This study was designed to assess patients with chronic hepatitis C (CHC) for the presence of thyroid autoimmunity and dysfunction, to evaluate the risk of thyroid disorders associated with interferon (IFN) therapy, and to survey the outcome of possible treatment-related thyroid injury. Out of 104 consecutive untreated patients (30 women and 74 men; mean age, 52.7 years), 8 (7.7%) were found seropositive for thyroid autoantibodies (ThyAb), whereas seropositivity in healthy controls was 1/98 (1.3%). The relative increase in risk of developing thyroid autoimmunity associated with CHC was 760% (95% CI, 220-1300%). No patients had abnormalities of thyroid function tests, but on IFN treatment, 3/3 patients showed a rapid over-range rise in circulating thyrotropin, which returned to normal after therapy discontinuation. In the other 5 seropositive patients who refused treatment, thyroid function remained normal. Out of the 58 initially seronegative patients who consented to IFN treatment, 9 (15.5%) developed thyroid autoimmunity. Seven of them (77.7%) had thyroid dysfunction: hypothyroidism in 4 cases, transient thyrotoxicosis in 2 cases. The last patient developed TSH-receptor antibodies and Graves' disease, requiring methimazole therapy. Thyroid function recovered in the former 6 cases following IFN discontinuation. In the 28 initially seronegative patients who refused IFN and participated in a preliminary tauroursodeoxycholic acid trial, antithyroglobulin antibodies alone appeared in one case, but no thyroid dysfunction was observed. The relative risk of thyroid autoimmune disorder associated with IFN therapy was 342% (28-636%). The patients with CHC were unlikely to develop thyroid dysfunction in the absence of IFN therapy, in spite of being ThyAb seropositive. Moreover, a considerable proportion of seronegative patients, when IFN-treated, developed thyroid autoimmunity and then thyroid dysfunction. Both in seropositive and seronegative patients immediate IFN discontinuation normalized thyroid function and hormone replacement therapy was not necessary.

Thyroid function and presence of thyroid autoantibodies were assessed in a group of 75 consecutive female patients with mood disturbances and in a group of 38 healthy women of similar age recruited as controls. Nine patients suffered from major (endogenous) depression and 66 from minor (neurotic) depression. The individual patients had normal values of circulating thyroid hormones. Nevertheless, endogenously depressed patients had total serum triiodothyronine (M +/- SE = 1.49 +/- 0.09 nmol/l) and both total (83.9 +/- 4.3 nmol/l) and free serum thyroxine (13.9 +/- 1.1 pmol/l) lower than in the group of minor depressed and in the group of controls (p < 0.01, in both comparison). The median value of serum thyrotropin was 5.22 mU/l in the major depressed patients versus 1.72 mU/l in the minor depressed and 1.69 mU/l in the controls. Thyroid function test results in the minor depressed group did not significantly differ from those in the controls. Five of the 9 endogenously depressed patients were subclinically hypothyroid, while none of the 66 patients with minor depressive disorder showed thyroid dysfunction. Antibodies against thyroglobulin and/or thyroid peroxidase were positive in all the 5 endogenously depressed women with subclinical hypothyroidism, revealing a symptomless autoimmune thyroiditis, which was also confirmed by ultrasonography in all cases and histopathologically demonstrated in one case. None of the endogenously depressed women without thyroid dysfunction and none of the 66 minor depressives were seropositive for thyroid autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract. The circadian rhythm of TSH secretion and its typical pattern were investigated during the spring of two successive years in a group of 12 adult women, and then in a group of 12 adult men, both having normal thyroid function. Blood samples were obtained from each individual every two h for 24 h. TSH was measured by RIA. Data were processed by inferential analysis and represented using the cosinor method. The chronobiological rhythm of TSH is in good agreement with the typical function of circadian rhythms both in men and in women, significance averaging ‰. The typical parameters of the rhythm (M = mesor, i.e. the mean level of the rhythm; A = amplitude of the sinusoidal function approximating the rhythm; Ø = acrofase, i.e. the lag from a reference timepoint of the crest time in the function) under the conditions used in our investigation were shown to be: Male subjects: mean ± se = 3.72 ± 0.21 mU/l, A (95% C.I.) = 1.15 (0.93–1.47) mU/l; Ø (95% C.I.) = 3.9° (−8.6° + 23.8°). Female subjects: mean ± SE = 5 ± 0.13 mU/l; A (95% C.I.) = 0.96 (0.86–1.11) mU/l; Ø (95% C.I.) = 8.8° (−0.2° + 20.5°). The patterns of TSH biorhythm are practically identical in both sexes. Taking into account the methods used and the results obtained we think that the circadian rhythm of TSH secretion is programmed in both sexes in order to meet the cyclic requirements of the target gland, while several other factors which mark the course of the day at the level of central nervous structures function as rhythm harmonizers.

Indobufen is a reversible inhibitor of platelet prostaglandin G/H-synthase. To verify the dose dependence of the antiplatelet effect of indobufen on ex vivo and in vivo indexes of thromboxane (TX) biosynthesis and TXAj-dependent platelet function, we studied nine patients with non-insulin-dependent diabetes mellitus (NIDDM). This was a randomized, double-blind, crossover study in which each patient was treated with three different daily regimens (50 rag BID, 100 mg BID, and 200 mg BID) of indobufen for 1 week, with a 7-day washout period between treatments. Urinary 11-dehydro-TXBj excretion averaged 58.2±21.8 ng/h at baseline. TX metabolite excretion was reduced dose dependently by indobufen: by 67% at 50 mg BID, 72% at 100 mg BID, and 81% at 200 mg BID. Platelet cyclooxygenase activity, ATP release, collageninduced platelet aggregation, and bleeding time also were modified dose dependently by indobufen. Biochemical demonstration of suppressed platelet TX A 2 in vivo was accompanied by evidence of inhibited platelet function as assessed ex vivo. Under pathophysiological conditions, such as NIDDM, which are associated with enhanced TX A 2 synthesis, more than 95% suppression of platelet cyclooxygenase activity may be necessary to produce virtually maximal inhibition of platelet TXA 2 biosynthesis in vivo. The inhibitor effect of the racemic mixture can be largely accounted for by the action of the S-isomer. 2Indobufen currently is used as an antithrombotic agent at a dosing regimen of 200 mg BID. At this dose, its antithrombotic effect is comparable to that of aspirin (325 mg TID) plus dipyridamole (75 mg TID) in preventing graft occlusion after coronary artery bypass surgery.3 Dose-ranging studies with indobufen were largely based on capacity-related measurements of platelet function ex vivo. 4 -7 Because the latter do not necessarily reflect the extent of platelet inhibition in vivo, we set out to explore the dose dependence of the antiplatelet effect of indobufen through ex vivo and in vivo measurements of thromboxane (TX) biosynthesis and TX A 2 -dependent platelet function. We performed a double-blind, crossover study in patients with non-insulin-dependent diabetes mellitus (NIDDM) with macrovascular complications because of previous evidence for enhanced TX A 2 biosynthesis in this setting.

Relapses of hyperthyroidism after treatment with radioiodine for uni- or multi-nodular goiter may be accompanied by the appearance of TSAb. However, this phenomenon has only emerged from one retrospective study on Northern European patients, in which it was not possible to determine whether TSAb also appeared in treated patients who did not relapse. The present study aimed to assess the appearance, immunogenic nature and clinical characteristics of hyperthyroidism relapse after treatment with 131I for nodular toxic goiter in patients from the Mediterranean area. A retrospective study was performed on 76 consecutive patients, born and resident in Sicily and aged 56-80 yr at diagnosis, who were treated with radioiodine. Serum aliquots obtained from the patients before 131I treatment and during a follow-up of 36-144 months were assayed for TSAb and TPOAb. The clinical charts of the patients were also re-examined. Twenty-six out of 76 patients (36.8%) had a hyperthyroidism relapse after a first treatment with 131I. Eight of the 26 (30.7%) also relapsed after the second treatment. Three out of 26 (11.5%) relapsed after a third treatment. The 50 patients who required only one treatment and the 18 who relapsed only once were all TSAb-negative at baseline, while 3/8 (37.5%) who relapsed also after the second treatment were already TSAb-positive at baseline. TSAb became positive in 3/18 patients (16.7%) who relapsed once, and in 4/8 (50.0%) of those who relapsed after a second treatment. One of these 7 TSAb-positive relapsers was also already TPOAb-positive at baseline and another became TPOAb-positive after treatment. The presence of circulating TSAb in 3/76 (3.9%) patients before treatment for toxic goiter more probably points to a diagnosis of Marine-Lenhart's syndrome. In contrast, the de novo appearance of TSAb in the presence of hyperthyroidism relapse in 4/76 (5.3%) patients suggests the development of a Graves'-like disease after radioiodine treatment. This occurrence does not seem to have precise ethnic grounds, since the incidence we observed in Mediterranean patients was similar to that previously reported in Northern European patients.