Pseudohypoparathyroidism Clinical Presentation

Patients with pseudohypoparathyroidism (PHP) can present in infancy, especially if significant hypocalcemia occurs.

Patients with PHP type 1a present with a characteristic phenotype, collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:

• Short stature
• Stocky habitus
• Obesity^[8]
• Developmental delay
• Round face
• Dental hypoplasia
• Brachymetacarpals
• Brachymetatarsals
• Soft tissue calcification/ossification

Patients may develop paresthesias, muscular cramping, tetany, carpopedal spasm, or seizure. Hypocalcemia in children or adolescents is often asymptomatic.^[9]

Patients with PHP type 1a may have disturbances in taste, smell, vision, and hearing, and they may be hyporesponsive to the biologic effects of other peptide hormones that use the alpha subunit of the Gsa protein to enhance cAMP production. The hormones under this class include thyrotropin, antidiuretic hormone, the gonadotropins, glucagon, adrenocorticotropin, and growth hormone–releasing hormone. Evaluate patients for signs and symptoms suggestive of deficiencies of any of these hormones. Primary hypothyroidism occurs in most patients with PHP type 1a.^{[10, 11]}

Reproductive dysfunction commonly occurs in persons with PHP type 1a. Women may have delayed puberty, oligomenorrhea, and infertility.

Features of hypogonadism may be less obvious in men. Testes may show evidence of maturation arrest or may fail to descend normally. Fertility appears to be decreased in men with PHP type 1a.

Within the spectrum of PHP type 1a, variability exists in osteoclast responsiveness to PTH. Some patients may have osteopenia and rickets.

Mentation is impaired in approximately half of patients with PHP type 1a and appears to be related to the Gsa deficiency rather than to chronic hypocalcemia, because patients with other forms of PHP and hypocalcemia have normal mentation.

Unusual presenting manifestations include neonatal hypothyroidism, Parkinson disease, and spinal cord compression. An interesting association between PHP type 1a and hypercalcitoninemia without any evidence of medullary thyroid carcinoma has been described.

Physical examination may reveal signs of hypocalcemia, including positive Chvostek sign (ie, twitching of facial muscles after tapping the facial nerve just in front of the ear) and/or Trousseau sign (ie, carpal spasm after maintaining an arm blood pressure cuff at 20mm Hg above the patient's systolic blood pressure for 3min). Occasionally, cataracts or papilledema are present.

Patients with PHP type 1b present with hypocalcemia without AHO. The severity of hypocalcemia can vary greatly among family members of the same kindred.

Patients with pseudo-PHP have the phenotype of AHO but with normal biochemical parameters. Patients with pseudo-PHP are often found in the same kindreds as those with PHP type 1a.

Albright hereditary osteodystrophy

Obesity is a common feature of AHO, although brachydactyly is the most reliable sign in the diagnosis of this condition (see the image below). The brachydactyly may be symmetrical or asymmetrical and may involve 1 or both hands or feet. Shortening of the metacarpals causes shortening of the digits, particularly the fourth and fifth digits. Shortening of the metacarpals may be recognized during physical examination as dimpling over the knuckles of a clenched fist (ie, Archibald sign). Shortening of the distal phalanx of the thumb is evident as a thumb in which the ratio of the width of the nail to its length is increased (ie, so-called murderer's thumb or potter's thumb).

Several other skeletal deformities have been described in AHO, including short ulna, bowed radius, deformed elbow, or cubitus valgus and coxa vara, coxa valga, genu varum, and genu valgum deformities.