Neonatal hypocalcaemia associated with rotavirus diarrhoea

We observed an association between rotavirus diarrhoea and hypocalcaemia in several patients and therefore started a prospective evaluation with measurement of calcium levels in all patients with rotavirus infection during a period of 8 months. We report on 54 infants with rotavirus gastro-enteritis. Serum concentrations of sodium, potassium, and total and ionized calcium were measured on admission. If hypocalcaemia was detected, total and ionized calcium were measured every day until recovery. Calcium was supplemented as calcium gluconate which was added to milk. Out of 54 newborns with rotavirus gastro-enteritis, 20 developed hypocalcaemia. All these newborns had severe diarrhoea. Seven infants were admitted because of convulsions, but EEG and ultrasonographic examination of the brain revealed no abnormalities. Once the infants' clinical condition and the consistency and frequency of the stool had improved, calcium concentrations increased and remained within the reference range without supplementation. CONCLUSION: Rotavirus gastro-enteritis seems to be a cause of neonatal hypocalcaemia.     

An ovarian leiomyoma: a case report

OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers. DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.     

The influence of hyperinsulinaemia on calcium-phosphate metabolism in renal failure

BACKGROUND: Patients with renal failure are characterized by impaired insulin-mediated glucose uptake. Insulin plays a major role in the maintenance of phosphate homeostasis but it remains to be determined whether in uraemia insulin-dependent renal and extrarenal phosphate disposal is also affected. METHODS: The effect of hyperinsulinaemia on serum concentrations of phosphate, ionized calcium and intact PTH as well as renal excretion of calcium and phosphate was studied under euglycaemic conditions (glucose clamp technique) in patients with advanced renal failure and in healthy subjects. Fifteen patients with renal failure (mean serum creatinine 917 micromol/l) and 12 control subjects were included. All subjects underwent a 3-h euglycaemic clamp with constant infusion of insulin (50 mU/m2/min) following a priming bolus. The urine was collected for 3 h before and throughout the clamp. RESULTS: The tissue insulin sensitivity (M/I) was lower in patients with renal failure than in control subjects (5.3+/-2.4 vs 6.7+/-1.8mg/kg/min per mU/ml, P= 0.001) but the phosphate lowering action of insulin was larger in patients with renal failure than in control subjects. Urinary calcium excretion increased (P < 0.05) and phosphate excretion did not change during the clamp in both groups. Despite a decrease of serum ionized calcium in the group of patients with renal failure and no change in the control group, plasma PTH fell significantly in both groups but this effect was still significant after 180 min only in the renal failure group. A significant correlation was observed between changes in serum phosphate and PTH induced by hyperinsulinaemia (r = 0.48, P < 0.01 ) CONCLUSIONS: Phosphate-lowering effect of insulin is well preserved in severe renal failure despite the resistance to insulin-stimulated glucose uptake. The decrease of serum PTH observed during hyperinsulinaemia appears to be independent of serum ionized calcium.     

Electrolyte quintet: Calcium

Abnormalities in serum calcium concentration may have profound effects on neurological, gastrointestinal, and renal function. Maintenance of the normal serum calcium is a result of tightly regulated ion transport by the kidney, intestinal tract, and bone, mediated by calcaemic hormones especially parathyroid hormone and 1,25-dihydroxyvitamin D3. Abnormalities in calcium transport that result in uncompensated influx into, or efflux from, the extracellular fluid, will result in hypercalcaemia or hypocalcaemia, respectively. When possible the biologically important ionised calcium concentration should be measured. A variety of common disorders are responsible for abnormalities in the serum calcium. Treatment of both hypercalcaemia and hypocalcaemia is dependent on the underlying disorder, the magnitude of the deviation of the serum calcium, and the severity of symptoms. Fortunately, in the case of hypercalcaemia, there is a broad selection of effective medications, especially the bisphosphonates. Treatment of hypocalcaemia relies on the provision of calcium and often vitamin D. In this article we review the mechanisms responsible for abnormalities in calcium homoeostasis, the differential diagnosis of hypercalcaemia and hypocalcaemia, and appropriate therapy.     

In vitro parathyroid hormone release in patients with secondary hyperparathyroidism

BACKGROUND: The purpose of this study was to determine the precise endocrine characteristics of parathyroid function in secondary hyperparathyroidism (sHPT). METHODS: We examined the effects of extracellular ionized calcium (Ca2+) varying from 0.5 to 2.0 mM on parathyroid hormone (PTH) release in parathyroid cell suspensions using a mid-regional PTH assay. Cells were obtained from 26 patients with sHPT who were divided into two groups according to the type of hyperplasia they exhibited, either nodular (n = 16) or diffuse (n = 10). For comparison, we also analyzed data from nine patients with primary hyperparathyroidism (pHPT; adenomas). RESULTS: Significant in vitro suppression of PTH release by Ca2+ was observed in the majority of subjects, regardless of the histologic abnormality. The pHPT group exhibited no significant relationship between clinical and in vitro data. In contrast, in the sHPT group (taken as a whole), suppression of PTH release by Ca2+ exhibited a plateau at a total serum calcium concentration of 2.5 mmol/L, and a parathyroid gland weight of 2 g. CONCLUSIONS: These findings suggest that there is a curvilinear relationship in sHPT, but not pHPT, between the in vitro calcium sensitivity of parathyroid cells and total serum calcium, as well as gland weight. The in vitro calcium sensitivity in sHPT remains constant when the total serum calcium concentration exceeds 2.5 mmol/L, or when the gland weight exceeds 2 g.     

The dependency of calcium set point on basal plasma calcium in dialysis patients: a better explanation for the discrepancies regarding its link with PTH secretion than methodological differences

BACKGROUND: The increase of calcium (Ca) set point in uremic hyperparathyroid patients and its decrease with calcitriol therapy are controversial. Besides methodological differences regarding the experimental protocol for obtaining the sigmoidal curve, mainly differences in definitions of maximal PTH (peak or steady value) and of calcium set point itself have been proposed for the discrepant conclusions. However, two other explanations are possible: the various aluminum load of the patients and the dependency of Ca set point upon the basal plasma ionized calcium (PCa). PATIENTS AND METHODS: Therefore the Ca set point was measured in 2 groups of patients on maintenance dialysis never exposed to aluminum, one of 7 patients with normosecretion of PTH (NPT) and the other of 8 patients with hyperparathyroidism (HPT) before and after 3 intravenous administration of 4 microg of alfacalcidol in a week. The sigmoidal curve was established during a zero Ca dialysis, without Ca replacement for the first 90 minutes and with intravenous infusion of 41 mmoles of Ca during the 150 last minutes. The curvilinear decrease of PCa induced a peak of PTH followed by a decrease while PCa was still decreasing up to the 90th minute. Therefore PTHmax was taken both at the peak and at its lower value observed at the 90th minute (steady PTHmax). Experimental determinations of the Ca set point were made using both definitions of Brown and Felsenfeld and both PTHmax values. In basal conditions, while using any of the values given by the same calculation methodology, Ca set point was not different in NPT and HPT patients. After alfacalcidol, no change in plasma PTH nor in Ca set point was observed in HPT patients. In contrast, in NPT patients alfacalcidol induced a significant decrease of plasma PTH concentrations in association with an increase in basal PCa and in Ca set point, whatever the definitions of the latter and of PTHmax. Calcitriol induced changes in Ca set point and basal PCa were correlated. CONCLUSIONS: 1) In normocalcemic dialysis patients never exposed to aluminium hyperparathyroidism is not explained by an increased Ca set point 2) Calcitriol suppressive effect on PTH secretion is neither explained by a decrease in Ca set point. 3) Ca set point as measured in vivo does not reflect an intrinsic characteristic of the parathyroid glands since it varies with basal PCa. Better than methodological differences, this dependency may explain the discrepant conclusions between the various clinical investigations.     

Calcium-regulated renal calcium handling in healthy men: relationship to sodium handling

Several studies have shown an increase in urinary calcium excretion in response to a calcium load. However, because of the inverse changes in PTH levels with a calcium load, the effect of changes in serum calcium per se on its own excretion is unclear in humans. In this study we used a PTH clamp protocol to further characterize calcium-regulated renal calcium and magnesium handling and the relationship of the former to sodium excretion. Eight normal male subjects were evaluated using a calcium clearance protocol with graded calcium infusions under a PTH clamp while in balance during a high and then during a low sodium diet. The curves describing calcium and magnesium excretion as a function of serum ionized calcium on the high sodium diet were best fitted by sigmoidal functions, with midpoints (the levels of calcium resulting in half-maximal increases in urinary cation excretion) of 1.51 and 1.49 mmol/L, respectively. The curve describing urinary sodium as a function of serum calcium was also sigmoidal on the high sodium diet, with a midpoint of 1.55 mmol/L. Our data taken in conjunction with those of previous studies evaluating sodium and calcium excretion in diseases characterized by inactivating or activating mutations in the calcium receptor, are consistent with the hypothesis that PTH-independent, calcium-dependent changes in renal calcium, magnesium, and sodium handling may be mediated at least in part by this receptor, which is known to be located in the loop of Henle.     

Tuberculosis among health care workers in British Columbia

BACKGROUND: The present study explores serum parathyroid hormone (PTH) and blood ionized calcium (Ca2+) levels in relation to the severity of disease and mortality in the intensive care unit (ICU). METHODS: In a pilot study, 37 consecutive critically ill patients admitted to the ICU were studied with determinations of serum PTH and total serum calcium within the first 24 h. In a following prospective study, patients suffering from sepsis (n = 13) or subjected to major surgery (n = 13) were investigated daily for 1 week with determinations of serum PTH and ionized calcium (Ca2+). Severity of disease was assessed by the APACHE II score and hospital mortality was recorded. RESULTS: In the pilot study, serum PTH levels were elevated (> 55 ng L-1) in 38% of the patients and were not related to serum calcium but showed a significant relationship to the APACHE II score (r = 0.39, P < 0.05). In the prospective study, serum PTH was elevated in 69% of the patients in both groups at inclusion, and 6 days later 87% of the septic and 37% of the surgery patients still showed elevated levels. Hypocalcaemia was more commonly seen in the septic patients [mean Ca2+ 1.03 +/- 0.08 (SD) mmol L-1] than in the surgical patients (1.14 +/- 0.06 mmol L-1) at inclusion. Both PTH and Ca2+ levels were significantly related to the APACHE II score (r = 0.46, P < 0.03, and r = -0.54, P < 0.009, respectively). Furthermore, PTH levels were significantly increased in non-survivors (n = 5) compared with survivors (mean 161 +/- 51 vs. 79 +/- 51 ng L-1, P < 0.005). CONCLUSION: Hypocalcaemia and increased levels of PTH were common findings in critically ill patients. These alterations in calcium homeostasis were related to the severity of disease and increased PTH levels were associated with a poor outcome.     

Serum levels of parathyroid hormone are related to the mortality and severity of illness in patients in the emergency department

Hypocalcaemia is a common finding in intensive care patients. In addition, raised levels of parathyroid hormone (PTH) have been described. The explanation and clinical importance of these findings are yet to be revealed. To investigate the occurrence of hypocalcaemia and elevated PTH levels and their relationship to morality and the severity of disease, serum levels of PTH, ionized calcium (Ca2+) and the cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured on arrival in the emergency department in a broad spectrum of 140 acutely ill patients patients suffering from common diseases such as stroke, acute abdominal disorders, obstructive lung diseases, heart failure, acute myocardial infarction, angina pectoris, trauma and infectious diseases. A score (APACHE II) was calculated to assess the severity of disease. Elevated PTH levels (> 55 pg ml-1) were seen in 16% of the patients, being most frequent in patients with myocardial infarction (28%) and congestive heart failure (42%). The levels were significantly correlated with the APACHE II score (r = 0.48, P < 0.0001) and with the length of stay in hospital (r = 0.26, P < 0.002). PTH was also significantly (P < 0.03) elevated in non-survivors compared with survivors and was found to be a stronger predictor of mortality (P < 0.01) than the APACHE II score (P < 0.02) in Cox's proportional hazard analysis. No close relationships were found between the cytokine levels and the indices of calcium metabolism. In conclusion, a rise in serum levels of PTH was common and related to the severity of disease and mortality in a mixed emergency department population.     

Secondary hyperparathyroidism is an expected consequence of parathyroidectomy for primary hyperparathyroidism: a prospective study

BACKGROUND: Parathyroidectomy for primary hyperparathyroidism (PHPT) can cause secondary hyperparathyroidism, with increased serum parathyroid hormone (PTH) and normal or low serum calcium concentrations. METHODS: A prospective study investigated 78 consecutive patients who underwent exploration for PHPT. Serum intact PTH and total calcium concentrations were measured the evening after operation and ionized Ca++ the following morning. These levels were reassayed 1 week later. RESULTS: Before operation, the mean PTH level was 138 +/- 15 pg/mL, total calcium concentration was 11.6 +/- 0.1 mg/dL, and ionized Ca++ concentration was 1.44 +/- 0.02 mmol/L. On the night of the operation, the PTH level was 11 +/- 2 pg/mL, and the total calcium concentration was 8.9 +/- 0.1 mg/dL. Fifty-five patients had hypoparathyroidism, with a PTH level less than 10 pg/mL. The day after the operation, the ionized Ca++ level was 1.14 +/- 0.01 mmol/L. One week later, PTH, ionized Ca++, and total serum calcium concentrations returned to normal levels. In 9 patients (12%), PTH levels were increased (98 +/- 16 pg/mL), although ionized Ca++ concentrations were normal (1.18 +/- 0.02 mmol/L), demonstrating secondary hyperparathyroidism. Risk factors for postoperative secondary hyperparathyroidism included older age, symptomatic hyperparathyroidism, higher preoperative PTH and alakaline phosphatase levels, and lower serum phosphorous levels. In 70% of these patients, PTH levels returned to normal in 3 to 12 months. CONCLUSIONS: Secondary hyperparathyroidism occurs in 12% of patients after surgical treatment of PHPT. It is transient, possibly compensating for relative hypocalcemia.     

A code of ethics for the medical dosimetrist--the American Association of Medical Dosimetrists experience

A previously well 70 year old woman was admitted to hospital following a three day history of vomiting and confusion. Her serum calcium was 6.58 mmol/l, phosphate 1.09 mmol/l, and alkaline phosphatase 91 iu/l. The mechanism of this hypercalcaemia was not obvious as there was no evidence of a primary malignancy, lymphadenopathy or hepatosplenomegaly. The calculation of indices of urinary excretion of calcium and phosphate suggested the presence of excessive parathyroid hormone (PTH) activity as the mechanism of hypercalcaemia. Plasma intact PTH, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol were not raised suggesting the presence of PTH related peptide (rP). This led to a systematic search for a malignancy, which revealed the presence of a high grade B cell non-Hodgkin's lymphoma confined to the bone marrow. Plasma PTH-rP was subsequently shown to be raised confirming the interpretation of the initial urinary and calcium excretion indices. This case highlights the value of standard laboratory measurements such as urinary calcium and phosphate excretion in cases of hypercalcaemia of obscure aetiology, which can complement measurements of PTH and other calcitropic hormones.     

Systemic and cellular calcium metabolism and hypertension

The calcium status of humans with essential hypertension and genetic animal models of hypertension is characterized by low serum ionized calcium concentration, increased urinary calcium excretion, and increased parathyroid hormone (PTH) concentration. Calcitriol metabolism and bone mineralization are also altered in hypertension. These alterations in systemic calcium metabolism may be linked to factors responsible for the elevated blood pressure. Cytosolic free calcium tends to be increased in most cells that have been studied from hypertensive humans and animals. Changes in cellular calcium metabolism may be partly mediated by calcium-regulating hormones that tend to be elevated in essential hypertension such as PTH and calcitriol. Administration of supplemental dietary calcium tends to suppress PTH, calcitriol, and intracellular free calcium. Further research is need concerning the observed association among systemic markers of calcium metabolism, cellular calcium metabolism, and arterial blood pressure regulation.     

Ionized hypocalcemia during out-of-hospital cardiac arrest and cardiopulmonary resuscitation is not due to binding by lactate

OBJECTIVE: To determine the relationship between ionized calcium concentrations and blood lactate levels during cardiac arrest and cardiopulmonary resuscitation (CPR). DESIGN: A prospective cohort study. SETTING: Emergency department (ED) and general intensive care unit in a city hospital (tertiary care center). PATIENTS AND PARTICIPANTS: 32 patients with out-of-hospital cardiac arrest; 14 of the patients had a return of spontaneous circulation (ROSC) and 18 of the patients died. INTERVENTIONS: Basic and advanced life support. MEASUREMENTS AND RESULTS: Concentrations of ionized and total calcium, bicarbonate, lactate, and pyruvate and pH were simultaneously determined immediately upon arrival at the ED, and at 30 and 60 min. Upon arrival at the ED, all patients had ionized hypocalcemia (1.09 +/- 0.02 mmol/l). Ionized and total calcium concentrations progressively decreased during and after CPR, but pH and bicarbonate concentrations did not show any significant changes. In patients who had ROSC, a significant, but perhaps not clinically relevant, relationship was observed between the ionized calcium concentrations and pH (r2 = 0.152, p = 0.0117). In the patients who died, there were significant correlations between ionized calcium and pH (r2 = 0.382, p = 0.0001) and bicarbonate concentrations (r2 = 0.298, p = 0.0006). No definite correlations were demonstrated when comparing ionized calcium concentrations with lactate and pyruvate concentrations. CONCLUSIONS: Ionized hypocalcemia during out-of-hospital cardiac arrest and CPR is not due to binding by both lactate and pyruvate, but may be partly due to complexing by bicarbonate, with some modifications due to variations in pH.     

Altered instantaneous and calcium-modulated oscillatory PTH secretion patterns in patients with secondary hyperparathyroidism

The relative contributions of increased parathyroid cell mass and altered control mechanisms of parathyroid hormone (PTH) secretion in secondary hyperparathyroidism are still controversial. In this study, endogenous pulsatile PTH secretion was analyzed by the multiparameter deconvolution technique to differentiate alterations in cell mass-dependent (PTH burst mass) and regulation-dependent (frequency, synchrony, calcium responsiveness) PTH release in uremic patients. PTH concentration versus time profiles were obtained in 13 uremic and 16 healthy adults under baseline conditions and during acute hypo- and hypercalcemia. Plasma PTH half-life was increased in patients compared with control subjects (4.7+/-1.9 versus 2.6+/-0.1 min, P < 0.005). The baseline PTH secretion rate was elevated eightfold in the patients as a result of an increased PTH mass secreted per burst (17.1+/-4.7 versus 2.0+/-0.4 pM, P = 0.0001), higher burst frequency (8.0+/-0.3 versus 6.8+/-0.3 h(-1), P < 0.01), and a higher tonic secretion rate (343+/-99 versus 30+/-4 pM/h, P = 0.0001). Acute hypocalcemia elicited an immediate, frequency- and amplitude-mediated selective increase in the pulsatile secretory component, which was fractionally weaker in patients (+595%) than control subjects (+1755%, P < 0.001). The acceleration and the amplification of PTH bursts were 35 and 60% lower in the patient group. Acute hypercalcemia suppressed total PTH secretion by 79% in control subjects but only by 63% in patients (P < 0.002). PTH burst frequency was reduced during hypercalcemia by 30% in control subjects, but remained unchanged in patients. In conclusion, uremic hyperparathyroidism is mediated by a marked increase in glandular secretion, but also by reduced PTH elimination. The increased spontaneous PTH burst frequency and the blunted responsiveness to changes in Ca2+ indicate partial uncoupling of hyperplastic parathyroid glands from the physiologic regulatory mechanisms that direct pulsatile PTH release.     

Assessment of parathyroid gland function: predictive value of a nomogram

Recent developments in measurement of intact parathormone (PTH) has enabled to generate a nomogram for parathyroid function. Blood levels of PTH can thus be interpreted in relation to calcemia. Intact PTH and calcium were assayed in blood from 99 healthy subjects studied under fasting conditions; 26 subjects were also studied during hyper- and hypocalcemia, induced by calcium and EDTA infusions, respectively. Serum levels of intact PTH which had been obtained in 99 patients were then analysed retrospectively by comparison with the nomogram. Patients whose intact PTH levels lie above the normal zone of the nomogram produce too much PTH relative to the blood calcium level (hyperparathyroidism); those falling under the normal zone produce too little (hypoparathyroidism).     

Hair casts in lichen ruber

To determine whether octreotide may acutely modify calcium homeostasis and/or inhibit the EGF production by the kidney, a subcutaneous injection of octreotide (100 micrograms) was administered to ten healthy volunteers. Blood and urine samples were collected at -30, 0, 60, 90, 120 and 180 minutes. Serum insulin, intact PTH, osteocalcin, total and ionized calcium and urinary EGF and creatinine were measured. There was no modification in serum PTH, osteocalcin and total or ionized calcium. There was no significant modification of urinary EGF, although a trend to decrease was evidenced.     

Control of hypercalcaemia of parathyroid carcinoma by immunisation

BACKGROUND: Patients with parathyroid tumours can develop extreme hypercalcaemia and osteitis fibrosa cystica. Clinical features result from the action of parathyroid hormone (PTH) on bone receptors. Because this hormone is produced in microgram quantities, inhibition of its metabolic effects with potent PTH antibodies should be possible. We tested whether an immunisation with synthetic human and bovine PTH peptides could stimulate autoantibodies against PTH. METHODS: A patient with metastatic parathyroid carcinoma in the lungs and pleura developed severe bone disease and extreme hypercalcaemia that proved resistant to conventional therapy. She was immunised with 200 microg human and bovine PTH peptides and 50 microg human PTH. Booster doses were also given at 4 weeks and 11 weeks. The patient was then seen every week. FINDINGS: Antibodies against PTH were produced within 4 weeks of initial immunisation and titres increased with repeated doses of immunogens. Total serum calcium concentrations, which had ranged from 3.5 mmol/L to 4.2 mmol/L over the previous 18 months, fell to between 2.5 mmol/L and 3.0 mmol/L over 6 months of therapy. This fall was accompanied by striking clinical improvement. INTERPRETATION: We believe this is the first use of immunotherapy to control remote, non-metastatic complications of malignant disease. B-cell tolerance to human PTH was broken by immunisation with PTH peptides in adjuvant. This therapeutic approach could be used to control excess hormone production in several types of endocrine tumour and may have applications in other diseases.     

Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol

Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism

Serum parathyroid hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional parathyroid gland mass rather than disturbances in calcium-sensing by the parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.     

Endocrinology 1995-1996

In a brief review of advances in endocrinology in the last two years the author discusses above all the vain expectations of a drug against obesity-the adipose tissue hormone leptin. Its elevated blood level in human obesity indicates that its secretion depends on the mass of adipose tissue and it is not certain whether leptin reduces the food intake in humans. Perhaps resistance to leptin is involved. New receptor diseases were revealed: mutation of LH receptors leads in both sexes to hypogonadism. Mutation of the calcium receptor in parathyroid cells leads to familial hypocalciuric hypercalcaemia or autosomal dominant hypocalcaemia. The complex regulation of the tonus of the vascular wall by endothelins is still the object of interest. Aquaporin is a renal protein which mediates the action of vasopressin. In the sphere of stress evidence is emerging on the participation of CRH in brain activity and the possibility to influence autoimmune inflammations and perhaps even AIDS by interference with the CRH-proopiomelanocortin-ACTH-cortisol system.