Classical and Nonclassical Manifestations of Primary Hyperparathyroidism

Area of Science:

• Endocrinology
• Bone and Mineral Metabolism

Background:

• Primary hyperparathyroidism (PHPT) diagnosis and management are challenged by its shift towards asymptomatic presentations.
• Nonclassical manifestations, including subclinical nephrolithiasis and vertebral fractures, are common in asymptomatic PHPT.
• The natural history and causal links between PHPT and cardiovascular/neuropsychological issues remain uncertain.

Approach:

• A comprehensive narrative review of classical and nonclassical PHPT manifestations.
• Literature search included systematic reviews (1940-2020) and original publications (2013-2020).
• Proposed refined definitions for asymptomatic PHPT phenotypes and diagnostic criteria for normocalcemic PHPT (NPHPT).

Key Points:

• Asymptomatic PHPT often involves subclinical nephrolithiasis and vertebral fractures.
• Causal relationships between PHPT and cardiovascular/neuropsychological abnormalities require further investigation.
• Limited evidence supports parathyroidectomy (PTX) benefits for nonclassical manifestations over observation.

Conclusions:

• Refining asymptomatic PHPT definitions into phenotypes with/without target organ involvement is crucial.
• Standardized diagnostic criteria for NPHPT, including multiple calcium measurements and exclusion of secondary causes, are recommended.
• Proposed definitions will aid understanding of natural history, intervention response, and evidence-based guidelines.