Complications
Relaxation of muscle is an active process requiring calcium; hypocalcaemia reduces the ability of muscle to relax, producing cramps, spasms, and ultimately tetany. Meticulous management of oral calcium and vitamin D is required to prevent this condition.
Repolarisation of myocardium requires calcium. Hypocalcaemia reduces the available calcium, resulting in prolongation of the QT interval, which can progress to ventricular tachycardia. Meticulous management of oral calcium and vitamin D is required to prevent this complication. Hypocalcaemia can be exacerbated during acute illness or alkalosis, and the risk of ventricular tachycardia is therefore increased.
The most common associated endocrinopathy. Signalling of thyroid-stimulating hormone (TSH) occurs through G-proteins, and the loss of this second messenger results in primary hypothyroidism. Many cases can be identified by screening at birth. Affected patients will require long-term levothyroxine with yearly monitoring of TSH and thyroid hormone levels.
Bone sensitivity to PTH is usually preserved, and elevated levels of PTH may lead to bone loss. The mainstay of prevention is to maintain a normal calcium level. Concomitant gonadotrophin resistance in patients with PHP can lead to low levels of testosterone and oestrogen, which can exacerbate bone loss. Hormone replacement is needed to prevent bone loss in these patients. NIH Osteoporosis and Related Bone Diseases National Resource Center Opens in new window
Occur as a result of paradoxical deposition of calcium in the lens. Avoiding excess calcium replacement and lowering of phosphate to physiological range are important to prevent extraskeletal calcium deposition. Routine ophthalmological examination should be performed to identify cataracts.
Short stature occurs as part of Albright's hereditary osteodystrophy, but can also occur due to defective growth hormone-releasing hormone signalling. Screening based on routine height and weight measurement should allow determination of inadequate growth. PTH-related protein (PTHrP), a crucial signal in linear growth, may also be affected by abnormalities of G-proteins. Little information is available regarding the use of growth hormone in these patients.[49]
Obesity is commonly seen. Age-appropriate counselling regarding appropriate caloric intake and exercise is a key component of prevention. In patients with intellectual disability, involvement of carers in exercise and appropriate caloric intake is mandatory.
Hyperphosphataemia is commonly seen in patients with PHP. Hyperphosphataemia results in the formation of calcium phosphate kidney stones.
Nephrolithiasis can be prevented by monitoring urine calcium levels. Dose adjustments are necessary in patients with hypercalciuria to avoid nephrolithiasis.
Patients should also be counselled on adequate fluid intake, because concentration of the urine increases the risk of stone formation.
Normalisation of phosphate levels also helps prevent this complication and can be achieved using phosphate-binding calcium supplements.
Signalling of gonadotrophins occurs through G-proteins, and a loss of this second messenger results in maturational delay, oligomenorrhoea, and infertility.
Gonadotrophin resistance is a feature of type 1a and 1c PHP.
Patients with type 1a PHP who develop pubertal delay and oligomenorrhoea should be screened for low sex steroid levels. Treatment with hormone replacement is usually required.
Some patients with Albright's hereditary osteodystrophy develop extraskeletal osteomas, which may be symptomatic. Surgical evaluation may be required for symptom amelioration.[50]
If a patient with PHP becomes pregnant, there is a risk of limb abnormalities developing in the fetus. The process of normal growth plate formation is regulated by the intricate interplay of a transcription factor, Indian hedgehog, and the (PTHrP).[53] PTHrP acts predominantly through the G-protein/cyclic adenosine monophosphate pathway in chondrocytes, and is the major regulator of calcium and phosphorus metabolism during pregnancy. The loss of G-protein signalling in the mother leads to PTHrP resistance, with early closure of the growth plate, and limb reduction defects.
Few case reports have been published regarding surveillance and treatment of PHP during pregnancy and lactation, though one retrospective observational study highly recommended intense biochemical, clinical, and pharmacological monitoring during pregnancy and breastfeeding.[54][55] More studies are needed to find out how best to prevent this complication.
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