Laboratory Studies
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. [13] 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.
Freson et al concluded that platelet-based testing can effectively be used in the diagnosis of Gsα defects. In their report, on the use of platelets to diagnose Gsα hypofunction, the investigators found that platelet aggregation responses varied according to Gsα signaling defects, thus providing a reflection of a patient's phenotype and genotype. [19]
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. [20]
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
Electrocardiogram may reveal prolongation of the QT interval secondary to hypocalcemia.
Patients with PHP type 1b may be evaluated for parathyroid-related bone disease. Consider bone mineral density (BMD) testing in this group of patients. [21]
Genetic Testing
Genetic testing and analysis of the GNAS1 gene can confirm diagnosis and identify the different variants of PHP. Patients affected by PHP-1b require testing for GNAS methylation changes; some laboratories will analyze exon A/B only as a screen, because the loss of methylation of this DMR on the maternally derived GNAS allele is present in all reported cases of both inherited and sporadic forms of PHP-1b. Patients with PHP-1b can be further analyzed for paternal uniparental isodisomy of chromosome 20q or small deletions within STX16 and GNAS; these tests have furthermore been shown to identify deletions within GNAS as the cause of some PHP-1a cases. [3]
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Patient with pseudohypoparathyroidism showing shortened fourth metacarpals.
