Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Choi HR ，Choi SH ，Hong N ，Rhee Y ，Kim JK ，Lee CR ，Kang SW ，Lee J ，Jeong JJ ，Nam KH ，Chung WY ... -  《-》

Normocalcaemic primary hyperparathyroidism: is nephrolithiasis more common than osteoporosis?

Normocalcaemic primary hyperparathyroidism (NPHPT) is often under-recognised in clinical practice. To determine the prevalence and clinical significance of NPHPT in an unselected sample in an acute hospital setting. Patients aged >18 years who had measurement of an elevated serum parathyroid hormone (PTH ≥ 7 pmol/L) during 12 months from 1 January 2017 to 31 December 2017 were retrospectively studied. NPHPT was defined by the presence of elevated serum PTH with normal albumin-corrected serum calcium on two or more occasions after excluding secondary causes. Patients were followed up for 2 years. Relevant data were collected by review of electronic medical records. Of the 2593 patients who had PTH measured during the study period, 1278 had serum PTH ≥ 7 pmol/L. Hypercalcaemic primary hyperparathyroidism (PHPT) was diagnosed in 174 patients. Secondary causes for elevated serum PTH were identified in 993 patients: 815 (chronic kidney disease - estimated glomerular filtration rate < 60 mL/min/1.73 m2 or renal transplant), 98 (vitamin D deficiency - 25(OH)D < 50 nmol/L), 28 (gastric bypass surgery), 38 (medications), 13 (malabsorption or post-thyroidectomy) and 1 (hypercalciuria). Data were incomplete for 80 patients. The prevalence of NPHPT with and without the exclusion of hypercalciuria was 0.19% (5) and 0.39% (10) respectively. The prevalence of nephrolithiasis in NPHPT was higher than PHPT (100% vs 15% among five patients (P < 0.001) and 50% vs 15% among 10 patients (P = 0.014)). The prevalence of osteoporosis was not significantly different between NPHPT and PHPT (20% vs 45% among five patients (P = 0.389) and 30% vs 45% among 10 patients (P = 0.518)). These findings give further credence to the diagnosis of NPHPT as a clinical entity. Nephrolithiasis may be a greater problem than osteoporosis in NPHPT compared with PHPT. This needs prospective evaluation.

Wu KCJ ，Anpalahan M 《-》

Normocalcemic Primary Hyperparathyroidism: A Comparison with the Hypercalcemic Form in a Tertiary Referral Population.

Normocalcemic primary hyperparathyroidism (NPHPT) is a formally recognized variant of primary hyperparathyroidism (PHPT), characterized by normal total and ionized serum calcium concentrations and elevated parathyroid hormone (PTH) levels, in the absence of secondary causes for hyperparathyroidism. NPHPT has been studied previously, but data are limited and confounded. We aimed to compare the clinical and biochemical data of normocalcemic and hypercalcemic subjects in a hospital-based population.We retrospectively analysed the medical records of 131 subjects diagnosed with PHPT at the university hospital Brussels (UZ Brussel) between January 1st 2007 and December 31st 2016, including 25 normocalcemic and 106 hypercalcemic subjects.The mean values of age, BMI, sex, serum 25-OH vitamin D levels and urinary phosphate excretion were comparable between both groups. Subjects diagnosed with NPHPT had significantly lower plasma PTH levels, lower urinary calcium excretion and lower serum creatinine levels compared to the hypercalcemic subjects with PHPT. Corresponding eGFR values were higher in the normocalcemic group. Normocalcemic subjects (NPHPT) presented with a high prevalence of nephrolithiasis (36%), fragility fractures (12%) and osteoporosis (25%). Clinical manifestations and BMD measurements revealed no statistically significant differences between both groups.Our data show a relative prevalence of 19% NPHPT in PHPT. NPHPT may present the earliest form of PHPT with an extension in time, but is not an indolent disease state. Normocalcemic subjects should be managed as hypercalcemic subjects with PHPT. Further research regarding the pathophysiology and natural course of NPHPT is required.

Pierreux J ，Bravenboer B 《-》

Biochemical characteristics and clinical manifestation of normocalcemic primary hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (nPHPT) is a condition characterized by persistently high levels of parathyroid hormone (PTH) and normal serum calcium levels in the absence of other causes for secondary hyperparathyroidism. The aim of the present study was to assess the clinical presentation and the biochemical characteristics in patients with nPHPT and to compare them with those in patients with hypercalcemic PHPT (hPHPT). The study included 316 patients (277 women and 39 men, average age 58.7 ± 12.1) diagnosed with PHPT. Total serum calcium, inorganic phosphates (PO4), PTH, urinary Ca (uCa), albumin, creatinine, 25(OH)D and bone markers (b-CTX and ALP) were examined in all of them. BMD of the lumbar spine (LS), distal third of the radius (DR), femoral neck (FN) and total proximal femur (TF) were measured by a dual-energy X-ray absorptiometry (DXA). The patients were divided into two groups according to albumin-corrected calcium (Ca) level - with hPHPT (Ca>2.62 mmol/L) and with nPHPT (Ca 2.12-2.62 mmol/l), without other causes for secondary hyperparathyroidism. The frequency of nPHPT was 15.2%. Normocalcemic patients had lower levels of PTH, higher PO4 and 25(OH)D, and smaller parathyroid adenomas. No significant difference in the frequency of osteoporosis, low-energy fractures, nephrolithiasis and gastrointestinal disorders was found between nPHPT and hPHPT. There was no difference in BMD between the two groups. The patients with nPHPT show a more favorable biochemical profile compared to those with hPHPT. Nevertheless, clinical manifestations and complications are similar, without a significant difference in the frequency of osteoporosis, nephrolithiasis, gastrointestinal disorders and low-energy fractures.

Yankova I ，Lilova L ，Petrova D ，Dimitrova I ，Stoynova M ，Shinkov A ，Kovatcheva R ... -  《-》

Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism is Associated with Improved Bone Mineral Density Regardless of Postoperative Parathyroid Hormone Levels.

Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p = 0.014), more bilateral cervical explorations (22% vs. 13%, p = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p = 0.002) and TH (1.64%, p = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. - 0.83%, p = 0.017). There was no difference in improvement at the LS or FN (p = NS). Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.

Lui MS ，Clemente-Gutierrez U ，Vodopivec DM ，Chang SL ，Shirali AS ，Huang BL ，Chiang YJ ，Fisher SB ，Grubbs EG ，Guise TA ，Graham PH ，Perrier ND ... -  《-》