Case 328: Brown Tumor in Hyperparathyroidism Due to Parathyroid Adenoma.

HISTORY: A 45-year-old female patient with diffuse osteoarticular pain, particularly low back pain, was referred by a rheumatologist for an updated radiologic evaluation. The patient had experienced these symptoms for many years and was diagnosed with human leukocyte antigen B27-negative spondyloarthritis approximately 11 years prior, based on findings of bilateral erosive sacroiliitis at pelvic radiography and bone scintigraphy with technetium 99m (99mTc) methylene diphosphonate. After 3 years of treatment with a tumor necrosis factor-α inhibitor (adalimumab), which was effective for pain, the patient was lost to follow-up. At the current presentation, approximately 8 years after being lost to follow-up, the patient presented with worsening low back pain. The presence of nonobstructing kidney stones on US images confounded the underlying cause of worsening pain. The patient also experienced fatigue and depressed mood. Routine blood tests revealed a normal blood cell count, creatinine level of 0.64 mg/dL (56.58 µmol/L) (normal range, 0.30-1.1 mg/dL [26.52-97.24 µmol/L]), C-reactive protein level of 1.1 mg/dL (normal, <1 mg/dL), and vitamin D level of 21 ng/mL (52.42 nmol/L) (normal range, 30-100 ng/mL [74.88-249.60 nmol/L]). Noncontrast MRI of the thoracic and lumbar spine, MRI of the sacroiliac joints, and CT of the abdomen and pelvis were performed.

Hyperaldosteronism and hyperparathyroidism. A disturbing friendship.

Classically, aldosterone actions are associated with the stability of the effective circulating volume and with blood pressure control, while parathormone actions are linked to bone mineral metabolism, calcium, and phosphate homeostasis. Nevertheless, the relationship between these two hormonal axes surpasses these areas. A bidirectional interrelation between calcium-phosphorus metabolism and blood pressure control can lead to alterations in both. This can have significant implications for the evolution and treatment of patients. To illustrate this relationship, we present two clinical cases that demonstrate the pathophysiology involved.).

Brown tumors: Retrospective analysis of 26 cases.

INTRODUCTION: Brown tumors are reactive osteolytic lesions caused by hyperparathyroidism. These rare lesions are non-neoplastic processes that result from bone resorption. The purpose of this study was to retrospectively review a 34-year experience with brown tumors in our institution. MATERIALS AND METHODS: We retrospectively analyzed the records of 26 consecutive patients with brown tumor who were treated in our institution between May 1988 and October 2020, with a mean follow-up of 36,1 months. RESULTS: 17 male (65,4%) and 9 female (34,6%) patients with a mean age of 41,6 were included in the study. Localized bone pain was present in 13 cases (50,0%) as the first presenting symptom. 3 patients (11,5%) presented with diffuse bone pain. 7 patients (26,9%) were diagnosed with brown tumor while being investigated for pathological fractures. The other 3 patients (11,5%) were diagnosed while being evaluated for hypercalcemia symptoms. 7 patients (26,9%) had solitary lesions, while 19 patients (73,1%) had multiple lesions. Pelvis, femur, ribs, tibia, proximal humerus and mandible were the most common sites of localization. 23 patients (88,5%) were diagnosed with primary hyperparathyroidism, while the other 3 patients (11,5%) had secondary hyperparathyroidism. A total of the 65 lesions, 23 (35.4%) underwent orthopedic surgery, and 42 (64.6%) were followed up conservatively after parathyroidectomy. Orthopedic surgery was performed in 21 of 26 patients, the other 5 cases were followed up conservatively. Intralesional curettage was performed in 19 cases (82,6%). The resulting cavity was filled with bone cement in 11 cases (47,8%). Bone grafting was applied in 8 cases (34,8%). No recurrence was observed in any of the patients. CONCLUSION: The diagnosis of brown tumor begins with clinical suspicion. Endocrinology and general surgery consultation is important before surgery. Treatment of brown tumors requires a multidisciplinary approach.

Association of Coronary Calcium Score on Cardiac PET During Pre-Kidney Transplant Assessment with Persistent Hyperparathyroidism: A Retrospective Study.

BACKGROUND Secondary hyperparathyroidism and coronary calcifications are common complications in chronic kidney disease. However, the relation between coronary calcium score (CCS) and persistent hyperparathyroidism (pHPT) after kidney transplantation (KT) remains unknown. MATERIAL AND METHODS This was a single-center retrospective study of KT candidates from January 2017 to May 2020. We collected patients' demographics, cardiovascular (CV) risk factors, and the findings of pre-KT CV imaging. We also collected parathyroid hormone (PTH) values before KT, at 1-6 months, 6-12 months, and 12-24 months after KT. We defined pHPT as PTH ≥25.5 pmol/L after 12 months post-KT. RESULTS A total of 111 KT recipients (KTRs) with a mean age of 50.4 years were included, of which 62.2% were men and 77.5% were living-donor KTRs. Dialysis modality used before KT was peritoneal dialysis in 9.9% and hemodialysis in 82.9%. Dialysis vintage was 3±2.9 years. The prevalence of pHPT was 24.3% (n=27), and the prevalence of severe coronary calcifications (CCS >400 Agatston units) was 19.8% (n=22). PTH values at baseline, 1-6 months, 6-12 months, and 12-24 months were not different among between CCS >400 or CCS <400 groups. However, pHPT after KT was significantly more prevalent in KTRs with severe CCS (37% vs 14.3%, p=0.014). Severe CCS was associated with less improvement of PTH values after KT (r=0.288, p=0.020). Otherwise, the findings of cardiac PET and coronary angiogram were not significantly different between pHPT and non-pHPT patients. CCS >400 was independently associated with pHPT after transplant (aOR=18.8, P=0.012). CONCLUSIONS Severe CCS on pre-KT cardiac assessment is associated with pHPT after KT.

Comparison of chronic kidney disease progression and associated complications between geriatric and non-geriatric groups.

There is no consensus on the physiologic decline in estimated glomerular filtration rate (GFR) due to geriatric conditions related with the aging or chronic kidney disease (CKD) itself. In this study, we aimed to compare the CKD progression and associated complications in a large sample of geriatric and non-geriatric patients. The data of in 506 patients at age between 30 to 90 years and diagnosed with CKD at stage 2 and above (15 mL/min/1.73 m2 ≤ eGFR < 90 mL/min/1.73 m2) were collected retrospectively and compared among geriatric (>65 years old) and non-geriatric individuals. The rate of hypertension was higher in geriatrics compared to non-geriatrics (96.6% vs 91.9%, P = .04). Among laboratory findings, only PTH level was significantly lower and HCO3 concentration was higher in geriatrics compared to non-geriatrics (P = .02, P < .001, respectively). There was no significant difference in last measured eGFR (P = .99) while that measured 4 years ago was lower in geriatrics compared to that of non-geriatrics (P < .001). eGFR change was smaller in geriatrics compared to non-geriatrics (P < .001), and rate of progressive renal disease among non-geriatric group (39%) was found to be significantly higher than in the geriatrics (17.2%) (P < .001). The prevalence of hyperkalemia was lower in geriatrics at stage 3a (P = .02); prevalence of hyperparathyroidism was lower in those at stage 3b (P = .02) and lastly the acidosis was observed significantly lower in geriatric patients at stage 3a, 3b, and 4 compared to the non-geriatrics at corresponding stages (P < .001, P = .03, and P = .04, respectively). The eGFR change was significantly smaller in geriatrics at stage 3b and 4 (P < .001 and P = .04, respectively) while the rate of progressed renal disease was lower in geriatrics at stage 3a and 3b (21.1% vs 9.9%, P = .03 and 41.2% vs 11.1%, P < .001, respectively). eGFR change in 4-year period and the rates of progressive renal disease are higher in the non-geriatrics and also the prevalence of secondary complications of CKD, such as hyperparathyroidism, acidosis, and hyperkalemia, are higher in non-geriatrics. This may reflect that decline of GFR in geriatric individuals is at least partially related to physiological aging rather than kidney disease. Therefore, devising age related CKD definitions might be appropriate.

A family case report of parathyroid carcinoma associated with CDC73 mutation in hyperparathyroidism-jaw tumor syndrome.

Background: Hereditary primary hyperparathyroidism (PHPT) accounts for 5-10% of all PHPT cases, necessitating genetic testing for diagnosis and management. Among these, hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disorder caused by CDC73 mutations with variable clinical presentations and incomplete symptoms. Case summary: The proband, diagnosed with PHPT, underwent parathyroidectomy at the age of 41 with pathological examination of parathyroid carcinoma (PC). Hereditary PHPT was initially suspected due to the early-onset PHPT and family history. Genetic testing identified a heterozygous CDC73 mutation, NM_024529.4: c. 687_688delAG (p. Arg229Serfs*37). Even in the absence of jaw tumors, the diagnosis of HPT-JT was confirmed based on the discovery of renal cysts. A secondary thyroidectomy was performed to reduce the risk of recurrence. Conclusion: Genetic testing is strongly recommended in cases of early-onset PHPT, family history, jaw tumors, renal and uterine involvement, atypical parathyroid tumors, and PC. This testing provides valuable information for personalized management, and counseling is available for affected families.

Pre-Transplant Hyperparathyroidism and Graft or Patient Outcomes After Kidney Transplantation.

The impact of pre-transplant parathyroid hormone (PTH) levels on early or long-term kidney function after kidney transplantation is subject of debate. We assessed whether severe hyperparathyroidism is associated with delayed graft function (DGF), death-censored graft failure (DCGF), or all-cause mortality. In this single-center cohort study, we studied the relationship between PTH and other parameters related to bone and mineral metabolism, including serum alkaline phosphatase (ALP) at time of transplantation with the subsequent risk of DGF, DCGF and all-cause mortality using multivariable logistic and Cox regression analyses. In 1,576 kidney transplant recipients (51.6 ± 14.0 years, 57.3% male), severe hyperparathyroidism characterized by pre-transplant PTH ≥771 pg/mL (>9 times the upper limit) was present in 121 patients. During 5.2 [0.2-30.0] years follow-up, 278 (15.7%) patients developed DGF, 150 (9.9%) DCGF and 432 (28.6%) died. A higher pre-transplant PTH was not associated with DGF (HR 1.06 [0.90-1.25]), DCGF (HR 0.98 [0.87-1.13]), or all-cause mortality (HR 1.02 [0.93-1.11]). Results were consistent in sensitivity analyses. The same applied to other parameters related to bone and mineral metabolism, including ALP. Severe pre-transplant hyperparathyroidism was not associated with an increased risk of DGF, DCGF or all-cause mortality, not supporting the need of correction before kidney transplantation to improve graft or patient survival.

Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.

Multiple brown tumors: a bone complication due to long-term untreated pseudohypoparathyroidism.

Bone lytic lesions are a possible complication of pseudohypoparathyroidism type 1B, in undertreated adult patients. Whole body [18F] F-fluorocholine PET/CT is a useful imaging tool to assess brown tumor progression in this context. We describe the case of a 33-year-old woman, referred for the diagnostic evaluation of lytic bone lesions of the lower limbs, in the context of asymptomatic pseudohypoparathyroidism. She had been treated with alfacalcidol and calcium during her childhood. Treatment was discontinued at the age of 18 years old because of the lack of symptoms. A femur biopsy revealed a lesion rich in giant cells, without malignancy, consistent with a brown tumor. Laboratory tests showed a parathyroid level at 1387 pg/ml (14-50). Whole-body Fluorocholine PET/CT revealed hypermetabolism of bone lesions. The final diagnosis was brown tumors related to hyperparathyroidism complicating an untreated pseudohypoparathyroidism. Genetic testing confirmed PHP type 1B. Pseudohypoparathyroidism with radiographic evidence of hyperparathyroid bone disease, is a very rare condition due to parathyroid hormone resistance in target organs, i.e., kidney resistance, but with conserved bone cell sensitivity. It has been reported in only a few cases of pseudohypoparathyroidism type Ib. Long-term vitamin D treatment was required to correct bone hyperparathyroidism. With this rationale, the patient was treated with calcium, alfacalcidol, and cholecalciferol. One-year follow-up showed complete resolution of pain, improvement in serum calcium, and regression of bone lesions on [18F]F-fluorocholine PET/CT. This case illustrates the usefulness of [18F]F-fluorocholine PET/CT for the imaging of brown tumors in pseudohypoparathyroidism type 1B, and emphasizes the importance of calcium and vitamin D treatment in adult patients, to avoid the deleterious effects of high parathyroid hormone on skeletal integrity.

Treatment of Hypercalcemic Hyperparathyroidism After Kidney Transplantation Is Associated With Improved Allograft Survival.

BACKGROUND: Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival. MATERIALS AND METHODS: We identified 280 KT recipients (2015-2019) with elevated post-KT adjusted serum calcium and parathyroid hormone (PTH). KT recipients were characterized by treatment: cinacalcet, parathyroidectomy, or no treatment. Time-varying Cox regression with delayed entry at the time of first elevated post-KT calcium was conducted, and death-censored and all-cause allograft failure were compared by treatment groups. RESULTS: Of the 280 recipients with tHPT, 49 underwent PTx, and 98 received cinacalcet. The median time from KT to first elevated calcium was 1 month (IQR: 0-4). The median time from first elevated calcium to receiving cinacalcet and parathyroidectomy was 0(IQR: 0-3) and 13(IQR: 8-23) months, respectively. KT recipients with no treatment had shorter dialysis vintage (P = .017) and lower PTH at KT (P = .002), later onset of hypercalcemia post-KT (P < .001). Treatment with PTx (adjusted hazard ratio (aHR) = 0.18, 95%CI 0.04-0.76, P = .02) or cinacalcet (aHR = 0.14, 95%CI 0.004-0.47, P = .002) was associated with lower risk of death-censored allograft failure. Moreover, receipt of PTx (aHR = 0.28, 95%CI 0.12-0.66, P < .001) or cinacalcet (aHR = 0.38, 95%CI 0.22-0.66, P < .001) was associated with lower risk of all-cause allograft failure. CONCLUSIONS: This study demonstrates that treatment of hypercalcemic tertiary HPT post-KT is associated with improved allograft survival. Although these findings are not specific to hypercalcemia of malignancy, they do demonstrate the negative impact of hypercalcemic tertiary HPT on kidney function. Hypercalcemic HPT should be screened and aggressively treated post-KT.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Treatment of hypokalemia with amiloride unmasked hypercalcemia and hyperparathyroidism: A case report.

Colonic pseudo-obstruction, also called Ogilvie's syndrome, occurs due to impaired intestinal propulsion, and may be caused by electrolyte imbalances such as hypokalemia and some endocrine disorders such as hyperparathyroidism. Secretory diarrhea due to intestinal pseudo-obstruction can cause hypokalemia. Diuretics such as amiloride can be used to treat hypokalemia, however in this case, treatment with amiloride induced hypercalcemia and unmasked hyperparathyroidism. A 73-year-old female with a history of hypertension and parathyroid adenoma presented with recurrent colonic pseudo-obstruction and chronic hypokalemia. Her hypokalemia was treated with amiloride, causing hypercalcemia of 14.4 mg/dL, elevated PTH, and altered mental status. Amiloride was subsequently discontinued with improvement in her symptoms, and her hyperparathyroidism was treated with cinacalcet. To our knowledge, this is the first report of amiloride unmasking hyperparathyroidism and inducing hypercalcemia.

Brown Tumour As An Unusual But Preventable Cause Of Spinal Cord Compression: Case Report And Literature Review.

Brown tumour is an infrequent, focal, and benign osteolytic lesion which is a consequence of abnormal bone metabolism in hyperparathyroidism (both primary and secondary). It is also known as Osteoclastoma. In the present era, we rarely encounter skeletal disease caused by primary hyperparathyroidism. Although it is a rare presentation because of advancement of treatment but still can be encountered because of lack of standard care so we should have high index of suspicion to avoid this preventable complication. We report here a case of brown tumour in the thoracic vertebra of a young female patient with End Stage Renal Disease, who presented with backache and bilateral lower limb weakness. MRI of the spine showed multiple non 20 enhancing abnormal signals involving vertebral body of C2, posterior elements of C6, and bilateral sacral vertebra, suggestive of healed fractures versus bone forming tumours. She underwent laminectomy. Her histopathology report was consistent with brown tumour of hyperparathyroidism.

A Diagnostic Journey.

We describe the case of a patient who came with features suggestive of diabetic ketoacidosis. On further evaluation of DKA, we found that it was caused by acute pancreatitis. This acute pancreatitis was found to be caused by hypercalcemia, which was in turn due to primary hyperparathyroidism. Imaging studies done for hyperparathyroidism revealed a thyroid nodule which later turned out to be malignant. This patient was also incidentally found to have hypertrophic obstructive cardiomyopathy.

Association of Anemia with Parathyroid Hormone Levels and Other Factors in Patients with End-Stage Renal Disease Undergoing Hemodialysis: A Cross-Sectional, Real-World Data Study in Pakistan.

End-stage renal disease (ESRD) patients are mostly managed with maintenance hemodialysis (MHD). ESRD patients on MHD also present with many complications, such as anemia, hyperparathyroidism, and hepatitis prevalence. This study depicts the real-world scenario of anemia among MHD and end-stage renal disease patients in the Pakistani population. A retrospective, multicentric, and real-world data analytical study was conducted at 4 dialysis centers in Pakistan. The study had a sample size of n = 342 patients on maintenance hemodialysis. The data were gathered from the medical records of patients. Data analysis was performed using STATA Version 16. Statistical significance was gauged at a 0.05 level of significance. According to our results, the mean age of the patients was 45 (±15) years. Most of the patients were male (n = 234, 68.4%), whereas 58.1% of the patients were maintained on twice-weekly hemodialysis. The most commonly reported comorbidities were hypertension and diabetes mellitus. The frequency of dialysis (P < 0.01) and comorbidities (P = 0.009) had a significant association with anemia in MHD patients. The majority of the patients had hyperparathyroidism (52%) with anemia. Upon performing binary logistic regression, multivariate analysis displayed a similar odds value for having anemia in patients with every additional month in the duration of hemodialysis (OR 1.01, P = 0.001), the odds of anemic patients having a positive antihepatitis-C antibody (OR 2.22, P = 0.013), and the odds of having anemia in patients in the age category below 45 years (OR 1.93, P = 0.013). In conclusion, the study results depict that every additional month in the duration of hemodialysis, age (<45 years), and positive anti-HCV antibody status, these variables were more likely to have anemia in our study MHD patients. While in our final multivariate model, no statistically significant association was observed between hyperparathyroidism and anemia.

Obstetrical and neonatal outcomes among pregnancies complicated by hyperparathyroidism.

PURPOSE: Severe hypercalcemia resulting from hyperparathyroidism may result in adverse perinatal outcomes. The objective of this study was to evaluate maternal and neonatal outcomes among pregnant women with hyperparathyroidism using a population database. METHODS: A retrospective cohort study was conducted using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999-2015. ICD-9 codes were used to identify women diagnosed with hyperparathyroidism during pregnancy. Perinatal outcomes between pregnant women with and without hyperparathyroidism were compared. Multivariate logistic regression, controlling for age, race, income, insurance type, hospital location, and comorbidities, evaluated the effect of hyperparathyroidism on perinatal outcomes. RESULTS: Of 13,792,544 deliveries included over the study period, 368 were to women with hyperparathyroidism. The overall incidence of hyperparathyroidism was 2.7/100,000 births, increasing from 1.6 to 5.2/100,000 births over the study period (p < 0.0001). Women with hyperparathyroidism were older and had more comorbidities, such as obesity, and pre-gestational hypertension and diabetes. Relative to the comparison group, women with hyperparathyroidism were more likely to deliver preterm, OR 1.69 (95% CI 1.24-2.29), to develop preeclampsia, 3.14 (2.30-4.28), and to deliver by cesarean, 1.69 (1.36-2.09). Infants born to mothers with hyperparathyroidism were more likely to be growth restricted, 1.83 (1.08-3.07), and to be diagnosed with a congenital anomaly, 4.21 (2.09-8.48). CONCLUSION: Hyperparathyroidism during pregnancy is associated with a significant increase in adverse perinatal outcomes, including preeclampsia, preterm delivery, fetal growth restriction, and congenital anomalies. As such, pregnancies among women with hyperparathyroidism should be considered high-risk, and specialized care is recommended in order to minimize maternal and neonatal morbidity.