What Is Pseudohypoparathyroidism (PHP)?

Hypoparathyroidism is a rare medical condition in which the body cannot produce enough parathyroid hormone (PTH) from the parathyroid glands. In contrast, people with pseudohypoparathyroidism (PHP) produce normal amounts of PTH, but they lack the receptors that respond to PTH.

PTH regulates the amount of phosphate and calcium by controlling how the body absorbs calcium during digestion and bone tissue break-down. Without PTH, or when the body cannot respond to PTH, blood levels of calcium become very low, and phosphate levels increase. That is why the symptoms of hypoparathyroidism and PHP are very similar.

What causes PHP?

There are two types of PHP. Type 1 is can be further subdivided into three subtypes (A, B, and C).  Some patients may have problems with hormonal secretion from the adrenal glands (adrenal insufficiency).

Mutations in a gene called GNAS, which provides the instructions necessary for making a portion of the receptor that recognizes PTH signals, can cause PHP type 1. Scientists don’t know the genetic causes of PHP type 2.

Is PHP a heritable disease?

Yes, PHP can be inherited, though some cases occur because of spontaneous mutations rather than a patient inheriting a disease-causing mutation from their parents.

Patients inherit PHP type 1A in a dominant manner. This means they develop the disease even if they inherit a single copy of a disease-causing mutation.

How do doctors diagnose it?

Doctors can diagnose PHP with blood tests to measure the levels of calcium, phosphorous, and PTH. If PTH and phosphate levels are high, while calcium levels are low, a patient may have PHP. It may be possible to confirm the diagnosis with genetic testing, looking for mutations in the GNAS gene.

How do doctors treat it?

The levels of calcium in PHP patients usually are not as low as in hypoparathyroidism. Doctors normally treat patients with calcium and vitamin D supplements. Some patients may need to control their phosphate levels with phosphate binders. These are medications that patients take with their meals. They bind to phosphate in food and reduce the amount that the body absorbs. Some patients may be able to maintain normal phosphate levels by consuming a low-phosphate diet.