Pseudohypoparathyroidism: causes, features, diagnosis and management

The parathyroid glands in the neck make parathyroid hormone (PTH), which helps control calcium levels. The NHS describes hypoparathyroidism as a condition where these glands do not work properly, so calcium may become too low. In pseudohypoparathyroidism the situation is different: the glands make PTH, often at high levels, but the body's tissues, mainly the kidneys, do not respond to it. The prefix pseudo means false, reflecting that it looks like hypoparathyroidism but the cause is resistance to the hormone rather than a lack of it.

The first international Consensus Statement, published in Nature Reviews Endocrinology in 2018, describes PHP and related disorders as metabolic disorders characterised by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to PTH and thyroid-stimulating hormone (TSH). They are caused primarily by molecular defects, mostly involving the GNAS gene region, that impair hormonal signalling.

The consensus notes that presentation and severity vary between affected individuals with considerable clinical and molecular overlap between the different types.

The consensus says that in the majority of patients with PHP the most important clinical manifestation is symptoms of hypocalcaemia due to PTH resistance. The NHS list for hypoparathyroidism is a practical guide to what low calcium can feel like: tingling or burning in the fingers, toes and face, muscle pain, stiffness and spasms, tummy pain, brittle nails, dry hair and skin and cataracts, with confusion, an irregular heartbeat and seizures being less common and more serious.

The consensus lists a diagnostic profile for the associated skeletal features known as Albright hereditary osteodystrophy: short fingers or toes due to early fusion of the growth plates (brachydactyly type E) and short adult stature relative to the unaffected parent as major criteria, with a stocky build and other features as additional criteria. Early-onset obesity and ectopic ossification, bone-like deposits in the skin or deeper tissues, are also described.

The consensus agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity, and that it should be confirmed by molecular genetic analysis. It defines PTH resistance as the association of hypocalcaemia, hyperphosphataemia and elevated PTH in the absence of vitamin D deficiency and when magnesium and kidney function are normal.

The statement notes that PTH resistance and the resulting changes in calcium, phosphorus and PTH can vary, and repeated testing might be required. In some types the first biochemical abnormalities to appear are raised PTH and phosphorus, followed by low calcium, and an interval of up to about 4.5 years may elapse between the first changes and low calcium. This is one reason the diagnosis is often delayed.

The tests that define PTH resistance are blood tests for calcium, phosphate, PTH, vitamin D, magnesium and kidney function, followed by genetic analysis. The consensus says that after exclusion of alterations in the known genes the patient should be referred to an expert centre.

The consensus says long-term treatment of hypocalcaemia associated with PTH resistance is similar to, but usually more aggressive than, that of primary hypoparathyroidism, with active vitamin D metabolites (calcitriol) or analogues (alfacalcidol) and oral calcium supplements as and when required. The approach is to reduce serum PTH into the upper part of the reference range, avoiding both PTH suppression, which can be associated with hypercalciuria and kidney calcification, and long-standing PTH excess, which might harm bone mineralisation or growth. The NHS says people with hypoparathyroidism usually need supplements for life and regular blood tests of calcium.

Patients should be screened at diagnosis and during follow-up for PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as ectopic ossifications and neurocognitive impairment. Management therefore involves endocrinology, genetics, dietetics, dental care and sometimes paediatrics and orthopaedics.

Doses and targets are individual and set by a specialist; the sources used here do not give patient-level doses and none should be taken from this page.

The NHS says to call 999 if someone is having a seizure for the first time or one lasting longer than is usual for them or over 5 minutes if unknown. For hypoparathyroidism it notes that if calcium becomes too low it can cause seizures and serious heart problems, which need hospital treatment with calcium through a vein. Ask your specialist team for a written plan describing which symptoms of low calcium need same-day help.

The consensus notes that genetic counselling is available in most expert centres once the molecular defect is identified, but that it can be challenging because the parent of origin of the gene change and clinical variability affect outcomes, and the severity in a parent does not predict severity in a child. Families can be directed to support groups.

Support for people with calcium and parathyroid conditions is offered by Parathyroid UK, which the NHS names as a UK charity for people living with parathyroid conditions. Because PHP is rare, the consensus recommends referral to an expert centre, and a GP can arrange referral to an endocrinology service in the NHS; a private endocrinology opinion is another route. This page relies on an international consensus statement and NHS pages on the related condition hypoparathyroidism because we did not find a UK patient leaflet on PHP that we could read in full.