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.

[A rare hyperthyroid syndrome]. / Una rara sindrome ipertiroidea.

The exophthalmos, myxedema, acropachy (EMA) syndrome is a rare extrathyroid syndrome, interesting about 1% of the patients affected by extrathyroid complications of Graves' disease. The ratio female/male is 3.4:1 and this case report is very rare. The patient, a 52-year-old man, presented a serious ophthalmopathy with pretibial myxedema, acropachy with joint pain. The triad manifested itself after some ophthalmopathy treatments, i.e. total thyroidectomy, steroidal retrobulbar therapy and radiotherapy. The patient received T4 therapy and the thyroid function status was normal. The appearance of the EMA syndrome coincided with the fast worsening of the ophthalmopathy. This case report confirms previous observations regarding the chronological sequence of presentations of extrathyroidal manifestations of autoimmune thyroid disease. The thyroid disease develops first, followed by ophthalmopathy, then dermopathy, and finally, acropachy. The thyroid acropachy shows some differences between pulmonary and paraneoplastic osteoarthropathy, due to the presence of thyroid dermopathy and ophtalmopathy (EMA) and to the different subperiosteal proliferation. Steroidal therapy improved the ophthalmopathy, the pretibial myxedema and the acropachy. The improvement obtained has been faster as regards the exophtalmos and myxedema, slower as regards the acropachy, but of the same importance. In conclusion, acropachy is the latest manifestation of EMA and coincides with the worsening of ophthalmopathy. The traditional steroidal therapy is effective to improve the syndrome.

[Beta-2-microglobulin in hyperthyroidism]. / La beta 2-microglobulina nell'ipertiroidismo.

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.

[Acute hyperparathyroidism associated with follicular carcinoma in the thyroid: possible role of juvenile cervical irradiation. Description of a case]. / Iperparatiroidismo acuto associato a carcinoma follicolare della tiroide: possibile ruolo dell'irradiazione cervicale giovanile. Descrizione di un caso clinico.

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.

[Bone metabolism in primary hypothyroidism in the adult]. / Studio del metabolismo osseo nell'ipotiroidismo primitivo dell'adulto.

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.

[Serum levels of the tartrate-resistant isoenzyme, acid phosphatase, for the evaluation of bone remodeling in hyperthyroidism]. / Il dosaggio sierico dell'isoenzima tartrato resistente della fosfatasi acida nella valutazione del rimodellamento osseo nell'ipertiroidismo.

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)

Hypercalcemia in malignancies: treatment with dichloromethylene diphosphonate (Cl2MDP).

Eleven hypercalcemic patients affected by various kinds of cancer were treated with dichloromethylene diphosphonate (Cl2MDP), 400 mg diluted in 500 ml of saline solution, i.v., during 3 h. Drug administration normalized plasma calcium levels in all treated patients, within 72 h for patients with lung cancer; within a longer period for other kinds of cancer. Moreover, Cl2MDP also reduced calciuria in treated patients. The use of the drug was not followed by side effects and was also well tolerated in patients with kidney insufficiency.

Serum immunoreactive calcitonin in lung cancer.

Serum immunoreactive calcitonin (iCT) assay was performed in 92 patients suffering from different kinds of cancer of the lung and in 42 healthy control subjects. Gel filtration of serum of patients suffering from microcytoma was carried out on Sephadex G75 to study the forms of circulating iCT. The obtained results (pg/ml M +/- SE) were: 1) normal subjects, 73 +/- 3; 2) epidermoidal cancer, 105 +/- 19; 3) adenocarcinoma, 116 +/- 47; 4) anaplastic carcinoma with large cells, 156 +/- 74; 5) microcytoma , 354 +/- 74; 6) chronic obstructive bronchitis, 38 +/- 6. Gel filtration of serum of patients with microcytoma demonstrated the same behavior as in normal subjects. We can conclude that iCT increases significantly in microcytoma with extensive disease (84% of cases): in this condition, the iCT assay can be useful as a marker in follow-up of disease.

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.

[Serum osteocalcin in hyperthyroidism]. / L'osteocalcina sierica nell'ipertiroidismo.

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.

Calcitonin in hepatoma and cirrhosis.

Plasma immunoreactive calcitonin (iCT) is elevated in primary liver cancer and its measurement has been proposed as a tumour marker. Since iCT is also frequently raised in alcoholic liver cirrhosis, it would be of practical relevance to distinguish this condition from primary hepatoma by measuring the plasma level of iCT. We measured plasma iCT levels in 23 subjects with primary liver cancer, in 27 with hepatic cirrhosis and in 42 healthy subjects who served as normal controls. A gel-chromatography analysis was carried out on the plasma of two cases of hepatoma, two of cancer and cirrhosis, and two of alcoholic liver cirrhosis. The subjects with primary liver cancer had values of plasma iCT (pg/ml; mean +/- SE) of 342 +/- 41; those with liver cirrhosis 159 +/- 22, and normal controls 73 +/- 3. The increase in primary liver cancer was significant in comparison both healthy subjects (P less than 0.001) and with cirrhotic patients (P less than 0.001). Twenty-two out of 23 patients with primary liver cancer and 13 out of 27 with liver cirrhosis had elevated iCT values (upper normal limit 113 pg/ml). There was no significant difference between plasma iCT values of patients with cancer and those with cirrhosis. However, we measured iCT values higher than 400 pg/ml only in patients with primary liver cancer. The gel-filtration analysis showed 3 or 4 peaks of iCT with a molecular weight higher than synthetic human calcitonin. The results suggest that plasma iCT levels can be considered a reliable marker of liver cancer, whereas its discriminating power between liver cancer and cirrhosis was not entirely satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)

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.