[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.

[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.

Dissociated 24-hour patterns of somatotropin and prolactin in fatal familial insomnia.

To assess the changes in the 24-hour profiles of serum somatotropin and prolactin levels during total disruption of the sleep/wake cycle sustained over several months, we studied 2 subjects affected by fatal familial insomnia, a rare disease characterized by selective thalamic degeneration that causes chronic sleep loss. Under standardized conditions and polysomnographic control, the patients underwent repeated 24-hour study sessions covering the entire clinical course of the disease. Hormones were assayed at 30-min intervals. Four healthy volunteers were used as controls. A sleep/wake cycle was always absent in fatal familial insomnia. Serum somatotropin and prolactin concentrations never exceeded the normal range of variation. The nocturnal elevation of somatotropin disappeared simultaneously with sleep loss, whereas a significant 24-hour component of variations in serum prolactin levels was present for months after total disruption of the sleep/wake cycle, with normally placed nocturnal acrophases. Complete obliteration of the 24-hour component was achieved for prolactin only in the advanced stages, through a progressive decrease in 24-hour amplitude of variation. Selective and progressive degeneration of the mediodorsal and anterior ventral nuclei of the thalamus causes an early obliteration of the 24-hour rhythm of somatotropin and a later disappearance of circadian prolactin rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)

[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)

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.

[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.

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.

[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.

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.

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.

[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.

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.

Lack of vegetative and endocrine circadian rhythms in fatal familial thalamic degeneration.

A total lack of neuroendocrine and vegetative circadian rhythms was observed in a patient with a familial degeneration of the anterior and dorso-medial thalamic nuclei. Our findings support the role of the thalamus in regulating the periodicity of endocrine and vegetative functions.

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.