Pseudohypoparathyroidism (PHP)

Pseudohypoparathyroidism (PHP) is a rare disorder in which the body’s metabolism does not respond to parathyroid hormone (PTH), although normal levels of the hormone are produced by the parathyroid glands. The parathyroid glands are four tiny glands located near and behind the thyroid gland in the neck.

Parathyroid hormone regulates the levels of calcium and phosphorus in the bloodstream, which is important for bone health and muscle function. When the body does not respond to parathyroid hormone, the levels of calcium in the blood can drop and the levels of phosphorus can rise to unhealthy levels.

It is different from hypoparathyroidism, which is a different condition caused by underactive parathyroid glands.

PHP is caused by inactivation of the GNAS or related genes. It sometimes occurs as an inherited gene mutation and sometimes as a spontaneous (de novo) gene change, not inherited from either parent.
Different forms of PHP affect patients differently and follow different patterns of inheritance.

• Type 1a is the most commonly diagnosed form of PHP. In addition to PTH resistance, patients also have Albright hereditary osteodystrophy, which is characterized by short stature, short hand bones (brachydactyly), round face, developmental delays and skin ossifications (bone development in the skin, also called osteoma cutis). Resistance to other hormones can also develop and lead to hypothyroidism, growth hormone deficiency and hypogonadism (low testosterone or estrogen levels). Type 1a pseudohypoparathyroidism can occur as a spontaneous mutation or be inherited in an autosomal dominant pattern from the mother.
• PHP 1b, PHP1 c and PHP 2 are similar to PHP 1a with subtle differences in clinical presentation or the way in which the disease develops or is inherited.
• Pseudopseudohypoparathyroidism (PPHP) is a less severe form of PHP. Patients with PHPP only have Albright hereditary osteodystrophy and do not develop PTH or other hormone resistance. PPHP can occur as a spontaneous mutation or be inherited in an autosomal dominant pattern from the father.

Symptoms of pseudohypoparathyroidism vary widely, and each child may experience symptoms differently. Symptoms of PTH resistance in children may include:

• Numbness or tingling around the mouth or in the hands or feet
• Uncontrollable, painful spasms of the face, hands, arms and feet
• Muscle spasms that cause difficulty breathing or speaking
• Muscle cramps
• Seizures
• Low blood pressure
• Emotional instability, anxiety or depression
• Dental problems, such as late-developing teeth or weakened tooth enamel
• Coarse, brittle hair
• Brittle, easily broken fingernails and toenails

Signs of Albrights Hereditary Osteodystrophy may include:

• Short stature
• Excessive weight gain
• Short hand bones
• Round face
• Short neck
• Blurred vision, cataracts or sensitivity to light
• Developmental delays
• Bony nodules that develop in the skin

The symptoms of pseudohypoparathyroidism may resemble other problems or medical conditions. Always consult your child's doctor for a diagnosis.

In addition to a complete medical history and physical examination, diagnostic tests for pseudohypoparathyroidism may include:

• Blood tests to measure levels of parathyroid hormone (PTH), calcium, phosphorus, magnesium, and other hormones including thyroid hormone, growth hormone, luteinizing hormone (LH), follicular stimulating hormone (FSH), estrogen or testosterone
• Urine tests to measure levels of excreted calcium and phosphorus
• Genetic tests of the GNAS and/or STX16 gene
• EKG to check for abnormal heart rhythm
• X-ray of the bones in the hand
• CT scan to check for brain abnormalities

Treatment for pseudohypoparathyroidism focuses on reducing symptoms by restoring and maintaining healthy levels of calcium and phosphorus in the blood. The specific treatments will be determined by your child's doctor in consultation with you.

Treatment may include:

• Calcium and vitamin D supplements
• Calcitriol, the active form of vitamin D available only by prescription
• Injections of calcium for immediate relief of severe symptoms
• Thyroid or growth hormone replacement, in patients found to have deficiencies of these hormones

Calcium and vitamin D supplements, when effective in reducing symptoms, are taken daily, as a lifelong treatment.

Diet may also be a part of treatment, with nutritional counseling to help patients and their families choose foods that are high in calcium and low in phosphorus.

Periodic blood tests are done to monitor calcium and phosphorus levels and adjust treatment as needed.

Ongoing care, coordinated by a primary care physician or specialist who is knowledgeable about pseudohypoparathyroidism is essential to the long-term health and well-being of patients. Because the disorder can affect different body functions, coordinated care by a team of appropriate specialists is needed.

Treatment of pseudohypoparathyroidism at Children’s Hospital of Philadelphia (CHOP) is managed by the Center for Bone Health, which provides comprehensive, coordinated care in collaboration with other specialty departments.

Depending on the patient’s diagnosis and condition, coordinated care might include specialists in:

• Orthopaedics
• Endocrinology
• Developmental pediatrics
• Neurology
• Pain management
• Dental care
• Physical and occupational therapy
• Nutrition
• Genetics