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In 1942, Fuller albright, an American endocrinologist, first discovered pseudohypoparathyroidim. Pseudohypoparathyoroidism is the first hormone resistance syndrome to be discovered.<ref>{{cite journal |vauthors=Albright F, Burnett CH, Smith PH, Parson |date=1942 |title=Pseudohypoparathyroidism- An example of ‘Seabright-Bantam syndrome’ |url= |journal= Endocrinology |volume=30 |issue= |pages=922–32 |doi= |access-date= }}</ref> | In 1942, Fuller albright, an American endocrinologist, first discovered pseudohypoparathyroidim. Pseudohypoparathyoroidism is the first hormone resistance syndrome to be discovered.<ref>{{cite journal |vauthors=Albright F, Burnett CH, Smith PH, Parson |date=1942 |title=Pseudohypoparathyroidism- An example of ‘Seabright-Bantam syndrome’ |url= |journal= Endocrinology |volume=30 |issue= |pages=922–32 |doi= |access-date= }}</ref> | ||
Albright hereditary osteodystrophy is a clinical entity initially described together with Pseudohypoparathyroidism in 1942. | Albright hereditary osteodystrophy is a clinical entity initially described together with Pseudohypoparathyroidism in 1942.{{cite journal |vauthors=Eyre WG, Reed WB |title=Albright's hereditary osteodystrophy with cutaneous bone formation |journal=Arch Dermatol |volume=104 |issue=6 |pages=634–42 |year=1971 |pmid=5002252 |doi= |url=}} | ||
==Classification== | ==Classification== | ||
Revision as of 14:26, 26 September 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]
Pseudohypoparathyroidism
Overview
Pseudohypoparathyroidism (PHP) refers to a group of rare endocrine disorders characterized by end organ resistance to the action of parathyroid hormone (PTH), manifestations include hypocalcemia, hyperphosphatemia, and increased serum concentration of PTH.
Historical Perspective
In 1942, Fuller albright, an American endocrinologist, first discovered pseudohypoparathyroidim. Pseudohypoparathyoroidism is the first hormone resistance syndrome to be discovered.[1]
Albright hereditary osteodystrophy is a clinical entity initially described together with Pseudohypoparathyroidism in 1942.Eyre WG, Reed WB (1971). "Albright's hereditary osteodystrophy with cutaneous bone formation". Arch Dermatol. 104 (6): 634–42. PMID 5002252.
Classification
- Pseudohypoparathyroidism is classified based on the measurement of serum and urinary cAMP and phosphate excretion levels after the injection of biologically active PTH into following types:[2]
- Pseudohypoparathyroidism type I
- Pseudohypoparathyroidism type II
- Pseudohypoparathyroidism type 1 is further classified into following subtype:[2]
- Pseudohypoparathyroidism type 1a
- Pseudohypoparathyroidism type 1b
- Pseudohypoparathyroidism type 1c subtypes.
- Pseudopseudohypoparathyroidism
Pathophysiology
Pseudohypoparathyroidism is characterized by end organ resistance to parathyroid hormone. Parathyroid hormone effect is mediated by the parathyroid hormone receptor type 1, which acts on a stimulatory guanine-nucleotide–binding (Gs) protein, which is composed of three subunits (α, β, and γ). The GNAS1 gene encodes Gsα subunit that mediates cyclic AMP stimulation by parathyroid hormone and by several other peptide hormones, including thyrotropin.[3] Gene mutation results in failure of signal transduction through Gsα inability to activate adenyl cyclase resulting in resistance of target tissues to parathyroid hormone evidenced by hypocalcemia and hyperphosphatemia, in the presence of high plasma PTH level.[4]
Genetics
Genetic mutations associated with pseudohypoparathyroidism are discussed below [5] [6] [7]
| Type of pseudohyoparathyroidism | Molecular Defect | Origin Of Mutation | Inheritence | |
|---|---|---|---|---|
| Pseudohypoparathyroidism type I | Type 1a | Heterozygous GNAS inactivating mutations that reduce expression or function of Gαs | Maternal | Autosomal Dominant |
| Type 1b | Familial- heterozygous deletions in STX16, NESP55, and/or AS exons or loss of methylation at GNAS | Maternal | Autosomal Dominant | |
| Sporadic- paternal Uniparental disomy of chromosome 20q in some or methylation defect affecting all four GNAS DMRs | Maternal | Genomic imprinting | ||
| Type 1c | Heterozygous GNAS inactivating mutations that reduce expression or function of Gαs | Maternal | Autosomal Dominant | |
| Pseudopseudohypoparathyroidism | Combination of inactivating mutations of GNAS1 and Albright's osteodystrophy | Paternal | Genomic imprinting | |
| Pseudohypoparathyroidism type II | Insufficient data to suggest genetic or familial source | N/A | N/A | |
Causes
Pseudohypoparathyroidism is caused by mutations involving primarily the GNAS gene that results in end organ resistance to parathyroid hormone.For a complete review of genes involved in pseudohypoparathyroidism click here.
Differentiating ((Page name)) from Other Diseases
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
OR
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
Epidemiology and Demographics
Incidence
- In Denmark, the incidence of postsurgical hypoparathyroidism is approximately 0.8 per 100,000 person-years.[8]
Prevalence
- In United States, the prevalence of hypoparathyroidism is approximately 37 per 100,000 person-years.[9]
- In Denmark, the prevalence of postsurgical hypoparathyroidism is approximately 22 per 100,000 person-years.[9]
- In Denmark, the prevalance of nonsurgical hypoparathyroidism is approximately 2.3 per 100,000 person-years.[10]
- In Japan, the prevalence of idiopathic hypoparathyroidism ranges from a low of 55 per 100,000 persons to a high of 88 per 100,000 persons with an average prevalence of 72 per 100,000 persons.[11]
- In Japan, the prevalence of pseudohypoparathyroidism ranges from a low of 0.26 per 100,000 persons to a high of 0.42 per 100,000 persons with an average prevalence of 0.34 per 100,000 persons.[11]
Age
- Majority of patients with hypoparathyroidism are 45 years or older.[12]
Gender
- Women are more commonly affected by hypoparathyroidism than men. The women to men ratio is approximately 3 to 1.[12]
Risk Factors
The most potent risk factor in the development of pseudohypoparathyroidism is a positive family history.
Screening
There is insufficient evidence to recommend routine screening for pseudohypoparathyroidism.
Natural History, Complications, and Prognosis
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
OR
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
OR
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
Diagnosis
Diagnostic Criteria
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
OR
The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
OR
The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
OR
There are no established criteria for the diagnosis of [disease name].
History and Symptoms
The majority of patients with [disease name] are asymptomatic.
OR
The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
Physical Examination
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
OR
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
OR
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
Laboratory Findings
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
OR
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
OR
[Test] is usually normal among patients with [disease name].
OR
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
OR
There are no diagnostic laboratory findings associated with [disease name].
Electrocardiogram
There are no ECG findings associated with [disease name].
OR
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
X-ray
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with [disease name].
OR
Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
CT scan
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
MRI
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Other Imaging Findings
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
Treatment
Medical Therapy
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
OR
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
OR
The majority of cases of [disease name] are self-limited and require only supportive care.
OR
[Disease name] is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for [disease name] is [therapy].
OR The optimal therapy for [malignancy name] depends on the stage at diagnosis.
OR
[Therapy] is recommended among all patients who develop [disease name].
OR
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
OR
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
OR
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
OR
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
Surgery
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
OR
Surgery is the mainstay of treatment for [disease or malignancy].
Primary Prevention
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].
OR
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
OR
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
Secondary Prevention
There are no established measures for the secondary prevention of [disease name].
OR
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
References
- ↑ Albright F, Burnett CH, Smith PH, Parson (1942). "Pseudohypoparathyroidism- An example of 'Seabright-Bantam syndrome'". Endocrinology. 30: 922–32.
- ↑ 2.0 2.1 Marx SJ (2000). "Hyperparathyroid and hypoparathyroid disorders". N. Engl. J. Med. 343 (25): 1863–75. doi:10.1056/NEJM200012213432508. PMID 11117980.
- ↑ Spiegel AM (2007). "Inherited endocrine diseases involving G proteins and G protein-coupled receptors". Endocr Dev. 11: 133–44. doi:10.1159/0000111069. PMID 17986833.
- ↑ Chase LR, Melson GL, Aurbach GD (1969). "Pseudohypoparathyroidism: defective excretion of 3',5'-AMP in response to parathyroid hormone". J. Clin. Invest. 48 (10): 1832–44. doi:10.1172/JCI106149. PMC 322419. PMID 4309802.
- ↑ Levine MA (2012). "An update on the clinical and molecular characteristics of pseudohypoparathyroidism". Curr Opin Endocrinol Diabetes Obes. 19 (6): 443–51. doi:10.1097/MED.0b013e32835a255c. PMC 3679535. PMID 23076042.
- ↑ Mantovani G (2011). "Clinical review: Pseudohypoparathyroidism: diagnosis and treatment". J. Clin. Endocrinol. Metab. 96 (10): 3020–30. doi:10.1210/jc.2011-1048. PMID 21816789.
- ↑ Lee S, Mannstadt M, Guo J, Kim SM, Yi HS, Khatri A, Dean T, Okazaki M, Gardella TJ, Jüppner H (2015). "A Homozygous [Cys25]PTH(1-84) Mutation That Impairs PTH/PTHrP Receptor Activation Defines a Novel Form of Hypoparathyroidism". J. Bone Miner. Res. 30 (10): 1803–13. doi:10.1002/jbmr.2532. PMC 4580526. PMID 25891861.
- ↑ Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L (2013). "Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study". J Bone Miner Res. 28 (11): 2277–85. doi:10.1002/jbmr.1979. PMID 23661265.
- ↑ 9.0 9.1 Clarke BL, Brown EM, Collins MT, Jüppner H, Lakatos P, Levine MA, Mannstadt MM, Bilezikian JP, Romanischen AF, Thakker RV (2016). "Epidemiology and Diagnosis of Hypoparathyroidism". J. Clin. Endocrinol. Metab. 101 (6): 2284–99. doi:10.1210/jc.2015-3908. PMC 5393595. PMID 26943720.
- ↑ Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L (2015). "The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study". J. Bone Miner. Res. 30 (9): 1738–44. doi:10.1002/jbmr.2501. PMID 25753591.
- ↑ 11.0 11.1 Nakamura Y, Matsumoto T, Tamakoshi A, Kawamura T, Seino Y, Kasuga M, Yanagawa H, Ohno Y (2000). "Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan". J Epidemiol. 10 (1): 29–33. PMID 10695258.
- ↑ 12.0 12.1 Powers J, Joy K, Ruscio A, Lagast H (2013). "Prevalence and incidence of hypoparathyroidism in the United States using a large claims database". J. Bone Miner. Res. 28 (12): 2570–6. doi:10.1002/jbmr.2004. PMID 23737456.