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=Causes= | =Causes= | ||
===Common Causes=== | ===Common Causes=== | ||
*Post-surgical (most common cause) | *Post-surgical (most common cause)<ref name="pmid11117980">{{cite journal |vauthors=Marx SJ |title=Hyperparathyroid and hypoparathyroid disorders |journal=N. Engl. J. Med. |volume=343 |issue=25 |pages=1863–75 |year=2000 |pmid=11117980 |doi=10.1056/NEJM200012213432508 |url=}}</ref> | ||
**[[Thyroidectomy]] | **[[Thyroidectomy]] | ||
**[[Parathyroidectomy]] | **[[Parathyroidectomy]] | ||
**Radical neck dissection | **Radical neck dissection | ||
*Autoimmune (2nd most common cause) | *Autoimmune (2nd most common cause)<ref name="pmid15141045">{{cite journal |vauthors=Eisenbarth GS, Gottlieb PA |title=Autoimmune polyendocrine syndromes |journal=N. Engl. J. Med. |volume=350 |issue=20 |pages=2068–79 |year=2004 |pmid=15141045 |doi=10.1056/NEJMra030158 |url=}}</ref> | ||
**Polyglandular autoimmune syndrome type 1 | **Polyglandular autoimmune syndrome type 1 | ||
***Also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or APECED), or acquired hypoparathyroidism associated with autoimmune hypothyroidism | ***Also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or APECED), or acquired hypoparathyroidism associated with autoimmune hypothyroidism | ||
| Line 80: | Line 80: | ||
*Isolated hypoparathyroidism | *Isolated hypoparathyroidism | ||
**Autosomal dominant | **Autosomal dominant | ||
***Autosomal dominant familial isolated hypoparathyroidism caused by PTH gene mutation | ***Autosomal dominant familial isolated hypoparathyroidism caused by PTH gene mutation<ref name="pmid2212001">{{cite journal |vauthors=Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM |title=Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism |journal=J. Clin. Invest. |volume=86 |issue=4 |pages=1084–7 |year=1990 |pmid=2212001 |pmc=296835 |doi=10.1172/JCI114811 |url=}}</ref> | ||
***Autosomal dominant familial isolated hypoparathyroidism caused by caused by glial cells missing 2 (GCM2) gene mutation - Dominant negative effect | ***Autosomal dominant familial isolated hypoparathyroidism caused by caused by glial cells missing 2 (GCM2) gene mutation - Dominant negative effect<ref name="pmid18712808">{{cite journal |vauthors=Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN |title=Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism |journal=Hum. Mutat. |volume=30 |issue=1 |pages=85–92 |year=2009 |pmid=18712808 |doi=10.1002/humu.20827 |url=}}</ref> | ||
***Autosomal dominant hypocalcemia | ***Autosomal dominant hypocalcemia<ref name="pmid27803672">{{cite journal |vauthors=Roszko KL, Bi RD, Mannstadt M |title=Autosomal Dominant Hypocalcemia (Hypoparathyroidism) Types 1 and 2 |journal=Front Physiol |volume=7 |issue= |pages=458 |year=2016 |pmid=27803672 |pmc=5067375 |doi=10.3389/fphys.2016.00458 |url=}}</ref> | ||
****Autosomal dominant hypocalcemia type 1 | ****Autosomal dominant hypocalcemia type 1 | ||
*****Calcium-sensing activating mutation | *****Calcium-sensing activating mutation | ||
| Line 88: | Line 88: | ||
*****Also known as familial hypercalciuric hypocalcemia | *****Also known as familial hypercalciuric hypocalcemia | ||
*****The activating mutation results in gain in function | *****The activating mutation results in gain in function | ||
*****Calcium-sensing receptor gene activating mutation can also cause Bartter syndrome type 5.This mutation cause the inhibition of apical potassium channel in the thick ascending limb of the loop of Henle in the kidney. | *****Calcium-sensing receptor gene activating mutation can also cause Bartter syndrome type 5.This mutation cause the inhibition of apical potassium channel in the thick ascending limb of the loop of Henle in the kidney.<ref name="pmid17048213">{{cite journal |vauthors=Vezzoli G, Arcidiacono T, Paloschi V, Terranegra A, Biasion R, Weber G, Mora S, Syren ML, Coviello D, Cusi D, Bianchi G, Soldati L |title=Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome |journal=J. Nephrol. |volume=19 |issue=4 |pages=525–8 |year=2006 |pmid=17048213 |doi= |url=}}</ref><ref name="pmid25932037">{{cite journal |vauthors=Choi KH, Shin CH, Yang SW, Cheong HI |title=Autosomal dominant hypocalcemia with Bartter syndrome due to a novel activating mutation of calcium sensing receptor, Y829C |journal=Korean J Pediatr |volume=58 |issue=4 |pages=148–53 |year=2015 |pmid=25932037 |pmc=4414630 |doi=10.3345/kjp.2015.58.4.148 |url=}}</ref> | ||
****Autosomal dominant hypocalcemia type 2 | ****Autosomal dominant hypocalcemia type 2 | ||
*****G protein G11 (GNA11) mutation | *****G protein G11 (GNA11) mutation | ||
**Autosomal recessive | **Autosomal recessive | ||
***Autosomal recessive familial isolated hypoparathyroidism caused by PTH gene mutation | ***Autosomal recessive familial isolated hypoparathyroidism caused by PTH gene mutation<ref name="pmid10523031">{{cite journal |vauthors=Sunthornthepvarakul T, Churesigaew S, Ngowngarmratana S |title=A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism |journal=J. Clin. Endocrinol. Metab. |volume=84 |issue=10 |pages=3792–6 |year=1999 |pmid=10523031 |doi=10.1210/jcem.84.10.6070 |url=}}</ref> | ||
***Autosomal recessive familial isolated hypoparathyroidism caused by glial cells missing 2 (GCM2) gene mutation<ref name="pmid18712808">{{cite journal |vauthors=Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN |title=Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism |journal=Hum. Mutat. |volume=30 |issue=1 |pages=85–92 |year=2009 |pmid=18712808 |doi=10.1002/humu.20827 |url=}}</ref> | ***Autosomal recessive familial isolated hypoparathyroidism caused by glial cells missing 2 (GCM2) gene mutation<ref name="pmid11602629">{{cite journal |vauthors=Ding C, Buckingham B, Levine MA |title=Familial isolated hypoparathyroidism caused by a mutation in the gene for the transcription factor GCMB |journal=J. Clin. Invest. |volume=108 |issue=8 |pages=1215–20 |year=2001 |pmid=11602629 |pmc=209530 |doi=10.1172/JCI13180 |url=}}</ref><ref name="pmid18712808">{{cite journal |vauthors=Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN |title=Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism |journal=Hum. Mutat. |volume=30 |issue=1 |pages=85–92 |year=2009 |pmid=18712808 |doi=10.1002/humu.20827 |url=}}</ref> | ||
**X-linked | **X-linked | ||
***X-linked recessive hypoparathyroidism | ***X-linked recessive hypoparathyroidism | ||
****Caused by mutation in gene variant FHL1 (exon 4, c.C283T, p.R95W) on chromosome locus Xq26-q27. | ****Caused by mutation in gene variant FHL1 (exon 4, c.C283T, p.R95W) on chromosome locus Xq26-q27.<ref name="pmid28444561">{{cite journal |vauthors=Pillar N, Pleniceanu O, Fang M, Ziv L, Lahav E, Botchan S, Cheng L, Dekel B, Shomron N |title=A rare variant in the FHL1 gene associated with X-linked recessive hypoparathyroidism |journal=Hum. Genet. |volume=136 |issue=7 |pages=835–845 |year=2017 |pmid=28444561 |pmc=5487855 |doi=10.1007/s00439-017-1804-9 |url=}}</ref> | ||
*Congenital multisystem syndromes | *Congenital multisystem syndromes | ||
**DiGeorge syndrome | **DiGeorge syndrome<ref name="pmid21049214">{{cite journal |vauthors=Fomin AB, Pastorino AC, Kim CA, Pereira CA, Carneiro-Sampaio M, Abe-Jacob CM |title=DiGeorge Syndrome: a not so rare disease |journal=Clinics (Sao Paulo) |volume=65 |issue=9 |pages=865–9 |year=2010 |pmid=21049214 |pmc=2954737 |doi= |url=}}</ref> | ||
**Autosomal dominant disorder | **Autosomal dominant disorder | ||
***Presents with thymus dysfunction, cardiac diseases, immunodeficiency, hypocalcemia, and other clinical problems | ***Presents with thymus dysfunction, cardiac diseases, immunodeficiency, hypocalcemia, and other clinical problems | ||
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***Also known as 22q11.2DS, autosomal dominant Opitz G/BBB syndrome, CATCH 22 Syndromes, Cayler cardiofacial syndrome, conotruncal anomaly face syndrome (CTAF), deletion 22q11.2 syndrome, Sedlackova syndrome, Shprintzen syndrome, VCFS, velocardiofacial syndrome, and velo-cardio-facial syndrome. | ***Also known as 22q11.2DS, autosomal dominant Opitz G/BBB syndrome, CATCH 22 Syndromes, Cayler cardiofacial syndrome, conotruncal anomaly face syndrome (CTAF), deletion 22q11.2 syndrome, Sedlackova syndrome, Shprintzen syndrome, VCFS, velocardiofacial syndrome, and velo-cardio-facial syndrome. | ||
***CATCH 22 stands for cardiac, abnormal facies, thymic aplasia, cleft palate, and hypocalcemia with 22q deletion | ***CATCH 22 stands for cardiac, abnormal facies, thymic aplasia, cleft palate, and hypocalcemia with 22q deletion | ||
**CHARGE syndrome | **CHARGE syndrome<ref name="pmid21995344">{{cite journal |vauthors=Jain S, Kim HG, Lacbawan F, Meliciani I, Wenzel W, Kurth I, Sharma J, Schoeneman M, Ten S, Layman LC, Jacobson-Dickman E |title=Unique phenotype in a patient with CHARGE syndrome |journal=Int J Pediatr Endocrinol |volume=2011 |issue= |pages=11 |year=2011 |pmid=21995344 |pmc=3216247 |doi=10.1186/1687-9856-2011-11 |url=}}</ref> | ||
***Autosomal dominant disorder | ***Autosomal dominant disorder | ||
***Presents with coloboma, heart defects, atresia choanae, retarded growth and development, genitourinary abnormalities, and ear anomalies and/or deafness. | ***Presents with coloboma, heart defects, atresia choanae, retarded growth and development, genitourinary abnormalities, and ear anomalies and/or deafness. | ||
***Caused by CHD7 G744S missense mutation | ***Caused by CHD7 G744S missense mutation | ||
**Kenny-Caffey syndrome | **Kenny-Caffey syndrome<ref name="pmid23087875">{{cite journal |vauthors=Metwalley KA, Farghaly HS |title=Kenny-Caffey syndrome type 1 in an Egyptian girl |journal=Indian J Endocrinol Metab |volume=16 |issue=5 |pages=827–9 |year=2012 |pmid=23087875 |pmc=3475915 |doi=10.4103/2230-8210.100645 |url=}}</ref> | ||
***Autosomal recessive inheritence | ***Autosomal recessive inheritence | ||
***Deletion of the TBCE gene responsible for encoding a protein that participates in beta-tubulin folding. | ***Deletion of the TBCE gene responsible for encoding a protein that participates in beta-tubulin folding. | ||
***Presents with hypoparathyroidism due to absent parathyroid tissue, growth retardation, medullary stenosis of tubular bones) | ***Presents with hypoparathyroidism due to absent parathyroid tissue, growth retardation, medullary stenosis of tubular bones) | ||
**Sanjad-Sakati syndrome | **Sanjad-Sakati syndrome<ref name="pmid22043344">{{cite journal |vauthors=Rafique B, Al-Yaarubi S |title=Sanjad-Sakati Syndrome in Omani children |journal=Oman Med J |volume=25 |issue=3 |pages=227–9 |year=2010 |pmid=22043344 |pmc=3191633 |doi=10.5001/omj.2010.63 |url=}}</ref> | ||
***Sanjad-Sakati syndrome in exclusively found in arabian descent popultion. | ***Sanjad-Sakati syndrome in exclusively found in arabian descent popultion. | ||
***Autosomal recessive disorder | ***Autosomal recessive disorder | ||
***Mutation in TBCE gene. | ***Mutation in TBCE gene. | ||
***Presents with hypoparathyroidism, intellectual disability, dysmorphism | ***Presents with hypoparathyroidism, intellectual disability, dysmorphism | ||
**Barakat syndrome | **Barakat syndrome<ref name="pmid11389161">{{cite journal |vauthors=Muroya K, Hasegawa T, Ito Y, Nagai T, Isotani H, Iwata Y, Yamamoto K, Fujimoto S, Seishu S, Fukushima Y, Hasegawa Y, Ogata T |title=GATA3 abnormalities and the phenotypic spectrum of HDR syndrome |journal=J. Med. Genet. |volume=38 |issue=6 |pages=374–80 |year=2001 |pmid=11389161 |pmc=1734904 |doi= |url=}}</ref><ref name="pmid10935639">{{cite journal |vauthors=Van Esch H, Groenen P, Nesbit MA, Schuffenhauer S, Lichtner P, Vanderlinden G, Harding B, Beetz R, Bilous RW, Holdaway I, Shaw NJ, Fryns JP, Van de Ven W, Thakker RV, Devriendt K |title=GATA3 haplo-insufficiency causes human HDR syndrome |journal=Nature |volume=406 |issue=6794 |pages=419–22 |year=2000 |pmid=10935639 |doi=10.1038/35019088 |url=}}</ref> | ||
***Autosomal recessive inheritance | ***Autosomal recessive inheritance | ||
***Mutations in the GATA3 gene | ***Mutations in the GATA3 gene | ||
***Also known as hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome | ***Also known as hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome | ||
***Presents with primary hypoparathyroidism, nerve deafness, steroid-resistant nephrosis | ***Presents with primary hypoparathyroidism, nerve deafness, steroid-resistant nephrosis | ||
**Kearns-Sayre syndrome | **Kearns-Sayre syndrome<ref name="pmid23769710">{{cite journal |vauthors=Schaefer AM, Walker M, Turnbull DM, Taylor RW |title=Endocrine disorders in mitochondrial disease |journal=Mol. Cell. Endocrinol. |volume=379 |issue=1-2 |pages=2–11 |year=2013 |pmid=23769710 |pmc=3820028 |doi=10.1016/j.mce.2013.06.004 |url=}}</ref> | ||
***Mitochondrial inheritence | ***Mitochondrial inheritence | ||
***Presents with mitochondrial myopathy, ophthalmoplegia, retinal degeneration, cardiac conduction defects, primary hypoparathyroidism) | ***Presents with mitochondrial myopathy, ophthalmoplegia, retinal degeneration, cardiac conduction defects, primary hypoparathyroidism) | ||
**Pearson marrow pancreas syndrome | **Pearson marrow pancreas syndrome<ref name="pmid9212183">{{cite journal |vauthors=Seneca S, De Meirleir L, De Schepper J, Balduck N, Jochmans K, Liebaers I, Lissens W |title=Pearson marrow pancreas syndrome: a molecular study and clinical management |journal=Clin. Genet. |volume=51 |issue=5 |pages=338–42 |year=1997 |pmid=9212183 |doi= |url=}}</ref> | ||
***Mitochondrial inheritence | ***Mitochondrial inheritence | ||
***Presents with lactic acidosis, neutropenia, sideroblastic anemia, pancreatic exocrine dysfunction, and hypoparathyroidism | ***Presents with lactic acidosis, neutropenia, sideroblastic anemia, pancreatic exocrine dysfunction, and hypoparathyroidism | ||
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=Symptoms= | =Symptoms= | ||
*Clinical symptoms depends on two features: | *Clinical symptoms depends on two features:<ref name="pmid28138323">{{cite journal |vauthors=Abate EG, Clarke BL |title=Review of Hypoparathyroidism |journal=Front Endocrinol (Lausanne) |volume=7 |issue= |pages=172 |year=2016 |pmid=28138323 |pmc=5237638 |doi=10.3389/fendo.2016.00172 |url=}}</ref> | ||
**Acuteness of hypocalcemia | **Acuteness of hypocalcemia | ||
**The absolute level of serum calcium | **The absolute level of serum calcium | ||
*Patients presents dramatically and tends to have more symptoms if there is an acute drop in serum calcium compared to patients with chronic hypocalcemia. | *Patients presents dramatically and tends to have more symptoms if there is an acute drop in serum calcium compared to patients with chronic hypocalcemia.<ref name="pmid8325292">{{cite journal |vauthors=Tohme JF, Bilezikian JP |title=Hypocalcemic emergencies |journal=Endocrinol. Metab. Clin. North Am. |volume=22 |issue=2 |pages=363–75 |year=1993 |pmid=8325292 |doi= |url=}}</ref> | ||
===Common symptoms=== | ===Common symptoms=== | ||
Common symptoms of hypoparathyroidism include:<ref name="pmid28138323">{{cite journal |vauthors=Abate EG, Clarke BL |title=Review of Hypoparathyroidism |journal=Front Endocrinol (Lausanne) |volume=7 |issue= |pages=172 |year=2016 |pmid=28138323 |pmc=5237638 |doi=10.3389/fendo.2016.00172 |url=}}</ref> | Common symptoms of hypoparathyroidism include:<ref name="pmid28138323">{{cite journal |vauthors=Abate EG, Clarke BL |title=Review of Hypoparathyroidism |journal=Front Endocrinol (Lausanne) |volume=7 |issue= |pages=172 |year=2016 |pmid=28138323 |pmc=5237638 |doi=10.3389/fendo.2016.00172 |url=}}</ref><ref name="pmid18535072">{{cite journal |vauthors=Cooper MS, Gittoes NJ |title=Diagnosis and management of hypocalcaemia |journal=BMJ |volume=336 |issue=7656 |pages=1298–302 |year=2008 |pmid=18535072 |pmc=2413335 |doi=10.1136/bmj.39582.589433.BE |url=}}</ref> | ||
*Tetany (hallmark of acute hypocalcemia) | *Tetany (hallmark of acute hypocalcemia) | ||
*Paresthesia in fingertips, toes, perioral area | *Paresthesia in fingertips, toes, perioral area | ||
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*Symptoms of acute cardiomyopathy | *Symptoms of acute cardiomyopathy | ||
*Wheezing and dyspnea (due to bronchospasm) | *Wheezing and dyspnea (due to bronchospasm) | ||
*Electrocardiographic changes that mimic myocardial infarction, or congestive heart failure (decreased cardiac contractility is related to low serum calcium and possibly parathyroid hormone deficiency, as there are PTH receptors in cardiac myocytes). | *Electrocardiographic changes that mimic myocardial infarction, or congestive heart failure (decreased cardiac contractility is related to low serum calcium and possibly parathyroid hormone deficiency, as there are PTH receptors in cardiac myocytes).<ref name="pmid24919035">{{cite journal |vauthors=Kimura S, Yoshioka K |title=Parathyroid hormone and parathyroid hormone type-1 receptor accelerate myocyte differentiation |journal=Sci Rep |volume=4 |issue= |pages=5066 |year=2014 |pmid=24919035 |pmc=4052750 |doi=10.1038/srep05066 |url=}}</ref> | ||
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=Differential Diagnosis= | =Differential Diagnosis= | ||
{| class="wikitable" | {| class="wikitable" | ||
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|- | |- | ||
| colspan="2" |Hypoparathyroidism | | colspan="2" |Hypoparathyroidism | ||
| | | | ||
| | | | ||
|↓ | |↓ | ||
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| -- | | -- | ||
|- | |- | ||
| colspan="2" |Hypomagnesemia | | colspan="2" |Hypomagnesemia<ref name="pmid26069819">{{cite journal |vauthors=Jahnen-Dechent W, Ketteler M |title=Magnesium basics |journal=Clin Kidney J |volume=5 |issue=Suppl 1 |pages=i3–i14 |year=2012 |pmid=26069819 |pmc=4455825 |doi=10.1093/ndtplus/sfr163 |url=}}</ref> | ||
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==References== | ==References== | ||
Revision as of 18:15, 28 September 2017
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Hyperparathyroidism Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Sandbox : anmol On the Web |
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American Roentgen Ray Society Images of Sandbox : anmol |
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]
Classification
| Classification of hyperparathyridism | |||
|---|---|---|---|
| Features | Primary hyperparathyroidism | Secondary hyperparathyroidism | Tertiary hyperparathyroidism |
| Pathology | Hyperfunction of parathyroid cells due to hyperplasia, adenoma or carcinoma. | Physiological stimulation of parathyroid in response to hypocalcaemia. | Following long term physiological stimulation leading to hyperplasia. |
| Cause | |||
| Associations | May be associated with multiple endocrine neoplasia. | Usually due to chronic renal failure or other causes of Vitamin D deficiency. | Seen in chronic renal failure. |
| Serum calcium | High | Low/Normal | High |
| Serum phosphate | Low/Normal | High | High |
| Management | Usually surgery if symptomatic. Cincacalcet can be considered in those not fit for surgery. | Treatment of underlying cause. | Usually cinacalcet or surgery in those that don't respond. |
Causes
Common Causes
- Post-surgical (most common cause)[1]
- Thyroidectomy
- Parathyroidectomy
- Radical neck dissection
- Autoimmune (2nd most common cause)[2]
- Polyglandular autoimmune syndrome type 1
- Also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or APECED), or acquired hypoparathyroidism associated with autoimmune hypothyroidism
- Isolated autoimmune hypoparathyroidism
- Polyglandular autoimmune syndrome type 1
Less Common Causes
- Infiltration and/or destruction of parathyroid glands
- Metal overload
- Iron overload
- Hemochromatosis
- Thalassemia (due to repeated blood transfusion)
- Copper overload
- Wilson's disease
- Aluminium deposition
- Usually seen in patients with end-stage renal disease on hemodialysis
- Hypermagnesemia
- Iron overload
- Radiation-induced destruction parathyroid glands
- Hypomagnesemia (reversible)
- Metastatic disease
- Granulomatous disease
- Amyloidosis
- Syphilis
- Metal overload
- Progressive systemic sclerosis
- Neonatal cause
- Maternal hyperparathyroidism
- Genetic causes
Genetic Causes
- Isolated hypoparathyroidism
- Autosomal dominant
- Autosomal dominant familial isolated hypoparathyroidism caused by PTH gene mutation[3]
- Autosomal dominant familial isolated hypoparathyroidism caused by caused by glial cells missing 2 (GCM2) gene mutation - Dominant negative effect[4]
- Autosomal dominant hypocalcemia[5]
- Autosomal dominant hypocalcemia type 1
- Calcium-sensing activating mutation
- Most common genetic form of hypoparathyroidism
- Also known as familial hypercalciuric hypocalcemia
- The activating mutation results in gain in function
- Calcium-sensing receptor gene activating mutation can also cause Bartter syndrome type 5.This mutation cause the inhibition of apical potassium channel in the thick ascending limb of the loop of Henle in the kidney.[6][7]
- Autosomal dominant hypocalcemia type 2
- G protein G11 (GNA11) mutation
- Autosomal dominant hypocalcemia type 1
- Autosomal recessive
- X-linked
- X-linked recessive hypoparathyroidism
- Caused by mutation in gene variant FHL1 (exon 4, c.C283T, p.R95W) on chromosome locus Xq26-q27.[10]
- X-linked recessive hypoparathyroidism
- Autosomal dominant
- Congenital multisystem syndromes
- DiGeorge syndrome[11]
- Autosomal dominant disorder
- Presents with thymus dysfunction, cardiac diseases, immunodeficiency, hypocalcemia, and other clinical problems
- Caused by 22q11.2 deletion
- Also known as 22q11.2DS, autosomal dominant Opitz G/BBB syndrome, CATCH 22 Syndromes, Cayler cardiofacial syndrome, conotruncal anomaly face syndrome (CTAF), deletion 22q11.2 syndrome, Sedlackova syndrome, Shprintzen syndrome, VCFS, velocardiofacial syndrome, and velo-cardio-facial syndrome.
- CATCH 22 stands for cardiac, abnormal facies, thymic aplasia, cleft palate, and hypocalcemia with 22q deletion
- CHARGE syndrome[12]
- Autosomal dominant disorder
- Presents with coloboma, heart defects, atresia choanae, retarded growth and development, genitourinary abnormalities, and ear anomalies and/or deafness.
- Caused by CHD7 G744S missense mutation
- Kenny-Caffey syndrome[13]
- Autosomal recessive inheritence
- Deletion of the TBCE gene responsible for encoding a protein that participates in beta-tubulin folding.
- Presents with hypoparathyroidism due to absent parathyroid tissue, growth retardation, medullary stenosis of tubular bones)
- Sanjad-Sakati syndrome[14]
- Sanjad-Sakati syndrome in exclusively found in arabian descent popultion.
- Autosomal recessive disorder
- Mutation in TBCE gene.
- Presents with hypoparathyroidism, intellectual disability, dysmorphism
- Barakat syndrome[15][16]
- Autosomal recessive inheritance
- Mutations in the GATA3 gene
- Also known as hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome
- Presents with primary hypoparathyroidism, nerve deafness, steroid-resistant nephrosis
- Kearns-Sayre syndrome[17]
- Mitochondrial inheritence
- Presents with mitochondrial myopathy, ophthalmoplegia, retinal degeneration, cardiac conduction defects, primary hypoparathyroidism)
- Pearson marrow pancreas syndrome[18]
- Mitochondrial inheritence
- Presents with lactic acidosis, neutropenia, sideroblastic anemia, pancreatic exocrine dysfunction, and hypoparathyroidism
- Mitochondrial encephalopathy
Symptoms
- Clinical symptoms depends on two features:[19]
- Acuteness of hypocalcemia
- The absolute level of serum calcium
- Patients presents dramatically and tends to have more symptoms if there is an acute drop in serum calcium compared to patients with chronic hypocalcemia.[20]
Common symptoms
Common symptoms of hypoparathyroidism include:[19][21]
- Tetany (hallmark of acute hypocalcemia)
- Paresthesia in fingertips, toes, perioral area
- Carpopedal spasms
- Circumoral numbness
- Abdominal pain
- Biliary colic
- Dysphoria
- Fatigue
- Muscle cramps
- Myoclonic jerks
- New onset seizure due to hypocalcemia or worsening of seizures
- Painful menstruation
Less common synptoms
Less common symptoms of hypoparathyroidism include:[19][21]
- Cognitive impairment
- Decreased concentration
- Hoarseness (due to laryngospasm)
- Neuromuscular irritability
- Palpitations due cardiac dysarrhythmias
- Personality disturbances and/or mood changes
- Symptoms of acute cardiomyopathy
- Wheezing and dyspnea (due to bronchospasm)
- Electrocardiographic changes that mimic myocardial infarction, or congestive heart failure (decreased cardiac contractility is related to low serum calcium and possibly parathyroid hormone deficiency, as there are PTH receptors in cardiac myocytes).[22]
- Cardiac manifestations
- prolonged QT interval and T-wave alternans, , and congestive heart failure due to decreased cardiac contractility related to low serum calcium and possibly PTH deficiency, as there are PTH receptors in cardiac myocytes.
Differential Diagnosis
| Differential diagnosis of hyperparathyroidism on the basis of hypocalcemia | |||||||
|---|---|---|---|---|---|---|---|
| Disorders | Mechanism of hypocalcemia | Key features | Laboratory findings | ||||
| Serum PTH | Serum Calcium | Serum Phosphate | Other findings | ||||
| Hypoparathyroidism | ↓ | ↓ | ↑ | ↓ 1,25 Dihydroxy vitamin D
Normal urinary cAMP Normal urinary phosphate | |||
| Pseudohypoparathyroidism | Type 1a | ↑ | ↓ | ↑ | ↓ 1,25 Dihydroxy vitamin D
↓ Urinary cAMP ↓ Urinary phosphate | ||
| Type 1b | ↑ | ↓ | ↑ | ↓ 1,25 Dihydroxy vitamin D
↓ Urinary cAMP ↓ Urinary phosphate | |||
| Type 1c | ↑ | ↓ | ↑ | ↓ 1,25 Dihydroxy vitamin D
↓ Urinary cAMP ↓ Urinary phosphate | |||
| Type 2 | ↑ | ↓ | ↑ | ↓ 1,25 Dihydroxy vitamin D
Normal urinary cAMP ↓ Urinary phosphate | |||
| Pseudopseudohypoparathyroidism | Normal | Normal | Normal | -- | |||
| Hypomagnesemia[23] | Inappropriately ↓ | Normal/↓ | -- | ↓ serum magnesium
↓/Normal serum potassium | |||
| Hypoalbuminemia | Normal albumin-corrected serum total calcium
Normal ionised calcium. |
↓ serum albumin | |||||
| Hypovitaminosis D | ↑ | ↓ | ↓/Low-normal | ||||
| Chronic kidney disease | ↑ | ↓/Normal | ↑ | ||||
References
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