renal function tests]]
 |-
-! 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: #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>
+** Excess milk fortified with [[vitamin D]]
-** 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>
+** Topical application of vitamin D analogue [[calcipotriol]]
 | style="background: #F5F5F5; text-align: center;" | --
 | style="background: #F5F5F5; text-align: center;" |↑
@@ Line 193: / Line 214: @@
 |-
 ! 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: #DCDCDC; text-align: center;" |Sarcoidosis
 | style="background: #F5F5F5;" |[[Hypercalcemia]] is causes by endogeous production of [[calcitriol]] by disease-activated [[Macrophage|macrophages]].
 | style="background: #F5F5F5;" |
@@ Line 215: / Line 236: @@
 ==References==
+<references />

Parathyroid adenoma differential diagnosis: Difference between revisions

Revision as of 14:03, 29 May 2019

Overview

Differential Diagnosis

References

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