admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

http://www.medicalonline.hu/download.php?id=18396

Hashimoto thyroiditis: clinical and diagnostic criteria.

Current smoking in population surveys is associated with a slight dose-dependent fall of serum TSH, likely secondary to a rise of serum FT4 and FT3 induced by activation of the sympathetic nervous system; it is independent of iodine intake. In contrast, the slightly greater thyroid size in smokers is observed in iodine-deficient but not in iodine-sufficient areas and caused by competitive inhibition of thyroidal iodide uptake by thiocyanate. Smokers have an increased prevalence of nontoxic goitre and thyroid multinodularity, at least in iodine-deficient areas. Current smoking reduces dose dependently the risk of thyroid cancer, which is more pronounced for papillary than for follicular types; the risk in former smokers approaches that of never smokers. The lower TSH and lower body mass index in smokers might contribute to this reduced risk. Current smoking lowers the risk of developing thyroid peroxidase and thyroglobulin antibodies and subclinical and overt autoimmune hypothyroidism; the effect is dose dependent, but disappears within 3 years after quitting smoking. There is evidence from an animal model of experimental autoimmune thyroiditis that anti-inflammatory effects of nicotine are involved. In contrast, smoking is a dose-dependent risk factor for Graves' hyperthyroidism and especially for Graves' ophthalmopathy. Smoking is related to a higher recurrence rate of Graves' hyperthyroidism, a higher risk on Graves' ophthalmopathy after 131I therapy and a less favourable outcome of GO treatment with steroids or retrobulbar irradiation. The observed associations with smoking likely indicate causal relationships in view of consistent associations across studies, the presence of dose-response effects and disappearance of associations after cessation of smoking.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cen.12222

Smoking and thyroid.

Autoimmune diseases have a high prevalence in the population and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroperoxidase, thyroid stimulating hormone receptor and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of thyroid stimulating hormone receptor antibodies on fibroblasts in Graves’ disease, studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroperoxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroperoxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in Graves’ disease and Hashimoto’s thyroiditis.

/pdf/thyroid-autoimmunity-role-of-anti-thyroid-antibodies-in-3cqbzja3ml.pdf

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

The last 10 years have seen some progress in understanding the etiology of autoimmune thyroid disease (AITD). The female preponderance can now be explained - at least in part - by fetal microchimerism and X-chromosome inactivation. The number of identified susceptibility genes for AITD is increasing (among others now including TSHR, TG, HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, and FOXP3), but these genes together probably do not explain more than about 10% of the heritability of AITD. As twin studies indicate that genes contribute for 70% of AITD, it follows that there must be many more loci, each of them contributing a little. While the genetic studies have clarified why various autoimmune diseases so often cluster in the same patient, the molecular mechanism of action of these genetic polymorphisms (frequently located in introns) has hardly been explained. Polymorphisms in AITD susceptibility genes may become helpful in clinical practice, e.g. in assessing risk of recurrent Graves' hyperthyroidism (GH) after a course of antithyroid drugs. Moderate alcohol intake decreases the risk on overt GH and overt Hashimoto's hypothyroidism. Current smokers - as well known - are at increased risk for Graves' disease, but - surprisingly - at diminished risk for Hashimoto's thyroiditis. Low selenium and low vitamin D levels might increase the risk of developing AITD, but data are still inconclusive. Current options for preventive interventions in subjects at risk to develop AITD are very limited.

/pdf/mechanisms-in-endocrinology-autoimmune-thyroid-disease-old-1carzg3mqz.pdf

MECHANISMS IN ENDOCRINOLOGY: Autoimmune thyroid disease: old and new players

Context: Vitamin D deficiency has been identified as a risk factor for a number of autoimmune diseases including type 1 diabetes and multiple sclerosis. Objective: We hypothesized that low levels of vitamin D are related to the early stages of autoimmune thyroid disease (AITD). Design: Two case‐control studies were performed. In the cross-sectional study A, euthyroid subjects with genetic susceptibility for AITD but without thyroid antibodies were compared with controls. Cases were subjects from the Amsterdam AITD cohort (euthyroid women who had first- or second-degree relatives with overt AITD) who at baseline had normal TSH and no thyroid antibodies; controls were healthy women examined at the same period. In the longitudinal study B, subjects who developed de novo thyroid peroxidase antibody (TPO-Ab) were compared with those who did not. Cases and controls were subjects from the Amsterdam AITD cohort who at baseline had normal TSH and no thyroid antibodies and during follow-up developed TPO-Ab (cases) or remained without thyroid antibodies (controls). Controls in both studies were matched for age, BMI, smoking status, estrogen use, month of blood sampling, and in study B for the duration of follow-up. Results: Serum 25(OH)D levels were as follows: study A: 21.0G7.9 vs 18.0G6.4 ng/ml (78 cases vs 78 controls, PZ0.01); study B: baseline, 22.6G10.3 vs 23.4G9.1; follow-up 21.6G9.2 vs 21.2 G9.3 ng/ml (67 cases vs 67 controls, NS). Conclusions: Early stages of thyroid autoimmunity (in study A genetic susceptibility and in study B development of TPO-Ab) are not associated with low vitamin D levels.

/pdf/vitamin-d-deficiency-is-not-associated-with-early-stages-of-51epxvojek.pdf

Vitamin D deficiency is not associated with early stages of thyroid autoimmunity

Objective: To evaluate the progression in time from euthyroidism to overt autoimmune hypothyroidism or to overt autoimmune hyperthyroidism. Subjects and methods: The design is that of a nested case–control study within the prospective Amsterdam autoimmune thyroid disease (AITD) cohort study in which 790 healthy euthyroid women with at least one first or second degree relative with documented AITD were followed for 5 years. Thyroid function tests were assessed annually. Contrast between cases (overt hypothyroidism – TSHO 5.7 mU/l and free thyroxine (FT4)!9.3 pmol/l and overt hyperthyroidism – TSH!0.4 mU/l and FT4O20.1 pmol/l, also referred to as events) and controls (matched for age and duration of follow-up). Results: At baseline, the 38 hypothyroid cases had already higher TSH and lower FT4 concentrations than their 76 controls, and the difference between both the groups persisted 1 year before occurrence of the event. In contrast, neither TSH nor FT4 values differed between the 13 hyperthyroid cases and their 26 controls at baseline or 1 year before the event. The prevalence of thyroid peroxidase-Ab was higher in both hypothyroid and hyperthyroid cases than in controls. At the time of event, hypothyroid cases were less common among current smokers (PZ0.083) and more common in the postpartum period (PZ0.006) than their controls, whereas hyperthyroid cases were pregnant more frequently (PZ0.063). Conclusions: The data suggest that progression toward overt autoimmune hypothyroidism is a gradual process taking several years, but in contrast overt autoimmune hyperthyroidism develops faster in terms of months.

/pdf/natural-history-of-the-transition-from-euthyroidism-to-overt-48418z0pem.pdf

Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study

Context: Autoimmune thyroid disease develops in genetic susceptible subjects, provoked by environmental factors. Little is known of the environment in the early stages of autoimmunity. Objective: We evaluated environmental factors contributing to de novo occurrence of thyroid antibodies. Design: We conducted a prospective cohort study of 521 euthyroid women without thyroid antibodies in serum who were relatives of autoimmune thyroid disease patients. Follow-up was 5 yr. Baseline characteristics were related to the occurrence of thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibodies. Exposure to environmental factors in the year prior to the occurrence of antibodies was investigated in a nested case-control study. Results: The 5-yr probability for conversion to TPO antibodies (TPO-Ab) and/or Tg antibodies (Tg-Ab) was 20.1%, and for TPO-Ab alone the probability was 14.5%. None of the baseline characteristics except TSH contributed to the risk of seroconversion. Each case (occurrence of antibodies) wa...

Grigoris Effraimidis

Papers

MECHANISMS IN ENDOCRINOLOGY: Autoimmune thyroid disease: old and new players

Vitamin D deficiency is not associated with early stages of thyroid autoimmunity

Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study

Discontinuation of Smoking Increases the Risk for Developing Thyroid Peroxidase Antibodies and/or Thyroglobulin Antibodies: A Prospective Study

Involvement of stress in the pathogenesis of autoimmune thyroid disease: a prospective study.