Proven Primary Hyperparathyroidism Research Articles

Sonographic Features of Atypical and Initially Missed Parathyroid Adenomas: Lessons Learned From a Single-Center Cohort.

Awareness of typical and atypical ultrasonographic (US) features of parathyroid adenomas (PAs) is crucial since US is the most widely used first-line imaging modality. The purpose of this study was to describe the atypical features of PAs on US and other possible factors leading to a false negative examination in a large single-center cohort. The US records of 457 PAs in 445 patients with biochemically proven primary hyperparathyroidism (PHPT) were evaluated in a prospectively maintained database. Atypical size, composition, shape, echogenicity, location, and vascular pattern on US were noted. For patients who previously had at least one negative US examination in referring centers, the main possible reason was defined accordingly. The study group included 359 female and 86 male patients with PHPT. Typical sonographic features were observed in 231 PAs (51%), whereas 226 (49%) had at least one atypical US feature. The most common atypical features were atypical size (29%), followed by atypical echogenicity (19%), shape (8%), location (7%), and composition (7%), respectively. There were 122 initially missed PAs in all groups. The most frequent main atypical US features leading to false negative examinations were atypical size (22.1%) and atypical location (18.8%). Inexperience was third most common reason (16.3%) for false negative US examinations. Almost half of PAs have at least one atypical feature on US. Awareness of the high prevalence of atypical US features could increase the accuracy of US examination and potentially decrease demand for more expensive second-line imaging modalities.

MON-532 Urinary Calcium Indices in Primary Hyperparathyroidism (PHPT) and Familial Hypocalciuric Hypercalcaemia (FHH): Is There a Need for Better Discrimination?

Introduction: Primary hyperparathyroidism (PHPT) has a prevalence of around 1% and requires surgery for definite treatment. On the other hand, familial hypocalciuric hypercalcaemia (FHH) is much rarer and does not need specific treatment. There may be considerable overlap in biochemical features in these conditions. Urine calcium indices are used to help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this retrospective cohort study was to review urinary calcium values in patients with proven PHPT and those with genetically proven FHH. Methods: Over six years (2011-2016), 265 patients with PHPT underwent surgery. Of these, 14 patients with intermittent or persistent hypercalcaemia within 6 months after surgery were excluded leaving 251 patients (female to male ratio 5:1) for final analysis. In the FHH arm, only genetically proven cases (n = 10) were included. Results: In the PHPT arm, pre-operative data was available for 24 hr urine calcium excretion (UCE) and fractional excretion of calcium (FeCa) in 93 patients; 24 hr UCE only in 95 patients; and FeCa only in 43 patients. 24 hr UCE was low (i.e. <2.5 mmol/L/24 hr) in 8 of 188 patients (sensitivity for PHPT - 95.7%). FeCa was low (<0.01) in 16 of 136 patients (sensitivity for PHPT - 88.2%). Most of the false negative (for PHPT) readings (all of 24 hr UCE and 87.5% of FeCa) could be explained by low vitamin D levels (<50 nmol/L), chronic kidney disease 3b or worse and drugs such as indapamide. In the subgroup of 93 patients who had both 24hr UCE and FeCa, low FeCa was seen in 10 patients, low 24 hr UCE in 5 patients and only one patient had low levels of both tests. In the FHH arm, both 24 hr UCE and FeCa results were available for 6 patients; 24 hr UCE only for 2 patients and FeCa only for 2 patients. Five of eight patients with 24 hr UCE had at least one normal or high level of urinary calcium and three of eight patients with FeCa had levels consistent with a diagnosis of PHPT. Conclusions: Vitamin D deficiency and chronic kidney disease should be considered as causes of low urine calcium excretion in patients with features of primary hyperparathyroidism. A significant proportion of gene positive FHH patients may have normal or high urinary calcium excretion at some stage. Research into better discrimination between these conditions would be clinically useful.

Ultrastructure of Hyperfunctioning Parathyroid Glands: Does it Explain Various Patterns of 99mTc-sestamibi Uptake.

The aim of this study was to correlate the uptake of 99mTc-methoxy-isobutyl-isonitrile (MIBI) with ultra-structural features of parathyroid adenomas. Twenty patients with proven primary hyperparathyroidism were evaluated prospectively. Preoperative double-phase 99mTc-MIBI scintigraphy was performed in all patients and the degree of tracer uptake by the parathyroid lesions was assessed visually and semi-quantitatively. The excised glands were examined histologically and ultrastructurally, and their features were correlated with the degree of the radiotracer uptake. At surgery, 21 parathyroid adenomas were removed (double adenoma in one patient and a solitary adenoma in each of the remaining 19 patients). 99mTc-MIBI scan detected 18 of the 21 adenomas. There was positive correlation between the degree of 99mTc-MIBI uptake and the mitochondrial contents of the parathyroid adenoma cells. Four adenomas with intense uptake had high content of mitochondria in the cells. The three false-negative scans had low-to-moderate mitochondrial content. 99mTc-MIBI uptake is related to the mitochondrial content of the parathyroid adenoma cells.

Serum PTH reference values established by an automated third-generation assay in vitamin D-replete subjects with normal renal function: consequences of diagnosing primary hyperparathyroidism and the classification of dialysis patients.

To determine parathyroid hormone (PTH) reference values in French healthy adults, taking into account serum 25-hydroxyvitamin D (25OHD), renal function, age, gender, and BMI. We studied 898 healthy subjects (432 women) aged 18-89 years with a normal BMI and estimated glomerular filtration rate (eGFR), 81 patients with surgically proven primary hyperparathyroidism (PHPT), and 264 dialysis patients. 25OHD and third-generation PTH assays were implemented on the LIAISON XL platform. Median PTH and 25OHD values in the 898 healthy subjects were 18.8 ng/l and 23.6 ng/ml respectively. PTH was lower in subjects with 25OHD ≥30 ng/ml than in those with lower values. Among the 183 subjects with 25OHD ≥30 ng/ml, those aged ≥60 years (n=31) had higher PTH values than younger subjects, independent of 25OHD, BMI, and eGFR (P<0.001). Given the small number of subjects aged ≥60 years, we adopted the 95% CI of PTH values for the entire group of 183 vitamin D-replete subjects (9.4-28.9 ng/l) as our reference values. With 28.9 ng/l as the upper limit of normal (ULN) rather than the manufacturer's ULN of 38.4 ng/l, the percentage of PHPT patients with 'high' PTH values rose to 90.1% from 66.6% (P<0.001), and 18.6% of the dialysis patients were classified differently in view of the KDIGO target range (two to nine times the ULN). When only subjects with 25OHD ≥30 ng/ml were included in the reference population, the PTH ULN fell by 22.4%, diagnostic sensitivity for PHPT improved, and the classification of dialysis patients was modified.

Blood pressure in patients with primary hyperparathyroidism before and after parathyroidectomy.

Studies were performed in 86 patients with proven primary hyperparathyroidism pre-operatively and 6-7 months after parathyroidectomy. The 29% incidence of hypertension between patients with primary hyperparathyroidism is higher as compared with the incidence of hypertension in the general population. Systolic and diastolic blood pressures were significantly higher in patients with primary hyperparathyroidism before operation than after parathyroidectomy (p less than 0.001). In patients hypertensive before operation both the systolic and diastolic blood pressure significantly fell after parathyroidectomy (p less than 0.001). The blood pressure was found to have normalized in 13 of the 25 patients with hypertension. Renal damage and changes in renin levels are not the mechanisms in the production of hypertension in hyperparathyroid patients.

PET with 18F-DOPA in the imaging of parathyroid adenoma in patients with primary hyperparathyroidism

Preoperative localization of parathyroid adenomas (PA) can shorten operation time and improve curative rate; it becomes especially important in minimally invasive surgical techniques. AIM of this study was to investigate whether positron emission tomography (PET) with 3-,4-dihydroxy-6- (18) F-fluorophenylalanine ( (18) F-DOPA), which showed very promising results in other neuroendocrine tumours, also helps to localize PA. Eight patients with proven primary hyperparathyroidism were studied preoperatively with PET. Seven also underwent scintigraphy with (99m) Tc-MIBI and ultrasonography of the neck. All patients were operated and the histological finding was used as a gold standard. All eight patients had a histologically proven PA. None of the PA showed any detectable uptake of (18) F-DOPA. However, ultrasonography detected 5/7 PA, scintigraphy detected 3/7 PA. These results suggest that PET with (18) F-DOPA is not useful in the detection of PA in patients with primary hyperparathyroidism.

Analysis of 645 Patients with Primary Hyperparathyroidism with Special References to Cholelithiasis

OBJECTIVE The clinical picture of primary hyperparathyroidism (PHPT) has changed during the past 50 years. It is currently unknown whether or not PHPT is associated with an increased risk of cholelithiasis. To determine the frequency of cholelithiasis in PHPT we analyzed 645 consecutive patients seen at Prague University Hospital from 1992 through 2002 and compared them with a of normocalcaemic control group. We investigated 645 patients with proven PHPT (518 female and 127 males aged 20-80 years) during a period of 10 years. To determine the frequency of cholelithiasis in normal population we analyzed 2,015 patients receiving periodic health examination at an outpatient ward from January 1998 to December 1998 (1505 females and 510 males aged 24-85 years). A detailed history, physical examination, biochemical measurements and abdominal ultrasonography were done. Cholelithiasis was proven in 157 of 518 women (30.3%) and in 11 of 127 men (8.66%) with PHPT. Their mean age was 59.67+/-12 years in women and 56.0+/-10 years in men. In the control group 260 of 1505 women (17.27%) and 54 of the 510 men (10.58%) had cholelithiasis. The mean age was 64.55+/-13.8 years in women and 61.2+/-12.4 in men. Only in the case of women, the difference was highly statistically significant (p<0.001). There were no significant differences between the mean values for the serum calcium level, bone alkaline phosphatase, total cholesterol, urinary hydroxyproline and body mass index in hyperparathyroid patients with and without cholelithiasis. However the hyperparathyroid women with cholelithiasis had an increased concentration of parathyroid hormone (236.1+/-56 pg/ml) compared with hyperparathyroid women without cholelithiasis (179.0+/-45 pg/ml), p<0.01. The mechanism of PTH associated gallstone formation may involve inhibition of gallblader emptying, hepatic bile secretion and sphincter Oddi motility as well as modification of bile composition. While it might be difficult to prove it seems likely that the association of cholelithiasis with primary hyperparathyroidism in women with a high concentration of parathyroid hormone is more than merely coincidental and from our study it is obvious that a significant association exists.

Relationship between serum parathyroid hormone, serum calcium and arterial blood pressure in patients with primary hyperparathyroidism: results of a multivariate analysis.

To evaluate the possible relationship between serum calcium, serum parathyroid hormone (PTH) levels and arterial blood pressure (BP) in patients with primary hyperparathyroidism (HPT). A retrospective population-based study. Charts of 194 patients with proven primary HPT were reviewed, and the main clinical and biochemical parameters were recorded. There were 48 men (24.7%) and 146 women (75.3%), with a median age of 59 years (range 23-82 years). Patients who used antihypertensive drugs or hormone replacement therapy had been previously excluded. All patients underwent successful parathyroidectomy, and were cured of their disease. There were no differences (P=NS) between men and women in systolic (143.3+/-19.1 vs 145.4+/-17.1 mmHg) and diastolic (87.1+/-12.3 vs 88.4+/-9.9 mmHg) BP, and in the main biochemical parameters. A significant (P<0.01) correlation was found between (i) serum calcium and serum PTH levels (r=0.39, F=88.36), (ii) age and BP, both systolic (r=0.61, F=118.16) and diastolic (r=0.48, F=64.5), and (iii) body mass index (BMI) and BP (r=0.45 and 0.36 respectively). There was no significant association of serum calcium levels with systolic (r=0.0974, t=1.3422, P=0.18) or diastolic (r=0.1117, t=1.5409, P=0.12) BP, and of serum PTH levels with systolic (r=-0.0349, t=-0.4783, P=0.63) or diastolic (r=-0.0793, t=-1.0913, P=0.28) BP. Multivariate analysis confirmed that none of the independent biochemical parameters significantly correlated with BP, both systolic and diastolic. In patients with primary HPT there is no relationship between PTH, calcium and BP. Thus, in hyperparathyroid patients, BP should be considered as an independent variable, mainly related to age and BMI.

Renin-angiotensin-aldosterone system in primary hyperparathyroidism before and after surgery

Twenty consecutive unselected patients with proven primary hyperparathyroidism (PH), 26 essential hypertensive (EH) patients, and 13 normotensives were studied. Blood pressure (BP) and, under constant salt intake, plasma renin activity (PRA), parathyroid hormone (PTH), urinary and plasma sodium, potassium, aldosterone (ALD), creatinine, total calcium, and phosphate were measured. Patients with PH were also studied 1 and 6 months after successful surgery. In patients with PH, systolic and diastolic BP was significantly lower ( P < .001) than in EH patients and higher ( P < .005) than in controls. Eight patients with PH (40%) had BP levels greater than 140 90 mm Hg. PTH and plasma and urinary calcium in patients with PH were significantly ( P < .01) higher than in controls, while PRA, ALD, phosphate, potassium, and sodium were superimposable in the three groups. PTH in patients with PH was weakly correlated with PRA (positively) and with plasma potassium (negatively) and was not associated with ALD, calcium, sodium, and BP levels. Surgery was followed by a significant reduction ( P < .01) in PTH, calcium, and urinary phosphate and an increase ( P < .02) in plasma phosphate, potassium, and sodium, whereas PRA, ALD, urinary potassium and sodium, and BP showed no change. In hypertensive patients with PH, PTH, PRA, and plasma and urinary ALD, calcium, and sodium did not differ from the values in normotensive PH patients, and variations in these humoral parameters after surgery were comparable in the two groups. In conclusion, our results show that hypertension is frequently associated with PH. However, the present data raise doubts about the assumption of a renin-mediated causal relationship between hyperparathyroidism and high BP. Indeed, as a unique finding in favor of the hypothesis of a stimulating role of PTH in renin secretion, we observed only a weak relation between PTH and PRA. Thus, unknown and/or unassessed factors related to parathyroid disease cannot be ruled out to explain the hypertension observed in some patients with PH.

Beta 2-microglobulin does not behave as a biological marker of bone remodelling in patients with primary hyperparathyroidism

Parathormone has been shown to increase the secretion and production of lysosomal enzymes including tartrate-resistant acid phosphatase. All our 68 patients with proven primary hyperparathyroidism had signs of hyperparathyroid bone disease. Tartrate-resistant acid phosphatase and bone alkaline phosphatase activities are raised as a result of enhanced bone remodelling. Serum beta 2-microglobulin concentration in patients with primary hyperparathyroidism was normal 1.6 (1.4–1.8) mg/l versus 1.8 (1.7–2.2) mg/l in 51 control subjects. In hyperparathyroid patients, serum beta 2-microglobulin concentration does not correlate with plasma tartrate-resistant acid phosphatase activity which is known to be a sensitive biological marker of bone remodelling (r=0.088). Our findings indicate that serum beta 2-microglobulin does not behave as a biological marker of remodelling in patients with enhanced remodelling in primary hyperparathyroidism.

Parathyroid adenomas: pre-operative localization with ultrasound combined with fine-needle biopsy.

Sixteen patients with biochemically proven primary hyperparathyroidism (PHPT) underwent ultrasonography (US), fine-needle aspiration (FNA) for cytologic sampling (n = 9), or intact parathormone assay (n = 3) before operation (n = 15) in order to determine the accuracy of the methods. Pre-operative US was found sensitive (100 per cent), but two thyroid lesions were initially diagnosed as parathyroid tumours by US (i.e. false positives). Parathyroid cells were detected in six cytologic specimens, one sample was insufficient and another inconclusive, while one was diagnosed as thyroid tissue. Parathormone assay revealed a high hormone content in all three patients who underwent the procedure. We conclude that US is sufficiently sensitive to detect enlarged parathyroid tumours. Specificity can be improved by US-guided FNA for cytology or parathormone assay prior to neck exploration.

Urine calcium and serum ionized calcium, total calcium and parathyroid hormone concentrations in the diagnosis of primary hyperparathyroidism and familial benign hypercalcaemia.

A relationship between serum concentrations of ionized calcium and parathyroid hormone (PTH) in persons without parathyroid overactivity was defined by performing an oral calcium load test. As a result, a serum PTH concentration greater than 2.6 pmol/L in a hypercalcaemic patient was regarded as suggestive of hyperparathyroidism. Fasting serum PTH concentrations in 58 patients with surgically and histologically proven primary hyperparathyroidism (PHPT) were all above 2.7 pmol/L (range 3.2-84.5). Thirteen of 20 patients with familial benign hypercalcaemia (FBH) had fasting serum PTH concentrations greater than 2.6 pmol/L (range 1.6-6.1). There was a significant correlation between serum PTH and age in the FBH patients only. Fasting urine calcium excretion (CaE) ranged from 14 to 222 mumol/L of glomerular filtrate in PHPT and 3-34 mumol/L of glomerular filtrate in FBH. The best biochemical discriminant between patients with PHPT and FBH was a plot of fasting serum PTH against CaE. A plot of post-calcium load PTH against post-load CaE showed no further significant advantage in discriminating between the two conditions.

The Prevalence of Diabetes Mellitus in Patients with Primary Hyperparathyroidism and Among Their Relatives

The prevalence of diabetes mellitus in a series of 205 patients with proven primary hyperparathyroidism was 7.8% (16 patients). Eight patients were known to have diabetes at first attendance (prevalence 3.9%), four were discovered at the time of diagnosis of hyperparathyroidism (combined prevalence 5.9%) and four subsequently. Diabetes had been diagnosed from age 39 yr onwards, and in those with diabetes hyperparathyroidism was diagnosed at age 44 yr or later. The prevalence of diabetes in primary hyperparathyroidism is significantly greater than in a series of 200 consecutive non-hyperparathyroid outpatients attending the same unit (3.0%, p less than 0.05), or in the general populations of Oxford and Poole, after matching for age and sex (p less than 0.05), or in the combined populations of Oxford, Poole, and Southall (white population) (p less than 0.05) after similar matching. However, the prevalence of diabetes in hyperparathyroidism did not differ significantly from that of the white population of Coventry, where the prevalence is higher than that of Oxford, Poole and Southall. For hyperparathyroid patients presenting at age 40 yr or over, the prevalence of known diabetes (4.7%) is significantly greater than in the general populations at similar age of Oxford, Poole, and Southall.

Flow cytometric dna analysis of parathyroid tumors with special reference to its diagnostic and prognostic value in parathyroid carcinoma

The nuclear DNA content of paraffin-embedded parathyroid tumors from 49 patients with proven primary hyperparathyroidism was determined by flow cytometric analysis. The lesions included 14 primary and 11 locally recurrent or metastatic lesions from 16 carcinoma patients, 28 single adenomas from 28 patients, and 15 hyperplastic glands from five patients with familial multiple endocrine neoplasia type 1. No abnormal DNA stemline was found in any of the hyperplastic glands. One (3.6%) of the adenomas was aneuploid. There was no difference in ploidy patterns between the primary and recurrent lesions of the carcinomas and five (31%) of the carcinomas expressed aneuploidy. Four of the five patients with aneuploid carcinoma had recurrences including pulmonary metastases. One of them died of this disease 12 years after the initial operation, and all except one of the others are hypercalcemic even after removal of the successive recurrent or metastatic tumors. Of the 11 patients with diploid carcinoma, four had either local recurrence or pulmonary metastasis. Two of them are living with normocalcemia 3 and 6 years, respectively, after removal of the recurrent tumors and the others are alive with mild hypercalcemia. The remaining seven patients with diploid carcinoma, however, have no recurrence 2 to 5 years after the initial operation. Thus aneuploid parathyroid carcinomas are likely to show more malignant behavior than those with a diploid DNA pattern. All of the patients with adenoma and hyperplasia have been normocalcemic after a mean follow-up interval of 37 months. This study indicates that flow cytometric analysis of nuclear DNA content is a valuable adjunct to histologic examination in the diagnosis of parathyroid carcinoma and the prediction of the clinical outcome.

Clinical and laboratory evaluation of a two-site immunoradiometric assay for intact parathyroid hormone.

The analytical performance and clinical utility of a direct immunoradiometric assay (IRMA) for intact 1-84 human parathyroid hormone (PTH) was evaluated. The assay is available commercially (Allégro intact PTH, Nichols Institute) and utilises two affinity purified region-specific antisera against either 1-34 (radiolabelled antibody) or 39-84 (solid phase antibody) human PTH. High assay sensitivity (detection limit, 1.4 pg 1-84 PTH/mL) permitted the measurement of PTH in all normocalcaemic individuals studied. Elevated results were obtained in all patients (21 studied) with histologically proven primary hyperparathyroidism (PHPT) and 34 out of 35 patients with presumptive PHPT. Thirteen out of 24 patients with non-parathyroid hypercalcaemia had suppressed results, but the remainder had concentrations within the reference range.

Urinary and nephrogenous cyclic AMP and renal phosphate handling in normal subjects and patients with parathyroid dysfunction.

Studies were performed in 60 patients with proven primary hyperparathyroidism pre-operatively and in 54 of these patients post-operatively, 22 patients with permanent hypoparathyroidism and 34 normal subjects. Urinary and nephrogenous cyclic AMP excretion were increased in the hyperparathyroid patients with an overlap of values with the normal group of 10 and 9%, respectively. Values fell in all patients post-operatively, and were decreased in those with permanent hypoparathyroidism. TmPO4 /GFR was decreased in the preoperative hyperparathyroid patients and rose postoperatively while it was increased in the hypoparathyroid patients with an overlap of values with the normal group of 9%. Post-operative hypocalcaemia due to bone hunger was associated with continuing normo- or hypophosphataemia and urinary cyclic AMP that exceeded 4.5 nM/dl GF while those who developed permanent hypoparathyroidism had hyperphosphataemia, increased TmPO4 /GFR and urinary cyclic AMP that was less than 3.5 nM/dl GF. Urinary and nephrogenous cyclic AMP were equally effective in characterizing patients with primary hyperparathyroidism and less effective in distinguishing patients with hypoparathyroidism from normal while TmPO4 /GFR estimates were more effective in delineating the hypoparathyroid state.

Primary hyperparathyroidism in children, adolescents, and young adults.

AbstractPrimary hyperparathyroidism (HPT) is considered a rare disease in children and an uncommon one in adolescents and young adults. Until 1975, only 60 children under the age of 16 years had been reported with proven HPT. Most had symptoms of weakness, irritability, anorexia, and weight loss. Severe hypercalcemia (serum calcium&gt;15 mg/ 100 ml) and radiologic evidence of bone changes were common findings, and suggested delayed diagnoses.This report is based on the clinical and laboratory findings in 53 young patients with proven primary HPT (range: 1–30 years of age) from 1971 to 1980, treated in one hospital. There were 29 male and 24 female patients, 26 of whom developed symptoms before age 18. Common symptoms included hematuria and renal colic (50%), renal calculi (50%), and hypertension with (6%) and without (3%) severe headaches. Although 64.2% of patients had adenomas, only 54% of patients under 18, and as many as 77.8% over 18, had them. The incidence of hyperplasia was markedly increased in the patients under 18 (38%) as compared to the patients over 18 (18.5%) or the group taken as a whole (30.2%). The following associated diseases were identified: MEA I syndrome (4); MEA II syndrome (4); von Recklinghausen's neurofibromatosis; papillary carcinoma of thyroid; craniopharyngioma; and multiple metaphyseal chondromatosis. One child had hereditary neonatal parathyroid hyperplasia.Primary hyperparathyroidism is more common than previously suspected in young people. Symptoms of renal stones, hypertension, persistent headaches, unexplained anorexia, and weight loss should prompt evaluation for primary HPT. If hyperplasia is found, the patient and family should be investigated for associated endocrinopathies.

Urinary Excretion of Cyclic AMP and Cyclic GMP in Primary Hyperparathyroidism with Reference to Clinical Signs and Symptoms

35 patients with surgically proven primary hyperparathyroidism (PHPT) were evaluated with regard to urinary cyclic AMP and cyclic GMP excretion. They showed no signs of bone disease or impaired renal function. Preoperatively, cyclic AMP was increased in 28 patients (80%). Mean excretory value for the whole group was 8.5 ± 0.8 micromoles/g creat/24 hours, compared with controls, 4.2 ± 0.13 micromoles/g creat/24 hours. Cyclic AMP excretion was normalized after surgery.

Cellular-level bone resorption in chronic renal failure and primary hyperparathyroidism. A tetracycline-based evaluation.

The mean depth of bone eroded in unit time at resorption centers was measured in tetracycline-labeled bone biopsies of 16 adult patients on periodic renal dialysis, of one adolescent boy with renal rickets and secondary hyperparathyroidism, and of two adult women with proven primary hyperparathyroidism. This index of cellular-level resorption was subnormal on haversian bone surfaces in all groups, and it was subnormal on cortical-endosteal bone surfaces in the dialysis group; there was insufficient material to evaluate the index on this latter surface in the other two groups. The results suggest that individual osteoclasts resorb bone more slowly than normal in naturally occurring human hyperparathyroid states of long standing.

Diffusible Serum Calcium

To the Editor.— In a patient with proven hyperparathyroidism, who demonstrated normocalcemia for a 12-month period ( 210 :2063, 1969), repeated total serum calcium values were within the normal range of the reporting laboratory: 8.8 to 11.0 per 100 ml. Though hypercalcemia is considered to be the most constant finding in primary hyperparathyroidism, a few cases have been reported showing a normal serum calcium level. In 1935, McLean and Hastings suggested that ionized serum calcium value increases in hyperparathyroidism. Subsequent reports have indicated that ionized serum calcium level is elevated in cases of primary hyperparathyroidism even though the total serum calcium level may be normal. Ionized serum calcium level can be determined by biological techniques. When it is estimated from the nomogram described by McLean and Hastings, however, 14 out of 35 patients with proven primary hyperparathyroidism had ionized calcium levels within the normal range. Total serum calcium is a composite