Asymptomatic Hyperparathyroidism Research Articles

Emerging pattern of asymptomatic hyperparathyroidism in South India - a six-year retrospective study.

Primary hyperparathyroidism (PHPT) is a common endocrine disease with a variable presentation. There is a recent increase in the number of asymptomatic cases due to the use of multichannel automated analyzers.

THU405 A Delicate Balance

Abstract Disclosure: N. Mohan: None. M.S. Shah: None. Introduction: Primary hyperparathyroidism is a disorder of excessive parathyroid hormone production causing increased calcium levels, usually due to a parathyroid adenoma. Commonly these cases are asymptomatic and detected incidentally on routine labs. They can be managed conservatively with sufficient fluid intake and avoiding dehydration. Congestive heart failure patients on diuretics with primary hyperparathyroidism require a delicate balance of their volume status to prevent exacerbation of either condition. We present a case of a woman with repeated hospitalizations due to poor volume status control. Clinical Case: An 82-year-old female with congestive heart failure (CHF), primary hyperparathyroidism (diagnosed 17 years ago), sick sinus syndrome with a pacemaker, and persistent atrial fibrillation presented to the emergency room with worsening b/l lower limb swelling for a few months. The remaining review of systems was largely negative. At home, she was on Losartan, Furosemide, and Carvedilol. Vitals were stable and physical exam revealed b/l lower extremity pitting edema. Chest x-ray showed cardiomegaly with mild pulmonary vascular congestion. Pertinent labs were NT pro-BNP 2190, Calcium 11.3 mg/dL, PTH 143 pg/mL, and Vit D, 25-hydroxy 48.6 ng/mL. The patient was started on IV diuretics and her home medications for CHF exacerbation. ECHO showed EF 39%, grade III diastolic dysfunction, severe pulmonary hypertension, mitral and tricuspid regurgitation. She was managed conservatively for her hypercalcemia and advised to maintain hydration at home. Spironolactone and Dapagliflozin were added to her regimen, and Furosemide was increased at discharge. The patient was re-admitted three weeks later with fatigue and decreased fluid intake. Vitals were stable and physical exam revealed dehydration. Pertinent labs were Calcium 13.4 mg/dL, Potassium 5.7 mmol/L, Creatinine 1.7 mg/dL (baseline 1.0), PTH 204 pg/mL, and Vit D 54.1 ng/mL. Repeat ECHO showed EF 15%. She was started on gentle 0.9% NS IV fluid to correct the hypercalcemia while preventing volume overload. Hypercalcemia and acute kidney injury improved with hydration. She was put on Cinacalcet 30 mg and home medications were modified for better volume control at discharge. Conclusion: This case highlights the complications of balancing the volume status with primary hyperparathyroidism and CHF. This patient’s primary hyperparathyroidism was well-controlled for more than fifteen years on adequate hydration. However, worsening CHF resulted in a higher requirement for diuretics, thereby worsening her hypercalcemia. Even though parathyroidectomy is an established treatment modality, she was not a suitable candidate due to age and comorbidities. Hence, to prevent such complications, parathyroidectomy must be considered early in patients with heart disease and even in asymptomatic hyperparathyroidism. Presentation: Thursday, June 15, 2023

Arrhythmia Resolution After Successful Parathyroidectomy for Primary Hyperparathyroidism.

The prevalence of primary hyperparathyroidism (PHPT) is increasing as routine laboratory testing for calcium and parathyroid hormone becomes more prevalent due to heightened awareness of the disease. PHPT affects multiple organ systems including the cardiovascular system. This case report highlights a patient with first degree atrio-ventricular block pre-operatively that resolved after resection of her parathyroid adenoma. This case emphasizes the importance of treating asymptomatic hyperparathyroidism to optimize cardiac function.

Abstract #1403692: Discrepancy Between Dual-Energy X-ray Absorptiometry and Quantitative Computed Tomography in Analyzing Bone Mineral Density in a Patient with Primary Hyperparathyroidism, Fractures and Degenerative Joint Disease - A Case Report and Review of Literature

Primary hyperparathyroidism is associated with lower bone mineral density (BMD). Dual-energy x-ray absorptiometry (DXA) is the gold standard to measure BMD and a T-score of less than -2.5 is an indication for parathyroidectomy. However, DXA has limitations in skeletal evaluation of patients with primary hyperparathyroidism and degenerative joint disease (DJD). The use of quantitative computed tomography (QCT) should be considered for these patients to accurately assess their BMD to guide proper management. 87-year-old female with a past medical history of primary hyperparathyroidism and DJD. She has a previous history of two left femoral fractures and underwent surgical repair. She was not considered for parathyroidectomy based on her age, serum calcium, and absence of renal and skeletal indications for surgery given that her BMD only reveals osteopenia. Patient experienced sudden-onset low back pain and MRI of the spine revealed L1 compression fracture and diffuse DJD. QCT showed severe osteoporosis with BMD of 21.8 mg/c (T-score equivalent of -5.64) while her DXA only showed osteopenia on the lumbar spine and right femoral neck with T-score of -1.4 and -2.3, respectively. Based on the history of vertebral fracture and QCT result, patient was referred for parathyroidectomy. Osteoporosis is a degenerative disease of the bone characterized by low BMD which predisposes patients to low-impact, fragility fractures. Regular assessment of BMD in patients with primary hyperparathyroidism is beneficial to evaluate the need for parathyroidectomy. While current guidelines suggest the use of DXA to assess BMD, it does not always reflect the accurate state of the bones. From the review of the literature, the difference of T-scores between DXA and QCT is due to an artifact from arthritic changes and degenerative disease. DXA evaluates cortical bone and findings can be influenced by degenerative changes and facet joint hypertrophy, which is strongly associated with the overestimation of the BMD. QCT, on the other hand, evaluates trabecular and cortical bone separately and is not affected by arthrosic changes and vascular calcifications. Clinicians should be aware of the discrepancy and should consider QCT instead of DXA for screening and diagnosing of osteoporosis in patients with primary hyperparathyroidism, DJD and history of fractures. If the skeletal assessment was done by QCT and not DXA, parathyroidectomy could have been done earlier preventing her vertebral fracture. Therefore, we suggest adding the option to perform QCT instead of DXA for the skeletal assessment of patients with asymptomatic hyperparathyroidism who has DJD.

Effect of Parathyroidectomy on Left Ventricular Mass Index in Patients With Primary Hyperparathyroidism.

Aim Primary hyperthyroidism (PHPT) is known to affect left ventricular structure and function and may contribute to increased cardiovascular morbidity and mortality. Whether parathyroidectomy (PTX) reverses left ventricular hypertrophy/remodeling among PHPT patients remains controversial. Method In this prospective, single-center study, we enrolled patients with the diagnosis of PHPT who were scheduled for PTX. Patients underwent a complete biochemical workup and an echocardiographic examination at baseline and a six-month follow-up. The primary objective was to compare the left ventricular mass index (LVMI) at baseline and six-month follow-up. Result Eighteen patients (15 female, three male, mean age 58.7 years) were enrolled. PTH and serum calcium returned to normal immediately post-PTX and remained normal at six months. LVMI at baseline was within normal limits and reduced further at the six-month follow-up. The left ventricular ejection fraction was in the normal range before the PTX and remained unchanged during follow-up. Conclusion Curative PTX reduced LVMI further within the normal range at six months in patients with asymptomatic hyperparathyroidism, providing evidence for benefit in an important non-traditional disease manifestation.

In patients with asymptomatic hyperparathyroidism, does parathyroidectomy or yearly monitoring lead to higher morbidity?

Bartlett, Stacy MD; Truong, Oanh MD; Haugh, Amy MLS; Simpkins, Courtney PharmD, BCPS; Castelli, Gregory PharmD, BCPS, BC-ADM Author Information

Refractory Yet Transient Neonatal Hypocalcemia Due to Hitherto Undiagnosed Asymptomatic Maternal Hyperparathyroidism: A Case Report

Hypocalcemia is one of the common causes of neonatal seizures and can result in significant morbidity. Among the multitude of etiologies, hypoparathyroidism as a consequence of maternal hyperparathyroidism is an uncommon one. We describe a neonate who presented with hypocalcemic seizures with relative hypoparathyroidism that unmasked a previously undiagnosed and asymptomatic maternal hyperparathyroidism, and explore the difficulties encountered in the management. Despite initial recalcitrance of hypocalcemia to therapy, parathyroid suppression was transient and recovered completely in few months.

Management of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is the unregulated overproduction of parathyroid hormone (PTH) resulting in abnormal calcium homeostasis. The disease profile has evolved over the last century from symptomatic hyperparathyroidism to asymptomatic hyperparathyroidism. Primary hyperparathyroidism is a biochemical diagnosis. Parathyroidectomy is the only established cure for this disease. Every effort is made to localize the offending gland preoperaively with various imaging modalities. These localization studies along with intraoperative parathormone monitoring will direct the surgeon to either a focused parathyroidectomy or a four gland exploration. All symptomatic patients and asymptomatic patients who meet the criteria for surgery should undergo parathyroidectomy if no medical contraindications exist. Pharmacologic approaches are reserved for those patients unfit or unwilling to undergo surgery.

Asymptomatic secondary hyperparathyroidism can mimic sacroiliitis on computed tomography

Secondary hyperparathyroidism (sHPT) as a result of chronic kidney disease (CKD) is a common health problem and has been reported to manifest at the sacroiliac joints (SIJ). The aim of this investigation was to systematically assess sacroiliac joint changes in asymptomatic sHPT as detected by high-resolution CT. Included in this IRB-approved retrospective case–control study were 56 patients with asymptomatic sHPT as well as 259 matched controls without SIJ disease. Demographic data were retrieved from electronic patient records. High-resolution computed tomography datasets of all patients were subjected to a structured scoring, including erosions, sclerosis, osteophytes, joint space alterations and intraarticular calcifications. Chi2 tests were used to compare frequencies of lesions. Erosions were significantly more prevalent in patients with sHPT, and were found mainly in the ventral (28.6% vs. 13.9%; p = 0.016) and middle (17.9% vs. 7.7%; p = 0.040) iliac portions of the SIJ. Partial ankylosis was rare in both cohorts (3.6% vs. 5.0%; p > 0.999); complete ankylosis was not observed. Neither extent not prevalence of sclerosis or calcifications differed significantly between groups. Joint lesions reminiscent of sacroiliitis can be found in a substantial portion of asymptomatic patients with secondary hyperparathyroidism. Further investigations into the clinical significance of these findings are warranted.

The incidence of nephrolithiasis and osteoporosis in patients with asymptomatic hyperparathyroidism

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

Clinical, Biochemical, and Radiological Profile of Normocalcemic Primary Hyperparathyroidism.

The clinical and radiological aspects of normocalcemic hyperparathyroidism (NHPT) are confounded by the differing methods used to rule out secondary hyperparathyroidism and by the small sample size. To assess the clinical, biochemical, and radiological profile of NHPT compared with primary hyperparathyroidism (PHPT) and control subjects. Multicentric cross-sectional study. Outpatient clinic. 47 NHPT, 41 PHPT, and 39 age- and sex-matched control subjects. Calcium metabolism and bone turnover markers (BTMs). Lumbar spine, total hip, femoral neck, one-third distal radius bone mineral density (BMD). Morphometric vertebral fracture (VF) assessed by dual-energy X-ray absorptiometry. NHPT patients had significantly higher parathyroid hormone, 25(OH)-vitamin D levels and lower calcium × phosphorus product than controls (P < .001). Compared with PHPT, the NHPT group had significantly higher 25(OH) vitamin D levels (P = .016). NHPT had BTM levels similar to controls and PHPT. NHPT, PHPT, and controls have similar lumbar spine and femoral neck BMD. NHPT and controls had a similar radial BMD, while patients with PHPT had a lower radial BMD than both patients with NHPT (P = .031) and controls (P < .05). Using the control group as the reference, after adjustment for interacting factors, there was no increase in risk of moderate-severe VF in NHPT (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.25-4.55), while PHPT had an increased risk (OR 3.81,95% CI 1.15-15.12). Seventy-nine percent of NHPT and 59% of PHPT patients fulfilled the criteria for asymptomatic hyperparathyroidism. The biochemical phenotype of NHPT is intermediate between PHPT and controls. In contrast, the bone phenotype resembles controls with normal bone turnover, no significant BMD impairment, and no increased risk of VF.

Assessing Bone and Kidney in Patients with Asymptomatic Hyperparathyroidism

Most cases of primary hyperparathyroidism (PHP) are diagnosed when mild hypercalcemia is noted incidentally on blood chemistry panels. An international

Prognostic Value of 99mTc-Sestamibi Parathyroid Scintigraphy in Predicting Future Surgical Eligibility in Patients With Asymptomatic Primary Hyperparathyroidism.

Patients with asymptomatic primary hyperparathyroidism might have a positive Tc-sestamibi parathyroid but do not meet criteria for surgical resection when the disease is diagnosed. However, many of these asymptomatic patients will become symptomatic or meet criteria for surgery later on. The aim of this study was to determine whether a positive sestamibi scan can precede future surgical eligibility in these patients. This retrospective study reviewed the records of 94 asymptomatic patients who had hyperparathyroidism and underwent Tc-sestamibi study with SPECT/CT imaging. Among them, 35 patients, including 12 with positive and 23 with negative sestamibi parathyroid scan, did not meet the criteria for surgery at the time of imaging, and follow-up record for at least 1 year was assessed on these patients. The imaging findings and the eligibility for surgery at the end of the follow-up were compared. With a median follow-up of 2.4 years (range, 1-4 years), among all 35 patients who were initially not eligible for surgery, 6 of 12 patients with a positive sestamibi scan became eligible for surgery, whereas 20 of 23 patients with negative scans remained ineligible for surgery. Positive parathyroid SPECT/CT predicted a higher possibility of meeting surgical criteria over time in asymptomatic hyperparathyroidism patients who are not surgery eligible at the time of presentation.

Parathyroid Hormone Polymorphism RS6254 is Associated with the Development and Severity of Osteoporosis in Asymptomatic but not Normocalcemic Hyperparathyroidism

Although normocalcemic and asymptomatic hyperparathyroidism (HPT) are becoming more common, they remain only partially understood. Parathyroid hormone ( PTH ) polymorphisms have been associated with disease severity in classical HPT. The aim of the present study was to evaluate the clinical effect of PTH polymorphism (rs6254) in normocalcemic and asymptomatic HPT. A prospective study of 61 consecutive patients with normocalcemic or asymptomatic HPT was carried out. Secondary causes of HPT were ruled out. All patients were followed for≥1 year. Calcium and phosphorus metabolism parameters were assessed at least twice during the follow-up period to classify as normocalcemic or asymptomatic HPT. Bone mineral density (BMD) and the rs6254 polymorphism genotype were also assessed. Genotype rs6254GG was observed in 23 patients (37.7%) whereas GA and AA genotypes were presented in 29 (47.5%) and 9 (14.8%) patients, respectively. Age, sex and genotype distributions were comparable in both groups. In asymptomatic but not normocalcemic HPT patients, the GG genotype was associated with a significantly higher level of intact PTH [200.2 (SD 76.5) vs. 113.3 (SD 25.9) pg/ml; p

Parathyroid Hormone Polymorphism RS6254 is Associated with the Development and Severity of Osteoporosis in Asymptomatic but not Normocalcemic Hyperthyroidism

Although normocalcemic and asymptomatic hyperparathyroidism (HPT) are becoming more common, they remain only partially understood. Parathyroid hormone (PTH) polymorphisms have been associated with disease severity in classical HPT. The aim of the present study was to evaluate the clinical effect of PTH polymorphism (rs6254) in normocalcemic and asymptomatic HPT. A prospective study of 61 consecutive patients with normocalcemic or asymptomatic HPT was carried out. Secondary causes of HPT were ruled out. All patients were followed for≥1 year. Calcium and phosphorus metabolism parameters were assessed at least twice during the follow-up period to classify as normocalcemic or asymptomatic HPT. Bone mineral density (BMD) and the rs6254 polymorphism genotype were also assessed. Genotype rs6254GG was observed in 23 patients (37.7%) whereas GA and AA genotypes were presented in 29 (47.5%) and 9 (14.8%) patients, respectively. Age, sex and genotype distributions were comparable in both groups. In asymptomatic but not normocalcemic HPT patients, the GG genotype was associated with a significantly higher level of intact PTH [200.2 (SD 76.5) vs. 113.3 (SD 25.9) pg/ml; p<0.01], and significantly lower Z-score densitometry at the femoral neck, proximal femur, and lumbar spine. Both remained significant after adjusting for major confounding factors by multiple linear regression. The present study supports the independent pathogenic effect of rs6254GA polymorphism on the development and severity of BMD complications in patients with asymptomatic but not normocalcemic HPT. Further studies are needed to confirm this finding and to assess the effect of other polymorphisms in normocalcemic and asymptomatic HPT.

Hyperparathyroidism due to Parathyroid Adenoma with Co-existing Vitamin D Deficiency – A Case Report

Primary hyperparathyroidism is often asymptomatic, may be detected during routine investigations or may present with features of hypercalcaemia. Vitamin D deficiency causing secondary hyperparathyroidism presents with musculoskeletal symptoms. Studies have shown an association between primary hyperparathyroidism and vitamin D deficiency. It has also been observed that when co-exist, these two conditions contribute to each other’s disease presentation and severity. This case report depicts initial asymptomatic hyperparathyroidism developing symptoms due to co-existing parathyroid adenoma and vitamin D deficiency in a 26-year-old muslim Bangladeshi female who responded well to adequate pre, per and post parathyroidectomy medical managementBirdem Med J 2015; 5(2): 104-106

Trabecular Bone Score in Patients with Normocalcemic Hyperparathyroidism

The effects of normocalcemic hyperparathyroidism (NHPT) on bone remain unclear. The objective of this study was to evaluate differences in the trabecular bone score (TBS) of NHPT patients and asymptomatic hypercalcemic hyperparathyroidism (HHPT) patients. We performed a prospective study that enrolled consecutive patients with asymptomatic hyperparathyroidism (NHPT and HHPT) with a follow-up ≥1 year at the University Hospital of Valladolid, Spain. Metabolic phosphocalcium plasma and urine parameters were evaluated in ≥2 determinations during follow-up to classify patients as NHPT patients or asymptomatic HHPT patients. A control group was enrolled during the same period. TBS and bone mineral density (BMD) were evaluated. Thirty-nine patients with asymptomatic HPT (24 with NHPT and 15 with HHPT) and 24 controls were recruited. NHPT patients and HHPT patients had a similar mean age, vitamin D level, TBS, and areal BMD (all sites). Compared to controls, symptomatic HPT patients had significantly higher parathyroid hormone (PTH) and calcium levels and significantly lower TBS and areal BMD at all sites (all P<.05). A significant negative relationship between TBS and PTH was found in asymptomatic HPT patients (r = -0.320, P = .043), which remained significant after adjustment for age, sex, and body mass index. There was no difference in the TBS between NHPT and HHPT patients. However, there was a reduction in the TBS of patients with asymptomatic HPT that was related to PTH levels but had no repercussion on bone mass. Higher levels of PTH seem to be responsible for this alteration in microarchitecture texture. aBMD = areal bone mineral density BMD = bone mineral density BMI = body mass index DXA = dual-energy X-ray absorptiometry HHPT = hypercalcemic hyperparathyroidism HPT = hyperparathyroidism HR-MRI = high-resolution magnetic resonance HR-pQcT = high-resolution peripheral quantitative computed tomography NHPT = normocalcemic hyper-parathyroidism PTH = parathyroid hormone TBS = trabecular bone score 25vitD = 25-hydroxyvitamin D.

High frequency of asymptomatic hyperparathyroidism in patients with fibromyalgia: random association or misdiagnosis?

Fibromyalgia (FM) and hyperparathyroidism may present similar symptoms (musculoskeletal pain, cognitive disorders, insomnia, depression and anxiety), causing diagnostic confusion. ObjectivesTo determine the frequency of asymptomatic hyperparathyroidism in a sample of patients with FM and to evaluate the association of laboratory abnormalities to clinical symptoms. MethodsCross-sectional study with 100 women with FM and 57 healthy women (comparison group). Parathyroid hormone (PTH), calcium and albumin levels were accessed, as well as symptoms in the FM group. ResultsIn FM group, mean serum calcium (9.6±0.98mg/dL) and PTH (57.06±68.98pg/mL) values were considered normal, although PTH levels had been significantly higher than in the comparison group (37.12±19.02pg/mL; p=0.001). Hypercalcemic hyperparathyroidism was diagnosed in 6% of patients with FM, and 17% of these women exhibited only high levels of PTH, featuring a normocalcemic hyperparathyroidism, with higher frequencies than those expected for their age. There was no significant association between hyperparathyroidism and FM symptoms, except for epigastric pain, which was more frequent in the group of patients concomitantly with both diseases (p=0.012). ConclusionsA high frequency of hyperparathyroidism was noted in women with FM versus the general population. Normocalcemic hyperparathyroidism was also more frequent in patients with FM. Longitudinal studies with greater number of patients are needed to assess whether this is an association by chance only, if the increased serum levels of PTH are part of FM pathophysiology, or even if these would not be cases of FM, but of hyperparathyroidism.

Frequência elevada de hiperparatireoidismo assintomático em pacientes com fibromialgia: associação ao acaso ou erro diagnóstico?

Fibromyalgia (FM) and hyperparathyroidism may present similar symptoms (musculoskeletal pain, cognitive disorders, insomnia, depression and anxiety), causing diagnostic confusion. ObjectivesTo determine the frequency of asymptomatic hyperparathyroidism in a sample of patients with FM and to evaluate the association of laboratory abnormalities to clinical symptoms. MethodsCross‐sectional study with 100 women with FM and 57 healthy women (control group). Parathyroid hormone (PTH), calcium and albumin levels were accessed, as well as symptoms in the FM group. ResultsIn FM group, mean serum calcium (9.6±0.98mg/dL) and PTH (57.06±68,98 pg/mL) values were considered normal, although PTH levels had been significantly higher than in the control group (37.12±19.02 pg/mL; p=0.001). Hypercalcemic hyperparathyroidism was diagnosed in 6% of patients with FM, and 17% of these women exhibited only high levels of PTH, featuring a normocalcemic hyperparathyroidism, with higher frequencies than those expected for their age. There was no significant association between hyperparathyroidism and FM symptoms, except for epigastric pain, which was more frequent in the group of patients concomitantly with both diseases (p=0.012). ConclusionsA high frequency of hyperparathyroidism was noted in women with FM versus the general population. Normocalcemic hyperparathyroidism was also more frequent in patients with FM. Longitudinal studies with greater number of patients are needed to assess whether this is an association by chance only, if the increased serum levels of PTH are part of FM pathophysiology, or even if these would not be cases of FM, but of hyperparathyroidism.

Clinical Expression of Calcium Sensing Receptor Polymorphism (A986S) in Normocalcemic and Asymptomatic Hyperparathyroidism.

Normocalcemic and asymptomatic hyperparathyroidism diagnosis are becoming more common. However, their pathophysiology is incompletely known. The aim of the present study was to evaluate the clinical effect of calcium-sensing receptor polymorphism (A986S) in normocalcemic and asymtomatic HPT. Prospective study conducted with 61 consecutive normocalcemic and asymptomatic HPT patients was followed up during a minimum period of 1 year. Secondary causes of hyperparathyroidism were ruled out. Calcium and phosphorus metabolism parameters were evaluated in at least 2 determinations during follow-up to classify as normocalcemic or asymptomatic hyperparathyroidism. Bone mineral density and A986S polymorphism genotype were also analyzed. Thiry-eight patients (62.3%) had the genotype A986A, and 23 (36.7%) patients had A986S (20 patients, 32.8%) or S986S (3 patients, 4.9%). Age, sex, and genotype distributions were comparable in both normocalcemic and asymptomatic hyperparathyroidism. In normocalcemic patients, S allele genotype was associated to statistically significant higher level of intact PTH: 92.0 (SD 18.5) vs. 110.6 (SD 24.4) pg/ml, p<0.05; and remained significant after adjustment by multiple linear regression. In asymptomatic hyperparathyroidism, A986A genotype resulted in a statistically significant higher level of intact PTH, alkaline phosphatase and procollagen amino-terminal propeptide; but only serum calcium remained as an independent predictor of serum intact PTH levels after a multiple linear regression. Bone mineral densitometry between genotypes did not show statistically significant differences. A986S polymorphism of CaSR is an independent predictor of PTH level in normocalcemic hyperparathyroidism patients, but not in asymptomatic hyperparathyroidism. More studies are needed to evaluate the effect of other polymorphisms in normocalcemic and asymptomatic hyperparathyroidism.