There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.

We previously reported that experimental elevations of serum 1,25-(OH)2-vitamin D [1,25-(OH)2-D] concentrations produced by the chronic oral administration of calcitriol, 0.75 micrograms every 6 hr, to healthy human males eating diets providing only 4 mmoles Ca/day stimulate net bone resorption as evidenced by more negative Ca balances and higher rates of urinary hydroxyproline excretion. To determine whether increased dietary Ca intake modifies this response we have compared serum 1,25-(OH)2-D and iPTH concentrations, Ca and PO4 balances, and urinary hydroxyproline excretion in three healthy human males adapted to diets providing 22.3 +/- 1.3 mmoles Ca/day and three healthy human males adapted to diets providing 9.3 +/- 0.7 mmoles Ca/day before and during the continuous oral administration of calcitriol 0.5 micrograms every 6 hr. For all six subjects, serum 1,25-(OH)2-D levels averaged 89 +/- 25 pM during control and 143 +/- 26 pM during calcitriol. Net intestinal Ca absorption and urinary Ca excretion rose during calcitriol but Ca balances did not change, averaging +2.2 +/- 2.2 mmoles/day during control and +4.3 +/- 2.2 mmoles/day during calcitriol for the subjects fed 22 mmoles Ca/day and -1.6 +/- 1.5 mmoles Ca/day during control and -1.7 +/- 2.0 mmoles Ca/day during calcitriol for the subjects fed 9 mmoles Ca/day. Urinary hydroxyproline excretion also did not change. Thus, when serum 1,25-(OH)2-D levels are elevated, the availability of dietary Ca appears to prevent more negative Ca balances and increased urinary hydroxyproline excretion suggesting that net bone resorption is not stimulated.

Serum immunoreactive calcitonin (iCT), serum immunoreactive parathyroid hormone (iPTH) and serum Ca, Mg, P and total protein levels were determined sequentially at 5 given periods of time from 1 to 48 h of age in 16 low birth weight infants. Mean +/- SD serum Ca levels decreased from 8.99 +/- 0.79 mg/100 ml at time 1--2 h to 7.00 +/- 0.51 mg/100 ml at time 12--14 h; there was a small further decrease at time 22--26 h: 6.79 +/- 1.07 mg/100 ml. There was no significant change in serum Mg, P or total protein during the same periods of time. Serum iPTH levels increased steadily from time 1--2 h to time 44--48 h reaching above normal range values. Serum iCT levels were non detectable (less than 150 pg/ml) in 11 among 15 infants at time 1--2 h. A marked increase in mean +/- SD serum iCT levels was observed at time 12--14 h (1850 +/- 872 pg/ml) and time 22--26 h (1462 +/- 806 pg/ml) followed by a decrease at time 44--48 h. A negative correlation was found between serum iCT levels and respectively gestational age (p less than 0.01) and serum Ca levels (p less than 0.01) at time 22--26 h while serum iCT levels correlated positively with serum iPTH levels (p less than 0.05). Evidence obtained from this study indicates that a secretion of calcitonin takes place during the early neonatal period in low birth weight infants and that this secretion is a contributing factor of the socalled "early-type" neonatal hypocalcemia.

Undecalcified sections of doubly tetracycline-labeled transiliac bone biopsy specimens obtained from ten hemodialyzed patients before and 10 to 16 months after parathyroidectomy (PTX) were analyzed. Before parathyroidectomy (total PTX with autotransplant in six patients and subtotal PTX in four patients), all the patients demonstrated histological evidence of hyperparathyroidism with increased resorption parameters. A high bone formation rate (BFR) was noted in all patients but one who had both an increase in the osteoid seam thickness and a low calcification rate characteristic of osteomalacia. A significant correlation was found between immunoreactive parathyroid hormone (iPTH) levels and BFR at the tissue and at the basic multicellular unit (BMU) levels. Parathyroidectomy was associated with a dramatic drop in resorption surfaces and osteoclast number as well as in bone formation rate at the tissue, BMU, and cell-levels. After PTX, the bone formation rate at the tissue level was low or in the lower range of normal values in six patients. The thickness index of osteoid seams was significantly reduced and no evidence of osteomalacia was present even in the six patients showing bone aluminum deposits after PTX. One of the three patients, who had an iPTH level within the normal range after PTX, showed an osteoid excess associated with a low bone formation rate. These date demonstrate that increased PTH secretion is an important factor of bone formation in dialyzed patients and that excessive reduction of the PTH secretion leads to an inactive bone.

OBJECTIVE

To describe our 3-year experience in the long-term efficacy and safety of percutaneous ethanol injection therapy (PEIT), as an alternative to surgery for the management of patients with primary hyperparathyroidism (p-HPT).

METHODS

Prospective study with a mean follow-up of 19.6 +/- 10.6 months.

METHODS

Our study population included 19 consecutive high risk patients with p-HPT, who met the criteria for surgery.

METHODS

Under ultrasonic guidance, ethanol (95%) was injected into parathyroid glands with a volume of>>or= 0.15 cm(3). With the aim of normalizing intact parathormone (iPTH) values, repeated ethanol injections were carried out, in an interval of 2 weeks, until normalization of iPTH was reached or until no residual blood supply was detected by ultrasound in the gland. Biochemical parameters were monitored throughout the study.

RESULTS

At 6-month follow-up, normalization of <em>iPTH</em> levels (10-65 ng/l) was achieved in 11 (58%) patients (responders). Of the eight remaining patients (nonresponders), six patients had reduced (but not normalized) <em>iPTH</em> levels and two patients required parathyroid surgery. Seventeen (11 responders and 6 nonresponders) of the 19 patients (89.5%) became normocalcaemic (serum Ca <or= 2.57 mmol/l) and remained so for a mean follow-up of 21 months (8-39 months). The odds ratio (P < 0.05) of response vs. no response to PEIT was 16.7-fold for pretreatment <em>iPTH</em> < 200 vs.>> 200 ng/l. The only complication was a transient dysphonia noticed in three patients.

CONCLUSIONS

PEIT is a safe and effective nonsurgical treatment for patients with p-HPT, who are unsuitable for surgical intervention.

We evaluated circulating levels of biologically active and immunoreactive intact parathyroid hormone [iPTH-(1-84)] in 47 newborns at birth and eight hypocalcemic preterm infants during the first 10 d of life. Use of two sensitive detection systems, the cytochemical bioassay and an immunoradiometric assay specific for intact parathyroid hormone, enabled us to compare plasma concentrations of PTH-like bioactivity (bioPTH) and iPTH-(1-84). Mean umbilical venous plasma bioPTH was elevated in nondiabetic term and preterm newborns [22.5 +/- 3.1 (+/- SEM) and 15.8 +/- 2.5 ng-equiv/L, respectively] compared with normal adult subjects (9.8 +/- 2.6 ng-equiv/L; p less than 0.01). Umbilical bioPTH was suppressed in five term infants of diabetic mothers (2.6 +/- 0.4 ng-equiv/L). In contrast, iPTH-(1-84) was low in term and preterm nondiabetic infants' and term infants of diabetic mothers' umbilical samples (5.4 +/- 1.5, 4.3 +/- 1.5, and 2.4 +/- 1.0 ng/L, respectively). Umbilical venous bioPTH was highly correlated with the magnitude of the transplacental calcium gradient (r = 0.90; p less than 0.05). In eight preterm infants studied longitudinally, by 24-36 h of life, declining plasma total and ionized calcium (1.71 +/- 0.04 and 0.78 +/- 0.03 mmol/L, respectively) were accompanied by a significant rise in both bioPTH (41.2 +/- 6.3 ng-equiv/L) and iPTH-(1-84) (56.3 +/- 11.6 ng/L). These data indicate that the 3rd trimester fetoplacental circulation contains levels of bioPTH several-fold higher than those of immunoreactive intact hormone. We also conclude that even hypocalcemic preterm newborn infants can significantly elevate circulating levels of PTH.

Obesity subjects individuals into metabolic and endocrine disorders. Thus obesity may increase the risk of vitamin D deficiency. This text aims at studying the prevalence of vitamin D deficiency and secondary hyperparathyroidism in obese children. In a non-randomized case control study on 52 obese children (body mass index (BMI) >95th percentile) aged 4 to 16 years undertaken at the outpatient endocrine clinic of the Children Hospital at Tabriz University between 2009-2011. This study was conducted to compare the prevalence of vitamin D deficiency and secondary hyperparathyroidism in obese children compared with 57 non obese (BMI < 85th percentile). 109 children including 52 (50.5%) boys and 57 (49.5%) girls were studied. Most of case (76.9%) and control (42.1%) groups suffered from degrees of vitamin D deficiency. There was meaningful statistical difference between two groups considering to vitamin D deficiency and parathyroid hormone (p = 0.001). A negative relations was found between iPTH and vit D level (p < 0.001, r = -0.2), BMI and 25-OH vit D (p < 0.001, r = -0.2). A positive relation was observed between parathyroid hormone and BMI (p = 0.009, r = 0.1). Obese children are at high risk at vitamin D deficiency and secondary hyperparathyroidism. BMI appears to be an important risk factor for vitamin D deficiency.

Little is known about the effects of thyroid hormone excess in male patients. Our aim was to evaluate bone mineral density (BMD), bone turnover markers, and thyroid function in male patients with treated thyroid cancer on long-term suppressive L-T4 therapy (TC) and in male patients with Graves' disease (GD). We studied 49 male patients (aged 45+/-12 years), 17 with TC (29-288 months on L-T4 suppressive therapy; free T4: 1.9+/-0.6 ng/dl [normal< or =2.0]; TSH: 0.2+/-0.3 microU/ml [Normal 0.5-5.0]) and 32 with recent onset GD (<12 weeks, free T4: 2.0+/-1.4 ng/dl; TSH: 1.07+/-1.8 microU/ml; TSHRAb 53+/-45% [normal < 15]). BMD was measured by dual X-ray absorptiometry (DXA, Hologic QDR1000w) at the lumbar spine (L2-L4, LS), femoral neck (FN), and Ward's triangle (WT). Results were expressed as Z-score (SD compared to national controls). Total alkaline phosphatase (ALP), osteocalcin (BGP), iPTH, serum phosphorus, serum, and 24 h urine calcium were measured as bone markers. Age, weight, and body mass index were comparable in both groups. Patients with TC and with GD showed reduced axial BMD (95% confidence interval: LS: TC (-1.27-0.01)(P = 0.046), GD (-1.06 to-0.38)(P < 0.001); FN: TC (-0.82 to-0.16)(P = 0.007), GD (-0.95 to-0.15)(P = 0.008); WT: TC (-0.82 to -0.18)(P = 0.004), GD (-0.97 to -0.08)(P = 0.024). No significant differences in BMD were found between the groups. Among bone markers, total ALP and osteocalcin levels showed higher levels in Graves' disease (ALP: 139+/-76 vs. 88+/-34, P < 0.01; BGP: 7.5+/-3.7 vs. 4.6+/-1.6; P < 0.001). Our data suggest a mild deleterious effect of thyroid hormone excess in the axial bone mass from male subjects. A skeletal status assessed by BMD in male patients with chronic TSH suppression by L-T4 or history of hyperthyroidism is recommended.

Kostmann's syndrome is a congenital disorder that causes an impairment of myeloid differentiation in the bone marrow characterized by severe neutropenia, which can be treated with recombinant human granulocyte colony-stimulating factor (G-CSF). We present the case of a 13-year-old boy with Kostmann's syndrome who was treated with recombinant human G-CSF from age 3.5 years. His growth and development was normal, although complicated by intermittent infections. Bone mineral density (BMD) measurement revealed severe osteopenia at the spine and hips (lumbar spine BMD 0.486 g/cm(2); Z score -3.6), and he was referred to the Endocrine Service. Relevant laboratory evaluation showed a pretreatment ionized calcium level at the upper limit of normal (1.28 mmol/L; range: 1.13-1.32 mmol/L), suppressed intact parathyroid hormone (iPTH) level (12 pg/mL; range: 10-65 pg/mL), and a low 1,25-dihydroxy vitamin D level (21 pg/mL; range: 24-65 pg/mL). He had evidence of increased bone turnover evidenced by elevated urinary deoxypyridinoline (DPD) cross-links (46.9 nmol/mmol creatinine; range: 2-34 nmol/mmol creatinine) and a simultaneous increase in markers of bone formation with elevated osteocalcin level (200 ng/mL; normal: 20-80 ng/mL) and alkaline phosphatase level (236 IU/mL; normal: 38-126 IU/mL). Because of clinical concern for his skeletal health, bisphosphonate therapy with intravenous pamidronate was initiated. One month after treatment, the iPTH and DPD cross-links were in the normal range (54 pg/mL and 17.7 nmol/mmol creatinine, respectively) and the 1,25-dihydroxy vitamin D level was elevated (111 pg/mL). Four months after treatment, there was a striking increase in BMD at the lumbar spine (+30.86%), femoral necks (left, +20.02%; right, +17.98%), and total hips (left, +18.40%; right, +15.94%). Seven months after bisphosphonate therapy, his biochemical parameters showed a return toward pretreatment levels with increasing urinary DPD cross-links (28.7 nmol/mmol creatinine) and decreasing iPTH (26 pg/mL). However, the BMD continued to increase (8 months posttreatment), but the magnitude of the increment was attenuated (lumbar-spine, +4.8%; left total hip, +1.2% and right total hip +2.4%), relative to BMD at 4 months. Eight months after the initial treatment, his iPTH was suppressed at 14 pg/mL and he again received pamidronate (at a lower dose); 3 months later, he had an additional increase in BMD (lumbar spine +7.4%, left total hip +3.9%, right total hip +2.7%), relative to the previous study. We hypothesize that prolonged administration of G-CSF as treatment for Kostmann's syndrome is associated with increased bone resorption, mediated by osteoclast activation and leading to bone loss. In children, the resulting osteopenia can be successfully managed with antisreorptive bisphosphonate therapy with significant improvement in bone density. Measurements of biochemical parameters of bone turnover can be used to monitor the magnitude and duration of the therapeutic response and the need for BMD reassessment and, perhaps, retreatment.

Tertiary hyperparathyroidism (tHPT) most commonly refers to a persistent secondary hyperparathyroidism even after successful renal transplantation. Parathyroidectomy (PTX) is an efficient method for treatment of tHPT. In this study, we examined our 31-year experience with patients who underwent PTX for tHPT after KTX and assessed the effects of PTX on graft function according to the type of surgery. Among 2,981 recipients who underwent renal allograft between April 1979 and Dec. 2010, 15 patients (0.5%) were identified as having tHPT and underwent PTX. Levels of intact parathyroid hormone (iPTH) and serum calcium were measured before and after PTX for evaluation of the therapeutic effect, and glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation for investigation of any effect on graft function. One patient showed persistent hyperparathyroidism and hypercalcemia after limited PTX. We experienced 14 successful PTXs, including 3 total PTX with autotransplantations, 8 subtotal PTXs, and 3 limited PTXs. Level of iPTH and serum calcium were at normal range after PTX. Estimated GFR decreased after PTX. Total PTX with autotransplantation showed a tendency of more decrease in the values of iPTH, and GFR after PTX than Subtotal PTX. PTX can cure tHPT-specific symptoms and signs by recovery of hypercalcemia, but may carry the risk of deterioration of kidney graft function. We suspect that subtotal PTX, rather than total PTX with AT, prevent any risk of kidney graft deterioration in surgical treatment of tHPT, and, in selective tHPT patients, limited PTX might be recommended.

This study describes the age-related changes of vitamin D metabolism and its related hormones, immunoreactive PTH (iPTH) and calcitonin (CT) in normal human subjects. The objective was to assess their roles in the changes in metabolism of calcium and phosphorus with age. Serum calcium and phosphorus levels declined linearly with age from newborn infants to older adults (r = -0.385, P less than 0.01; r = -0.568, P less than 0.01). The serum calcium and phosphorus levels in adults of 51 yr of age or more were significantly lower than those in children and younger adults of 50 yr of age or less (P less than 0.025, P less than 0.01), whereas the calcium and phosphorus levels in cord blood were significantly higher than those in children and younger adults (P less than 0.025, P less than 0.01). The serum concentration of 1 alpha,25-dihydroxyvitamin D (1 alpha,25-(OH)2-Vit D) did not change in children and younger adults, being 42.0 +/- 1.4 (SE) pg/ml, but it significantly decreased to 31.4 +/- 1.9 pg/ml in older adults (P less than 0.01). There were no significant age-related changes in the serum concentrations of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, or vitamin D-binding protein (DBP) among children, younger adults and older adults. The concentrations of all vitamin D metabolites and DBP in cord serum were significantly lower than those in children and younger adults (P less than 0.01). Serum iPTH levels were higher in older adults (P less than 0.05) and lower in cord blood (P less than 0.1), compared with those in children and younger adults, whereas the serum CT level was higher in cord serum (P less than 0.01). No sex differences were found in the serum concentrations of calcium, phosphorus, vitamin D metabolites, DBP, iPTH, and CT. The serum concentration of calcium or phosphorus did not correlate significantly with that of 1 alpha 25-(OH)2-Vit D by simple correlation analysis. Multivariate analysis, however, showed that the change in the serum concentration of 1 alpha,25-(OH)2-Vit D, as well as iPTH and CT, contributed to their correlation with the change in the serum concentrations of calcium and phosphorus. These data indicate that change in vitamin D metabolism might play some role in the age-related change of serum calcium and phosphorus levels in children and adults, but that calcium and phosphorus metabolism in the fetus might be regulated by some mechanisms other than vitamin D metabolism.

BACKGROUND

We have found that postoperative tetany occurs in patients with Graves' disease who have secondary hyperparathyroidism caused by a deficiency in calcium and vitamin D concomitant with transient hypoparathyroidism after surgery. There are seasonal variations in serum 25-hydroxyvitamin D (25[OH]D) concentrations. The purpose of this study was to investigate the effects of seasonal changes in calcium homeostasis on the incidence of postoperative tetany in patients with Graves' disease who undergo subtotal thyroidectomy.

METHODS

A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25(OH)D, and 1,25-dihydroxyvitamin D (1,25[OH]2D) in female patients with Graves' disease who underwent subtotal thyroidectomy during the summer (n = 89) and during the winter (n = 89).

RESULTS

The serum levels of calcium, magnesium, and 25(OH)D were significantly higher, but iPTH levels and 1,25(OH)2D levels were lower in summer than in winter. The percentage of vitamin D deficiency (25(OH)D < 25 nmol/L) was 23% in summer and 62% in winter (P < .001). iPTH was below the detection limit on the first postoperative day in 15 patients (13.8%) in summer and in 13 patients (11.4%) in winter. In summery, tetany developed in only 4 of 15 patients and in one patient whose iPTH level was below normal (incidence of tetany, 5.6%). In winter, however, tetany developed in 6 of 13 patients and in 4 patients whose iPTH level was below normal (incidence of tetany, 11.2%).

CONCLUSIONS

Patients with Graves' disease are more susceptible to calcium and vitamin D deficiency during the winter than during the summer, resulting in the tendency toward a higher incidence of postoperative tetany in winter.

A 48-year-old women admitted with polyuria and polydipsia. She was found to be hypercalcemic despite suppressed parathormone (iPTH) levels. Subsequently checked parathormone related-protein (PTHrP) level was 2.5 pmol/L (expected normal level <1.3 pmol/L). An extensive workup for a malignancy revealed no abnormality, except for an uterine leiomyoma, 7.1 cm in size. Total abdominal hysterectomy and salpingo-oophorectomy were performed. After the surgical removal of uterine leiomyoma, serum calcium (9.3 mg/dL), iPTH (29.4 pg/mL), and PTHrP (<1.3 pmol/L) levels were normalized. The diagnosis of humoral hypercalcemia of benignancy secondary to PTHrP was confirmed. One month later, her calcium and iPTH levels were normal and 1 year later still remain within the normal ranges. Our case indicates that PTHrP associated hypercalcemia does not solely result from a malignant tumor. Benign tumors like uterine leiomyoma might also cause humoral hypercalcemia.

BACKGROUND

Increased serum parathyroid hormone-related peptide (PTHrP) concentration is used to diagnose humoral hypercalcemia of malignancy (HHM) in humans and animals. A commercially available assay for human PTHrP has diagnostic utility in the dog, but has not been assessed in cats.

OBJECTIVE

The goals of this study were to determine serum or plasma levels of PTHrP in a population of hypercalcemic cats and to determine whether increased PTHrP concentration was associated with malignancy. In addition, we validated immunoradiometric assays (IRMAs) for intact parathormone (iPTH) and PTHrP for use with feline samples.

METHODS

A retrospective analysis of iPTH and PTHrP results from 322 hypercalcemic cats (ionized calcium concentration>> 1.4 mmol/L) was performed. Immunoassays for human iPTH and PTHrP (residues 1-84) were validated using standard methods, and reference intervals were calculated using values from 31 healthy adult cats. Hypercalcemic cats were classified as parathyroid-independent (iPTH < 2.3 pmol/L), equivocal (iPTH 2.3-4.6 pmol/L), or parathyroid-dependent (iPTH>> 4.6 pmol/L). Seven cats with detectable or increased PTHrP concentrations were evaluated further for underlying disease. Formalin-fixed neoplastic tissues were immunohistochemically stained using rabbit antibody to human midregion PTHrP.

RESULTS

Assays for iPTH and PTHrP showed acceptable precision for feline samples. The reference interval for iPTH was 0.8-4.6 pmol/L and for PTHrP was < 1.5 pmol/L. The majority of hypercalcemic cats (263/322, 81.7%) were parathyroid-independent, with fewer cats in the equivocal (32/322, 9.9%) and parathyroid-dependent (27/322, 8.4%) groups. In 31 (9.6%) cats, PTHrP concentration was>> 1.5 pmol/L (range 1.5-26.6 pmol/L). All 7 cats for which follow-up information was available had HHM; 6 had carcinomas (4 lung carcinomas, 1 undifferentiated carcinoma, 1 thyroid carcinoma) and 1 had lymphoma. All tumors had mild to moderate positive staining for PTHrP; however, lung carcinomas from normocalcemic cats also stained positive.

CONCLUSIONS

Human IRMA for PTHrP (1-84) can be used to measure PTHrP in cats. Malignancies, particularly carcinomas, appear to secrete PTHrP and induce HHM in this species. Immunohistochemistry alone cannot predict the occurrence of HHM in cats.

In 82 patients, a preoperative diagnosis of primary hyperparathyroidism has been established by means of transfemoral neck vein catheterization and measurement of serum immunoreactive parathyroid hormone (iPTH). Twenty-five of these patients have had cancer in other parts of the body but with no evidence of recurrence or metastasis. One patient had carcinoma of the colon with metastases, and four were members of families with multiple endocrine adenomatosis (MEA, Types I and II). In six other hypercalcemic patients, high levels of iPTH were found also in the effluent blood from cancer sites other than the parathyroid gland, secondary to ectopic hormone production or pseudohyperparathyroidism. In addition, a high serum level of iPTH was found in the superior vena cava of a seventh patient who had carcinoma of the breast but no clinical or radiological signs of recurrence or metastasis with the exception of an enlarged liver. This iPTH finding was interpreted as being, probably, the result of parathyroid adenoma in either the neck or the mediastinum. At the time of operation, a transcervical mediastinal search was made. Four normal cervical parathyroid glands were found; three were removed. Hypercalcemia persisted after operation, and the patient died. At postmortem examination, microscopic study revealed that the disease had metastasized to lungs and hilar lymph nodes. There was massive metastasis in the liver; the liver contained a large amount of iPTH. The results of these investigations suggest that (1) venous catheterization of the neck veins and the effluent blood from extraparathyroid tumors aid in identifying and localizing iPTH production; (2) primary benign hyperparathyroidism is not uncommon in patients with cancer, and its co-existence must be recognized; (3) high serum iPTH level in the superior vena cava may be found in patients with metastatic or primary cancer of the thoracic cavity; and (4) hyperparathyroidism may be the first hint of a familial multiple endocrine syndrome.

BACKGROUND

While normocalcemic hyperparathyroidism is well recognized in primary hyperparathyroidism (PHP), less is known about patients with high calcium but normal intact parathyroid hormone (iPTH). We aimed to describe this entity and designated it normohormonal primary hyperparathyroidism (NHPHP).

METHODS

From a prospectively maintained database of patients undergoing bilateral parathyroid exploration for PHP, we identified and compared those with preoperative iPTH levels below (NHPHP) and above (typical PHP) normal reference peak (60 pg/mL).

RESULTS

NHPHP occurred in 46 of 843 patients (5.5%) undergoing initial parathyroidectomy for PHP. All had hypercalcemia (11.1 mg/dL). Regarding preoperative iPTH, 7 patients (15%) had values <40 pg/mL, 19 (41%) had values <60 pg/mL; and 20 (44%) had intermittent values >60 pg/mL. Unlike patients with elevated iPTH, nearly all NHPHP patients had additional testing delaying the operation. Imaging correctly localized NHPHP parathyroid disease in 80%. At the time of operation, 74% of NHPHP patients had single adenomas. Intraoperatively postmobilization, using the same assay that was used preoperatively, 82% had PTH levels >60 pg/mL (mean, 279 pg/mL). During the follow-up period, iPTH levels remained lower among NHPHP patients (21 pg/mL) compared to 41 pg/mL for patients with preoperative iPTH 60 to 100 pg/mL and 56 pg/mL for patients with preoperative iPTH 100 to 200 pg/mL (P < .0001).

CONCLUSIONS

Lower PTH set points may exist in some patients with otherwise typical PHP features. Although high normal iPTH is inappropriate for hypercalcemia and should suggest PHP, this disorder may occur with iPTH levels as low as 5 pg/mL. Awareness of the unusual phenotype of NHPHP may facilitate earlier diagnosis and surgery.

OBJECTIVE

To determine the relationship between preoperative plasma 25-hydroxyvitamin D (25[OH]D) levels and severity of primary hyperparathyroidism (PHPT) and to explore whether presurgical 25(OH)D levels could predict the likelihood of positive results on technetium Tc 99m sestamibi scintigraphy.

METHODS

Retrospective analysis.

METHODS

Tertiary university referral center.

METHODS

A total of 421 consecutive patients underwent preoperative sestamibi scintigraphy and parathyroid exploration. Patients with cholecalciferol (vitamin D) deficiency, defined as plasma levels lower than 25 ng/mL, were compared with patients having no vitamin D deficiency. We explored the relationship between 25 (OH)D levels and intact parathyroid hormone (iPTH) levels, alkaline phosphatase (ALKP) levels, adenoma weight, binary sestamibi scan results, and postoperative serum calcium levels (at 1 week and 6 months).

METHODS

We hypothesized that severity of hypovitaminosis D would correlate with severity of PHPT and predict the likelihood of a positive finding on sestamibi scan.

RESULTS

Concentrations of iPTH and ALKP and parathyroid adenoma weight were significantly higher in patients with lower 25(OH)D levels (P < .01 for all). Patients with hypovitaminosis D had a greater percentage decrease in serum calcium levels 1 week and 6 months postoperatively (P < .05). Median 25(OH)D levels were lower in patients with positive sestamibi scan results (P < .001).

CONCLUSIONS

Patients with hypovitaminosis D present with more advanced indices of PHPT. Parathyroid sestamibi scanning is more likely to show positive results for this subset of patients who may then benefit from sestamibi scan-directed surgical intervention.

OBJECTIVE

To find out why female sex is the most important risk factor for tetany, as calcium and bone metabolism may differ between the sexes.

METHODS

Prospective study.

METHODS

Thyroid centre, Japan.

METHODS

45 men (mean age 35 years, SD 13) and 178 women (mean age 33 years, SD 12) with Graves disease treated by subtotal thyroidectomy.

METHODS

Measurement of serum concentrations of intact parathyroid hormone (iPTH), calcium, electrolytes, 25-hydroxyvitamin D (25 (OH) D), and 1,25-dihydroxyvitamin D (1,25 (OH) 2D).

METHODS

Mean values of these substances, together with reductions in serum calcium concentration, relative youth, increased alkaline phosphatase activity, large goitre, and increased serum TSH binding inhibitory globulin concentration.

RESULTS

Women had significantly lower calcium concentrations than men (mean (SD) 2.37 (0.13) compared with 2.43 (0.07), p = 0.003). Serum calcium concentrations correlated significantly with concentrations of 25 (OH) D (p < 0.001). 121 of the women (68%) compared with 13 (29%) of men had vitamin D deficiency as defined as 25 (OH) D < 25 nmol/l (p < 0.05). 15 patients (8%) developed tetany postoperatively compared with I man (2%, p = 0.2).

CONCLUSIONS

Women with Graves disease are more susceptible to calcium and vitamin D deficiency than men, which may account for the higher incidence of postoperative tetany among women with the disease.

We assessed the effect of chronic hyperglycemia on bone mineral density (BMD) and bone remodeling in patients with type 2 diabetes mellitus. We investigated 42 patients with type 2 diabetes under stable control for at least 1 year, 22 of them with good metabolic control (GMC: mean age = 48.8 +/- 1.5 years, 11 females) and 20 with poor metabolic control (PMC: mean age = 50.2 +/- 1.2 years, 8 females), and 24 normal control individuals (CG: mean age = 46.5 +/- 1.1 years, 14 females). We determined BMD in the femoral neck and at the L2-L4 level (DEXA) and serum levels of glucose, total glycated hemoglobin (HbA1), total and ionic calcium, phosphorus, alkaline phosphatase, follicle-stimulating hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OH-D), insulin-like growth factor I (IGFI), osteocalcin, procollagen type I C propeptide, as well as urinary levels of deoxypyridinoline and creatinine. HbA1 levels were significantly higher in PMC patients (12.5 +/- 0.6 vs 7.45 +/- 0.2% for GMC and 6.3 +/- 0.9% for CG; P < 0.05). There was no difference in 25-OH-D, iPTH or IGFI levels between the three groups. BMD values at L2-L4 (CG = 1.068 +/- 0.02 vs GMC = 1.170 +/- 0.03 vs PMC = 1.084 +/- 0.02 g/cm(2)) and in the femoral neck (CG = 0.898 +/- 0.03 vs GMC = 0.929 +/- 0.03 vs PMC = 0.914 +/- 0.03 g/cm(2)) were similar for all groups. PMC presented significantly lower osteocalcin levels than the other two groups, whereas no significant difference in urinary deoxypyridine was observed between groups. The present results demonstrate that hyperglycemia is not associated with increased bone resorption in type 2 diabetes mellitus and that BMD is not altered in type 2 diabetes mellitus.

Fibroblast growth factor 23 (FGF23) plays a central role in phosphate (P) homeostasis. However, the precise mechanism of how FGF23 secretion is regulated remains to be elucidated. In the present study, we examined the effect of intravenous pamidronate administration on serum levels of FGF23. Thirteen patients with osteogenesis imperfecta were treated with two cycles of 3-day pamidronate infusion. Blood samples at pre- and post-drip pamidronate infusion were evaluated for serum calcium, P, intact PTH (iPTH), 1,25(OH)(2)D, intact FGF23 (FGF23), type I collagen cross-linked N-telopeptides (NTx), bone-specific alkaline phosphatase (BAP), and TmP/GFR. During the two cycles, FGF23 levels decreased significantly preceding the decline in P levels. Although the change in P levels became less apparent during the second cycle, the reduction in FGF23 levels was similar during both cycles. Moreover, absence of correlation between FGF23 and P indicates that FGF23 attenuation is independent of the decrease in P levels during pamidronate infusion. Significant correlation between NTx suppression and the decrease in FGF23 levels during the 1st cycle (r = 0.665, P = 0.013) suggests that inhibition of osteoclast function may have some role in suppressing FGF23 levels. Because pamidronate dose was most associated with the decrease in FGF23 levels during the second cycle, pamidronate may directly attenuate osteocyte/osteoblast-mediated FGF23 production. This is the first evidence of a rapid fall in FGF23 levels following pamidronate infusion, raising the possibility that inhibition of bone resorption and/or direct effects of pamidronate may suppress secretion of FGF23.

BACKGROUND

Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values.

METHODS

Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals.

RESULTS

Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values.

CONCLUSIONS

Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.

BACKGROUND

Chronic renal failure is frequently associated with secondary hyperparathyroidism and immunological disorders. Recent studies support the hypothesis that high levels of parathyroid hormone (PTH) may contribute to the impairment of the cellular and humoral immune response by an immunosuppressive effect on T- and B-cell functions. However, many studies indicate that excess PTH exerts a stimulatory effect on T lymphocytes. Since reports about the immunomodulatory effect of PTH are controversial, our aim was to compare the effect of low and high levels of intact PTH (iPTH) in hemodialysis patients.

METHODS

The study was performed on 14 hemodialysis patients with high levels of iPTH (GI), 12 patients with low levels of iPTH (GII) and 13 volunteers (GIII), for whom time of dialysis, iPTH, total number of lymphocytes, B, CD4+, CD8+, lymphoproliferative response to phytohemagglutin (PHA), pokeweed mitogen (PWM) and candidin, IgG and IgM production in vitro in response to PWM, and interleukin (IL)-2 and IL-6 production in vitro in response to PHA were determined.

RESULTS

Patients with high iPTH levels had significantly higher responses to PHA than patients with low iPTH. Lymphocyte transformation by PWM and candidin antigen was similar in both groups of patients, but significantly decreased when compared to controls. CD4+ cell counts were significantly increased in GI, and there was a positive correlation between the lymphoproliferative response to PHA and iPTH levels and CD4+ number.

CONCLUSIONS

The present study suggests that high levels of iPTH in hemodialysis patients affect T-cell function, increasing the lympho-proliferative response to PHA and the CD4+ number.

The aim of the study was to assess impaired tubular phosphate reabsorption and renal function among patients on cyclosporine- or tacrolimus-based immunosuppression for 2 years after kidney transplantation. Among 60 cadaveric kidney allograft recipients observed for 48 months, 40 received cyclosporine, azathioprine, and prednisone (group A and B). Group C consisted of 20 patients receiving tacrolimus with steroid withdrawal at 3 months after transplantation. Renal function and calcium-phosphate metabolism-iPTH, 25-OHD, 1,25(OH)(2)D concentration, phosphate reabsorption (TRP; mmol/L), and tubular maximum phosphate reabsorption per glomerular filtration rate (TmPO(4)/GFR; mmol/L)-were assessed at 1, 6, 12, 18, and 24 months (groups A and C) or 24, 30, 36, 42, and 48 months (group B). Renal function after 24 months of observation was significantly better among tacrolimus-treated patients (serum creatinine concentration mumol/L; C: 94.6 +/- 16.8 vs A: 110.5 +/- 22.1 vs B: 121.1 +/- 30.9; P < .05). Among tacrolimus-treated recipients, TRP and TmPO(4)/GFR remained within normal values during the whole observation period. In groups A and B, TRP improved during the first year of observation; after 2 years it reached values observed in group C (TRP: A: 0.67 +/- 0.1; B: 0.72 +/- 0.13; C: 0.76 +/- 0.07; P = NS), whereas TmPO(4)/GFR remained low in group A after 2 years (A: 0.78 +/- 0.19; B: 0.91 +/- 0.25; C: 0.94 +/- 0.15; P < .05). Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared with cyclosporine-treated recipients. Tacrolimus-based immunosuppression led to better kidney allograft function during 2-year observation.

Deficient serum 25-hydroxyvitamin D [25(OH)D] may contribute to the impaired bone turnover of end stage renal disease patients. In 112 hemodialysed patients we analysed the relation between 25(OH)D and bone alkaline phosphatase (BALP), beta-CrossLaps (beta-CTx) and iPTH. We analysed parameters according to the manufacturers' instructions. We found potentially significant vitamin D deficiency: 71% of patients had 25(OH)D levels below 50 nmol/L. In patients with iPTH below 150 pg/mL (n = 57), we observed significantly low 25(OH) (p < 0.01). In addition, patients with iPTH above 300 pg/mL had higher BALP levels (p < 0.05). There were negative correlations between serum 25(OH)D and both BALP and iPTH (r = -0.225, p < 0.05 and r = -0.331, p < 0.05). Beta-CTx levels were significantly higher in patients who did not receive vitamin D supplementation (p < 0.01). In addition, reduced BALP and iPTH levels indicate decreased bone turnover. Recorded data could signify that vitamin D deficiency may contribute to the impaired bone metabolism of hemodialysis patients.