scholarly journals Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?

2021 ◽  
Vol 10 (21) ◽  
pp. 5179
Author(s):  
Edmat Akhtar Khan ◽  
Lynda Cheddani ◽  
Camille Saint-Jacques ◽  
Rosa Vargas-Poussou ◽  
Vincent Frochot ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Sickle Cell ◽  
Fractional Excretion ◽  
Urinary Calcium ◽  
High Rate ◽  
Calcium Handling ◽  
Control Group ◽  
Calcium Excretion ◽  
Calcium Reabsorption ◽  
Chronic Hemolysis

Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients; (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT; (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p < 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.

scholarly journals High Rate of Occult Urolithiasis in Normocalcemic Primary Hyperparathyroidism

2019 ◽  
Vol 44 (5) ◽  
pp. 1189-1195 ◽  
Author(s):  
Alyne Layane Pereira Lemos ◽  
Sergio Ricardo de Lima Andrade ◽  
Lívia Laeny Henrique Pontes ◽  
Patricia Moura Cravo Teixeira ◽  
Elba Bandeira ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Kidney Stones ◽  
Urinary Calcium ◽  
Normal Serum ◽  
Urinary Calcium Excretion ◽  
High Rate ◽  
Calcium Excretion ◽  
History Of ◽  
Serum Pth

Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevations in serum parathyroid hormone levels in the presence of normal serum calcium concentrations after exclusion of secondary hyperparathyroidism. We have previously demonstrated no differences in the prevalence of clinically active urolithiasis between NPHPT and hypercalcemic asymptomatic PHPT, and that it is significantly higher in postmenopausal osteoporotic women with NPHPT in comparison to women with normal serum PTH and calcium concentrations. Few studies have addressed the occurrence of silent or occult kidney stones in asymptomatic hypercalcemic PHPT, but no data are available for NPHPT. Objective: To determine the presence of occult urolithiasis in NPHPT patients using routine abdominal ultrasonography. Methods and Results: We studied 35 patients with NPHPT (mean age 63.2 ± 10.7 years, 96% women; serum PTH 116.5 ± 39.2 pg/mL, 25OHD 38.5 ± 6.82 ng/mL, total calcium 9.1 ± 0.56 mg/dL; albumin 4.02 ± 0.37 g/dL; BUN 34.35 ±10.23 mg/dL; p = 3.51 ± 0.60 mg/dL; estimated glomerular filtration rate 88.44 ± 32.45 mL/min/1.73 m2, and 24-h urinary calcium excretion 140.6 ± 94.3 mg/24 h). The criteria for the diagnosis of NPHPT were as follows: serum PTH above the reference range (11–65 pg/mL), normal albumin-corrected serum calcium concentrations, normal 24-h urinary calcium excretion, serum 25OHD above 30 ng/mL, estimated GFR (MDRD) above 60 mL/min/1.73 m2 (with the exclusion of medications such as thiazide diuretics, lithium, bisphosphonates, and denosumab), a history of clinical symptoms of urolithiasis, and a family history of kidney stones. Thirty-five patients were evaluated and 25 of them met the inclusion criteria. Five patients presented nephrolithiasis corresponding to 20% of the study population. There were no statistically significant differences in any of the clinical or laboratory variables studied between patients with or without urolithiasis, although mean serum PTH levels were higher in patients with stones (180.06 ± 126.48 vs. 100.72 ± 25.28 pg/mL, p = 0.1). The size of the stones ranged from 0.6 to 0.9 cm and all of the stones were located in the renal pelvis. Conclusion: We found a high prevalence of occult kidney stones in NPHPT patients, similar to what is observed in clinically manifested urolithiasis, in hypercalcemic PHPT.

Hypercalcaemia of Malignancy: Evidence for a Non-Parathyroid Humoral Agent with An Effect on Renal Tubular Handling of Calcium

1984 ◽  
Vol 66 (2) ◽  
pp. 187-191 ◽  
Author(s):  
S. H. Ralston ◽  
I. Fogelman ◽  
M. D. Gardner ◽  
F. J. Dryburgh ◽  
R. A. Cowan ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Calcium Excretion ◽  
Renal Handling ◽  
Calcium Reabsorption ◽  
Humoral Agent ◽  
Calcium Infusion ◽  
Calcium Load ◽  
Renal Tubular

1. The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. 2. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. 3. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. 4. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.

Acute decrease of urine calcium by amiloride in healthy volunteers under high sodium diet

2021 ◽  
Author(s):  
Dusan Harmacek ◽  
Anne Blanchard ◽  
Gregoire Wuerzner ◽  
Marc Maillard ◽  
Xavier Jeunemaitre ◽  
...  
Keyword(s):  
Animal Studies ◽  
Collecting Duct ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
High Sodium ◽  
Calcium Reabsorption ◽  
Excretion Rates ◽  
Low K

Abstract Background Amiloride is a competitive blocker of the epithelial sodium channel (ENaC) in the renal collecting duct. It is a less potent diuretic than thiazides or loop diuretics, but is often used in association for its potassium-sparing profile. Whether amiloride has hypocalciuric effect similar to thiazides remains unclear. Animal studies and experiments on cell lines suggested that amiloride increases calcium reabsorption in the distal nephron, but human studies are scarce. Methods We performed a post hoc analysis of a study with 48 healthy males (age, 23.2 ± 3.9 years) who were assigned to a high sodium (Na)/low potassium (K) diet for 7 days before receiving 20 mg of amiloride p.o. Urinary excretions of electrolytes were measured at 3 and 6 hours afterward; we calculated the relative changes in urinary excretion rates after amiloride administration. Results The high Na/low K diet led to an expected suppression of plasma renin and aldosterone. Amiloride showed a mild natriuretic effect associated with a decreased kaliuresis. Urinary calcium excretion dropped substantially (by 80%) 3 hours after amiloride administration and remained low at the 6th hour. At the same time, fractional excretion of lithium decreased by a third, reflecting an increased proximal tubular reabsorption. Conclusion During a high Na/low K diet, amiloride had a strong acute hypocalciuric effect, most probably mediated by increased proximal calcium reabsorption, even though distal effect cannot be excluded. Further studies should establish if chronic amiloride or combined amiloride/thiazide treatment may decrease calciuria more efficiently and be useful in preventing kidney stones.

scholarly journals Exercise-induced hemolysis in sickle cell anemia: shear sensitivity and erythrocyte dehydration

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 1055-1060 ◽  
Author(s):  
OS Platt
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Control Group ◽  
Shear Forces ◽  
Vigorous Exercise ◽  
Shear Rates ◽  
Small Vessels ◽  
Shear Sensitivity ◽  
Chronic Hemolysis ◽  
Exercise Induced

Abstract We describe a steady-state patient with sickle cell anemia (SS disease) who developed sporadic hemoglobinuria, historically related to vigorous exercise. We studied him and four other patients with SS disease and demonstrated exercise-induced hemoglobinemia. To see if SS erythrocytes were abnormally fragile when exposed to shear forces that could be generated in small vessels of exercising muscles, we exposed them to physiologic shear rates in a cone-plate viscometer. We show that SS erythrocytes are more shear sensitive than normal erythrocytes. This phenomenon is directly related to the presence of dehydrated cells as demonstrated by the increasing shear sensitivity of increasingly dehydrated cells separated on Stractan density gradients. Normal shear sensitivity could be restored to dehydrated layers by restoring normal hydration. Restoration of shear stability was complete in all layers except for the most dense ISC layer. A control group of patients with SC disease exhibited no exercise-induced hemoglobinemia, no abnormal shear sensitivity of whole blood, and only rare dehydrated ISCs. These studies suggest that the exercise-induced hemolysis in SS patients is related to the lysis of dehydrated, shear-sensitive cells. This same process may also contribute to the chronic hemolysis of SS disease--a phenomenon known to correlate with the numbers of dehydrated ISCs.

Urinary calcium indices in primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH): which test performs best?

2020 ◽  
pp. postgradmedj-2020-137718
Author(s):  
Muhammad Fahad Arshad ◽  
James McAllister ◽  
Azhar Merchant ◽  
Edmund Rab ◽  
Jacqueline Cook ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
International Workshop ◽  
Significant Proportion ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Clearance Ratio ◽  
Urine Calcium ◽  
Genetic Studies ◽  
Urine Calcium Excretion ◽  
Control Study

AimPrimary hyperparathyroidism (PHPT) is much more common than familial hypocalciuric hypercalcaemia (FHH), but there is considerable overlap in biochemical features. Urine calcium indices help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this study was to compare urinary calcium values in patients with PHPT and FHH.MethodsThis was a case–control study of patients with PHPT who had successful surgery and genetically proven FHH between 2011 and 2016. Due to low FHH numbers, patients from neighbouring hospitals and outside study period (2017–2019) were allowed to improve power. Data on demographics and urinary calcium were obtained from electronic records and compared between the two groups.ResultsDuring the study period, 250 patients underwent successful PHPT surgery, while in the FHH arm, 19 genetically proven cases were included. The median (IQR) 24-hour urine calcium excretion (UCE) in the PHPT group was 8.3 (5.6–11.2) mmol/24 hours compared with 3.2 (2.1–6.1) mmol/24 hour in the FHH group (p<0.001). Median (IQR) calcium to creatinine clearance ratio (CCCR) in the PHPT and FHH groups was 0.020 (0.013–0.026) and 0.01 (0.002–0.02), respectively (p=0.001). The sensitivity of urinary tests for PHPT was 96% for UCE (cut-off ≥2.5 mmol/24 hour) and 47% for CCCR (cut-off >0.02). The specificity of the urinary tests for FHH was 29.4% for UCE (cut-off <2.5 mmol/24 hour) and 93% for CCCR (cut-off <0.02).Conclusions24-hour UCE is more sensitive in diagnosing PHPT; however, it is less specific in ruling out FHH as compared with CCCR, when the cut-offs suggested by the International guidelines from the fourth international workshop are used. A significant proportion of patients with PHPT would have also required genetic studies if the guidelines were followed.

scholarly journals Influence of renal function on clinico-pathological features of primary hyperparathyroidism

2003 ◽  
pp. 597-602 ◽  
Author(s):  
H Yamashita ◽  
S Noguchi ◽  
S Uchino ◽  
S Watanabe ◽  
T Murakami ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Primary Hyperparathyroidism ◽  
Normal Renal Function ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Calcium Excretion ◽  
Pathological Features ◽  
Function Group ◽  
Renal Function Group

OBJECTIVE: Disturbed renal function may play an important role in the clinico-pathological presentation of primary hyperparathyroidism (pHPT). We studied the influence of renal function on the clinico-pathological characteristics of 141 patients (123 women and 18 men) with surgically proven pHPT. METHODS: The 141 patients were assigned to one of two groups based on creatinine clearance (C(cr)) level: a renal insufficiency group (n=37) in which C(cr) of patients was <70 ml/min and a normal renal function group (n=104) in which C(cr) was > or =70 ml/min. Clinical presentation and biochemical indices were evaluated and compared between the two groups. RESULTS: Age, and frequency of hypertension and of diabetes mellitus were significantly (P<0.001, P<0.05 and P<0.05 respectively) higher in the renal insufficiency group than in the normal renal function group. Serum levels of calcium, intact parathyroid hormone and bone Gla protein were significantly (P<0.05) higher and the excised parathyroid weighed significantly more (P<0.05) in the renal insufficiency group than in the normal renal function group; however, serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and 24 h urinary calcium excretion were significantly (P<0.001 and P<0.05 respectively) lower in the former than in the latter group. There was a significant inverse correlation between C(cr) level and serum calcium (r=0.315, P<0.001) and a significant positive correlation between C(cr) level, 1,25(OH)(2)D (r=0.315, P<0.001), and 24 h calcium excretion (r=0.458, P<0.0001). CONCLUSIONS: Clinico-pathological features of pHPT were notably influenced by even moderate renal insufficiency. Urinary calcium excretion decreased according to the decrease in glomerular filtration rate. Therefore, endocrinologists need to appraise urinary calcium excretion and renal function of pHPT patients when considering surgery or in discriminating familial hypocalciuric hypercalcemia.

scholarly journals The Calcimimetic Cinacalcet Normalizes Serum Calcium in Subjects with Primary Hyperparathyroidism

2003 ◽  
Vol 88 (12) ◽  
pp. 5644-5649 ◽  
Author(s):  
Dolores M. Shoback ◽  
John P. Bilezikian ◽  
Stewart A. Turner ◽  
Laura C. McCary ◽  
Matthew D. Guo ◽  
...  
Keyword(s):  
Placebo Group ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Urinary Calcium ◽  
Dose Finding ◽  
Calcium Excretion ◽  
Normal Range ◽  
Urine Calcium ◽  
Novel Therapy ◽  
Double Blind

Abstract Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to circulating serum calcium, reducing the secretion of PTH and the serum calcium concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the management of primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with primary hyperparathyroidism were given cinacalcet (30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined cinacalcet-treated patients (normal range, 8.4–10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10–65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum calcium normalized after the second dose on d 1 and remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2–4 h after dosing in all cinacalcet-treated groups. The fasting and 24-h urine calcium to creatinine ratios were similar in the cinacalcet and placebo groups. This study demonstrates that cinacalcet safely normalized serum calcium and lowered PTH concentrations without increasing urinary calcium excretion in the study subjects, indicating the potential benefit of cinacalcet as a medical treatment for primary hyperparathyroidism.

scholarly journals Vitamin D Repletion in Patients with Primary Hyperparathyroidism and Coexistent Vitamin D Insufficiency

2005 ◽  
Vol 90 (4) ◽  
pp. 2122-2126 ◽  
Author(s):  
Andrew Grey ◽  
Jenny Lucas ◽  
Anne Horne ◽  
Greg Gamble ◽  
James S. Davidson ◽  
...  
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Serum Alkaline Phosphatase ◽  
Vitamin D Insufficiency ◽  
Urinary Calcium ◽  
Urinary Calcium Excretion ◽  
Total Serum ◽  
Calcium Excretion ◽  
Intact Pth

Abstract Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium &lt;12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] &lt;20 μg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 μg/liter (50 nmol/liter), mean levels of serum calcium and phosphate did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P &lt; 0.01) and 26% at 12 months (P &lt; 0.01). There was an inverse relationship between the change in serum 25(OH)D and that in intact PTH (r = −0.43, P = 0.056). At 12 months, total serum alkaline phosphatase was significantly lower, and urine N-telopeptides tended to be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.

Urinary calcium excretion in severe preeclampsia and eclampsia

2006 ◽  
Vol 44 (1) ◽  
Author(s):  
Metin Ingec ◽  
Hakan Nazik ◽  
Sedat Kadanali
Keyword(s):  
Serum Levels ◽  
Urinary Calcium ◽  
Severe Preeclampsia ◽  
Urinary Calcium Excretion ◽  
Control Group ◽  
Calcium Excretion ◽  
Total Calcium ◽  
Group 4 ◽  
Mild Preeclampsia ◽  
Group 2

AbstractUrinary calcium levels in women with mild preeclampsia, severe preeclampsia and eclampsia were evaluated in this study. We collected 24-h urine samples from 35 mild preeclamptic (Group 1), 30 severe preeclamptic (Group 2), and 17 eclamptic patients (Group 3). The control group (Group 4) consisted of 35 healthy pregnant women. Serum levels of total calcium and creatinine, and urinary calcium were measured. These values were compared in the four groups. The mean maternal age and parity were similar in all groups. There were no statistically significant differences in the serum levels of total calcium and creatinine (p>0.05). Urinary calcium excretion in patients with preeclampsia and eclampsia was significantly lower than in controls (p<0.0001). Urinary calcium levels between mild preeclampsia and severe pre-eclampsia, and severe preeclampsia and eclampsia were similar (p>0.05), but were lower in eclampsia than in mild preeclampsia (p<0.05). In conclusion, urinary calcium excretion is reduced in patients with severe preeclampsia or eclampsia. However, the decrease in urinary calcium excretion cannot be used to identify the severity of preeclampsia, or to predict impending eclampsia.

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