Normocalcemic Primary Hyperparathyroidism Research Articles

Comparison of normocalcemic versus hypercalcemic primary hyperparathyroidism in a hypercalciuric renal stone population.

Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. Our objective was to compare hypercalcemic hyperparathyroidism (HPHPT) versus NHPT hypercalciuric renal stone patients. We took advantage of a routine calcium load test performed in hypercalciuric renal stone patients to assess retrospectively among PHPT patients, prevalence and characteristics of NHPT and HPHPT under a calcium restricted diet. Among 1671 hypercalciuric patients included, 91 patients have a final diagnosis of PHPT(post load ionized calcium (iCa)>1.31 mmol/L and PTH>30 pg/ml). Prevalence of NHPT is 40% of all PHPT, however according to total serum calcium 4/35 NHPT and 7/56 HPHPT would have been misclassified in the other group. 18/35 NHPT and 40/56 HPHPT underwent parathyroidectomy. No significant characteristics related to parathyroid weight, stone composition or bone remodeling biomarkers is detected between groups. Whereas iCa is higher in HPHPT in fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Of notice, renal calcium excretion (FECa) post load increases by 303% in NHPT but only 176% in HPHPT (p=0.01) likely explained by a lesser PTH decrease (p=0.02). However, a strong negative association (p<0.0001) detected between pooled pre and post load iCa and PTH only in NHPT group suggests a persistent efficient PTH-CaSR control within parathyroid glands in this group. Our data show the relevance of dynamic tests to unmask NHPT in hypercalciuric renal stone patients.

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.

Hyperparathyroidism and Peripheral Arterial Disease.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

Twenty-four hour Holter ECG in normocalcemic and hypercalcemic patients with hyperparathyroidism.

To investigate the occurrence of arrhythmias in patients with normocalcemic (NC) primary hyperparathyroidism (PHPT) compared to both hypercalcemic PHPT patients and control subjects by means of 24-h Holter ECG. Thirteen NCPHPT postmenopausal patients were enrolled and age-matched with 13 hypercalcemic PHPT patients and 13 controls. Every subject underwent basal ECG, 24-h Holter ECG and mineral metabolism biochemical evaluation. PHPT patients had higher mean serum calcium levels compared to both NCPHPT and controls; there was no difference in mean serum calcium levels between NCPHPT and controls. Both NCPHPT and PHPT patients had significantly higher mean PTH levels compared with controls. There were no differences in ECG parameters between the three groups, except for QTc interval. PHPT patients had normal QTc interval values, but significantly shorter mean values compared with those of controls and NCPHPT patients. During 24-h Holter ECG recording, 100% of PHPT patients had supraventricular premature beats (SVPBs), compared to 46% of NCPHPT (p = 0.005) and to 53% of controls (p = 0.01). PHPT patients experienced ventricular premature beats (VPBs) (69.2%) vs 15% of NCPHPT patients (p = 0.01) and 23% of controls (p = 0.04). There was no difference between NCPHPT and controls subjects concerning occurrence of both VPBs and SVPBs. NCPHPT patients did not experience an increased occurrence of arrhythmias compared to controls, while PHPT patients showed an increased occurrence compared to both controls and NCPHPT. Our findings are most probably related to the short QTc interval caused by hypercalcemia observed in PHPT patients, but not in NCPHPT.

The Ca∗Cl/P Ratio: A Novel and More Appropriate Screening Tool for Normocalcaemic or Overt Primary Hyperparathyroidism

ObjectiveThe main purpose of this study was to explore the diagnostic performance of the Ca∗Cl/P ratio for primary hyperparathyroidism (PHPT), especially normocalcaemic PHPT (NPHPT), to assist health care providers in making reliable and rapid clinical identifications. MethodsFrom January 1, 2013, to March 31, 2023, 230 PHPT patients, including 65 with NPHPT and 230 sex- and age-matched controls, were enrolled in this retrospective study. Differences between hypercalcaemic PHPT (HPHPT) and NPHPT and between them and their respective controls were analyzed. The diagnostic accuracy of the Ca∗Cl/P ratio, Ca/P ratio, Cl/P ratio and albumin-corrected calcium was assessed by the area under the receiver operating characteristic curve. ResultsCompared with corresponding controls, NPHPT and HPHPT patients both had significantly higher Ca ∗ Cl/P ratios (271.64 ± 51.74 vs 192.71 ± 26; 419.91 ± 139.11 vs 199.14 ± 36.75, P < .001). In the overall cohort, the ROC-AUC of the Ca∗Cl/P ratio (0.964, 95% CI = 0.943-0.979) for diagnosis of PHPT patients was superior to albumin-corrected calcium (0.959, 95% CI = 0.934-0.973), the Ca/P ratio (0.956, 95% CI = 0.934-0.973), and the Cl/P ratio (0.923, 95% CI = 0.895-0.946). A Ca ∗ Cl/P ratio above 239.17 mmol/L, with sensitivity (0.952), specificity (0.922), PPV (0.924), NPV (0.951) and accuracy (0.937), can distinguish PHPT patients from healthy individuals. Furthermore, the Ca ∗ Cl/P ratio yielded a sensitivity of 0.831, specificity of 0.938, PPV of 0.931, NPV of 0.847 and accuracy of 0.885 for NPHPT. ConclusionThe Ca∗Cl/P ratio provides excellent diagnostic power for diagnosis of PHPT, especially NPHPT.

Thiazide diuretics and primary hyperparathyroidism.

Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.

SAT176 Comparison Of Prevalence For Normocalcemic Primary Hyperparathyroidism (NPHPT) Using Different 25(OH)D Levels: A Systematic Review

Abstract Disclosure: I.N. Farooqi: None. X. Wang: None. The familiar topic of vitamin D deficiency remains controversial in the context of bone metabolism and health, with findings supportive of differing thresholds for supplementation. While the Fifth International Workshop has not delineated exact cutoffs for 25(OH)D to rule out the secondary cause of vitamin D deficiency in evaluations of NPHPT, we believe higher thresholds will yield fewer rates of diagnosis. We postulate that a review of existing literature yields significant differences in the reported prevalence of NPHPT when comparing 25(OH)D cutoffs of ≥30ng/mL versus ≥20ng/mL. PubMed searches were conducted using the key words “normocalcemic primary hyperparathyroidism,” “prevalence,” “trial,” and 7400 studies were initially found. Excluding studies from before 2010, those using population sizes less than 100 subjects, and abstracts, we found a total of 14 articles for which full-text review was performed. We examined 9 studies using the 25(OH)D cutoff ≥20ng/mL and 5 studies using ≥30ng/mL for our analysis. Although research on NPHPT has been done worldwide, including Europe, East Asia, North and South Americas, none were found in Africa, South Asia, and Australia. Our review identified 9/14 studies in Canada, USA, UK, Sweden, Czech Republic, Italy, Belgium, and China which used 25(OH)D ≥20ng/mL to exclude vitamin D deficiency, with a prevalence range of 0.18-21%, averaging 5.81%. Conversely, the remaining 5/14 studies from Brazil, USA, Spain, and Italy using ≥30ng/mL as the lower limit of 25(OH)D for diagnosing NPHPT yielded prevalence rates ranging 0.02-8.9% with an average of 3.17%. The prevalence of NPHPT is 8.9% in the Brazilian study by Marques et al. in 2011 and 6% in the Spanish study by Garcia-Martin in 2012, while the remainder of North American and European studies using the ≥30ng/mL cutoff from 2015 onward reported prevalence rates of only 0.02-0.6%. Of the total number of publications reviewed since 2015, 30% of the studies implemented the higher threshold of ≥30ng/mL. Previously documented prevalence rates of NPHPT among healthy adults have used 25(OH)D ≥20ng/mL to define the exclusion of vitamin D deficiency; however, our current review of several studies since 2010 demonstrates a significantly lower prevalence of the disease when the cutoff is raised to ≥30ng/mL. Our findings suggest greater specificity in the exclusion of vitamin D deficiency in more recent publications. Recent research examining free 25(OH)D as a more effective marker for vitamin D status suggests total 25(OH)D ≥30ng/mL may still be insufficient to completely exclude vitamin D deficiency in NPHPT. Thus, the role of varying 25(OH)D cutoffs is interesting and requires further investigation on a geographic level, as it may provide more insight into interethnic variations, correlation with seasonality and sunlight exposure, and healthcare access in regions where such studies have yet to be conducted. Presentation: Saturday, June 17, 2023

Normocalcemic Primary Hyperparathyroidism. A Case Report and Literature Review

Normocalcemic primary hyperparathyroidism (PHP) has been proposed to be a new phenotype of the disease. It is characterized by persistently high levels of parathyroid hormone (PTH) and normal calcium levels. Since there are no known causes of secondary hyperparathyroidism or PTH elevation, the exact biological mechanism is not known. It could be the first stage of the disease or a unique situation marked by resistance of the kidneys and bones to the effects of PTH. This is a disease that is getting more and more common. It is often found when evaluating perimenopausal women with low bone mass or when evaluating or following up on patients with osteoporosis. Normocalcemic PHP has a diverse and varied phenotype that ranges from cases with no usual PHP symptoms to cases with symptoms and specific complications. The method to diagnosing secondary hyperparathyroidism should focus on ruling out all possible causes, especially vitamin D deficiency (25-OH vitamin D levels less than 30ng/mL) and kidney function impairment (glomerular filtration rate less than 60 mL/min, as measured by CKD- EPI). Not much is known about its past in the wild. Some people get hypercalcemia, but more than 75% of them don't. There don't seem to be any ways to predict who will get hypercalcemia, so measuring total and adjusted calcium levels once a year is recommended. Even though measuring ionic calcium is a part of what it means to have Normocalcemic PHP and is recommended by some writers during follow-up, there are a number of real problems with it that should be kept in mind.

The evolution of primary hyperparathyroidism publications and global productivity from past to present: A bibliometric analysis during 1980 to 2022.

The aim of this study was to perform a descriptive analysis of scientific articles about primary hyperparathyroidism (PHPT) using bibliometric approaches. By analyzing the links between the various research components (authors, journals, institutions, countries) of the academic outputs, it was aimed to summarize the intellectual structure of PHPT, identify recent research trends, and determine the global productivity. Three thousand nine hundred fifty-four articles on PHPT published between 1980 and 2022 were pulled from the Web of Science database and analyzed using bibliometric approaches. Bibliometric network visualization maps were used to identify trending topics, citation analysis, and international collaborations. Spearman correlation coefficient was used for correlation analysis. The 3 most prolific authors are Bilezikian JP. (n = 87), Silverberg SJ. (n = 72) and Akerstrom G. (n = 57). The top 3 most productive institutions were Columbia University (n = 133), Udice French Research Universities (n = 127) and Uppsala University (n = 98). The top 3 most productive journals were Surgery (n = 216), Journal of Clinical Endocrinology and Metabolism (n = 201) and World Journal of Surgery (n = 148). The top 3 contributing countries to the PHPT literature were United States of America (n = 1062, 26.8%), Italy (346, 8.7%) and United Kingdom (274, 6.9%). The most studied topics from past to present are parathyroidectomy, hypercalcemia, parathyroid hormone/adenoma/glands, calcium/calcimimetics, scintigraphy/sestamibi, bone mineral density, ultrasound, vitamin D, osteoporosis, minimally invasive parathyroidectomy, brown tumor, nephrocalcinosis/nephrolithiasis, multiple endocrine neoplasia type 1, normocalcemia, pregnancy, imaging/preoperative imaging, parathyroid cancer/carcinoma, asymptomatic primary hyperparathyroidism, and cinacalcet. The trending topics in recent years were normocalcemic primary hyperparathyroidism, trabecular bone score, children, CDC73, microwave ablation, radiofrequency ablation, denosumab, cinacalcet, preoperative imaging, imaging, diagnosis, CT, PET, PET/CT, 4D/CT, SPECT/CT, F-18-fluorocholine, quality of life, fractures, and metabolic syndrome. We can say that there will be an increasing research trend on PHPT in the coming years. In addition to the Western countries such as the United States and European countries with large economies, Japan and Turkey were also identified as leading countries in the development of the PHPT literature. This study provides significant information about the intellectual structure and global productivity of PHPT to clinicians and other researchers interested on PHPT.

Genetic aspects underlying the normocalcemic and hypercalcemic phenotypes of primary hyperparathyroidism.

Hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. We investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism. Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral Center. The data of both groups were compared with 54 in house-controls and 503 subjects from the 1000 Genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis. The NPHPT group differed significantly at SNPs in OPG and ESR1. Also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes. Our NPHPT patient set harbored a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies.

Normocalcemic primary hyperparathyroidism; a mini-review

Normocalcemic primary hyperparathyroidism (NPHT) is a subtype of primary hyperparathyroidism (PHPT) characterized by elevated levels of parathyroid hormone (PTH) within the normal range of serum calcium. In traditional PHPT, high serum calcium levels are typically seen, whereas in normocalcemic PHPT, calcium levels are within the normal range. NPHT is often diagnosed incidentally when routine blood tests reveal elevated PTH levels while calcium levels remain normal. The exact prevalence of NPHT is not well established due to variations in diagnostic criteria and inconsistent screening practices. The clinical significance and management of NPHT are still a subject of debate. Some studies suggest that NPHT may have similar long-term complications as traditional PHPT, such as kidney stones, osteoporosis, and cardiovascular disease. However, other research indicates that NPHT may have a more benign course with a lower risk of developing these complications.

FGF-23 levels in patients with normocalcemic primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1398160: A Rare Case of Water Clear Cell Parathyroid Adenoma Escaping Sestamibi Scan and Neck Ultrasound – A Diagnostic Conundrum of a Rare Pathological Intity with a Rare Presentation

Parathyroid water-clear cell hyperplasia (WCCH) and water-clear cell adenoma (WCCA) are extremely rare causes of primary hyperparathyroidism (PHPT). WCCH contributes to < 1% of all PHPT however WCCA is exceptionally rare and has been reported only in less than 30 case reports. We are presenting a very rare indolent pathological entity with a very rare presentation escaping common diagnostic measures of Sestamibi scan and neck ultrasound. A 63-year-old female presented for evaluation of severe osteoporosis with a T-score of -3.6. Laboratory workup revealed elevated parathyroid hormone (PTH) of 122 pg/ml (reference range 12-88 pg/ml), Normal calcium 9.8 mg/dl, Normal vitamin D 50 ng/ml, and normal magnesium 2.2 mg/dl. 24-hour urine calcium was 421 mg/24H. Diagnosis was consistent with normocalcemic PHPT and meeting surgical criteria with osteoporosis and high urine calcium. Sestamibi scan did not identify any focal activity. CT H&N revealed an 8 mm mass inferior and posterior to right thyroid lobe with partial washout and slightly different enhancement compared to thyroid gland. Neck ultrasound (US) reported that previously noted tissue activity on the CT H&N is not visualized and most likely represents normal thyroid tissue. Patient was referred to otolaryngology surgery and underwent four gland explorations, including right inferior and left superior parathyroidectomy. Pathology of superior parathyroid gland revealed parathyroid water clear cell adenoma. 3-month Postoperative PTH 29.4 pg/ml and calcium level of 9.3 mg/dl. Solitary parathyroid adenoma (SPA) attributes to 80-85% of PHPT. Majority of cases is due to Chief cell adenomas, less frequent pathologies include oxyphil cell adenoma, lipoadenoma, WCCA or mixed type. Scientific literature regarding WCCA presentation and diagnosis is blurred due to its rarity. Clinical presentation of WCCA resembles other etiologies of PHPT, though some data suggest that is frequently indolent and manifests with mild PHPT. Literature suggests that WCCA has low biochemical activity and most cases had normal to mildly elevated calcium-our patient support this hypothesis-. Hypercalcemia does not manifest until significant growth of the adenoma, though few reported cases manifested with hypercalcemia. Unlike other SPA where Sestamibi scan sensitivity is 91%, literature suggests possibility of false-negative results with WCCA which is hypothesized to be attributed to its different histology of glycogen-rich vacuolized cytoplasm that leads to fast Sestamibi wash-out, for the same reason data suggest that US is more decisive given high water content of cells -Our patient didn’t follow this rule and escaped Sistamibi and US though seen on CT- which still makes the diagnosis of WCCA a conundrum. Some cases underwent surgical excision based on clinical diagnosis which led to revision of PHPT and/or hypercalcemia. There is no available data suggesting different long-term follow-up regimens for WCCA compared to other SPA. Further literature with longer follow-up is needed for this extremely rare entity for a comprehensive understanding of its natural course.

Normocalcemic primary hyperparathyroidism is an early stage of primary hyperparathyroidism according to fibroblast growth factor 23 level.

Normocalcemic primary hyperparathyroidism is a variant of primary hyperparathyroidism with consistently normal albumin-adjusted or free-ionized calcium levels. It may be an early stage of classic primary hyperparathyroidism or could represent primary kidney or bone disorder characterized by permanent elevation of PTH level. The study aims to compare the FGF-23 levels in patients with PHPT, NPHPT, and normal calcium and PTH levels. Our study included patients who were referred to the endocrinology clinic with a presumptive diagnosis of primary hyperparathyroidism, an isolated increased level of PTH, or reduced bone densitometry. For each patient, we performed blood analysis of FGF-23, calcium, phosphate, vitamin D [25(OH)D3], estimated glomerular filtration rate (eGFR), bone turnover markers, and urine analysis for calcium/creatinine ratio. Our study included 105 patients. Thirty patients with hypercalcemic hyperparathyroidism (HPHPT group), thirty patients with elevated PTH and normal calcium levels (NPHPT group), and 45 patients with normal calcium and PTH levels in the control group. FGF 23 level was 59.5± 23 pg/ml in the NPHPT group, 77 ± 33 pg/ml in the HPHPT group, and 49.7 ± 21.7 pg/ml in the control group (p=0.012). The phosphate level was lowest in the HPHPT group: 2.9 ± 0.6 vs 3.5 ± 0.44 in the NPHPT and 3.8 ± 0.5 in the control groups (p=0.001). No differences were found in eGFR, 25(OH)D3, C-terminal telopeptide type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels, and bone densitometry scores between the three study groups. Our findings suggest that NPHPT is an early stage of PHPT. Further studies are needed to determine the role of FGF-23 and its usefulness in NPHPT.

FCH-PET/CT in Primary Hyperparathyroidism With Discordant/Negative MIBI Scintigraphy and Ultrasonography.

The contribution of [18F]F-fluorocholine (FCH)-positron emission tomography (PET)/computed tomography (CT) in normocalcemic primary hyperparathyroidism (nPHPT) remains unknown. To evaluate the sensitivity and specificity of FCH-PET/CT in a cohort of osteoporotic patients with nPHPT and discordant or negative [99mTc]Tc-sestamibi scintigraphy and ultrasonography who all underwent parathyroidectomy (PTX). Longitudinal retrospective cohort study in patients referred for osteoporosis with mild biological primary hyperparathyroidism. Tertiary referral center with expertise in bone metabolism and surgical management of hyperparathyroidism. Among 109 patients with PHPT analyzed, 3 groups were individualized according to total serum calcium (tCa) and ionized calcium (iCa): 32 patients with hypercalcemia (HtCa group), 39 patients with normal tCa and elevated iCa (NtCa group), and 38 patients with both normal tCa and iCa (NiCa). All patients had biochemical follow-up confirming or not the success of PTX. To evaluate the performance of FCH-PET/CT in terms of sensitivity and specificity, and to compare with first-line imaging procedures in the setting of nPHPT. The sensitivity of FCH-PET/CT was 67% in the hypercalcemic group, 48% in the NtCa group (P = .05 vs HtCa), and 33% in the NiCa group (P = .004 vs HtCa). Specificity ranged from 97% to 99%. FCH-PET/CT was positive in 64.3% of patients with negative conventional imaging, with biochemical resolution after PTX in 77.8% of patients. Triple negative imaging was observed in 20 patients, with PHPT resolution in 85% of these patients. This study highlights the contribution of FCH-PET/CT in a well-phenotyped cohort of normocalcemic patients with discordant or negative findings in [99mTc]Tc-sestamibi scintigraphy and ultrasonography. However, negative imaging in nPHPT does not rule out the possibility of surgical cure by an experienced surgeon.

The Eucalcemic Patient With Elevated Parathyroid Hormone Levels.

Primary hyperparathyroidism (PHPT) is classically characterized by hypercalcemia with elevated or inappropriately normal parathyroid hormone (PTH) levels. Elevated PTH levels in the presence of normal calcium levels are not infrequently found during the evaluation of metabolic bone disorders or kidney stone disease. This can be caused by secondary hyperparathyroidism (SHPT) or normocalcemic primary hyperparathyroidism (NPHPT). NPHPT is due to autonomous parathyroid function whereas SHPT is caused by a physiologic stimulation to PTH secretion. Many medical conditions and medications can contribute to SHPT, and differentiation between SHPT and NPHPT may be difficult. Cases are presented to illustrate examples. In this paper, we review the distinction between SHPT and NPHPT as well as end organ effects of NPHPT and outcomes of surgery in NPHPT. We suggest that the diagnosis of NPHPT be made only after careful exclusion of causes of SHPT and consideration of medications that can increase PTH secretion. Further, we advise a conservative approach to surgery in NPHPT.

DXA-based bone strain index in normocalcemic primary hyperparathyroidism.

The natural history and bone involvement of normocalcemic hyperparathyroidism (NHPT) are not fully clarified yet. The bone strain index (BSI) is a deformation index based on the finite element method and can be applied to DXA scans. In this study, we aim to assess BSI in subjects with NHPT. A case-control study included 170 subjects: 40 subjects with NHPT, 50 subjects with primary hypercalcemic hyperparathyroidism (PHPT), and 80 controls (age- and sex-matched with the NPTH group). Lumbar spine (LS) bone mineral density (BMD), femoral neck (FN) BMD, total hip (TH) BMD, and TBS were similar between NHPT and both PHPT and controls. FN-BSI was lower in NHPT compared to PHPT (1.52 ± 0.31 vs 1.72 ± 0.42 p = 0.031) while there were no differences between NHPT and controls. TH-BSI was lower in NHPT compared to PHPT (1.36 ± 0.23 vs 1.52 ± 0.34, p = 0.030), while there were no differences between NHPT and controls. LS-BSI was not different between NHPT and both PHPT and controls. The trabecular and cortical bones assessed by BSI seem not to be significantly impaired in NHPT. Further prospective studies are needed to confirm these findings and to give an insight into the natural history of NHPT to improve knowledge and management of this condition.

Normocalcemic primary hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (PHPT) is a newer phenotype of PHPT defined by elevated PTH concentrations in the setting of normal serum calcium levels. It is increasingly being diagnosed in the setting of evaluation for nephrolithiasis or metabolic bone diseases. It is important to demonstrate that PTH values remain consistently elevated and to measure ionized calcium levels to make the diagnosis. A diagnosis of normocalcemic disease is one of exclusion of secondary forms of hyperparathyroidism, including vitamin D deficiency, renal failure, medications, malabsorption, and hypercalciuria. Lack of rigorous diagnostic criteria and selection bias of the studied populations may explain the different rates of bone and renal complications. The natural history still remains unknown. Caution should be used in recommending surgery, unless clearly indicated. Here we will review the diagnostic features, epidemiology, clinical presentation, natural history, medical and surgical management of normocalcemic PHPT.

Surgery for primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is typically treated with surgery, and it remains the only definitive therapy, whose techniques have evolved over previous decades. Advances in preoperative localization exams and the intraoperative PTH monitoring have become the cornerstones of recent parathyroidectomy techniques, as minimally invasive techniques are appropriate for most patients. Nevertheless, these techniques, are not suitable for PHPT patients who are at risk for multiglandular disease, especially in those who present with familial forms of PHPT that require bilateral neck exploration. This manuscript also explores other conditions that warrant special consideration during surgical treatment for PHPT: normocalcemic primary hyperparathyroidism, pregnancy, reoperation for persistent or recurrent PHPT, parathyroid carcinoma, and familial and genetic forms of hyperparathyroidism.

Normocalcemic non-renal hyperparathyroidism

Parathyroid hormone (PTH) is produced by the parathyroid glands, which are the main regulators of calcium and phosphorus metabolism. Hyperparathyroidism is a clinical condition associated with an increase in serum PTH content. The state of parathyroid glands depends very much on the amount of vitaminD, magnesium and boron in the blood because, according to official data, substantiated by a number of scientific studies, the majority of the world population (80%) has a lack/deficiency of vitamin D. This fact explains the high prevalence of thyroid diseases (hyperplasia, adenoma, hyperparathyroidism) and associated pathology. Previous studies have shown that a deficiency/lack of vitaminD was found in 85–94% of Ukraine population. A deficiency/lack of vitamin D compensatorily stimulates an increase in PTH synthesis. Doctors very rarely determine the level of PTH, which prolongs the progression of hyperparathyroidism, and they detect it only with severe associated changes in other systems. Hyperparathyroidism occurs when one or more of the parathyroid glands become hyperactive, gradually leading to elevated serum parathyroid hormone levels and hypercalcemia. The diagnostic criteria for hyperparathyroid conditions are very vague, which is confusing and leads to unnecessary surgeries instead of simple vitamin D and boron therapy. Normocalcemic primary hyperparathyroidism is a diagnosis of exclusion, and it can be considered only after careful assessment of the causes of secondary hyperparathyroidism, including that associated with a lack of vitamin D. The most common form of hyperparathyroidism is normocalcemic non-renal hyperparathyroidism. Prophylactic use of vitamin D in the correct individualized doses (25(OH)D range of 100–150 nmol/l or 40–60 ng/ml) should reduce the risk of parathyroid pathology but only 10% of the population receives such therapy, others do not know that it is useful. The only way to eliminate the gradual progression of parathyroid disorders is to administer individual prophylactic or therapeutic doses of vitaminD.