[Proposal of a computerized method to assess work related stress according to legal requirements in Italy]. / Aggiornamento delle Linee di indirizzo della Regione Toscana sullo stress lavoro-correlato. Realizzazione di un software per l'applicazione facilitata del modello di valutazione proposto alla luce delle indicazioni tecniche del documento di coordinamento tecnico delle regioni.

Assessing psychosocial factors in occupational environment requires complicated procedures according to most methods. The project of Tuscany region has the aim to realize a free computerized instrument for a gradual risk assessment with two different modes, expert and beginner. A decisional flow chart helps to approach the risk assessment step by step on the basis of company features, management and organization problems and company symptoms of stress. This experience means a proposal of a computerized method for a quantitative assessment of psychosocial risks at workplace, but at the same time offers a detailed analysis of the problems in the organization suggesting different priority to solve them.

[Quality oriented education: the experience of the Prevention Department of the Empoli Local Health Company n 11]. / La formazione per la qualità: l'esperienza del Dipartimento della Prevenzione della Azienda USL 11 di Empoli.

Quality management (QM) is a key issue for the Italian National Health System (NHS). Regione Toscana is currently undertaking a pilot programme to promote QM in Prevention Departments (PD). An introductory training to such programme was devised in the PD of the Local Health Unit no.11 Empoli, since the management was persuaded that all staff should be provided with basic knowledge concerning quality before being enrolled in QM programmes. Managers in charge of PD Units were offered a one-day training,focused on their role in promoting and achieving a QM culture, as an opportunity to be directly involved in the drafting of the DP quality handbook and in improving working procedures. The whole staff took part in a more extensive two-days course, including the basic concepts about QM in health systems, and the illustration of the programme in Regione Toscana; they were also asked to draw up some working procedures according to the draft already used in the Local Health Unit no.11, to be included in the DP quality handbook. The goal of this training programme was to implement a process capable of improving integrated working procedures through the competence, autonomy and responsibility of PD professionals.

Neuromuscular symptoms and dysfunction in subclinical hypothyroid patients: beneficial effect of L-T4 replacement therapy.

DESIGN, PATIENTS AND MEASUREMENTS: The presence of neuromuscular symptoms was ascertained by questionnaire in 33 consecutive patients with subclinical hypothyroidism (sHT) as compared to 44 age- and sex-matched controls. Blood was sampled for PTH, magnesium, phosphate, and total and ionized calcium determination. Patients reporting three or more symptoms were also studied by surface electromyography (sEMG). The study was repeated following a six-month L-T4 course. RESULTS: Neuromuscular symptoms were significantly more frequent in patients than in controls (P = 0. 0001), and correlated with TSH values (r = 0.52; P = 0.0001). Among patients showing three or more symptoms (n = 11), sEMG documented the presence of repetitive discharges in 8 patients. L-T4 therapy led to a significant improvement of symptoms (P = 0.0001); persistent repetitive discharges were no longer observed. Total and ionized calcium values, always within the normal limits, were significantly lower in patients than controls (P < 0.0001). An inverse relationship was observed between ionized calcium and: TSH values (r = -0.69, P = 0.0001); the number of neuromuscular symptoms (r = -0.53, P = 0.0001). L-T4 replacement induced a significant increase in both total and ionized calcium levels (P < 0.01 and P < 0.0001, respectively). CONCLUSIONS: Neuromuscular symptoms and dysfunction are rather common in subclinical hypothyroidism, and may be associated with abnormalities in serum calcium balance and surface electromyography. The ability of L-T4 treatment to reverse all these changes suggests that subclinical hypothyroidism patients may require early therapy not only to prevent progression to frank hypothyroidism, but also to improve their neuromuscular dysfunction.

Thyroid function and autoimmunity in Parkinson's disease: a study of 101 patients.

Thyroid disease is the endocrine dysfunction most frequently reported in association with idiopathic Parkinson's disease (PD). The aim of this study was to assess thyroid autoimmunity and function in PD, and to verify the effect of long term l-dopa and/or dopamine therapy on thyroid function. We studied 101 consecutive PD outpatients and seventy age- and sex-matched neurological non-PD patients as controls. They were evaluated for free thyroid hormones, TSH and thyroid autoantibodies. No significant difference in the prevalence of thyroid autoimmunity and dysfunction was found between PD patients and neurological controls (10.8% in PD patients vs 10% in neurological controls). Further, treatment with l-dopa and/or dopaminergic drugs and the stage of Parkinson's disease did not affect thyroid function. In conclusion, the prevalence of thyroid autoimmunity in PD patients appeared similar to that as described in the general population, though thyroid dysfunction was observed in over than 10% of PD patients. Indeed, neurologists should be alerted to the possible complications arising from thyroid dysfunction in Parkinson's disease, but thyroid function tests should be performed only when justified on clinical grounds.

Appearance of Graves' disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma.

In this report we describe an unusual patient with hyperfunctioning thyroid adenoma in whom percutaneous ethanol injection (p.e.i.) therapy was followed by typical Graves' disease. His history revealed the presence of a sister with Hashimoto's thyroiditis. 99-mTc thyroid scintiscan showed focal uptake in the nodule, with suppression of extranodular parenchyma. P.e.i. therapy was followed by the development of severe hyperthyroidism. One month after a second p.e.i. cycle, recurrence of hyperthyroidism associated with diffuse 99-mTc uptake by the gland was observed. TSH-receptor and thyroglobulin autoantibodies were undetectable before p.e.i. therapy, appeared during the first cycle, and showed a further increase after the second p.e.i. therapy cycle. Though spontaneous switch to Graves' disease cannot be excluded in patients with toxic nodules, the massive release of thyroid materials from follicular cells, among these TSH-receptor antigenic components partially denatured by ethanol, may indeed trigger an autoimmune response to the TSH-receptor, thus accounting for this observation. Patients with possible autoimmune disposition, as selected by familiar history and/or laboratory markers should be carefully monitored during p.e.i. treatment.

Five-year follow-up of percutaneous ethanol injection for the treatment of hyperfunctioning thyroid nodules: a study of 117 patients.

UNLABELLED: Percutaneous ethanol injection (PEI) has been suggested as an alternative to radioiodine and surgery for the treatment of autonomous thyroid nodules (ATN). OBJECTIVE: In this study we have defined the long-term efficacy and safety of PEI for the treatment of ATN, and we have attempted to optimize the clinical usefulness and improve the technical approach to PEI treatment. PATIENTS: One hundred and seventeen patients with ATN, 26 males and 91 females, aged 48 +/- 12.9 years (mean +/- SD), were offered PEI when other established treatments were refused or contraindicated. Seventy-seven patients were affected by toxic adenoma (60 with a single nodule, 17 with a multinodular goitre); 40 patients suffered from a pretoxic single nodule. METHODS: Sterile 95% ethanol was administered weekly under sonographic control by a 20-22 gauge needle without anaesthesia or pharmacological sedation. During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. According to hormone and scintigraphic data, three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra-nodular tissue uptake, along with elevated free T4 (FT4) and free T3 (FT3) and undetectable TSH levels); partial cure (normalization of FT4 and FT3 levels, with low/ undetectable TSH levels; persistent suppression of extra-nodular uptake); complete cure (normal thyroid hormone and TSH levels; restored extra-nodular uptake). RESULTS: The patients were followed for up to 5 years (median 2.5). PEI therapy was well tolerated by all patients. Complete cure was achieved in all pretoxic patients and in 60 (77.9%) patients with toxic adenoma, while partial cure was observed in 7 cases (9.1%) and failure in 10 (13%). PEI treatment proved similarly effective in toxic patients with a single nodule or with multinodular goitre (87 vs 88.2%, respectively). At the end of treatment, a significant shrinkage of nodule volume was observed in all patients (P = 0.0001). Toxic patients with pretreatment volume > 40 ml (n = 8) did not show a significant difference in treatment response rate as compared to those with volume < 40 ml. Recurrence of hyperthyroidism was never observed during follow-up, independently of thyroid status before treatment. Only one patient with significant thyroid autoantibody serum levels before PEI treatment, developed sub-clinical hypothyroidism at 3 years. The administration of methimazole and/or propranolol did not modify PEI outcome. CONCLUSION: Our data confirm the efficacy and safety of percutaneous ethanol injection for the therapy of autonomous thyroid nodules. The very low incidence of hypothyroidism along with the absence of recurrence of hyperthyroidism suggests that percutaneous ethanol injection is the treatment of choice in patients with pretoxic thyroid adenoma. Percutaneous ethanol injection appears an effective alternative procedure in toxic patients with a high surgical risk even if they have large nodules, and in younger ones in whom radioiodine is contraindicated. Patients may be submitted to anti-thyroid drug and/or beta-blocker therapy if it is necessary, but this does not affect percutaneous ethanol injection treatment outcome. Finally, not only single autonomous thyroid nodules but also toxic multinodular goitre may be successfully treated by percutaneous ethanol injection.

Age-related modifications in the regulation of the hypothalamic-pituitary-thyroid axis.

We studied the hypothalamic-pituitary-thyroid function in two groups of healthy elderly subjects: group A (n = 23, age range 65-80 years), and group B (n = 11, age range 81-92 years), and in 32 controls, aged 20-60. A TRH test for TSH and prolactin was performed in all subjects, while the TSH circadian modulation was evaluated in elderly subjects only. Group B showed significantly lower fT3 and TSH, and higher fT4 levels with respect to controls (fT3: 4.4 +/- 0.2 vs. 5.2 +/- 0.2 pmol/l, p < 0.05; fT4: 13.1 +/- 0.9 vs. 11.4 +/- 0.4 pmol/l, p < 0.05; TSH: 1.07 +/- 0.21 vs. 1.46 +/- 0.13 mIU/l, p < 0.05). Morning TSH showed an inverse correlation with age (r = -0.42; p < 0.02) among the 34 elderly subjects, but not among controls. Evidence for TSH circadian modulation was found only in group A (nighttime TSH: 1.60 +/- 0.17, vs. daytime: 1.25 +/- 0.13 mIU/l, p < 0.001). The TRH-stimulated TSH peak was reduced among all elderly subjects with respect to controls (A: 6.26 +/- 0.64 mIU/l, p = 0.01; B: 5.02 +/- 0.58 mIU/l, p < 0.01). The maximal PRL response was also blunted (A: 25.7 +/- 2.6 micrograms/l, B: 27.7 +/- 5.2 micrograms/l, p < 0.0005). In conclusion, a resetting of the pituitary threshold of the TSH feedback suppression, along with complex alterations in peripheral thyroid hormone levels, may progressively develop in older people, becoming apparent only with extreme senescence. Moreover, the TSH nocturnal surge may be lost with increasing age, thus providing evidence also for hypothalamic dysfunction.

Percutaneous ethanol injection therapy of autonomous nodule and amiodarone-induced thyrotoxicosis.

A patient with amiodarone-induced thyrotoxicosis and autonomous nodule was treated with percutaneous ethanol injection (PEI) in 8 sessions. Preinjection thyroid hormone levels showed a marked elevation, peaking before the third session. The thyroid hormone increments following each procedure never exceeded 20% of the preinjection levels. FT4 plasma levels thereafter declined to within the normal range by the sixth session (day 21), while FT3 levels, though markedly reduced, were still slightly elevated; also, the thyroid hormone increments following ethanol injection were not observed after the fifth session. These findings suggest that a significant, but not sustained, increase in thyroid hormone levels is induced by PEI and may account for the lack of acute deterioration of clinical status, which remained under control with medical treatment alone. Normal serum thyroid hormone levels were observed at the 3 and 12 month follow-up. The use of percutaneous ethanol injection therapy for amiodarone-induced hyperthyroidism should be restricted to patients with preexisting thyroid hyperfunctioning nodule, and it may be a practical alternative to surgery in addition to medical treatment. Special caution should be exercised with patients with severe underlying heart disorders, since their clinical status might seriously worsen in case of acute elevations of serum thyroid hormones following ethanol injection. To this purpose, a close monitoring of serum thyroid hormones is recommended in order to institute a prompt adjustment in their medical therapy and/or in their PEI protocol.

Percutaneous aspiration and ethanol sclerotherapy for thyroid cysts.

Benign thyroid cysts often recur after aspiration; the effectiveness of tetracycline instillation in the case of recurrence has been questioned. We, therefore, tested the efficacy of percutaneous ethanol injection in 20 patients with "pure" cyst relapsing after aspiration. After evacuation, 95% ethanol was instilled under sonographic guidance and re-aspirated 5 min later. The procedure was performed twice for larger cysts. Follow-up studies were carried out after 1, 3, 6, and 12 months. In case of recurrence at 1 month, patients (n = 5) were submitted to a second session. A slight burning sensation was the only adverse effect. No recurrences were observed at 3 and 6 month follow-up; only one patient with recurrence after 1 month had relapsed at 12 months. A significant shrinkage (P < 0.0001 vs. pretreatment) was observed in all other cases at 12 months; cysts were not detectable in seven patients (35%). No significant variations in thyroid hormone levels were detected during treatment or follow-up. Serum thyroglobulin levels markedly increased 3 h after ethanol injection. One month after treatment, thyroglobulin returned to pretreatment levels, thus excluding progressive thyroid damage. Percutaneous ethanol injection may prove a safe and effective tool for the therapy of thyroid cysts.

Subclinical hypothyroidism: neurobehavioral features and beneficial effect of L-thyroxine treatment.

Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of L-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month L-thyroxine course (0.1-0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ) = 89.1 +/- 2.9; P = 0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P = 0.03), anxiety (P = 0.05), somatic complaints (P = 0.0005), and depressive features (P = 0.002) scales; the total score was also significantly higher (42.0 +/- 3.8; P = 0.005). After L-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9 +/- 4.0; P = 0.002 (treated versus untreated)]; somatic complaints (P = 0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P = 0.04) significantly decreased with respect to untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of hyperfunctioning thyroid adenoma: current trends]. / Trattamento dell'adenoma tiroideo iperfunzionante: nuovi orientamenti.

Thyroid adenoma is commonly associated with surgery and radiometabolic treatment; recently, according to previous successful reports, percutaneous ethanol injection therapy under sonographic guidance, has been introduced as an alternative. This technique has already been favourably used in the treatment of focal lesions, such as liver cancer and hyperparathyroidism. In our experience, we have treated with such therapy 69 patients affected by thyroid adenoma (55 females, 14 males; 28 pretoxic, 41 toxic). Ethanol (0.5-2.8 mL/mL nodular tissue) was injected, under sonographic guidance, in 4-9 sessions (1 weekly). Thyroid hormone profile was assessed during treatment and at 3 and 6 months follow-up. Apart from local transient pain in 21% sessions, two cases of pyrexia (38.5 degrees-1 day) and 3 cases of transient dysphonia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 33 out of 41 toxic patients (80%); a significant increase of TSH levels was seen in both groups (p < 0.001). With follow-up, significant volume shrinkage (70-80% volume reduction--p < 0.0001) as well as structural alterations of the nodule, were consistently recorded at sonography, in both groups; a linear relationship (p < 0.0001) between pretreatment volume and volume reduction was found. At scintiscan functional activity of extranodular parenchyma was found in 75% of patients affected by pretoxic adenoma and in 63.1% of patients with toxic adenoma. These data confirm that percutaneous ethanol injection therapy is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; so it represents a valid and safe alternative to standard therapeutic tools of thyroid adenoma.

Percutaneous ethanol injection treatment of autonomously functioning single thyroid nodules: optimization of treatment and short term outcome.

Twenty-five patients with solitary autonomous thyroid nodules (15 nontoxic, 10 toxic) received percutaneous ethanol injection treatment (PEIT) under sonographic guidance in 4-7 sessions (1-2 weekly). To test different doses, smaller nodules (volume less than 15 mL) were given 0.75-2.8 mL ethanol/mL nodular tissue while larger nodules received 0.5-1 mL/mL. Except for 1 patient who developed hyperpyrexia, no relevant adverse effects were observed. A slight, asymptomatic increase in serum thyroid hormone levels was observed in both groups during the treatment. Three months after treatment, a biochemical and clinical remission of hyperthyroidism was observed in 8 of 10 patients with toxic nodules. A significant increase of TSH level was seen in both groups (p less than 0.01). Significant shrinkage of volume (p less than 0.001) as well as structural alterations of nodules were consistently recorded at sonography. A linear relationship (r = 0.98; p less than 0.0001) between pretreatment volume and volume reduction was found both for large and small nodules, thus suggesting that even limited ethanol doses may be therapeutically effective. A recovery of extranodular parenchyma activity at scintiscan occurred in 16 (64%) of 25 patients. These data confirm that PEIT is effective in obtaining functional ablation and in inducing remission of hyperthyroidism. Adverse effects are infrequent. In spite of the small patient sample, a 0.5-1 mL ethanol dose per each mL of tissue appears as effective as larger doses and seems appropriate for treatment.

Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation.

OBJECTIVE: We have evaluated the efficacy of percutaneous ethanol injection as an alternative to surgery and iodine-131 treatment in solitary autonomous thyroid adenoma. DESIGN: Percutaneous ethanol injection (0.5-2.8 ml ethanol/ml nodular tissue) was performed under sonographic guidance in 3-5 (1-2 weekly) sessions; a 7.5 MHz linear real-time scanner (Toshiba, mod. 32B) was used for sonographic studies. The thyroid hormone profile was assessed during treatment and for the next 6 months. PATIENTS: Fifty-six patients (40 females, 16 males, mean age 46 +/- SD 9 years; 30 pretoxic, 26 toxic) were included in the study: their pretreatment technetium-99 m thyroid scan showed a single hot nodule with total suppression of extranodular tissue in 45 and near-total suppression in 11. MEASUREMENTS: Thyroid hormones, antithyroglobulin and antiperoxidase antibodies were measured by specific radioimmunoassay, while thyrotrophin was evaluated by ultrasensitive immunoradiometric assay. RESULTS: Apart from a case of transient pyrexia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following a treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 18 out of 22 toxic patients (81.8%); a significant increase of TSH levels was seen in both groups (P less than 0.01). With follow-up, significant volume shrinkage (P less than 0.001) as well as structural alterations of the nodule were consistently recorded at sonography; a linear relationship (r = 0.98; P less than 0.0001) between pretreatment volume and volume reduction was found. At scintiscan, functional activity of extranodular parenchyma was found in 40 out of 56 patients (71.4%), 16/26 (61.5%) in the hyperthyroid group, 24/30 (80.0%) in the pretoxic group. CONCLUSIONS: These data confirm that percutaneous ethanol injection is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; adverse effects seem infrequent.

Resection of liver gastrinoma leading to persistent eugastrinemia. Case report.

In a 30-year-old man with Zollinger-Ellison syndrome, the only detectable gastrinoma was in the right liver lobe. Removal of the lobe, without additional gastric surgery, was followed by normalization of the gastrin level. Long-term follow-up confirmed the good result. The usefulness of quick intraoperative gastrin assay is stressed.

Somatostatin effect in postprandial hypoglycemia.

The effect of the administration of oral glucose with or without a simultaneous intravenous somatostatin infusion on blood glucose, immunoreactive insulin, C-peptide, and glucagon levels in seven patients with idiopathic postprandial hypoglycemia was studied. Oral glucose alone induced an excessive insulin response and hypoglycemia, whereas a slight suppression in glucagon levels without any increase at the hypoglycemic nadir was observed. The simultaneous administration of somatostatin significantly reduced the insulin response and induced a slower rise of blood glucose; no hypoglycemia developed. Only minor variations in glucagon were observed with respect to the basal test. A rebound in insulin, C-peptide, and glucagon levels was observed at the end of the somatostatin infusion. These data show that somatostatin can suppress glucose-induced hypoglycemia in these subjects, thus suggesting that its long-acting analogues might be worth a therapeutic trial in severe idiopathic postprandial hypoglycemia.

Distribution of calcitonin- and somatostatin-containing cells in thyroid lymphoma and in Hashimoto's thyroiditis.

Eleven cases of thyroid lymphoma were studied by the immunoperoxidase avidin-biotin technique with calcitonin and somatostatin rabbit antisera. In 6 cases of non-Hodgkin lymphoma, in thyroid tissue residual to the lymphomatous infiltration, the C cell density was markedly increased and clustering was often observed; the C cells often took part in the follicular lining, frequently with polar distribution; these elements displayed a strong positivity for calcitonin, while the number of somatostatin-containing cells was lower and the staining less intense. In the only case of Hodgkin's lymphoma of the thyroid gland the staining was negative; in other 4 cases of non-Hodgkin lymphoma no residual thyroid tissue was found and the staining was also negative. As Hashimoto's thyroiditis is often associated with thyroid lymphoma, 13 cases of Hashimoto's thyroiditis were also studied; no C cells were observed and both stainings were negative. These data show that an increase in the C cell number may be a hallmark of thyroid lymphoma and that hyperplastic C cells show an intensive positivity for calcitonin. On the other hand, C cell hyperplasia is not present in Hashimoto's thyroiditis, in spite of the close association with thyroid lymphoma. Furthermore, we provide evidence that somatostatin-containing cells are present both in normal thyroid glands and in thyroid lymphoma.