L. Bartalena

More on smoking habits and Graves' ophthalmopathy.

Since a relationship between cigarette smoking and the occurrence of Graves’ ophthalmopathy has been recently postulated, we reviewed the smoking habits of 1730 women, including subjects without thyroid disease, with nontoxic goiter (NTG), toxic nodular goiter or toxic adenoma (TNG), Hashimoto’s thyroiditis (HT), Graves’ disease without ophthalmopathy (GD) or with ophthalmopathy (GO). The prevalence of smokers in NTG, TNG and HT was about 30%, not different from that of controls. Smokers were 47.9% in GD and 64.2% in GO groups. The latter figures were highly different from those of the other groups and also from each other. The percentage of heavy smokers was higher in patients with more severe ophthalmopathy. No clear explanation for this phenomenon can be offered. The absence of a high prevalence of smokers among patients with nontoxic goiter, nonautoimmune hyperthyroidism and Hashimoto’s thyroiditis, limits the impact that smoking might have had in the pathogenesis of goiter, hyperthyroidism and autoimmune phenomena of GD and GO.

Cerebral visual impairment in preterm infants with periventricular leukomalacia

Neonatal brain lesions are the main cause of cerebral visual impairment in infancy, i.e., of a visual deficit caused by damage to posterior visual pathways. Visual outcome of preterm infants with periventricular leukomalacia (PVL) was investigated in 14 subjects affected by severe cystic PVL, another 34 with moderate PVL (prolonged periventricular echodensities), and 18 control preterm infants. All cases with significant ocular abnormalities (such as retinopathy of prematurity state III or upwards, optic nerve atrophy, or major refraction problems) were excluded. Visual acuity, visual field, eye alignment, fixation and following, optokinetic nystagmus, and visual threat were tested at 1 year of corrected age. A high incidence of cerebral visual impairment, consisting mainly of low visual acuity, severe oculomotor disorders, and reduced visual field, was found in infants with severe PVL. Visual defects were less frequent and less severe in the moderate PVL group, and very rare in the control group. The results of neuroimaging, and especially of magnetic resonance imaging, correlated with the visual outcome and indicate lesions at the level of optic radiations as the main anatomic substrate of the visual impairment. All infants with PVL need a visual follow-up, from the first months of life, the results of which are important both for visual and motor rehabilitation of these cases and for their daily care.

Relationship of the increased serum interleukin-6 concentration to changes of thyroid function in nonthyroidal illness

Variations in the serum concentration of interleukin-6 (IL-6) have been reported concomitantly with thyroid dysfunction: increased serum IL-6 levels have been found in patients with thyroidal destructive processes, such as subacute thyroiditis, some forms of amiodarone-induced thyrotoxicosis, or after percutaneous ethanol injection into “hot” thyroid nodules, as a result of the cytokine release from the damaged thyrocyte. In addition, recent in vitro evidence suggests that IL-6 might account, at least in part, for changes of thyroid economy found in nonthyroidal illness (NTI). In this cross-sectional study we addressed this problem by measuring serum IL-6 levels in 71 patients with NTI, due to neoplasia(n=25), chronic liver disease (n=9), chronic renal failure (n=28), or other chronic nonthyroidal disorders (n=9). These patients had reduced mean serum total T3 (TT3) and free T3 (FT3) concentrations, normal total and free T4 levels, normal TSH values, and increased serum reverse T3 (rT3) concentration (with the exception of chronic renal failure patients, who had normal rT3 levels). Serum IL-6 concentration was increased above normal (i.e. >100 fmol/L) in almost all NTI patients, especially in those with low T3 values (median value: 258 fmol/L, range 73–3210, vs 152 fmol/L, range <12.5–460, in patients with normal TT3 values, p<0.001). Serum IL-6 values in NTI patients were negatively correlated with serum FT3 values (r=0.56, p<0.001), and positively correlated with serum rT3 values (r=0.78, p<0.001). The increased serum IL-6 levels might represent a systemic reaction to disease, possibly mediated by stimulation of IL-6 synthesis and release induced by other cytokines, such as IL-1 and tumor necrosis factor. Whether IL-6 is simply a marker of NTI or is responsible, at least in part, for abnormalities of thyroid function tests, as suggested by previous in vitro evidence, remains to be established.

Neuropsychological assessment in schoolchildren from an area of moderate iodine deficiency

Neuropsychological assessment was carried out in schoolchildren from a montane area of Eastern Tuscany (Tiberina Valley). This area was found to be moderately iodine deficient (mean urinary iodine excretion: 39 ώg/g creatinine), with a cumulative goiter prevalence of 51.9% in schoolchildren aged 6-14 yr (goiter prevalence in the control iodine-sufficient area: 5.6%). No significant differences in serum TT4, TT3, FT4I, TSH levels between the endemic and control areas were found, whereas serum thyroglobulin values were significantly higher in the iodine-deficient area (61±8 vs 17±1 ng/ml, p < 0.01). No differences were found as to the height, body weight and pubertal development in the two areas. Neuropsychological assessment, performed in a representative sample of 50 schoolchildren from the endemic area and 50 schoolchildren from the control area, matched for age, sex and socioeconomical conditions, failed to show major differences between the two groups in the global neuropsychological performance and cognitive levels. However, minor but significant differences were noted in the information vocabulary and coding subtests, at least in children aged 8. Although familial cultural influences might play a role, it would appear that some marginal impairment, with particular regard to motor-perceptual functions, be present in areas of moderate iodine deficiency.

Neuroimaging and functional outcome of neonatal leukomalacia

Leukomalacia is a major cause of neurological impairment in the high-risk newborn. It can be identified during the early postnatal period by means of ultrasound (US) imaging of the brain, through the anterior fontanel. Magnetic resonance imaging (MRI) permits an optimal differentiation of brain tissue and of its abnormalities, without resorting to ionizing radiation or intravenous contrast. It is particularly appropriate for following the evolution of leukomalacia, after fontanel closure. Ninety-five fullterm and preterm infants with cystic and non-cystic leukomalacia, documented by US, were clinically followed-up until at least 12 months of corrected age. Thirty-two had a severe neurological outcome (mainly cerebral palsy, sometimes associated with mental retardation and/or cerebral visual impairment). The prognosis was worse in cystic leukomalacia than in prolonged flare. Electroencephalogram (EEG) carried out in the first 2 weeks of life provided valuable indexes of further outcome, especially for US findings of more uncertain prognosis. MRI was carried out at around 12 months of corrected age, by means of an apparatus operating at 0.5 Tesla. The main categories of abnormalities observed were the following: cystic lesions, enlarged ventricles with irregular outlines, delayed myelination, high intensity areas in the long TR (repetition time) images within the white matter, cortical atrophy. MRI findings correlated well with the results of US imaging and often with motor, cognitive and visual impairments. Nevertheless, clinical features cannot be predicted by neuroimaging alone and a comprehensive approach, including longitudinal functional and electrophysiological testing, is highly recommended.

Increased serum interleukin-6 concentration in patients with subacute thyroiditis: relationship with concomitant changes in serum T4-binding globulin concentration

Interleukin-6 (IL-6) is the main media-tor of the acute phase response. Increased serum concentrations of the cytokine have been found in patients with nonthyroidal inflammatory disorders and infections. In 18 patients with subacute thyroiditis (SAT) evaluated within 1–2 weeks after the onset of the disease, serum IL-6 values, as assessed by an ELISA method having a limit of detection of 25 fmol/L, ranged 139.2–543.9 fmol/L (mean±SE, 287.2±28.2 fmol/L). These values were significantly higher than those of 25 normal healthy controls (mean±SE, 26.2±5.5 fmol/L, range <25-99.4), 18 of whom had serum IL-6 values below the detection limit. The increase in serum IL-6 levels in SAT patients appeared to be related to the inflammatory disorder and not to thyrotoxicosis, because 18 Graves’ disease patients and 13 patients with toxic adenoma or toxic multinodular goiter had significantly lower serum IL-6 concentrations (101.7+35.2 fmol/L, range <25–251, for Graves’ disease, 79.6±41.4 fmol/L, range <25–168.5, for toxic adenoma, p<0.001 vs SAT for both groups) despite the markedly higher levels of total and free thyroid hormones. Neither free T4 nor free T3 values were correlated with serum IL-6 levels both in SAT and Graves’ patients. Twelve SAT patients were reevaluated 3–4 months later, after remission of the disease and at least one month after glucocorticoid withdrawal. At the final observation, all SAT patients showed a normalization of IL-6 concentration, which was undetectable in 8/12 (meaniSE, 22.8±5.4 fmol/L, p<0.001 vs acute phase values). Mean serum TBG concentra-tion was reduced in SAT patients at the time of first observation (19.3+1.1 mg/L, p<0.001 us controls). While no correlation could be found between serum TBG and serum total or free thyroid hormone levels, serum TBG concentration was inversely correlated with serum IL-6 concentration (r=0.69, p<0.01). Remission of the disease was associated with a significant increase in mean serum TBG concentration to 24.3±1.1 mg/L (p<0.001 vs acute phase values). In conclusion, SAT is associated with an increased serum concentration of IL-6, which normalizes upon remission of the disease. The rise in serum IL-6 levels may at least in part account for the concomitant decrease in serum TBG concentration.

An update on medical management of Graves' ophthalmopathy.

Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease, is a disorder of autoimmune origin, the pathogenic mechanisms of which are still incompletely understood. Although GO is severe in only 3–5% of affected individuals, quality of life is severely impaired even in patients with mild GO. Management of severe GO can be either medical or surgical (orbital decompression, eye muscle or lid surgery). Medical management relies on the use of highdose systemic glucocorticoids or orbital radiotherapy, either alone or in combination. Studies carried out in the last 5 yr have shown that glucocorticoids are more effective through the iv route than through the oral route. However, particular attention should be paid to possible liver toxicity of iv glucocorticoids. Recent randomized clinical trials have, with one exception, confirmed that orbital radiotherapy is an effective and safe therapeutic procedure for GO. At variance with previous encouraging data, recent randomized clinical trials have shown that currently available SS analogs are not very effective in the management of GO. Antioxidants might have a role, at least in mild forms of GO. Particular attention should be paid to correction of risk factors (cigarette smoking, thyroid dysfunction, radioiodine therapy) involved in GO progression.

High prevalence of subacute thyroiditis during summer season in Italy

Eighty consecutive patient6 with typical subacute thyroiditis were evaluated. Sex distribution showed a higher incidence in females (F/M 3.2/1), with a mean age of 44 yr. In the majority of patients (51 /80 = 66%) the onset of the disease was between June and September (46% in July and August). The remaining cases were distributed in the other months without a clear monthly prevalence. These results indicate that the seasonal distribution of subacute thyroiditis is almost superimposable to that of established infections due to some enteroviruses (Echovirus, Coxsackie A and B viruses), suggesting that summer enterovirus infections may be responsible for a large proportion of cases of subacute thyroiditis.

Constantly discontinuous EEG patterns in full-term neonates with hypoxic-ischaemic encephalopathy

OBJECTIVES Selected EEG features were evaluated in 21 constantly discontinuous tracings recorded on the same number of full-term neonates with hypoxic-ischaemic encephalopathy. METHODS The tracings were examined without using interval amplitude as the basis for distinguishing between burst-suppression and nonburst-suppression patterns. RESULTS The results were related to outcomes and other clinical parameters (severity of hypoxic-ischaemic encephalopathy, pO2 levels and drug intake). CONCLUSIONS Features defining the grade of EEG discontinuity (i.e. maximum interval duration, minimum burst duration and interval amplitude) significantly related to outcome and, in most cases, to the grade of hypoxic-ischaemic encephalopathy. Other features (amplitude of slow waves within the burst and incidence of abnormal EEG transients) related to PO2 levels. The consumption of anticonvulsant drugs increased EEG discontinuity, but this effect did not seem dose-related. Finally, the persistence of a constantly discontinuous EEG pattern after the first week of life is a sign of unfavourable prognosis. In full-term neonates with hypoxic-ischaemic encephalopathy quantitative analysis of all constantly discontinuous EEGs seems more useful than only describing burst-suppression patterns on the basis of interval amplitude.

Octreotide treatment does not affect the size of most non­ functioning pituitary adenomas

The somatostatin analogue, octreotide (OC) has commonly been used in the management of growth hormone- and thyrotropin-secreting pituitary tumors, and shown to be effective both on hormone production and tumor size. Because OC receptors may be expressed also in some nonfunctioning pituitary adenomas, it has been postulated that OC might play a role in the treatment of these tumors as well. In the present study, the morphological effects of OC administration, as assessed by computer tomography (CT) scan, were evaluated in 8 patients (5 men, 3 women, age range 25–79 yr) affected by non-functioning pituitary tumors. The drug was given sc at the dose of 100 μg tid for 3–6 months. No significant change in visual field or tumor size occurred after OC treatment in 7 patients, whereas one showed a significant improvement of visual field associated with a decreased tumoral mass. These data suggest that OC is not an effective drug in the management of nonfunctioning pituitary adenomas.