What is Pseudohypoparathyroidism (PHP), a rare genetic disorder characterized by resistance to Parathyroid Hormone (PTH)?

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From the Research

Pseudohypoparathyroidism (PHP) is a rare genetic disorder characterized by resistance to parathyroid hormone (PTH) in target tissues, primarily the kidneys and bones, leading to hypocalcemia, hyperphosphatemia, and elevated PTH levels, as reported in a recent study 1. This condition mimics hypoparathyroidism in its clinical presentation, hence the name "pseudo" hypoparathyroidism. The most common form, type 1a, is caused by mutations in the GNAS gene and presents with low blood calcium levels, high phosphate levels, and normal or elevated PTH levels 2. Patients often display distinctive physical features known as Albright hereditary osteodystrophy, which may include short stature, rounded face, short neck, brachydactyly (shortened fingers and toes), and subcutaneous calcifications.

Clinical Presentation and Diagnosis

The clinical presentation of PHP can vary, and diagnosis may be delayed due to the rarity of the condition and the similarity of its symptoms to those of other disorders 3. A diagnosis of PHP should be considered in patients with hypocalcemia, hyperphosphatemia, and elevated PTH levels, particularly if they also exhibit features of Albright hereditary osteodystrophy 4. Laboratory tests and molecular analyses are crucial in the diagnostic process, as they can help identify the underlying genetic defects and distinguish PHP from other conditions 1.

Treatment and Management

Treatment of PHP focuses on managing hypocalcemia with calcium supplements and active vitamin D analogs, such as calcitriol, typically at a dose of 0.25-2.0 mcg daily 1. Patients require regular monitoring of calcium, phosphate, and PTH levels, as well as kidney function and urinary calcium excretion, to prevent complications like kidney stones. Unlike true hypoparathyroidism, simply replacing PTH is ineffective because the underlying problem is hormone resistance rather than hormone deficiency 2.

Key Considerations

  • PHP is a rare genetic disorder characterized by resistance to PTH in target tissues.
  • The most common form, type 1a, is caused by mutations in the GNAS gene.
  • Patients often display distinctive physical features known as Albright hereditary osteodystrophy.
  • Treatment focuses on managing hypocalcemia with calcium supplements and active vitamin D analogs.
  • Regular monitoring of calcium, phosphate, and PTH levels is necessary to prevent complications.

References

Research

Pseudohypoparathyroidism Type IB with Subclinical Hypothyroidism: a Pedigree Investigation and Literature Review.

Diabetes, metabolic syndrome and obesity : targets and therapy, 2024

Research

Genetics of pseudohypoparathyroidism: bases for proper genetic counselling.

Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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