Primary Hyperparathyroidism: A Tale of Two Cities Revisited - New York and Shanghai

Abstract

In the 1970s, with the advent of biochemical multichannel screening in the United States and other western countries, the clinical presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disorder. However, in Asian countries, like China, PHPT did not show this evolution, but rather continued to be a symptomatic disease with target organ involvement. In this paper, we revisit the clinical features of PHPT in New York and Shanghai, representative United States and Chinese cites, over the past decade. The questions we address are whether the disease evolved in China to a more asymptomatic one and, whether in the United States further changes are evident. The results indicate that while PHPT continues to present primarily as an asymptomatic disease in the United States, a new phenotype characterized by normal serum calcium and high parathyroid hormone levels, normocalcemic PHPT, has emerged. Data from Shanghai demonstrates a trend for PHPT to present more commonly as an asymptomatic disorder in China. However, most patients with PHPT in China still manifest classical symptoms, i.e. nephrolithiasis and fractures. A comparison of the two cohorts shows that Chinese patients with PHPT are younger, with higher serum calcium and PTH levels, and lower 25-hydroxyvitamin D levels than patients in New York. Normocalcemic PHPT has not yet been recognized in Shanghai. In summary, although the phenotypes of PHPT in both cities are evolving towards less evident disease, sharp clinical and biochemical differences are still apparent in PHPT as expressed in China and the United States.

Keywords: asymptomatic; normocalcemic primay hyperparathyroidism; symptomatic.

Figure 1

Symptomatic and asymptomatic primary hyperparathyroidism in New York City, from 1984–1993 and 2010–2013. Symptomatic PHPT refers to symptoms related with hypercalcemia, such as skeletal and renal diseases, neuromuscular, gastrointestinal, articular, hematologic, cardiovascular and central nervous system manifestations. With the exception of the emergence of normocalcemic PHPT in the United States, the clinical phenotype of PHPT has not changed substantially over the past 20 years. Since the normocalcemic individuals have only recently been systemically identified, the percentage noted in this figure is likely to be an underestimate of its true prevalence.

Figure 2

Percentage increase of total, symptomatic, and asymptomatic primary hyperparathyroidism from 2007–2010 compared to 2006 in Chinese patients.

Figure 3

Symptomatic and asymptomatic primary hyperparathyroidism in China, represented by Beijing from 1958–1993 and Shanghai from 2001–2010. There has been a dramatic increase in the proportion of patients diagnosed with asymptomatic disease.

Figure 4

Comparison of the differences in current presentation of primary hyperparathyroidism in New York City and Shanghai. Note the continued higher prevalence of symptomatic disease in the Chinese cohort, as well as relatively high occurrence of parathyroid cancer. Normocalcemic primary hyperparathyroidism is noted in the American cohort but not in the Chinese population.