Nephrogenous Cyclic Adenosine Monophosphate Research Articles

ODP102 Indicators for the effects of calcimimetics on hypercalcemia in the elderly patients with primary hyperparathyroidism.

Abstract Primary hyperparathyroidism (PHPT) is the most common disorder causing hypercalcemia, in which parathyroid hormone (PTH) is excessively secreted from a parathyroid tumor. PHPT occurs mainly in elderly women, and patient with PHPT present symptoms including nephrolithiasis, bone fracture, and cognitive impairment or can be asymptomatic. Excessive secretion of PTH leads to elevated serum levels of alkaline phosphatase as well as calcium and decreased serum inorganic phosphate level. Parathyroid surgery is the only established treatment, and the treatment reduces elevated serum levels of calcium and PTH, increases bone mineral density, reduces the occurrence of bone fractures, and decreases the risk of renal stones. However, some PHPT patients, especially elderly patients, refuse to undergo surgical therapy for various reasons including perceived risk. Calcimimetic treatment, including cinacalcet and evocalcet administration, has also been reported to be effective for reducing serum calcium level in patients with PHPT. However, the relationship between the efficacy of calcimimetic treatment for PHPT and patient characteristics related to the effectiveness of calcimimetics remains to be elucidated. To investigate the relevance of clinical parameters to the effectiveness of calcimimetics for PHPT, we retrospectively analyzed patients with PHPT who received calcimimetic treatment in our department. We included nine patients including 8 females (88.9%) and one male (11.1%) in the study. The median age of the patients was 81 years (interquartile range (IQR): 61-86 years). Laboratory tests before calcimimetic treatment revealed that median level of serum corrected calcium (cCa) was high (11.1 (IQR: 10.5-12.7) mg/dL), serum inorganic phosphate was low (2.3 (2.3-2.4) mg/dL), and plasma intact PTH was high (251. 0 (198.3-498.5) pg/mL). The fractional excretion of calcium was higher than 1% (1.3% (1.12-1.48%)), %tubular reabsorption of phosphate was low (79.9% (77.1-83.9%)), nephrogenous cyclic adenosine monophosphate (cAMP) was high (3.4 (2.4-4. 0) nmoL/dL GF), and urinary cAMP was normal (4.3 (4. 0-5.3) μmoL/day). Median reduction rate of serum cCa level due to calcimimetic treatment was 5.8% (0-13.4%) at the first follow-up (median treatment duration: 22 (20-29) days). Notably, reduction rate of serum cCa level had significant correlations with age (R=0.95), dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) in the femoral neck (R=-0.92), and urinary cAMP level (R=-0.85). Thus, the present study suggested that elevated serum cCa levels may be reduced by treatment with calcimimetics more effectively in PHPT patients of relatively advanced age, patients with low DEXA %YAM, and patients with low urinary cAMP. Presentation: No date and time listed

Renal Phosphate Handling: Independent Effects of Circulating FGF23, PTH, and Calcium.

ABSTRACTExcess fibroblast growth factor 23 (FGF23), excess PTH, and an increase in extracellular calcium cause hypophosphatemia by lowering the maximum renal phosphate reabsorption threshold (TmP/GFR). We recently reported two cases of X‐linked hypophosphatemia (XLH) with severe tertiary hyperparathyroidism who had normalization of TmP/GFR upon being rendered hypoparathyroid following total parathyroidectomy, despite marked excess in both C‐terminal FGF23 (cFGF23) and intact FGF23 (iFGF23). We explored the effects of FGF23, PTH, and calcium on TmP/GFR in a cross‐sectional study (n = 74) across a spectrum of clinical cases with abnormalities in TmP/GFR, PTH, and FGF23. This comprised three groups: FGF23‐dependent hypophosphatemia (n = 27), hypoparathyroidism (HOPT; n = 17), and chronic kidney disease (n = 30). Measurements included TmP/GFR, cFGF23, PTH, ionized calcium, vitamin D metabolites, and bone turnover markers. The combined effect of cFGF23, PTH, and ionized calcium on TmP/GFR was modeled using hierarchical multiple regression and was probed by moderation analysis with PROCESS. Modeling analysis showed independent effects on TmP/GFR by cFGF23, PTH, and ionized calcium in conjunction with a weak but significant effect of the interaction term for PTH and FGF23; probing showed that the effect was most prominent during PTH deficiency. Teriparatide 20 μg daily was self‐administered for 28 days by one case of X‐linked hypophosphatemia with hypoparathyroidism (XLH‐HOPT) to assess the response of TmP/GFR, cFGF23, iFGF23, nephrogenous cyclic adenosine monophosphate (NcAMP), vitamin D metabolites, and bone turnover markers. After 28 days, TmP/GFR was lowered from 1.10 mmol/L to 0.48 mmol/L; this was accompanied by increases in NcAMP, ionized calcium, and bone turnover markers. In conclusion, the effect of FGF23 excess on TmP/GFR is altered by PTH such that the effect is ameliorated by hypoparathyroidism and the effect is augmented by hyperparathyroidism. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency

Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 ± 10.7 years) and 14 age (48.6 ± 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT x), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT x, and PINP in AGHD and healthy subjects ( P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher ( P < 0.05), whereas the MESOR values for phosphate, CT x ( P < 0.05), and PINP ( P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP ( P < 0.001) and higher urinary calcium excretion ( P < 0.05). Maximum cross-correlation between PTH and phosphate ( r = 0.75) was observed when PTH was lagged by 1.5 h in healthy individuals, suggesting that changes in phosphate precede changes in PTH concentration. PTH/CT x and PTH/PINP showed maximum correlation when CT x ( r = 0.68) and PINP ( r = 0.71) were lagged by 3 h. In AGHD patients, compared to controls the maximum correlation between PTH/phosphate ( r = 0.88, P = 0.007), PTH/CTx ( r = 0.61, P = 0.027), and PTH/PINP ( r = 0.65, P = 0.028) was observed when the lag time was reduced by 1.5 h in all variables, with changes in PTH and phosphate occurring at concurrent time points. Our data suggest decreased end-organ sensitivity to the effects of PTH in AGHD patients, resulting in a significantly lower NcAMP, low bone turnover, and higher calcium excretion in the presence of significantly higher PTH concentrations. We have also demonstrated that changes in serum phosphate precede those of PTH, which in turn precede changes in bone resorption and formation in healthy individuals. This relationship was altered in AGHD patients. These results suggest a possible role for GH in regulating PTH secretion and the bone remodeling process.

Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia.

Fibrous dysplasia (FD) of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. It arises from postzygotic activating mutations of the GNAS1 gene. Hypophosphatemia due to renal phosphate wasting has been reported in association with FD as a part of the McCune-Albright Syndrome (MAS), which is characterized by FD, skin hyperpigmentation, and precocious puberty. To date, the prevalence and mechanism of phosphate wasting has not been well studied. We evaluated 42 patients with FD/MAS. Serum and urine samples were tested for indices of mineral metabolism, amino acid handling, and markers of bone metabolism. Twenty (48%) patients had some degree of renal phosphate wasting. Nephrogenous cyclic adenosine monophosphate (cAMP) was normal in FD patients, suggesting that the underlying cause of phosphate wasting is not the presence of activating GNAS1 mutations in the kidney. In addition, there was evidence of a more generalized renal tubulopathy as represented by the presence of abnormal vitamin D metabolism, proteinuria in 36 (86%) patients, and aminoaciduria in 39 (94%) patients. Renal phosphate wasting significantly correlated with the degree of bone involvement, as assessed by serum and urine markers of bone metabolism, suggesting that a circulating factor produced by FD bone and impacting on the kidney may be the mechanism. These data show that phosphaturia as part of a generalized renal tubulopathy represents the most common extraskeletal manifestation of FD and that the observed tubulopathy is similar to that seen in tumor-induced osteomalacia (TIO).

A threshold for low-protein-diet–induced elevations in parathyroid hormone

We reported previously that lowering dietary protein intake in young healthy women to 0.7 g/kg depressed intestinal calcium absorption and was accompanied by elevations in parathyroid hormone (PTH). Moderate amounts of dietary protein (1.0 g/kg) did not appear to perturb calcium homeostasis. The purpose of this study was to evaluate the effect of graded intakes of dietary protein (0.7, 0.8, 0.9, and 1.0 g/kg) on calcium homeostasis. The experiment consisted of 2 wk of a well-balanced diet containing moderate amounts of calcium, sodium, and protein followed by 4 d of an experimental diet containing 1 of 4 amounts of protein. Eight young healthy women received the 4 amounts of protein in random order. The average age of the subjects was 23.1 +/- 2.3 y, their weight was 64 +/- 3 kg, and their body mass index (in kg/m(2)) was 24.3 +/- 0.9. Elevations in PTH developed by day 4 of the diets containing 0.7 and 0.8 g protein/kg but not during the diets containing 0.9 or 1.0 g protein/kg. By day 4 of the 0.7- and 0. 8-g/kg diets, midmolecule PTH, calcitriol, and nephrogenous cyclic adenosine monophosphate were 1.5-3.5-fold higher than on day 0. Calcitropic hormones on day 4 of the diets containing 0.8 and 0.9 g protein/kg were within the normal range and 23-57% lower than values observed with the 0.7- and 0.8-g/kg diets (P < 0.005). Mean 24-h urinary calcium was 3.29 +/- 0.35 mmol with the diet containing 0.7 g protein/kg and 3.54 +/- 0.46 mmol with the diet containing 1.0 g protein/kg. Our data suggest that in young healthy women consuming a well-balanced diet, the current recommended dietary allowance for protein (0.8 g/kg) results in short-term perturbations in calcium homeostasis.

Increased circulating concentrations of parathyroid hormone in healthy, young women consuming a protein-restricted diet

Increasing dietary protein induces hypercalciuria and a negative calcium balance. Despite this, the influence of dietary protein on the parathyroid hormone (PTH) I-a-hydroxylase axis is not well understood. We therefore examined the effect of three amounts of dietary protein: low (0.7 g/kg), medium (1.0 g/kg), and high (2.1 g/kg) on mineral metabolism and the PTH-1-alpha-hydroxylase axis in 16 healthy women aged 26.7 +/- 1.3 y. By day 4, urinary calcium decreased significantly with the low-protein diet and increased significantly with the high-protein diet compared with the medium-protein diet (control). Also by day 4, there were striking elevations in serum PTH and calcitriol [1,25-dihydroxyvitamin D] in subjects consuming the low-protein diet. Serum PTH, by two different assays, was 1.5-2.4 times higher and by day 14 1.6-2.7 times higher during the low-protein diet compared with the medium-protein diet. This was accompanied by a significant increase in both nephrogenous cyclic adenosine monophosphate (cAMP), a sensitive and specific indicator of PTH bioactivity, and serum calcitriol by day 14. In comparison, there were relatively minor changes in the calcitropic hormones with the medium- and high-protein diets. The stimulus for the elevation in PTH induced by protein restriction is unclear, but probably does not involve a simple renal mechanism and could reflect either a decline in intestinal calcium absorption, a reduction of bone turn-over, or both. Our data indicate that dietary protein is a powerful regulator of calcium metabolism. Further study is needed to both clarify the mechanisms by which these changes are induced and to better define the amount of dietary protein that will optimize skeletal health in young women.

Spinal Cord Compression by Heterotopic Ossification Associated with Pseudohypoparathyroidism

This report describes a 37-year-old man presenting with a gait disturbance due to spastic paraparesis. Physical findings showed typical features of Albright's hereditary osteodystrophy, including short stature, obesity, brachydactyly and dental hypoplasia. He was diagnosed as having pseudohypoparathyroidism type Ia, on the basis of his hypocalcaemia, hyperphosphataemia, increased plasma level of parathyroid hormone (PTH), and the unresponsiveness to exogenous PTH loading of his urinary excretion of both nephrogenous cyclic adenosine monophosphate and phosphate. Magnetic resonance imaging and myelographic computed tomographic scans clearly demonstrated severe compression of the spinal cord at T 9/10 by tumour-like ossifications of the paravertebral ligaments. Neurosurgical decompression therapy was, therefore, performed to alleviate his spastic paraparesis. This was a rare case of pseudohypoparathyroidism complicated with spinal cord compression caused by ectopic ossification of the ligaments.

An Unusual Case of Diffuse Focal Osteolysis with Disseminated Osteoclastosis

We report the unusual case of a 31-year-old woman referred for inflammatory pain of the long bones associated with diffuse focal osteolysis, elevated erythrocyte sedimentation rate (ESR) and hypercalcemia. Corticosteroid therapy produced dramatic symptomatic improvement, and biological parameters returned to normal. Biochemical markers of bone remodeling, particularly those of resorption, were strikingly elevated. Parathyroid hormone, parathyroid hormone-related protein, nephrogenous cyclic adenosine monophosphate and calcitriol levels were normal. Investigations for infectious disease and malignancy were negative. The histology of the lesions consisted of cortical osteolysis caused by intense osteoclastic resorption, with several foci of osteogenesis, without malignant cells. The patient died 9 months after the onset of symptoms, following a "malignant" course: severe hypercalcemia, extension of lytic bone lesions and spontaneous fractures. To our knowledge, such a peculiar picture with quite unusual radiologic findings, disseminated focal cortical lesions and a progressive course, without evidence for a tumoral process, has never been described. This case suggests either the presence of an unknown systemic osteoclast-activating factor from an occult tumor or a primary malignant hyperosteoclastosis.

Changes in calciotrophic hormones and biochemical markers of bone turnover in normal human pregnancy

Plasma concentrations of parathyroid hormone-related protein (PTHrP), parathyroid hormone, alkaline phosphatase, osteocalcin and albumin-adjusted calcium were measured along with nephrogenous cyclic adenosine monophosphate (NcAMP) in 10 normal women longitudinally through pregnancy. In addition, an assessment of bone resorption was made in these same subjects by the measurement in true fasting urine specimens of the calcium/creatinine ratio (Ca/Cr), hydroxyproline/creatinine ratio (HP/Cr), pyridinoline/creatinine ratio (Pyr/Cr) and deoxypyridinoline/creatine ratio (Dpyr/Cr). The PTHrP level rose through pregnancy from (mean +/- SEM) 0.8 +/- 0.2 pmol/l in the first trimester to 2.7 +/- 0.2 pmol/l 6 weeks postpartum (p < 0.0001). Serum alkaline phosphatase rose from 94 +/- 8 U/l (first trimester) to 347 +/- 25 U/l at term (p < 0.0001). A significant positive correlation was evident between PTHrP and alkaline phosphatase up to term (r = 0.44, p < 0.005). Parathyroid hormone concentrations remained unchanged during pregnancy but rose significantly postpartum from 1.8 +/- 0.2 pmol/l (first trimester) to 3.1 +/- 0.5 pmol/l (p < 0.0001). Similarly, osteocalcin, a marker of bone formative activity, remained unchanged through pregnancy but rose significantly at 6 weeks after delivery to 0.38 +/- 0.05 nmol/l from 0.19 +/- 0.03 nmol/l (first trimester) (p = 0.019). No significant change was noted in serum-adjusted calcium or NcAMP, either through pregnancy or at the postpartum assessment. Fasting urinary Ca/Cr fell through pregnancy from 0.70 +/- 0.11 (first trimester) to a nadir of 0.19 +/- 0.04 6 weeks postpartum (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Coincidental occurrence of primary hyperparathyroidism and cancer‐associated hypercalcaemia in a middle‐aged man

Primary hyperparathyroidism (PHPT) is found not uncommonly in patients with cancer. In this report, however, we describe a patient where both humoral hypercalcaemia of malignancy and PHPT were present coincidentally. A 47-year-old man was found to have PHPT due to parathyroid hyperplasia. Serum parathyroid hormone (PTH) levels, which were elevated before parathyroidectomy, were undetectable post-operatively; however, hypercalcaemia persisted. Nephrogenous cyclic adenosine monophosphate was elevated along with this undetectable PTH, indicative of the presence of a PTH-like factor in the serum. This was confirmed by the finding of an elevated level of PTH-related protein (PTHrP) in plasma (9.1 pmol/l, normal < 2.6 pmol/l). Secondary carcinoma was identified in a lesion in the region of the manubrium sternii. This stained positively for PTHrP by immunocytochemistry and PTHrP messenger RNA was detected by in-situ hybridization. This case illustrates the value of sensitive PTH assays in distinguishing PHPT from other causes of hypercalcaemia and also shows the importance of considering primary hyperparathyroidism in the differential diagnosis of the patient with cancer and hypercalcaemia.

Clinical and laboratory studies of a new immunoradiometric assay of parathyroid hormone-related protein

Parathyroid hormone-related protein (PTHrP) was measured in plasma by a new immunoradiometric assay (IRMA) from Nichols Institute. The assay is specific for PTHrP and shows excellent parallelism when measuring keratinocyte fluid, samples with high PTHrP content, and PTHrP-supplemented plasma. A precision profile established the assay detection limit at 0.7 pmol/L. PTHrP was unstable in plasma, but the degradation rate was patient-specific. Because delay in separation resulted in loss of PTHrP immunoreactivity, samples were collected into tubes containing protease inhibitors (aprotinin, leupeptin, pepstatin, and EDTA) and separated within 30 min. Among normal subjects, 78% had PTHrP values greater than the detection limit; the reference range established was < 0.7-2.6 pmol/L. Of patients with hypercalcemia associated with malignancy, 46% had PTHrP > 2.6 pmol/L. PTHrP was increased in patients with breast (73%), genitourinary (64%), or lung (46%) malignancy but was rarely above normal in patients with hematological (29%) or gastrointestinal (33%) malignancy. PTHrP and nephrogenous cyclic adenosine monophosphate (NcAMP) were strongly correlated (r = 0.63, P < 0.01) in 37 patients with PTHrP values greater than the detection limit, but 8 patients had PTHrP and parathyroid hormone [PTH(1-84)] values below the limit of detection with inappropriate or increased NcAMP. Five of these eight patients had small cell carcinoma of lung. These patients may have secreted a factor that is not detected by the IRMAs of PTHrP or PTH used in this study but that produces hypercalcemia by means of cAMP-mediated mechanisms.

Effect of Intravenous Calcium Infusion on Indices of Activity of the Parathyroid Glands and on Urinary Calcium and Sodium Excretion in Normotensive and Hypertensive Subjects

The effect of an intravenous calcium gluconate load (10 mg/kg over 5 min) on plasma ionized calcium concentration, parathyroid hormone (PTH), and the rate of urinary excretion of calcium, sodium, and nephrogenous cyclic adenosine monophosphate (NcAMP) was examined in 26 patients with essential hypertension and 27 age- and sex-matched normotensive subjects. Prior to calcium administration hypertensives had lower plasma ionized calcium concentration (P < .01) and higher PTH levels (P < .001) and excreted more calcium (P < .05) and NcAMP (P < .001) in the urine compared to normotensives. Following calcium infusion, plasma ionized calcium did not differ significantly between the two groups, but PTH levels remained higher in the hypertensive subjects at both 60 min (P < .001), and at 120 min (P = .02) post-load. Post-load values for both urinary calcium excretion and urinary sodium excretion were significantly higher in the hypertensive subjects than in the control group. Both before and after calcium infusion, urinary calcium excretion was positively correlated with urinary sodium excretion in each of the two groups, but for the same level of sodium excretion, hypertensives excreted more calcium in the urine, compared to normotensives, both before (P < .05) and after calcium infusion (P < .001). A positive correlation between basal plasma renin activity (PRA) values and plasma ionized calcium values obtained before (r = 0.42, P = .03) or at 60 min (r = 0.41, P = .03) and 120 min (r = 0.42, P = .03) after calcium infusion existed only in the hypertensive subject group. Post-load urinary sodium excretion values were negatively correlated to basal PRA values in both groups (r = -0.55, P < .01 and r = -0.58, P < .01 for hypertensives and normotensives, respectively), but a similar negative correlation between post-load urinary calcium excretion values and basal PRA values existed only in the hypertensive subject group (r = -0.50, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term treatment with growth hormone on bone and mineral metabolism in children with growth hormone deficiency

The effects of growth hormone (GH) deficiency and recombinant human GH replacement (0.6 IU/kg per week) on bone and mineral metabolism in 26 GH-deficient children were studied for 12 months. Before therapy, all children had significantly reduced serum levels of osteocalcin, carboxyl-terminal propeptide of procollagen type I, and 1,25-dihydroxyvitamin D, whereas serum ionized calcium, phosphate, intact parathyroid hormone, calcitonin, and 25-hydroxyvitamin D concentrations were in the normal range. All children had significant reduction of bone density for their chronologic, statural, and bone ages. During therapy with recombinant human GH, a decrease of serum ionized calcium levels and increases of phosphate, osteocalcin, carboxyl-terminal propeptide of procollagen type I, and intact serum levels of parathyroid hormone were found. A significant increase of serum levels of 1,25-dihydroxyvitamin D was found at 12 months. The urinary phosphate/urinary creatinine ratio decreased, whereas values for nephrogenous cyclic adenosine monophosphate and the ratio of the maximum rate of renal tubular reabsorption of phosphate to the glomerular filtration rate increased. Bone density significantly improved at 12 months, with a complete recovery in 12 children (46.2%). Significant relationships were found among growth velocity, bone density, maximum tubular reabsorption/glomerular filtration rate ratio, and serum levels of carboxyl-terminal propeptide of type I procollagen. The changes in serum levels of this propeptide during the first week of recombinant human GH treatment were positively related to growth velocity at 6 and 12 months and to bone density at 12 months of treatment, whereas the changes in osteocalcin levels were not. We conclude that recombinant human GH treatment caused significant modifications of mineral metabolism and significantly increased bone density, and that measurement of serum levels of the propeptide during the first week of recombinant human GH administration may be a useful tool in predicting improved growth velocity and bone density during long-term recombinant human GH replacement.

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy.

In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n = 13), 45 mg (n = 9), and 90 mg (n = 13) in an attempt to see what factors influenced the response of serum calcium to pamidronate. The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into "good" and "poor" responders depending on whether a normal serum calcium was obtained. Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r = 0.45, P = 0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean +/- SEM): 65.0 +/- 9.4 nmol/liter GF (poor responders) versus 29.6 +/- 6.3 (good responders), P = 0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r = -0.41, P = 0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF +/- 0.09 (poor responders) versus 0.76 mmol/liter GF +/- 0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response.(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep shift dissociates the nocturnal peaks of parathyroid hormone (1- 84), nephrogenous cyclic adenosine monophosphate, and prolactin in normal men

Sleep shift dissociates the nocturnal peaks of parathyroid hormone (1- 84), nephrogenous cyclic adenosine monophosphate, and prolactin in normal men

Intact parathyroid hormone concentration and cyclic AMP metabolism in thyroid disease.

In 35 thyrotoxic patients and 35 patients receiving thyroxine replacement therapy mean serum intact parathyroid hormone concentrations were lower than in euthyroid normal volunteer controls. In 20 hypothyroid patients intact PTH was increased relative to euthyroid controls. Mean serum adjusted calcium was increased in thyrotoxic patients relative to euthyroid controls and in 8 toxic patients with elevated serum adjusted calcium (greater than 2.60 mmol/l) intact PTH was below the assay detection limit (less than 0.5 pmol/l). Indices of PTH activity were consistent with intact PTH measurements in thyrotoxic patients with nephrogenous cyclic adenosine monophosphate lower, tubular maximum reabsorption of phosphate higher, and urinary calcium creatinine ratio higher than controls. In hypothyroid patients these indices of PTH activity suggest relative end organ resistance to PTH with nephrogenous cyclic adenosine monophosphate similar, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio lower than in controls. In treated hypothyroid patients nephrogenous cyclic adenosine monophosphate was higher, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio higher than in controls. These results are compatible with the hypothesis that thyroid status modifies the renal responses to PTH (1-84).

Urine calcium excretion, nephrogenous cyclic-adenosine monophosphate and serum parathyroid hormone levels in patients with essential hypertension.

To evaluate the role of calcium and the parathyroid gland in the pathophysiology of essential hypertension, creatinine clearance, urinary excretion of sodium, calcium and nephrogenous cyclic adenosine monophosphate (NcAMP) and serum parathyroid hormone (PTH) levels were measured in 25 newly diagnosed essentially hypertensive patients before institution of any treatment and in 25 age- and sex-matched normal volunteers. While no significant differences in creatinine clearance, serum total calcium levels or 24-hour sodium excretion existed between the two groups, hypertensives had a higher mean (+/- SD) 24-hour calcium excretion rate (199.0 +/- 44.7 vs. 152.8 +/- 33.6 mg, p less than 0.001), a higher mean NcAMP excretion rate (2.54 +/- 0.8 vs. 1.87 +/- 0.5 nmol/100 ml glomerular filtrate, p less than 0.001) and a higher mean serum PTH concentration (1.87 +/- 0.6 vs. 1.53 +/- 0.4 ng/ml, p less than 0.001) than the normotensives. A significant positive correlation existed between calcium and sodium excretion in both hypertensives (r = 0.66, p less than 0.001)) and normotensives (r = 0.67, p less than 0.001), but given the same levels of creatinine clearance and sodium excretion, hypertensives excreted more calcium than normotensives (p less than 0.001)). In both hypertensives and normotensives, serum PTH levels were positively correlated with NcAMP excretion (r = 0.42, p less than 0.05, and r = 0.41, p less than 0.05, respectively) and the ratio of urinary sodium to urinary calcium excretion (r = 0.59, p less than 0.001, and r = 0.75, p less than 0.001), respectively). The above results suggest that in essential hypertension, increased activity of parathyroid glands may occur as a consequence of increased urinary calcium losses which are presumably due to an intrinsic defect in renal calcium handling.

The Frequency and Mechanisms of Urolithiasis in Acromegaly

It is generally accepted that acromegaly is often associated with hypercalciuria, but there are few reports on the frequency and the mechanisms of urolithiasis. Recently we consecutively experienced 2 cases of acromegaly with urolithiasis, and these experiences made us investigate the association between urolithiasis and acromegaly. Among 18 acromegalies from 1977 to March 1990 (10 males, 8 females, 24-64 years old), 13 cases (72%) fulfilled the criteria of hypercalciuria (urinary calcium (u-Ca) greater than or equal to 200 mg/day or u-Ca/urinary creatinine (u-Ca/u-Cr) greater than or equal to 0.15), and 7 cases (39%) suffered from urolithiasis that was diagnosed by KUB (4 cases) or X-ray computed tomography (CT) (3 cases). Especially in the last 2 years, 5 out of 7 cases (71%) were complicated with urolithiasis and all 7 cases were associated with hypercalciuria. These results suggest that hypercalciuria and urolithiasis are both much more frequent than previously reported. In 6 cases who were treated by pituitary adenomectomy from 1988-1989 (4 males, 2 females, 24-59 years old), we examined Ca metabolism before and after operation. Before operation, the levels of serum growth hormone (GH), u-Ca (mg/day), u-Ca/u-Cr (in all cases) and plasma somatomedin-C (Sm-C) (in 4 cases) were increased above the normal range. To determine the etiology of hypercalciuria, we performed the oral Ca load test under restriction of Ca (400 mg/day) and P (650 mg/day) intake. The results suggested that the hypercalciuria might be mainly due to the increased absorption of Ca from the intestine (so-called "Absorptive hypercalciuria"). However, the levels of serum vitamin D (Vit. D) metabolites were all within the normal range before operation. After operation, GH and u-Ca/u-Cr (in 5 cases) and u-Ca (mg/day) (in all cases) decreased significantly compared with before operation, and the levels of Sm-C (in all cases), serum 25-(OH)D3, 1 alpha, 25-(OH)2D3 (in 4 cases) and 24,25-(OH)2D3 (in 3 cases) were also reduced after operation. Surprisingly, u-Ca and u-Ca/u-Cr normalized only in 4 cases who showed a reduction in 1 alpha, 25-(OH)2D3 levels after operation, although there were no correlations between u-Ca (mg/day) or u-Ca/u-Cr and 1 alpha, 25-(OH)2D3. Significant correlations were found between u-Ca (mg/day) or u-Ca/u-Cr and Sm-C. The parathyroid function evaluated by the rapid Ca infusion test or nephrogenous cyclic adenosine monophosphate (NcAMP) was normal before and after operation.(ABSTRACT TRUNCATED AT 400 WORDS)

Marked hypophosphatemia with decreased serum 1,25-dihydroxyvitamin D in a patient with hepatocellular carcinoma complicating liver cirrhosis.

A 61-year-old male with hepatocellular carcinoma (HCC) complicating liver cirrhosis presented hypophosphatemia progressing with HCC expansion and serum alpha-fetoprotein elevation. These changes were associated with an increased fractional excretion of phosphate and decreased theoretical phosphate threshold. There was increased nephrogenous cyclic adenosine monophosphate despite normal serum parathyroid hormone. Serum 1,25-dihydroxyvitamin D levels were markedly reduced with normal 25-hydroxyvitamin D levels. There were no symptoms of osteomalacia, however, a slightly increased osteoid seam was elicited on autopsy. The hypophosphatemia could be explained by presumed secretion from HCC of humoral factors which have a phosphaturic effect and also inhibit 25-hydroxyvitamin D-1 alpha-hydroxylase in renal tubular cells.

Biochemical evaluation of calcium stonepatients: How soon can it be done after stone surgery/passage?

Biochemical evaluations were done two times for 29 outpatients with calcium stone disease, the first time within one month after surgical extraction or passage of stones and the second time two months or more later. Classification of the etiologic basis for the stone disease was the same after both tests in 27 patients. In the other 2 patients the diagnosis was changed from renal to absorptive hypercalciuria. Both of these patients had creatinine clearance rates less than 60 percent of normal during the first test. One also had multiple residual stones during both evaluations, and the second had a urinary tract infection during the first test that resolved with a normal creatinine clearance by the second test period. When nephrogenous cyclic adenosine monophosphate (cAMPn) assays were done on fasting specimens in these patients, the results were consistent with absorptive hypercalciuria. Almost all patients can be evaluated and placed in management programs within a few weeks after surgery. If cAMPn assays are not done, patients with decreased renal function secondary to residual stones or infection can be tested at a later time.