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Pseudohypoparathyroidism Workup

  • Author: Mini R Abraham, MD; Chief Editor: George T Griffing, MD  more...
 
Updated: Dec 11, 2015
 

Approach Considerations

Laboratory studies for the diagnosis of pseudohypoparathyroidism (PHP) include serum calcium tests (including measurement of serum total calcium and ionized calcium) to confirm a hypocalcemic state. Serum phosphate levels are elevated in PHP.

Determining the serum concentration of intact PTH, using an immunoradiometric assay (IRMA), is also diagnostic.[9] When the serum concentration of PTH in a hypocalcemic patient is increased, the patient has either a form of PHP or secondary hyperparathyroidism.

Assessment of skeletal and renal responsiveness to PTH is accomplished by measurement of changes in serum calcium, phosphorus, cAMP, and calcitriol concentrations and in urinary cAMP and phosphorus excretion after administration of the biosynthetic N-terminal fragment of PTH.

Consider thyroid function tests and measurement of gonadotropin and testosterone or estrogen levels. Also consider assessment of growth hormone function with insulinlike growth factor-1.

In a study, Freson et al concluded that platelet-based testing can effectively be used in the diagnosis of Gsa defects. In their report, on the use of platelets to diagnose Gsa hypofunction, the investigators found that platelet aggregation responses varied according to Gsa signaling defects, thus providing a reflection of a patient's phenotype and genotype.[15]

A study by Todorova-Koteva et al demonstrated the use of commercially available recombinant PTH injections and concomitant measurement of cAMP in urine to diagnose PTH resistance, especially in nonphenotypically evident pseudohypoparathyroidism.[16]

Imaging studies

Radiography of the hand may show a specific pattern of shortening of the bones, in which the distal phalanx of the thumb and the third through fifth metacarpals are shortened most severely. Radiography may also show small soft tissue opacities (calcifications/ossifications). Computed tomography (CT) scanning may reveal calcification of the basal ganglia.

Other Tests

Additional studies in PHP include the following:

  • Electrocardiogram - May reveal prolongation of the QT interval secondary to hypocalcemia
  • Analysis of the GNAS1 gene - Helps to identify the specific genetic defect in patients with PHP type 1a

Patients with PHP type 1b[17] may be evaluated for parathyroid-related bone disease. Consider bone mineral density (BMD) testing in this group of patients.

 
 
Contributor Information and Disclosures
Author

Mini R Abraham, MD Consulting Staff, Overland Park Medical Specialists

Mini R Abraham, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Stanley Wallach, MD Executive Director, American College of Nutrition; Clinical Professor, Department of Medicine, New York University School of Medicine

Stanley Wallach, MD is a member of the following medical societies: American College of Nutrition, American Society for Bone and Mineral Research, American Society for Clinical Investigation, American Society for Clinical Nutrition, American Society for Nutritional Sciences, Association of American Physicians, and Endocrine Society

Disclosure: Nothing to disclose.

Kent Wehmeier, MD Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine

Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

References
  1. Bastepe M. The GNAS locus and pseudohypoparathyroidism. Adv Exp Med Biol. 2008. 626:27-40. [Medline].

  2. Nakamura Y, Matsumoto T, Tamakoshi A, et al. Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan. J Epidemiol. 2000 Jan. 10(1):29-33. [Medline].

  3. Sanchez J, Perera E, Jan de Beur S, et al. Madelung-like deformity in pseudohypoparathyroidism type 1b. J Clin Endocrinol Metab. 2011 Sep. 96(9):E1507-11. [Medline]. [Full Text].

  4. Davies SJ, Hughes HE. Imprinting in Albright's hereditary osteodystrophy. J Med Genet. 1993 Feb. 30(2):101-3. [Medline].

  5. Juppner H, Schipani E, Bastepe M, et al. The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3. Proc Natl Acad Sci U S A. 1998 Sep 29. 95(20):11798-803. [Medline].

  6. Wu WI, Schwindinger WF, Aparicio LF, Levine MA. Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of G alpha(s). A cause of pseudohypoparathyroidism type Ib. J Biol Chem. 2001 Jan 5. 276(1):165-71. [Medline].

  7. Bliek J, Verde G, Callaway J, et al. Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2009 May. 17(5):611-9. [Medline].

  8. Long DN, McGuire S, Levine MA, et al. Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Galpha(s) in the development of human obesity. J Clin Endocrinol Metab. 2007 Mar. 92(3):1073-9. [Medline]. [Full Text].

  9. Shalitin S, Davidovits M, Lazar L, et al. Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia. Horm Res. 2008. 70(3):137-44. [Medline].

  10. Balavoine AS, Ladsous M, Velayoudom FL, et al. Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH. Eur J Endocrinol. 2008 Oct. 159(4):431-7. [Medline].

  11. Mantovani G, Bondioni S, Linglart A, Maghnie M, Cisternino M, Corbetta S. Genetic analysis and evaluation of resistance to thyrotropin and growth hormone-releasing hormone in pseudohypoparathyroidism type ib. J Clin Endocrinol Metab. 2007 Sep. 92(9):3738-42. [Medline].

  12. Vlaeminck-Guillem V, D'herbomez M, Pigny P, Fayard A, Bauters C, Decoulx M, et al. Pseudohypoparathyroidism Ia and hypercalcitoninemia. J Clin Endocrinol Metab. 2001 Jul. 86 (7):3091-6. [Medline].

  13. Landreth H, Malow BA, Shoemaker AH. Increased Prevalence of Sleep Apnea in Children with Pseudohypoparathyroidism Type 1a. Horm Res Paediatr. 2015. 84 (1):1-5. [Medline].

  14. Mahmud FH, Linglart A, Bastepe M, et al. Molecular diagnosis of pseudohypoparathyroidism type Ib in a family with presumed paroxysmal dyskinesia. Pediatrics. 2005 Feb. 115(2):e242-4. [Medline].

  15. Freson K, Izzi B, Labarque V, et al. GNAS defects identified by stimulatory G protein alpha-subunit signalling studies in platelets. J Clin Endocrinol Metab. 2008 Dec. 93(12):4851-9. [Medline].

  16. Todorova-Koteva K, Wood K, Imam S, Jaume JC. Screening for parathyroid hormone resistance in patients with nonphenotypically evident pseudohypoparathyroidism. Endocr Pract. 2012 Nov-Dec. 18(6):864-9. [Medline].

  17. Weinhaeusel A, Thiele S, Hofner M, et al. PCR-based analysis of differentially methylated regions of GNAS enables convenient diagnostic testing of pseudohypoparathyroidism type Ib. Clin Chem. 2008 Sep. 54(9):1537-45. [Medline].

  18. Neary NM, El-Maouche D, Hopkins R, Libutti SK, Moses AM, Weinstein LS. Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B. J Clin Endocrinol Metab. 2012 Sep. 97(9):3025-30. [Medline]. [Full Text].

  19. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Pseudohypoparathyroidism - epidemiology, mortality and risk of complications. Clin Endocrinol (Oxf). 2015 Sep 21. [Medline].

  20. Ritter C, Göbel CH, Liebig T, Kaminksy E, Fink GR, Lehmann HC. An epigenetic cause of seizures and brain calcification: pseudohypoparathyroidism. Lancet. 2015 May 2. 385 (9979):1802. [Medline].

 
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Patient with pseudohypoparathyroidism showing shortened fourth metacarpals.
 
 
 
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