Objective: Selenium (Se) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the iodothyronine selenodeiodinases that catalyse the extrathyroidal production of tri-iodothyronine (T 3 ). Thus, Se deficiency may seriously influence the generation of free radicals, the conversion of thyroxine (T 4 ) to T 3 and the autoimmune process. Therefore, we performed a randomised, placebo-controlled prospective study to investigate the effects of Se treatment on patients with autoimmune thyroiditis (AIT). Design and methods: Sixty five patients aged 22-61 years (median age 48 years) with AIT were recruited into two groups. Group I (Gr I) ðn ¼ 34Þ was treated with selenomethionine (Seme) 200 mg, plus L-thyroxine (LT 4 ) to maintain TSH levels between 0.3-2.0 mU/l, whereas group II (Gr II) ðn ¼ 31Þ received LT 4 plus placebo over a period of 6 months. Moreover, the pharmacokinetics of Seme were studied in 10 patients and eight volunteers at baseline and 2 h, 4 h, 6 h and 24 h after oral administration of a 200 mg tablet of Seme. Finally, Se levels were measured at the end of the study in some patients of both groups and their results were correlated with thyroid hormone levels. Results: In the pharmacokinetics study, basal serum concentration of Se ð75^6 mg=lÞ was within the reference range (70 -125 mg/l), it promptly increased at 2 h, peaked at 4 h ð147^17 mg=l; P , 0:0001Þ and it was abundant in serum at 24 h. In Gr I, antibodies against thyroid peroxidase (anti-TPO) levels showed an overall decrease of 46% at 3 months (from 1875^1039 U=l to 1013^382 U=l; P , 0:0001) and of 55.5% at 6 months. In Gr II the overall decrease of anti-TPO amounted to 21% at 3 months and to 27% at 6 months (from 1758^917 U=l to 1284^410 U=l; P , 0:005). There were no significant changes of antibodies against thyroglobulin levels between the groups. At the end of this study Se levels were found to be statistically significantly increased in Gr I (n = 9/34) compared with Gr II ðn ¼ 11=31Þ ð97^8:4 vs 79^8; P , 0:01Þ but no correlation with thyroid hormone was found. Conclusions: Seme is proven to be rapidly absorbed by the gastrointestinal tract. It appears to be useful as adjunctive therapy with LT 4 in the treatment of AIT. The exact mechanism(s) is not very well determined, it might enhance the activity of detoxifying enzymes and enforce the defense against oxidative stress.

Patients with hypothyroidism are considered to have an increased risk of developing atherosclerosis; because endothelial dysfunction is an early sign of atherosclerosis, we investigated whether endothelial dysfunction is present in patients with hypothyroidism. Thirty-five subjects with various TSH levels were investigated by high-resolution ultrasound imaging of the brachial artery to assess endothelial and smooth muscle responses. Flow-mediated, endothelium-dependent vasodilatation was significantly higher in subjects with TSH 0.4-2 microIU/mL (11.8 +/- 2.7%), compared with subjects with TSH 2.01-4 microIU/mL (6.8 +/- 2.9%), 4.01-10 microIU/mL (5.2 +/- 6.3%) and >10 microIU/mL (4.0 +/- 4.4%); TSH levels correlated inversely to endothelium-dependent dilatation. Thus, flow-mediated vasodilatation, a marker of endothelial function, is impaired not only in patients with mild hypothyroidism but also in subjects with "high-normal" serum TSH levels (ie, 2.01-4.0 microIU/mL) that may be characterized as possibly abnormal.

Both hyper- and hypothyroidism may result in menstrual disturbances. In hyperthyroidism, amenorrhea was described as early as 1840 by von Basedow. The most common manifestation is simple oligomenorrhea (decreased menstrual flow). Anovulatory cycles are very common. Increased bleeding may occur, but is rare in hyperthyroidism. Nowadays hyperthyroidism is diagnosed earlier than it once was, and so the clinical picture is generally milder. So, menstrual disorders are less common than in previous series. In a recent paper, 21.5% of 214 patients had disturbances in their cycle, compared to 50% in some older series. In hypothyroidism, on the contrary, polymenorrhea (increased menstrual bleeding) is more common. Defects in hemostasis may contribute to this. Anovulation may be represent. Fertility is reduced in both hyper- and hypothyroidism, and the outcome of pregnancy is more often abnormal than in euthyroid women. It is of interest that in juvenile hypothyroidism precocious puberty has been described. This is probably due to a "spillover" effect of the glucoprotein hormones: TSH, which is markedly increased in hypothyroidism, has a small FSH- and LH-like effect. Galactorrhea may also be present in hypothyroidism, possibly because TSH, the hypophyseal TSH-releasing hormone, increases the secretion of both TSH and PRL.

Objective: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T 4 ) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range ('highnormal' TSH compared with 'low-normal' TSH). Design and Methods: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol >7.5 mmol/l). Those with 'high-normal' TSH (2.0-4.0 mU/ml) as well as those with 'low-normal' TSH (0.40-1.99 mU/ml) were randomly assigned to receive either 25 or 50 mg T 4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 mg T 4 respectively and groups C and D (high-normal TSH) received 25 and 50 mg T 4 respectively. Serum T 4 , tri-iodothyronine (T 3 ), TSH, free thyroxine index, resin T 3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL, LDL), and triglycerides were determined before and at the end of the two-month treatment period. Results: TSH levels were reduced in all groups. The most striking effect was observed in group D (TSH levels before: 2.77 Ϯ 0.55, after: 1.41 Ϯ 0.85 mU/ml, P < 0:01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0:01) and LDL (P < 0:01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. Conclusions: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration.

We present a patient with hyperthyroidism associated with McCune-Albright syndrome (MAS). MAS is a sporadic genetic disease characterized by polyostotic fibrous dysplasia, cafe au lait cutaneous spots and endocrinopathies (peripheral precocious puberty, thyroidopathies, acromegaly, etc.). It is caused by an activating mutation of the gene for the Gs alpha membrane-associated protein, which mediates the thyrotropin (TSH)-induced and other hormone-induced activation of adenylyl cyclase. A 13-month-old girl was diagnosed with MAS. Precocious puberty was treated initially with testolactone and later with oophorectomy. Subclinical hyperthyroidism was detected biochemically at birth, and 10 months later, it became clinically evident, albeit mild, with absence of goiter. A concomitant liver dysfunction precluded treatment with thionamides and she was sporadically treated with beta-blockers. The combination of increased free thyroxine (T4) and triiodothyronine (T3) with low plasma thyrotropin (TSH) levels in the absence of thyroid-stimulating autoantibodies persisted until the age of 6 years, when she was referred to our unit. Hyperthyroidism was then clinically evident with cardiac hyperactivity, and it was cured with administration of radioiodine (131I). Thyroid disease is the second most common endocrinopathy associated with MAS, and since 1936, 63 cases of thyroidopathies have been described, including 19 nodular (14 with and 5 without hyperthyroidism) and 23 diffuse (20 with and 3 without hyperthyroidism) goiters, and 18 cases of hyperthyroidism without goiter. The previously described somatic activating mutation of the gs alpha gene in the ovaries, the liver and the peripheral blood of our patient, in the absence of stigmata, autoimmunity might be incriminated for the secretory and mitotic activation of the thyroid gland. We suggest the treatment of choice of hyperthyroidism in MAS patients should be 131I administration because: (a) hyperthyroidism is very likely to recur after withdrawal of antithyroid medication; (b) the morbidity of these patients is elevated; (c) oophorectomized patients do not need to be advised to avoid procreation during the months after 131I administration; and (d) finally, even in the usual cases of hyperthyroidism in childhood, 131I treatment is becoming more popular worldwide.