Analysis of voice in patients with untreated active acromegaly.

BACKGROUND: Voice changes are common clinical findings of acromegaly, although scanty data are available so far. OBJECTIVE: To analyze features and quantify changes of voice in patients with untreated active acromegaly. DESIGN AND METHODS: This was a pilot case-control study. Voice was analyzed using the Multi Dimensional Voice Program software, which generates 33 parameters related to fundamental frequency (F0), micro-perturbation of F0 and amplitude, noise, tremor, voice breaks and irregularities, and diplophony. PATIENTS: Thirteen consecutive patients (8 women, 5 men, mean age 48+/-9 yr) with active acromegaly, at first diagnosis, and 13 sex- and age-matched normal subjects (controls). RESULTS: Patients with untreated active acromegaly had mean values of parameters related to F0 significantly lower than those of controls, although mostly remaining in the normal range. Most acromegalic patients had micro-perturbation of F0, as indicated by higher mean of absolute or percentage jitter values than those of controls; micro-perturbation of amplitude was a common feature of voice in most acromegalic men. Noise-related parameters were also affected by acromegaly, being higher in male acromegalic patients than in controls and acromegalic women. On the contrary, parameters related to tremors, voice breaks, voice irregularities and diplophony did not differ in acromegalic patients and controls. CONCLUSIONS: Patients with untreated active acromegaly had low-pitched voice characterized by lowering F0 and increased values related to noise, micro perturbation of frequency, and amplitude.

Thyroid function differently affects serum cystatin C and creatinine concentrations.

Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p<0.05), and significantly decreased in short-term, long-term and mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%) hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C values. In the prospective study, restoration of euthyroidism by either methimazole or L-T4 therapy was associated with normalization of mean serum Cys C concentrations. In conclusion, thyroid dysfunction affects serum Cys C concentration, possibly influencing the production rate of the protein. However, the observation that hyper- or hypothyroid patients have normal serum Cys C levels limits its use as a marker of peripheral thyroid hormone effect.

Effects of a mixture of polychlorinated biphenyls (Aroclor 1254) on the transcriptional activity of thyroid hormone receptor.

Polychlorinated biphenyls (PCBs) are environmental contaminants which may affect thyroid function. PCBs may reduce serum thyroid hormone (TH) concentrations by either displacing T4 from TH transport proteins or increasing its hepatic metabolism. The reduced serum T4 causes neurological and growth defects in animals exposed to PCBs during the perinatal period, which can partially be reverted by T4 administration. In addition to a hypothyroid-like syndrome, a direct action of PCBs on TH-sensitive genes has been postulated. In the present study the effects of Aroclor 1254 (ARO), a mixture of PCBs, on transcription of TH-dependent genes were investigated. A reporter plasmid containing the TH-responsive element (TRE) of malic enzyme (ME) gene was used in transient transfections to assess the responsiveness to ARO. ARO (10 microM) reduced the CAT activity by about 50% and competed with T3 to reduce the induction of transcription. Cotransfection of TH receptor (TR) and a wild type TRE was required to reveal ARO inhibitiry effect, which was abolished by a mock reaction not containing TR or by a mutated TRE. ARO reduced the 125I-T3 binding to TR by 30%, but did not affect the interaction of TR with a 32P-labeled TRE in gel shift assay. ARO is likely to produce a conformational change in in vitro translated TR, leading to its increased proteolysis by trypsin. These results demonstrate that ARO interacts with TR, thereby affecting the transcription of TH-sensitive genes, and provide a molecular basis to further explain the complex effects of PCBs on TH disruption.

Psychotropic drug use in Italy, 1984-99: the impact of a change in reimbursement status.

After years of corruption surrounding drug reimbursement, in 1994, a change in drug reimbursement status was implemented in Italy according to cost-effectiveness criteria. The aim of this study was to assess the impact of these changes on the use of psychotropic drugs. National trends in antipsychotic, antidepressant and benzodiazepine prescriptions were analysed from 1984 to 1999. During the study period, prescriptions of antipsychotic drugs were stable from 1984 to 1994 but, in the subsequent 5 years, increased by 54%. Although the use of atypical compounds in 1999 accounted for only 6% of total antipsychotics sold, the cost of these new drugs accounted for almost one-half the total antipsychotic expenditure. The use of benzodiazepines increased by 53%. In 1999, the psychotropic drugs lorazepam and alprazolam were the most sold by value. From 1984 to 1999, the total antidepressants sold increased by 55%. Although the use of selective serotonin reuptake inhibitors and newer antidepressants in 1999 accounted for less than 50% of total antidepressants sold, the cost of these drugs accounted for 65% of total antidepressant expenditure. This analysis highlights specific areas of concern which should become the object of public health programs.

A novel mutation in the pendrin gene associated with Pendred's syndrome.

OBJECTIVE: Pendred's syndrome is an autosomal recessive disorder characterized by goitre, sensorineural deafness and iodide organification defect. It is one of the most frequent causes of congenital deafness, accounting for about 10% of hereditary hearing loss. It is caused by mutations in the pendrin (PDS) gene, a 21 exon gene located on chromosome 7. The aim of this study was to examine an Italian family affected with Pendred's syndrome at the molecular level. PATIENTS: Thirteen subjects belonging to a family from Southern Italy were evaluated for the clinical and genetic features of Pendred's syndrome. MEASUREMENTS: Exons 2-21 of the PDS gene were amplified from peripheral leucocytes by the polymerase chain reaction; mutation analysis was performed by single strand conformation polymorphism, direct sequencing and restriction analysis. RESULTS: The index patient had the classical triad of the syndrome and harboured two mutations in the PDS gene in the form of compound heterozygosity. He was found to be heterozygous for a cytosine to adenosine mutation at nucleotide 1523 in exon 13 and for a IVS 1001 + 1G --> A mutation. The former is a novel mutation which results in a change of 508 threonine to asparagine in the putative eleventh transmembrane domain. The latter mutation in the donor splice site has already been described in other patients and is thought to lead to aberrant splicing and premature protein truncation. Three subjects who were heterozygous for one mutation had normal phenotypes. Two subjects had sensorineural deafness and were heterozygous for a single mutation. Goitre was found only in patients with Pendred's syndrome and was absent in all other individuals, albeit residing in an iodine-deficient area. CONCLUSIONS: We have identified a novel mutation in the pendrin gene causing Pendred's syndrome, and confirm that molecular analysis is a useful tool for a definitive diagnosis. This is particularly relevant in cases such as in the subjects of our family in which the clinical features might be misleading and other genetics factors might be responsible for deafness.

Antidepressant drug use in Italy since the introduction of SSRIs: national trends, regional differences and impact on suicide rates.

Little is known about the use of antidepressant drugs in Italy since the introduction of selective serotonin reuptake inhibitors (SSRIs). To fill this gap, we examined antidepressant drug sales data from 1988 to 1996 for the whole country, and for the years 1995 and 1996 on the regional level. National suicide trends from 1988 to 1994 were also examined to assess whether the increasing use of SSRI antidepressants was associated with changes in suicide rates. From 1988 to 1996 an increase of antidepressant sales of 53% was recorded. This increase reflected increasing use of SSRIs, which in 1996 accounted for more than 30% of total antidepressants sold. The analysis of regional differences demonstrated heterogeneity between north, center, and south. In the south prescriptions of antidepressants and use of SSRIs were lower than in the rest of the country. In the 7-year period over which SSRI use increased, male suicide rates increased from 9.8 to 10.2 per 100,000 inhabitants, and female suicide rates declined from 3.9 to 3.2 per 100,000. These data suggest that SSRIs gave a new impetus to antidepressant sales. However, possible public health benefits related to the shift from old to new antidepressants have yet to be demonstrated.

The age of patients with thyrotoxicosis factitia in Italy from 1973 to 1996.

Thyrotoxicosis factitia, a syndrome due to the surreptitious ingestion of excess thyroid hormones, has generally been diagnosed in young or middle-aged women with psychopathological disturbances. We reviewed all the cases seen at our Institution over a 24-yr period, from 1973 to 1996. All 25 patients were women. Analysis was restricted to 17 patients who were born and lived in Tuscany (our region), since only these patients were distributed during the whole observation period. Diagnosis of thyrotoxicosis factitia was based on the following parameters: elevated serum total and/or free thyroid hormone levels, undetectable serum thyrotropin levels, low/undetectable serum thyroglobulin concentration, normal urinary iodine excretion, low/suppressed thyroidal radioactive iodine uptake (RAIU), absence of goiter, absence of circulating anti-thyroid antibodies. Surreptitious ingestion of thyroid hormone pill was eventually admitted by all patients. Age at diagnosis was >50 yr in 7/17 patients (41%): 6 of them were distributed in the period 1995-1996, and one in 1988. Patients older than 60 yr were 5/17 (29%), all in the last two years of the period under investigation. There was an increase in the age of patients with thyrotoxicosis factitia (p=0.02), which lost a statistical significance when the patients of the 1995-1996 period were excluded from analysis (p=0.88). This study provides evidence of an increased age of patients with thyrotoxicosis factitia in more recent years. From a practical standpoint, our study suggests that thyrotoxicosis factitia should be suspected and adequately looked for even in old patients with thyrotoxicosis of inexplicable origin, especially in the absence of goiter and thyroid autoimmune phenomena, and when common causes of low-RAIU hyperthyroidism, such as a load with iodine-containing drugs or subacute thyroiditis, have been excluded.

Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves' hyperthyroidism.

Effectiveness of radioiodine for Graves' hyperthyroidism depends also on its intrathyroidal persistence. The latter is enhanced by lithium by blocking iodine release from the thyroid. One hundred ten patients with Graves' hyperthyroidism were randomly assigned to treatment with radioiodine or radioiodine plus lithium, stratified according to goiter size (< or =40 or >40 mL) and evaluated for changes in thyroid function and goiter size, at monthly intervals, for 12 months. Cure of hyperthyroidism occurred in 33 of 46 patients (72%) treated with radioiodine and in 45 of 54 patients (83%) treated with radioiodine plus lithium. The probability of curing hyperthyroidism was higher and its control prompter (P = 0.02) in the radioiodine-plus-lithium group. Patients with < or =40-mL goiters had similar persistence of hyperthyroidism (13%), but lithium-treated patients had hyperthyroidism controlled earlier (P = 0.04). Among patients with >40-mL goiters, hyperthyroidism was cured in 6 of 15 patients (40%) treated with radioiodine alone and in 12 of 16 patients (75%) treated with radioiodine plus lithium (P = 0.07), and cure occurred earlier in the latter (P = 0.05). Goiters shrank in both groups (P < 0.0001), more effectively and promptly (P < 0.0005) in the radioiodine-plus-lithium group. Serum free T4 and T3 levels increased shortly after therapy only in the radioiodine group (P < 0.01). Lithium carbonate enhances the effectiveness of radioiodine therapy, in terms of prompter control of hyperthyroidism, in patients with small or large goiters. In the latter group, lithium also increases the rate of permanent control of hyperthyroidism.