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Biomedical subjects

P Legovini

Publications and source records attributed to P Legovini.

18 recordsLinked to original sources

Long-term effects of octreotide on markers of bone metabolism in acromegaly: evidence of increased serum parathormone concentrations.

The effects of octreotide on biochemical markers of bone turnover were evaluated in patients with active acromegaly. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before and after 4 months of treatment in 27 patients (short-term treatment) and after 12 and 24 months of treatment in 15 patients (long-term treatment). In the short-term, octreotide significantly decreased the levels of serum GH, IGF-I, calcium, osteocalcin, carboxyterminal propeptide of type I collagen and alkaline phosphatase plus urinary excretion of calcium. Short-term treatment significantly increased serum parathormone levels (before treatment 30.1 +/- 9.57 and at 4 months 46.1 +/- 24.98 ng/L, p < 0.001) and urinary excretion of phosphate; urinary excretion of hydroxyproline was unchanged. The same results were observed during long-term treatment, except that there was no significant difference of serum calcium and alkaline phosphatase levels before and after treatment. Parathormone concentrations were still higher at 24 months compared with those prior to treatment (before treatment 31.9 +/- 9.74 and at 24 months 44.9 +/- 21.18 ng/L, p < 0.05). The changes of most bone markers during octreotide therapy can be explained by the decrease of serum GH and IGF-I concentrations. On the other hand, the rise of parathormone concentrations suggests that octreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the octreotide could contribute to this secondary hyperparathyroidism. The clinical consequences of these alterations of bone metabolism need to be further clarified.

Acromegaly

[Acute hyperparathyroidism associated with follicular carcinoma in the thyroid: possible role of juvenile cervical irradiation. Description of a case].

Acute onset of primary hyperparathyroidism is uncommon; neuropsychiatric signs are prominent clinical features in acute hypercalcemia and they can subside after normalization of serum calcium. Radiation therapy is a well-known risk factor for non medullary thyroid cancer, but it induces also parathyroid tumors. Data from the literature show that patients previously treated with neck radiation have an increased risk of primary hyperparathyroidism. Furthermore concomitant thyroid cancer is more frequent in radiation-induced hyperparathyroidism than in sporadic primary hyperparathyroidism. The case of a 63-year-old female patient who at the age of 14 had been irradiated to the neck for goiter and at the age of 50 had been repeatedly hospitalized for psychosis is presented. She was admitted to the hospital for suspected recurrence of psychosis, but clinical findings and urgent biochemical data showed on the contrary that she had a severe hypercalcemic crisis. Serum parathormone concentrations, neck echography and 99mTc-Sestamibi scintigraphy suggested hyperfunction of the right lower parathyroid gland; therefore the patient was operated on. Pathological examination disclosed a parathyroid adenoma but also two foci of follicular cancer in the right thyroid lobe with a metastasis to a lymph node were observed. Neuropsychiatric signs disappeared after normalization of calcemia and 6 months after operation the patient is free from psychiatric symptoms, despite she had stopped neurolectic drugs. It is underlined that patients who had received neck irradiation must be carefully observed because they are at increased risk of primary hyperparathyroidism and concurrent thyroid cancer.

Acute Disease

Increased serum levels of carboxyterminal propeptide of type 1 collagen (PICP) in hyperthyroidism.

Type 1 collagen is the major organic constituent of the bone: its synthesis is reflected by the serum levels of type 1 procollagen C-terminal propeptide (PICP), which is therefore considered an index of osteoblastic activity. Serum PICP along with other serum and urinary markers of bone metabolism were measured in 16 untreated premenopausal females affected by Graves' disease and also in 7 of them after attainment of euthyroidism by methimazole treatment. Before treatment PICP was higher than sex and age-matched controls (324.19 +/- 101.74 vs. 131.44 +/- 26.25 micrograms/l, p < 0.001). Osteocalcin, alkaline phosphatase, serum calcium and urinary excretions of calcium and hydroxyproline were significantly increased with respect to controls, whereas parathormone was lower. Treatment induced a significant decrease of PICP, as well as calcemia, calciuria and hydroxyprolinuria compared to pretreatment values, while osteocalcin and alkaline phosphatase did not significantly differ. Non parametric correlation analysis showed positive correlation of free T3 and PICP (rs = 0.73, p < 0.005), osteocalcin and alkaline phosphatase; PICP was also significantly correlated with osteocalcin and alkaline phosphatase. Our data suggest that hyperthyroidism due to Graves' disease causes an increase of serum concentrations of PICP, which decrease after attainment of euthyroidism. The differences between PICP and BGP as markers of bone synthesis need to be further clarified.

Alkaline Phosphatase

[Serum levels of the tartrate-resistant isoenzyme, acid phosphatase, for the evaluation of bone remodeling in hyperthyroidism].

Tartrate-resistant acid phosphatase (TRAP) is one of the acid phosphatase isoenzymes. It is secreted by osteoclasts so it has been proposed as a marker of bone resorption. Bone turnover is high in hyperthyroidism due to an increase in both bone resorption and formation. The aim of the study was to measure serum TRAP as well as other markers of bone metabolism in 20 fertile age females affected by Graves-disease; 11 patients were also studied after euthyroid state was attained by means of a 6 month course of methimazole treatment. TRAP was measured with the colorimetric method using p-nitrophenylphosphate as substrate. Free thyroid hormones, TSH, serum calcium (corrected for albumin concentration), phosphate, osteocalcin, alkaline phosphatase, parathormone intact molecule, and urinary excretions of calcium, phosphate and hydroxyproline were measured, too. Twenty-eight healthy fertile women made up the control group. Untreated patients had a significant increase of TRAP, osteocalcin, serum calcium, alkaline phosphatase and urinary excretion of calcium and hydroxyproline. A significant fall in all these parameters but alkaline phosphatase was disclosed comparing patients before and after treatment, nevertheless only urinary calcium became not significantly different from the controls. TRAP showed a significant correlation with free T3 levels but not with hydroxyproline excretions. This survey on fertile age women with Graves' disease shows a significant increase in serum concentration of TRAP, which decreases, but doesn't get normalization, when euthyroidism is attained by a six month course of methimazole therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase

Bone turnover in overt and subclinical hyperthyroidism due to autonomous thyroid adenoma.

Parameters of bone turnover were measured in 20 premenopausal women affected by autonomous thyroid adenoma: 7 patients were suffering from overt hyperthyroidism with raised values of free thyroid hormones; 13 were clinically euthyroid and had normal values of free thyroid hormones. In all cases serum TSH concentrations were below the lower normal limit of our laboratory (< 0.4 mU/l). Eleven healthy premenopausal women were studied as a control group. Patients with overt hyperthyroidism disclosed a significant enhancement of both bone resorption (increased serum calcium and urinary excretion of hydroxyproline) and bone formation (increased serum levels of osteocalcin and alkaline phosphatase) when compared both to controls and to patients with subclinical hyperthyroidism. No significant alterations of bone metabolism parameters were found in patients with subclinical hyperthyroidism in comparison with controls. Therefore, in premenopausal women affected by autonomous thyroid adenoma the bone turnover appeared to be significantly increased when the serum values of free thyroid hormones were raised in the group of patients with overt hyperthyroidism.

Adenoma

Increased serum beta 2-microglobulin concentrations in hyperthyroid states.

Serum beta 2-microglobulin concentrations were determined in 21 untreated hyperthyroid patients (12 with Graves' disease, and nine with toxic nodular adenoma) and in 20 healthy controls. All subjects had normal serum creatinine concentrations and urine analysis. Both total and free thyroid hormones were significantly higher in the hyperthyroid groups than in controls. Beta 2-microglobulin concentrations were significantly increased in both groups of hyperthyroid patients compared with controls. No difference was found in the thyroid hormone and beta 2-microglobulin concentrations between both sets of patients. The beta 2-microglobulin and thyroid hormone concentrations were not correlated. These data show that hyperthyroidism is another cause of increased beta 2-microglobulin production along with viral infections, immunologically mediated diseases, and malignant neoplasms. The increased serum beta 2-microglobulin concentration in thyroid hyperfunction is probably related to metabolic rate, even if autoimmunity might contribute to its overproduction.

Adenoma

Clodronate treatment increases serum osteocalcin in normocalcemic osteolytic bone metastases.

28 consecutive patients with multiple osteolytic bone metastases due to various types of cancer were treated with 300 mg/day of sodium clodronate given intravenously as a 3-hour infusion, 16 patients were treated for 10 days and 12 for 20 days. Our findings showed that clodronate administration causes an increase in serum osteocalcin (sBGP) in the group of patients treated for 20 days (p less than 0.05), a reduction in serum Ca in both groups of patients (p less than 0.01), an increase in serum alkaline phosphatase (p less than 0.05 and p less than 0.01), a reduction in urinary Ca (p less than 0.01) and a reduction in uOHP (p less than 0.05). The raise in sBGP may be attributed to the reduction of sCa and to the consequent secondary hyperparathyroidism. The increase in sBGP can be considered as the expression of osteoblasts stimulation following an adequate period of therapy with sodium clodronate.

Adult

Serum bone GLA-protein in hypercalcemia of primary hyperparathyroidism and malignancy.

Serum bone GLA-protein, a modern and sensitive marker of bone turnover, was measured in 15 patients with primary hyperparathyroidism, 18 patients with hypercalcemia of malignancy, 41 patients with bone metastasis without hypercalcemia, and 29 healthy subjects. Serum bone GLA-protein was increased in primary hyperparathyroidism (17.6 +/- 3.9 ng/ml) and normal in hypercalcemia of malignancy (5.2 +/- 2.8 ng/ml; p less than 0.001 vs hyperparathyroidism) and in normocalcemic patients with bone metastases. In primary hyperparathyroidism parathyroid hormone correlated positively with urinary calcium excretion (p less than 0.05) and with urinary hydroxyproline excretion (p less than 0.001). The sensitivity of serum bone GLA-protein measurements in differentiating between primary hyperparathyroidism and hypercalcemia of malignancy was 91% and the specificity 84%. Thus this marker appears to be a useful tool for the differential diagnosis of hypercalcemias.

Adult

HLA antigens and haplotypes associated with idiopathic haemochromatosis in Veneto: peculiar association with HLA-A3,B35.

HLA-A and HLA-B antigens were determined in 16 unrelated subjects orginating from Veneto affected by idiopathic haemochromatosis (IH). HLA-A3 was found in 13/16 patients vs. 300/1,348 controls (p less than 0.00005). Prevalences of A3,B35 haplotype were 0.4375 in patients vs. 0.0816 in controls (p less than 0.0005). Linkage disequilibrium analysis proved the existence of a positive third-order linkage disequilibrium among IH, HLA-A3 and HLA-B35 alleles. Our data confirm the close association of IH and HLA-A3 and prove the peculiar association of the disease with A3,B35 haplotype in north-eastern regions of Italy. The positive third-order linkage disequilibrium suggests a remote event (mutation, recombination or immigration) as origin for IH and A3,B35 association.

Alleles

111Indium-pentetreotide pituitary scintigraphy and hormonal responses to octreotide in acromegalic patients.

GH secreting pituitary adenomas are frequently visualized by scintigraphy with the somatostatin analogue 111Indium-pentetreotide. We studied 111Indium-pentetreotide scintigraphy and hormonal responses to octreotide in 12 acromegalic patients. Nine patients with active acromegaly were studied before pituitary adenomectomy; 6 of these and 3 other patients were studied after operation. GH was measured after a single s.c. dose of 100 micrograms of octreotide (acute test). The patients were preoperatively treated with 100 micrograms s.c. tid octreotide for 3 months as were patients who had been unsuccessfully operated; GH and IGF-I were measured at the end of this period (chronic treatment). A decrease of the hormones higher than 50% of basal values was considered a positive response in both acute test and chronic treatment. Eight/nine unoperated patients had a pituitary adenoma visualized by scintigraphy and a positive response to both the acute test and chronic treatment; one patient had no evidence of tumor at scintigraphy and he did not respond to octreotide. Scintigraphy was negative in all of the three patients cured by surgery. Six patients still had active disease after adenomectomy: scintigraphy was positive only in one case, although GH responded to octreotide treatment in all patients. Conclusions. 111In-pentetreotide scintigraphy frequently visualizes pituitary adenomas and predicts GH responses to octreotide in unoperated acromegalic patients. In unsuccessfully operated patients scintigraphy is infrequently positive and does not predict which patients will respond to octreotide. These data and the cost of 111In-pentetreotide scintigraphy do not warrant its extensive clinical use in acromegaly.

Acromegaly

[Beta-2-microglobulin in hyperthyroidism].

The aims of the study were to clarify the cause of increased serum beta 2-microglobulin as a marker of thyroid hyperfunction. Serum beta 2-microglobulin was measured in 31 untreated hyperthyroid patients, all of them with normal renal function. Twenty-one subjects were affected by diffuse toxic goiter and 10 by toxic adenoma. Serum free thyroid hormones, TSH, anti-thyroglobulin and anti-microsomal antigen autoantibodies were determined, too. Thyroid hormone and creatinine levels did not differed between both sets of patients. beta 2-microglobulin was higher than normal in 90% of cases with diffuse toxic goiter and in 70% of those with toxic adenoma (p less than 0.05), but mean beta 2-microglobulin concentrations didn't differ between the two groups. No difference was found in beta 2-microglobulin levels in diffuse toxic goiter group according to the presence or absence of autoantibodies. beta 2-Microglobulin and thyroid hormones were not correlated in either diffuse toxic goiter and toxic adenoma groups. These data confirm the high prevalence of elevated beta 2-microglobulin concentrations in hyperthyroidism. As renal function was normal, this rise is due to beta 2-microglobulin overproduction. This increased production is a hormone mediated effect, even if lymphocyte activation may contribute in diffuse toxic goiter. beta 2-microglobulin is not correlated with thyroid hormone concentrations so that at present it isn't a useful marker of hyperthyroidism severity for practical purposes.

Adenoma

[Bone metabolism in primary hypothyroidism in the adult].

The aim of the study was to investigate bone metabolism in adult onset idiopathic myxedema. We studied 13 untreated patients (11 women and 2 men, age ranging 24-64 years) and, as a control group 15 healthy subjects (13 women and 2 men, age ranging 24-64 years). The hypothyroid group had significantly lower urinary excretion of hydroxyproline (4.40 +/- 0.63 vs. 8.60 +/- 1.3 mg/g, p less than 0.05) and serum concentration of osteocalcin (4.45 +/- 0.41 vs. 7.76 +/- 0.55 ng/ml, p less than 0.001). This low urinary excretion of hydroxyproline points to reduced osteoclastic bone resorption, while the low serum level of osteocalcin supports the view that osteoblastic bone formation is sluggish, too. Therefore bone metabolism in adult myxedema is characterized by a general reduction of remodelling. The stimulating actions of thyroid hormones on both bone resorption and new synthesis are further supported by the positive correlations between free hormone fractions and either urinary hydroxyproline and serum osteocalcin. Serum calcium, phosphorus, urinary calcium and phosphorus, and serum calcitrophic hormones (vitamin D, calcitonin, parathyroid hormone, measured as intact molecule) did not differed between the two groups; this finding might be related to the low fraction of active bone in hypothyroidism. The slow bone turnover seems to have few clinical consequences, but replacement therapy might produce accelerated osteoporosis, perhaps as a result of bone hypersensitivity to thyroid hormones.

Adult

[Serum osteocalcin in hyperthyroidism].

Several bone metabolism biochemical parameters were measured to evaluate the increased serum osteocalcin (sBGP) in hyperthyroidism. Twenty patients (19 women and 1 man, aged 22-69) and 20 age and sex-matched healthy subjects were examined. The following serum measurements were performed: calcium, phosphate, mid-molecule PTH, calcitonin, 25OH vitD, alkaline phosphatase, total and free thyroid hormones; urinary excretion of calcium, hydroxyproline and creatinine was also measured. The results (mean +/- standard error) show significant increases of sBGP (16.4 +/- 1.02 ng/mL; p less than 0.001), serum calcium (10.1 +/- 0.1 mg/dL; p less than 0.001), alkaline phosphatase (144.0 +/- 11.7 UI/L; p less than 0.001), urinary calcium (315.6 +/- 48.5 mg/g urinary creatinine; p less than 0.001) and hydroxyproline (43.0 +/- 6.1 mg/g urinary creatinine; p less than 0.001). A significant correlation between total and free thyroid hormones and sBGP was found. Accelerated bone turnover in hyperthyroid patients is therefore confirmed: both osteoclastic bone resorption, as suggested by increased serum and urinary calcium and urinary hydroxyproline, and osteoblastic bone formation, as suggested by increased serum osteocalcin and alkaline phosphatase, are stimulated.

Adult

[Hypogonadism in idiopathic hemochromatosis].

We studied the prevalence and the pathogenesis of hypogonadism in 16 male patients affected by idiopathic haemochromatosis. Thirteen patients were untreated, 14 had liver cirrhosis; alcohol intake was actually less than 80 g/die. LH and FSH were measured in the basal state and after iv. bolus of 100 micrograms of synthetic gonadotropin-releasing hormone. Plasma concentrations of testosterone, LH-FSH were determined, respectively, by RIA and LIA. Ten patients complained of loss of libido and potency (Group A): this group, as compared to controls, had significant reductions of testosterone, basal gonadotropins and pituitary responses. Nine of these patients disclosed testicular hypotrophy and low blood testosterone: 8 showed hypogonadotropic hypogonadism with low testosterone and LH-FSH responses, often accompanied by reduced basal concentrations of gonadotropins; one patient had a primitive testicular failure with low testosterone but a high response of LH to the GnRH. The other 6 patients had normal sexual activity (Group B): their testicular volumes and testosterone concentrations were normal, but 2 patients disclosed both LH and FSH hyperresponsiveness to the GnRH, which suggests an early primitive testicular failure. Our data emphasize the high prevalence of hypogonadism in male haemochromatosis subjects and disclose that sexual activity, testicular volume and laboratory results are tightly correlated. Stimulation with GnRH proved that hypothalamic-pituitary dysfunction is by far the most frequent cause of testicular failure in idiopathic haemochromatosis.

Adult