eMedicine Specialties > Endocrinology > Parathyroid Gland

Pseudohypoparathyroidism: Differential Diagnoses & Workup

Author: Mini R Abraham, MD, Consulting Staff, Saint Luke's Medical Group
Coauthor(s): Romesh Khardori, MD, Chief, Division of Endocrinology, Metabolism and Molecular Medicine, Professor, Department of Internal Medicine, Southern Illinois University School of Medicine
Contributor Information and Disclosures

Updated: Aug 5, 2009

Differential Diagnoses

Other Problems to Be Considered

Secondary hyperparathyroidism
Autoimmune polyglandular syndromes
Vitamin D deficiency

Workup

Laboratory Studies

  • Serum calcium (including measurement of serum total calcium and ionized calcium) to confirm hypocalcemic state: Serum phosphate levels are elevated.
  • Determination of the serum concentration of intact PTH7 by immunoradiometric assay (IRMA): 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: Assessment 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, in addition to growth hormone function assessed by insulinlike growth factor-1.

Freson et al reported on the use of platelets to diagnose Gsa hypofunction, finding in their study that platelet aggregation responses varied according to Gsa signaling defects, thus providing a reflection of a patient's phenotype and genotype.9  They concluded that such platelet-based testing can effectively be used in the diagnosis of Gsa defects.

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).
  • CT scanning may reveal calcification of the basal ganglia.

Other Tests

  • An electrocardiogram may reveal prolongation of the QT interval secondary to hypocalcemia.
  • Analysis of the GNAS1 gene helps identify the specific genetic defect in patients with PHP type 1a.
  • Patients with PHP type 1b10 may be evaluated for parathyroid-related bone disease. Consider bone mineral density (BMD) testing in this group of patients.

More on Pseudohypoparathyroidism

Overview: Pseudohypoparathyroidism
Differential Diagnoses & Workup: Pseudohypoparathyroidism
Treatment & Medication: Pseudohypoparathyroidism
Follow-up: Pseudohypoparathyroidism
Multimedia: Pseudohypoparathyroidism
References
Further Reading
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References

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

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

  3. 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. Sep 29 1998;95(20):11798-803. [Medline].

  4. 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. Jan 5 2001;276(1):165-71. [Medline].

  5. 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. May 2009;17(5):611-9. [Medline].

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

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

  8. 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. Oct 2008;159(4):431-7. [Medline].

  9. 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. Dec 2008;93(12):4851-9. [Medline].

  10. 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. Sep 2008;54(9):1537-45. [Medline].

  11. Bastepe M, Juppner H. Pseudohypoparathyroidism. New insights into an old disease. Endocrinol Metab Clin North Am. Sep 2000;29(3):569-89. [Medline].

  12. Bringhurst FR, Demay MB, Kronenberg HM. Hormones and disorders of mineral metabolism. In: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: WB Saunders Company; 1998:1155-1209.

  13. Farfel Z, Bourne HR, Iiri T. The expanding spectrum of G protein diseases. N Engl J Med. Apr 1 1999;340(13):1012-20. [Medline].

  14. Germain-Lee EL, Groman J, Crane JL, et al. Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. J Clin Endocrinol Metab. Sep 2003;88(9):4059-69. [Medline].

  15. Iiri T, Herzmark P, Nakamoto JM, et al. Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function. Nature. Sep 8 1994;371(6493):164-8. [Medline].

  16. Jan de Beur SM, Ding CL, LaBuda MC, et al. Pseudohypoparathyroidism 1b: exclusion of parathyroid hormone and its receptors as candidate disease genes. J Clin Endocrinol Metab. Jun 2000;85(6):2239-46. [Medline].

  17. Levine MA. Hypoparathyroidism and pseudohypoparathyroidism. In: DeGroot, Jameson, et al, eds. Endocrinology. 4th ed. Philadelphia, Pa: WB Saunders Company; 2001:1133-1153.

  18. Levine MA, Jap TS, Hung W. Infantile hypothyroidism in two sibs: an unusual presentation of pseudohypoparathyroidism type Ia. J Pediatr. Dec 1985;107(6):919-22. [Medline].

  19. 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. Mar 2007;92(3):1073-9. [Medline]. [Full Text].

  20. 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. Sep 2007;92(9):3738-42. [Medline].

  21. Mantovani G, Maghnie M, Weber G, et al. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene. J Clin Endocrinol Metab. Sep 2003;88(9):4070-4. [Medline].

  22. Murray TM, Rao LG, Wong MM, et al. Pseudohypoparathyroidism with osteitis fibrosa cystica: direct demonstration of skeletal responsiveness to parathyroid hormone in cells cultured from bone. J Bone Miner Res. Jan 1993;8(1):83-91. [Medline].

  23. Nakamoto JM, Zimmerman D, Jones EA, et al. Concurrent hormone resistance (pseudohypoparathyroidism type Ia) and hormone independence (testotoxicosis) caused by a unique mutation in the G alpha s gene. Biochem Mol Med. Jun 1996;58(1):18-24. [Medline].

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

  25. Pearson DW, Durward WF, Fogelman I, et al. Pseudohypoparathyroidism presenting as severe Parkinsonism. Postgrad Med J. Jul 1981;57(669):445-7. [Medline].

  26. Root AW, Diamond FB Jr, Mimouni FB. Parathyroid and vitamin D-related disorders in children and adolescents. In: Pediatric Endocrinology. ed. Philadelphia, Pa: WB Saunders Company; 1996:477-507.

  27. Shriraam M, Bhansali A, Velayutham P. Vitamin D deficiency masquerading as pseudohypoparathyroidism type 2. J Assoc Physicians India. Jun 2003;51:619-20. [Medline].

  28. Srivastava T, Alon US. Stage I vitamin D-deficiency rickets mimicking pseudohypoparathyroidism type II. Clin Pediatr (Phila). May 2002;41(4):263-8. [Medline].

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

  30. Wagar G, Lehtivuori J, Salven I, et al. Pseudohypoparathyroidism associated with hypercalcitoninaemia. Acta Endocrinol (Copenh). Jan 1980;93(1):43-8. [Medline].

  31. Yamamoto Y, Noto Y, Saito M, et al. Spinal cord compression by heterotopic ossification associated with pseudohypoparathyroidism. J Int Med Res. Nov-Dec 1997;25(6):364-8. [Medline].

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Keywords

pseudohypoparathyroidism, parathyroid, parathyroid hormone, hypocalcemia, parathyroid gland, parathyroid glands, PTH, pseudopseudohypoparathyroidism, hyperphosphatemia, Albright hereditary osteodystrophy, Albright's hereditary osteodystrophy, pseudo-PHP, stimulatory G protein, Gsa, GNAS1, testotoxicosis, dental hypoplasia, brachymetacarpals, brachymetatarsals, brachydactyly

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Contributor Information and Disclosures

Author

Mini R Abraham, MD, Consulting Staff, Saint Luke's Medical Group
Mini R Abraham, MD is a member of the following medical societies: American Association of Clinical Endocrinologists and Endocrine Society
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Novo Nordisk Honoraria Speaking and teaching

Coauthor(s)

Romesh Khardori, MD, Chief, Division of Endocrinology, Metabolism and Molecular Medicine, Professor, Department of Internal Medicine, Southern Illinois University School of Medicine
Romesh Khardori, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society of Andrology, Endocrine Society, and Illinois State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

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 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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor 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, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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