Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism

Area of Science:

• Endocrinology
• Genetics
• Bone and Mineral Metabolism

Background:

• Primary hyperparathyroidism (PHPT) is a prevalent endocrine disorder, predominantly affecting postmenopausal women, with global incidence influenced by diagnostic screening availability.
• The condition arises from parathyroid gland overgrowth and altered calcium-sensing receptor (CaSR) expression, disrupting calcium homeostasis.
• PHPT manifests with skeletal complications due to dysregulated bone remodeling and kidney stones from increased calcium load.

Approach:

• This narrative review synthesizes four decades of research (1980-2020) on PHPT epidemiology, pathophysiology, and genetics.
• It examines the role of parathyroid hormone in calcium regulation and the cellular mechanisms underlying PHPT.
• The review discusses the genetic underpinnings of PHPT, including its association with multiple endocrine neoplasia syndromes and familial forms.

Key Points:

• Screening practices significantly impact PHPT epidemiological data, with a trend towards asymptomatic presentations globally.
• Dysregulated parathyroid gland growth and reduced CaSR expression are central to PHPT pathophysiology.
• Genetic testing aids in diagnosing PHPT, differentiating it from familial hypocalciuric hypercalcemia (FHH), and enables carrier and prenatal testing.

Conclusions:

• PHPT epidemiology is evolving, influenced by diagnostic accessibility and screening populations.
• Understanding the pathophysiology involving CaSRs and parathyroid hyperplasia is crucial for managing PHPT.
• Genetic analysis offers valuable diagnostic and preventative insights for specific PHPT cases and families.