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Introduction: Vitamin D deficiency is common among hemodialysis (HD) patients and is an important component in the pathogenesis of secondary hyperparathyroidism (SHPT). We herein report our experience on the impact of cholecalciferol supplementation on PTH levels in a group of HD patients. Patients and methods: We selected 122 HD patients. The main selection criteria were 25- hydroxyvitamin D (25(OH)D) levels ≤30 ng/mL and SHPT defined as PTH levels >300 pg/mL or PTH levels between 150-300 pg/mL during therapy with cinacalcet or paricalcitol. 82 patients agreed to receive cholecalciferol at the fixed dose of 25,000 IU per week orally for 12 months, while the remaining 40 represented the control group. The main endopoints of the study were the reduction in PTH levels ≥30% compared to baseline values and the increase of 25(OH)D levels to values >30 ng/mL. Results: At follow-up PTH levels decreased in the supplemented group from 476 ±293 to 296 ± 207 pg/mL (p<0.001), 25(OH)D levels increased from 10.3 ± 5.7 to 33.5 ± 11.2 ng/mL (p<0.001), serum calcium increased from 8.6 ± 0.5 to 8.8 ± 0.6 mg/dL (p<0.05) while serum phosphorus did not change. In this group the mean doses of paricalcitol were significantly reduced, from 8.7 ± 4.0 to 6.1 ± 3.9 µg/week (p<0.001). Moreover, in this group there were a significant increase of hemoglobin levels, from 11.6 ± 1.3 to 12.2 ± 1.1 g/dL (p <0.01) and a significant reduction of erythropoietin doses (p<0.05). In the control group the 25(OH)D and PTH levels did not change, while cinacalcet doses increased from 21 ±14 to 43 ± 17 mg/d (p<0.01). Conclusions: Vitamin deficiency is very common in HD patients. Cholecalciferol treatment significantly increased serum 25(OH)D levels, significantly decreased PTH levels and paricalcitol doses, concurrently entailing a better control of anemia., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Chronic kidney disease (CKD) is a relevant health problem due to its worldwide increasing prevalence and the morbidity and mortality linked to its complications. Since the early stages of CKD, although patients are completely asymptomatic, important mineral homeostasis disorders occur. These disorders, involving serum levels of calcium, phosphorus, parathyroid hormone, and vitamin D, have a striking impact on patient prognosis as they affect the cardiovascular system. The new term of Chronic Kidney Disease-Mineral Bone Disease (CKD-MBD) was introduced to label bone disease during CKD as a systemic disorder tightly linked to cardiovascular calcifications and disabilities. Vitamin D deficiency has a main role in the pathogenesis of CKD-MBD, throughout the pleiotropic actions of this hormone. Vitamin D receptors (VDRs) are ubiquitous and their activation has shown protective effects against secondary hyperparathyroidism development and anti-hypertensive, anti-inflammatory, anti-fibrotic, immunomodulating, anti-proliferative, anti-diabetic and anti-proteinuric properties. These mechanisms explain, at least in part, vitamin D status influence in avoiding and delaying cardiovascular disease and CKD progression. These findings strongly support the importance of an early diagnosis of mineral homeostasis disorders in CKD and the need for correction of vitamin D deficiency to prevent related disabilities and major events.

Hyperphosphatemia is pivotal in some complications secondary to kidney dysfunction. Current guidelines suggest that hyperphosphatemia due to kidney dysfunction develops only when kidney function is reduced to <50%. This paper deals with the relationship of age to phosphatemia and with the possible influences of this relationship on hyperphosphatemia due to kidney dysfunction. In pediatric age phosphatemia decreases during growth. A recent epidemiological study showed a decrease in phosphatemia with age among adults also. This decrease differs between men and women, being continuous in men but not women because of a transitory increase in phosphatemia during menopause. Data also show that age-associated differences in phosphatemia among adults are explained by differences in the maximum reabsorption of phosphate in the renal proximal tubule (TmP/GFR). Other studies suggest that the opposite influences on TmP/GFR of growth hormone (stimulation) and estrogens (inhibition) are the determinants of the changes in TmP/GFR and phosphatemia associated with age. The inverse relationship of age with phosphatemia leads to the hypothesis that, in the presence of a disorder increasing phosphatemia, the prevalence of hyperphosphatemia would be higher in young adults than in elderly people, who have lower phosphatemia in health. A large clinical study supports this hypothesis, showing that hyperphosphatemia secondary to kidney dysfunction is approximately four times higher at age <65 than at age >65 years. Data suggest that the relation between kidney function and phosphatemia should be re-evaluated considering possible confounding due to age.

Length of hospital stays for thyroid surgery has decreased significantly over the last years. Hypoparathyroidism is one of the main obstacles to short-stay hospitalization. The aim of this study was to evaluate length of hospital stay in our experience, its relationship with complications observed and feasibility of short-stay hospitalization regimen. Between September 2002 and December 2005, 932 patients underwent total thyroidectomy in our institution. Serum calcium and phosphorus values were obtained at 6 hours after operation and on postoperative day 1 and 2. Discharge was possible on the morning of the first postoperative day in 2 patients (0.2%), the second day in 687 (73.7%), third day in 167 (17.9%), fourth in 44 (4.7%), fifth in 22 (2.4%), after the fifth in 10 (1.1%). Complications observed were hypoparathyroidism in 393 patients (42.1%), neck hematoma in 12 (1.3%), bilateral recurrent nerve palsy in 5 (0.5%), unilateral recurrent nerve palsy in 4 (0.4%), glottic hemorrhagic edema in 1 (0.1%) and foreign body granuloma and/or fistula in 5 (0.5%). Hypocalcemia was observed on post-operative day 1 in 338 patients (86%), on day 2 in 50 (12.72%) and on day 3 in 5 (1.27%). Serum calcium and phosphorus determination 6 hours after operation and on postoperative day 1 permits an early treatment of hypocalcemia and to shorten length of hospital stay. A normal serum calcium level on postoperative day 1 lets suppose an easy discharge on the second. Earlier discharge is to be reserved to selected patients and not always meets their favour.

Aim: It is well-know that hyperthyroidism is one of the key causes of secondary osteoporosis. High values of thyroid hormones increase the bone mineral turnover speed by promoting osteoclastic and osteoblastic activities. The aim of our study is to evaluate the increase of bone mineral density (BMD) in osteoporotic and hyperthyroid patients treated with only antithyroid drugs versus patients treated with antithyroid drugs and diphosphonates., Methods: Twenty-six elderly male patients, 65-75 years, were selected. In all these patients, thyroid function (FT3, FT4, TSH, Tg, AbTg, AbTPO) was evaluated at baseline and after 6 and 12 months from the start of medical treatment; the following were evaluated: BMD, calcium serum, phosphorus serum, alkaline phosphatase, PTH and 24 hours urinary calcium, phosphorus and hydroxyprolin. Thirteen patients (group 1) were treated with antithyroid drugs (methimazole 5-20 mg/die/os) and diphosphonates (alendronate 10 mg/die/os). The control group of 13 patients (group 2) was treated with antithyroid drugs only., Results: After 6 months of treatment, the patients of group 1 showed a mean increase of 2.5% in lumbar spine BMD compared with a mean increase of 0.3% in group 2 (p<0.01). After 12 months, group 1 showed a mean increase of 6.2% in lumbar spine BMD, compared with a mean increase of 2% in group (p<0.001)., Conclusions: The combination of antithyroid and diphosphonates drugs appears to be more efficacious than antithyroid therapy alone for the treatment of osteoporosis in male hyperthyroid patients.

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.

The management of secondary hyperparathyroidism is of crucial importance in the treatment of end stage renal disease (ESRD) patients. In particular, hypercalcemia, hyperphosphatemia, and elevated calcium x phosphate (Ca x P) product should be taken into consideration during administration of vitamin D metabolites for the control of PTH secretion. During the last 10 years, many authors have been studying the efficacy of new non-calcemic vitamin D analogs on suppressing secondary hyperparathyroidism in ESRD patients. In this brief review, we analyzed three new vitamin D analogs: 22-oxacalcitriol (Maxacalcitriol), 19-nor-1a, 25(OH)2D2 (Paracalcitriol), and 1a (OH)2D2 (Doxacalciferol). In addition, calcimimetic agents may represent a new pharmacologic choice to the treatment of secondary hyperparathyroidism, binding parathyroid calcium sensing receptors (CaSR) and reducing PTH secretion. These compounds may represent an important tool for the treatment of both secondary hyperparathyroidism and soft tissue calcifications in ESRD patients. In conclusion, a combined use of non calcemic phosphate binders, new vitamin D analogs and calcimimetics should be seriously considered to further improve the already known therapy of secondary hyperparathyroidism in ESRD patients.

Introduction: The dialytic management of hyper-phosphoremia, which is inadequate because of insufficient intra-dialytic removal of phosphate (P), is further limited by PDR-P, i.e. the significant increase in serum P levels during the early postdialytic period. Patients and methods. To investigate the effects of enhanced P removal by haemodiafiltration on the inter-dialytic phosphoremia, we studied 12 uremic patients that were switched, with cross-over randomised modality, to a single session of standard hemodialysis (HD) and hemodiafiltration (HDF) (Acute Study). Blood samples were obtained before the treatment, at the end (T0), after 30, 60, 90 and 120 minutes, and at 24, 48 and 68 hours. During both dialytic treatments the whole effluent dialysate was collected to evaluate the intradialytic removal of P. Thereafter, patients were randomised to receive either HD or HDF for three months, in the presence of constantly similar Kt/V, food intake and dose of phosphate binder (Chronic Study)., Results: Acute Study. Compared to HD, P removal in HDF was about 44% greater in the presence of identical predialytic P levels (6.0+/-0.2 and 5.9+/-0.4 mg/dl) and Kt/V (1.35+/-0.06 and 1.34+/-0.05); however, the inter-dialytic decline of serum P levels did not differ (-50+/-3% versus -42+/-3%, p=0.098). In HDF, PDR-P was faster (30 min versus 90 min) and better (at T120: +69+/-6% versus +31+/-4%, p<0.001). The higher P levels were maintained throughout the inter-dialytic period whereas Ca x P changed in parallel. Chronic Study. During the three months, pre-dialytic serum P diminished in HDF (from 5.8+/-0.2 to 4.4+/-0.3 mg/dl, p<0.05), while it remained unchanged in HD. A similar pattern of changes was detected in Ca x P., Conclusions: Enhancement of P removal, acutely amplifies the extent of PDR-P, but allows better control of Ca-P homeostasis in the medium term. This effect is likely to be dependent on the enhanced mobilisation of phosphate from a deep compartment.

The authors report three cases of primary hyperparathyroidism (HPT) in patients with differentiated thyroid carcinoma (DTC) developed a few years after initial surgical and radiometabolic treatment of DTC. The early diagnosis of HPT in these patients was made possible because of laboratory tests performed during follow-up, including the assay of serum calcium and serum phosphorus levels. Scinti-graphy using 99mTc-MIBI enabled the correct preoperative localisation of a single parathyroid adenoma in two of these patients and multiglandular pathology in the third.

The authors report the results of US-guided percutaneous ethanol injection into parathyroid glands of 11 patients with primary (2) and secondary (9) hyperparathyroidism. Selection criteria for choosing ethanol treatment were the patient's refuse of surgery and high surgical risks for age or severe chronic intercurrent conditions. At 18 months' follow-up, PTH serum levels had normalized in 2 primary and 2 secondary hyperparathyroidism patients; in all the others but one, PTH levels markedly decreased--always > 50% relative to pretreatment values. Serum calcium and phosphorus levels also decreased, which was not always the case with alkaline phosphatase. After injection, the glands became progressively hyperechoic, gland volume decreased and calcifications appeared. Parenchymal flow disappeared on color-Doppler US images. This study confirms the capabilities of US-guided ethanol injection in hyperfunctioning parathyroids, even though complications may occur and the condition recur. This method is thus suggested as an effective alternative to surgery.

The authors evaluate the efficacy of salmon calcitonin and aminosuberic analogue of eel calcitonin in the prevention of post-oophorectomy osteoporosis in rats. Both drugs, administered at the same dosage, are equally effective in preventing oophorectomy bone loss in rats. Besides, plasma biochemical evaluations demonstrate that calcitonins reduce bone turnover in treated rats, compared with control oophorectomized ones.

The investigation on several forms of uremic osteodystrophy by means of bone mineral content (BMC) measurement led to contradictory conclusions. BMC in 27 patients on periodical hemodialysis treatment was measured correlating it to the seric levels of Ca, P, Mg, alkaline phosphatase (AP), calcitonin (Ct), osteocalcin (BGP), intact parathormone (PTHi), c-terminal and mean molecule PTH. Patients on dialysis treatment from a long period of time showed high AP and low BMC levels. This correlation proved significant just for the values recorded at a third distal site of radius. Patients with BMC under the normal range showed higher BGP levels and a longer period of dialytic treatment than those presenting normal BMC. The former showed a Ct inverse correlation as to age and mineralization indexes. Higher values of Ct and BMC have been reported in males rather than in females. Hence BMC is not suited to investigate different kinds of uremic osteodystrophy. Seric PTH dosage is certainly best fitted to discriminate patients affected with hyperparathyroidism from those with low turnover osteodystrophy. BMC determination is a valid support to evaluate the bone mineral loss in patients on haemodialysis treatment. It significatively correlates to the duration of the dialytic treatment; it is higher in female than in male population; it mainly affects cortical components rather than trabecular ones and is related to a seric Ct decrease.

Fourteen patients undergoing periodic dialysis who had been taking AL(OH)3 as an intestinal chelant of phosphorus have been examined. AL(OH)3 was replaced by CaCO3 for a period of 6 months. At the end of the study, statistically significant reductions were evidenced in alkaline phosphatase, basal serum aluminiaemia and its increase after Desferal test, while the bicarbonates (HCO3) were found to be increased. Statistically non-significant increases were observed in calcaemia, PTH, and pH. It is concluded that the replacement of AL(OH)3 with CaCO3 is effective in controlling phosphoraemia, in diminishing serum concentrations and tissue deposits of Al and in improving uraemic acidosis.

Within the limits of a program of preventive medicine for the people in working age we have gived started to a proceeding of methods' standardization and definition of the limits of the "normal" variability of any biochemicals parameters. The research, beginned how quality control (day to day control, between batch control, inter-laboratory control) for the instrumentation in use (Autoanalyzer SMA 12/60) is continued defining for 12 bio-chemical constants the normal bounds of the variability in relation with sex and age of the individual subjects and this in prevision of an enlargement of those bounds with the view of the preventing in the local people.

Thirty-seven osteodystrophic and chronically haemodialyzed patients have been treated for 1-22 months by means of 1,25(OH)2D3. Under treatment a marked improvement of symptomatology and radiographic findings has been observed in the majority of cases; from the haematochemical viewpoint a rise of calcemia and phosphoremia, a fall in alkaline phosphatase and a variable course of PTH have been observed. Several episodes of asymptomatic hypercalcemia ceased with posology reduction; only 3 cases needed stopping the treatment for this reason, one of them definitively; 12/37 cases needed hypophosphoric diets and increase in oral aluminium hydroxide doses to control hyperphosphoremia. The Authors conclude that, to achieve a correct management of a 1,25(OH)2D3 therapy for renal osteodystrophy, is mandatory a strict and accurate biochemical control: in this way is possible to obtain an effective modulation of the posology avoiding the appearance of side-effects as hypercalcemia and ectopic calcifications.

The effect of propranolol on certain insulin-induced metabolic changes in man. The effects of 0.2 mg/kg/body weight propranolol perfused in 10' on insulin-induced (0.15 I.U./Kg i.v.)changes in blood glucose, pyruvate, lactic acid, phosphorus, and potassium levels were examined in 12 normal volunteers. The blood glucose curve was substantially unaffected. Insulin-induced increases in lactate and pyruvate were inhibited to a varying degree, namely 78% (61-93%) and 44% (0.94%) respectively. The fall in phosphorus was reduced in a more constant manner (mean 48; range 37-57%) in all subjects, while that of potassium was not altered. The data indicate that these insulin-induced changes are significantly, though variably, attributable to beta-adrenergic activity on the part of endogenous catecholamines released during insulin-induced hypoglycaemia.

The behaviour of glycaemia, insulinaemia, phosphoraemia, somatotropinaemia,free glycerol and triglyceridaemia was studied in six patients with A.L.S. following sugar load (1 g/Kg) in fasting. The results of glycaemia and insulinaemia were in tune with published data which have pointed to reduced sugar tolerance and reduced insulin secretion in patients with A.L.S. In the present experiments, particularly significant were the phosphoraemia responses. The failure of inorganic phosphorus values to fall after glucose loading suggests that the glycidic intolerance of these patients is related above all to a reduction in functioning muscular mass rather than to insufficient insulin secretion. The reduction in nervous tissue may also be of importance in this sense. In fact, not all biohumoral parameters investigated were similar to those of diabetes because the behaviour of somatotropinaemia, free glycerol and plasma triglycerides was normal. The changed behaviour of phosphorus would thus indicate altered glucose uptake at peripheral tissue level.

One of the most important complication of patients with chronic renal failure is osteodystrophy. This causes skeletal deformities, growth failure, bone pain and decreased physical activity. Osteodystrophy is more frequent among children than uraemic adults. In fact, 50-80% of children with chronic renal failure may occur in metabolic bone disease and the incidence tends to be higher in those children who have been in uraemic state for a long time before starting chronic haemodialysis. Osteodystrophy is a result of: 1) lesions of rickets; 2) lesions of osteitis fibrosa: 3) osteosclerosis. In contrast to adult, metastatic calcifications are virtually never observed in uraemic children. Hyperphosphoraemia, that is secondary to the reduction of G.F.R., may be the principal responsible of hyperparathyroidism that is the main cause of osteodystrophy. Hyperparathyroidism is also maintained and increased by deficit of 1,25(OH)2D3 which is responsible for lesions of rickets. Haemodialysis may markedly improve osteitis fibrosa and it is efficacious in reversing the mineral defect. Dialysate calcium concentration should be maintained at approximately 3,5 mEq/l. In this case we can raise serum calcium. On the contrary dialysate has to be lacking in phosphorus to correct hyperphosphoraemia. It must be noted that we have to prepare a dialysate with deionized water lacking in aluminum to avoid encephalopathy compliance.

The AA., on the basis of their recent studies, offer a new hypothesis on the role of calcitonin, as a regulator of phosphorus metabolism. In addition the AA. confirm the clear interrelationship between calcitonin and other hormones as gastrin and autonomous nervous system.

The Authors studied the possible pathogenetic factors in hypocalcemia of 66 low birth weight healthy newborn infants, 28 preterm and 38 small for gestational age babies. To clarify the pathogenesis of neonatal hypocalcemia, the Authors determined daily in the first week of life serum calcium, phosphorus and magnesium concentrations, the serum natrium and kalium level and E.A.B. on capillary blood. Total serum proteins was determined on the 2nd and on the 7th day of age. The incidence of hypocalcemia was 25.7% for all considered babies: 32.1% for preterm infants and 21% for small for gestational age babies. The hypocalcemia of preterm babies appears early during the first three days of life and it results not correlated with the serum phosphorus and the serum magnesium concentrations. On the contrary the small for gestational age babies show a "late" hypocalcemia directly related with an elevated serum concentration of phosphorus and with a reduced serum magnesium level. Both the preterm and the small for gestational age newborn infants had asymptomatic hypocalcemia and the orally administration of high doses of calcium gluconate 10% was able to normalize rapidly the serum calcium level.

It is known that, particularly in Nordic States, many patients undergoing antiepileptic therapy with Phenobarbital and Phentoin present disorders of the phospho-calcium metabolism, both clinical and biochemical. For what concerns the mediterranean area, few are the papers written concerning this subject in these last years. In this paper we attempt to provide a "case study" contribution (100 cases) to enable us to study the above-mentioned alteration focusing on an area half way between Central and Southern Europe. The Authors discuss the possible mechanism implicated in this affection.

An unusual case of eosinophilic gastroenteritis is described, together with its differential diagnosis from allergic enteropathy. Numerous biopsies and other instrumental examinations pointed to small intestine as the only site and eosinophilic enteritis as a suitable classification. Disappearance of the clinical symptoms was obtained with corticosteroid management in the space of 6 months.

This paper deals with the determination of red blood cell phosphorilated compounds, by automated ion exchange chromatography, in clinically healthy subjects, in two patients with hypochomic iron deficiency anemia and in four patients with macrocytic folic acid deficiency anemia. In the cases of nutritional anemia examined significant variations in the level of glycolitic phosphorilated compounds have been observed. The total acid-soluble phosphate content presents a marked increase in patients with anemia, compared with clinically healthy subjects. Very high increase in the 2,3 DPG, F1, 6DP, R5P, G1, 6DP and IMP red blood cell content is observed. On the contrary, ATP red blood cell concentration presents a marked decrease in all the patients.

A case is told with osseous fractures occurred during uremia in a periodically dialyzed man treated with phosphate-binding substances in excessive doses. The healing time is studied to value the effectiveness of normalized phosphatemia and the vitamin D treatment necessity.

Calcaemia and phosphoraemia have been evaluated in a group of patients suffering from gastroduodenal ulcer and in a control group suffering from various pathologies of surgical interest. A significant correlation was found to exist between these values and the presence of gastroduodenal ulcer and this is considered worthy of further clinical and experimental study.

Five untreated patients with Paget's disease and one who had been unsuccessfully treated with porcine calcitonin for 2 years were given 20 mg/kg/day disodic ethydronate. Alkaline phosphatase and urinary hydroxyproline values were examined and the progress of the calcitonin test was followed. In addition to being of great importance and in line with the other two parameters in following the course of the disease, this test was found to be an excellent pointer to the moment when no further response is being obtained from treatment with calcitonin.

Determinations of serum calcium (Ca), phosphorus (P) and calcitonin (CT) were carried out in two groups of full term newborn infants: 80 on bottle feeding (group A) and 80 breast feeding (group B). Samples of blood were drawn at 1, 6, 12, 24, 48, 72, 96 and 168 hours of life. Each newborn was tested no more than twice. No differences between the two groups could be detected before the 72th hour. At that time, the Ca of group A was significantly lower than Ca of group B while the CT and P were significantly higher in the same group A. So that, the P serum level appears to be one of the most important factor regulating the homeostasis of Ca after the first 72 hours of life.