Pseudohypoparathyroidism Workup
- Author: Mini R Abraham, MD; Chief Editor: George T Griffing, MD more...
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.[13]
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[14] may be evaluated for parathyroid-related bone disease. Consider bone mineral density (BMD) testing in this group of patients.
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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].
Sanchez J, Perera E, Jan de Beur S, et al. Madelung-like deformity in pseudohypoparathyroidism type 1b. J Clin Endocrinol Metab. Sep 2011;96(9):E1507-11. [Medline]. [Full Text].
Davies SJ, Hughes HE. Imprinting in Albright's hereditary osteodystrophy. J Med Genet. Feb 1993;30(2):101-3. [Medline].
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].
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].
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].
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].
Shalitin S, Davidovits M, Lazar L, et al. Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia. Horm Res. 2008;70(3):137-44. [Medline].
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].
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].
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].
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].
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].
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