Changing trends in clinical presentation of primary hyperparathyroidism across countries over time

Primary hyperparathyroidism (PHPT), the third most common endocrine disorder, was so eloquently described first by Fuller Albright as a polymorphic condition in his classic paper and monograph as early as 1934. Over the decades, the clinical presentation of PHPT in developed countries has shifted significantly from a disease primarily affecting the bones and kidneys to an asymptomatic condition often discovered incidentally. In developing countries, the high prevalence of vitamin D deficiency is one of the main factors influencing the clinical presentation of PHPT. In Europe and North America, PHPT is predominantly asymptomatic. In South America, China, and Eastern parts of Europe, such as Turkey, Bulgaria, and Russia, there is an ongoing transition from symptomatic to asymptomatic cases. Asia shows variability: symptomatic cases dominate in the Indian subcontinent, Middle East, and Southeast Asia, while transitional patterns with predominant asymptomatic cases have now been reported in China, and Japan reports mostly asymptomatic cases. Factors influencing these changes include advancements in diagnostic technologies, detection of incidental parathyroid adenomas during thyroid ultrasonography, regional differences in vitamin D deficiency, dietary habits, and genetic polymorphisms in vitamin D and calcium-sensing receptors. A higher prevalence of nephrolithiasis in certain climates contributes to regional variations. This review examines the dynamic nature of PHPT's clinical presentation, shaped by geographic, genetic, and environmental influences. Also, this review highlights the importance of addressing global disparities in an attempt to optimize patient outcomes.