High Rate of Occult Urolithiasis in Normocalcemic Primary Hyperparathyroidism

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.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1772 ◽

2005 ◽

Vol 90 (4) ◽

pp. 2122-2126 ◽

Cited By ~ 153

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 <12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] <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 < 0.01) and 26% at 12 months (P < 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.

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Normocalcemic primary hyperparathyroidism

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302010000200004 ◽

2010 ◽

Vol 54 (2) ◽

pp. 106-109 ◽

Cited By ~ 61

Author(s):

John P. Bilezikian ◽

Shonni J. Silverberg

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Serum Calcium ◽

Kidney Stones ◽

Bone Disease ◽

Clinical Phenotype ◽

Mineral Metabolism ◽

Historical View ◽

History Of ◽

Excessive Secretion

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease.

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

Journal of Clinical Medicine ◽

10.3390/jcm10215179 ◽

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.

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URINARY CALCIUM EXCRETION IN PRIMARY HYPERPARATHYROIDISM: RELATIONSHIP TO 25-HYDROXYVITAMIN D STATUS

Endocrine Practice ◽

10.4158/ep.11.1.37 ◽

2005 ◽

Vol 11 (1) ◽

pp. 37-42 ◽

Cited By ~ 9

Author(s):

Aaron D. Bussey ◽

Jan M. Bruder

Keyword(s):

Primary Hyperparathyroidism ◽

Urinary Calcium ◽

Urinary Calcium Excretion ◽

Calcium Excretion ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D

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

Acta Endocrinologica ◽

10.1530/eje.0.1480597 ◽

2003 ◽

pp. 597-602 ◽

Cited By ~ 17

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.

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The Calcimimetic Cinacalcet Normalizes Serum Calcium in Subjects with Primary Hyperparathyroidism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-021597 ◽

2003 ◽

Vol 88 (12) ◽

pp. 5644-5649 ◽

Cited By ~ 188

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.

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Successful Parathyroidectomy May Not Resolve Hypercalciuria in Patients With Primary Hyperparathyroidism

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.459 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A226-A226

Author(s):

Neriy Izkhakov ◽

Heranmaye Prasad ◽

Nicholas John Vernetti ◽

Samer Nakhle

Keyword(s):

Primary Hyperparathyroidism ◽

Serum Calcium ◽

Clinical Case ◽

Case Series ◽

Urinary Calcium ◽

Long Term Effects ◽

Normal Range ◽

History Of ◽

Average Serum

Abstract Background: Hypercalciuria, with twenty-four-hour urinary calcium of >400 mg/day, is one of the indications for parathyroidectomy in patients with primary hyperparathyroidism. We report five cases where hypercalciuria is not resolved following a successful parathyroidectomy (normalization of serum calcium) in such patients. Here resolution of hypercalciuria is defined as twenty-four-hour urinary calcium of less than 200 mg/day. Clinical Case: This is a case series of five patients who remained hypercalciuric at 6 to 19 months after successful parathyroidectomy. Pre-parathyroidectomy, average PTH was 95 pg/dL (Min 69 pg/dL, Max 120 pg/dL), average serum calcium was 11.0 mg/dL (min 10.3 mg/dL, max 12.0 mg/dL), and average twenty-four-hour urinary calcium was 455 mg/day (min 386 mg/day, max 551 mg/day). Calcium levels were corrected to normal range post-parathyroidectomy and remained in normal range. However, hypercalciuria did not resolve. Post-parathyroidectomy, average PTH was 44 pg/dL (min 25 pg/dL, max 69 pg/dL), average serum calcium was 9.6 mg/dL (min 9.3 mg/dL, max 9.8 mg/dL), and average twenty-four-hour urinary calcium was 284 mg/day (min 201 mg/day, max 376 mg/day). Two patients who had history of nephrolithiasis prior to parathyroidectomy continued to develop nephrolithiasis at six and sixteen months after successful parathyroidectomy. Conclusions: This case series showed that hypercalciuria may not resolve following a successful parathyroidectomy in patients with primary hyperparathyroidism and elevated twenty-four-hour urinary calcium at 6 to 19 months after surgery. Further observations to evaluate long term effects of parathyroidectomy on hypercalciuria is needed.

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Association of parathyroid adenoma and familial hypocalciuric hypercalcaemia in a teenager

Acta Endocrinologica ◽

10.1530/eje-09-0257 ◽

2009 ◽

Vol 161 (1) ◽

pp. 207-210 ◽

Cited By ~ 28

Author(s):

C Brachet ◽

E Boros ◽

S Tenoutasse ◽

W Lissens ◽

G Andry ◽

...

Keyword(s):

Parathyroid Adenoma ◽

Serum Calcium ◽

Receptor Gene ◽

Causal Link ◽

Urinary Calcium ◽

High Serum ◽

Calcium Excretion ◽

Loss Of Function ◽

Mixed Family ◽

History Of

ObjectiveFamilial hypocalciuric hypercalcaemia (FHH) is clinically characterized by mild to moderate parathyroid hormone (PTH)-dependent hypercalcaemia, autosomal dominant pattern of inheritance, and normal to frankly reduced urinary calcium excretion in spite of a high serum calcium (clearance (Ca)/clearance (Cr)<0.01). FHH has a benign course and should be differentiated from primary hyperparathyroidism. It is usually caused by a heterozygous loss-of-function mutation in the calcium-sensing receptor gene (CASR).DesignWe report the case of a 16-year-old patient with hypercalcaemia and a mixed family history of parathyroid adenoma and mild hypercalcaemia. Serum calcium was 14 mg/dl with a serum iPTH of 253 pg/ml.ResultsA neck 99mTc-sesta MIBI tomoscintigraphy showed a definite hyperactivity in the left upper quadrant. A surgical four-gland exploration confirmed a single parathyroid adenoma. After surgical resection of a left superior parathyroid adenoma, the patient's hypercalcemia improved but did not normalize, returning to a level typical of FHH. An inactivating mutation in exon 4 of the CASR gene, predicting a p.Glu297Lys amino acid substitution was found.ConclusionsThus, this 16-year old patient presented with the association of FHH and a single parathyroid adenoma. The young age of the patient and the association of parathyroid adenoma and FHH in his grandmother argue for a causal link between CASR mutation and parathyroid adenoma in this family. This case contributes to illustrate the expanding clinical spectrum of CASR loss-of-function mutations.

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CALCIUM

The Professional Medical Journal ◽

10.29309/tpmj/2010.17.04.3027 ◽

2010 ◽

Vol 17 (04) ◽

pp. 698-701

Author(s):

MUHAMMAD ISHAQ ◽

ISRAR AHMED AKHUND ◽

MOULA BUX LAGHARI ◽

Muhammad Sabir

Keyword(s):

Urinary Tract ◽

Serum Calcium ◽

Upper Urinary Tract ◽

Urinary Calcium ◽

Stone Disease ◽

Urinary Calcium Excretion ◽

Calcium Excretion ◽

Stone Formers ◽

Study Results ◽

Urinary Tract Stone

Aims & Objectives: To evaluate the effects of Serum Calcium and Urinary Calcium excretion on upper urinary tract stone diseases in the Peshawar (a high stone incidence belt). Subjects & Methods: One hundred patients (age 20-60years) who were suffering severely from upper urinary tract stone disease were selected from LRH and Hayatabad Medical Complex Hospitals of Peshawar, same numbers of healthy controls from the same region were also selected for the study. Results: When results were summed up and testParameters were compared, it was seen that mean Serum Calcium in stone formers was greater than that of non-stone formers (P<0.001). Same pattern was also observed (P< 0.001) in both groups regarding mean urinary calcium excretion. Conclusions: We concluded that calcium is a definitive risk factor in upper urinary tract stone disease. However we suggest further work and research on wide scale population inorder to evaluate this relation.

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