Hashimoto's thyroiditis and autoimmune gastritis

The term "thyrogastric syndrome" defines the association between autoimmune thyroid disease and chronic autoimmune gastritis (CAG), and it was first described in the early 1960s. More recently, this association has been included in polyglandular autoimmune syndrome type IIIb, in which autoimmune thyroiditis represents the pivotal disorder. Hashimoto's thyroiditis (HT) is the most frequent autoimmune disease, and it has been reported to be associated with gastric disorders in 10-40% of patients while about 40% of patients with autoimmune gastritis also present HT. Some intriguing similarities have been described about the pathogenic mechanism of these two disorders, involving a complex interaction among genetic, embryological, immunologic, and environmental factors. CAG is characterized by a partial or total disappearance of parietal cells implying the impairment of both hydrochloric acid and intrinsic factor production. The clinical outcome of this gastric damage is the occurrence of a hypochlorhydric-dependent iron-deficient anemia, followed by pernicious anemia concomitant with the progression to a severe gastric atrophy. Malabsorption of levothyroxine may occur as well. We have briefly summarized in this minireview the most recent achievements on this peculiar association of diseases that, in the last years, have been increasingly diagnosed

Early detection of biochemically occult autonomous thyroid nodules

Objective: Autonomously functioning thyroid areas may be associated with subclinical or overt hyperthyroidism, but may exist even in the presence of normal TSH. This study was aimed at comparing the rate of autonomously functioning areas and their cardiac sequelae in patients with nodular goitre studied with the usual and a novel approach. Design and methods: In total 490 adult outpatients with thyroid nodular goitre, living in a mild iodine-deficient area, were selected in our referral centre for thyroid diseases from 2009 to 2014 on the basis of a suspicion of thyroid functional autonomy. They were divided in three groups according to a non-conventional approach (excessive response to thyroxine treatment: group 1) or conventional approach (low/normal TSH with clinical suspicion or low TSH: groups 2 and 3). All patients of the study with the suspicion of thyroid functional autonomy underwent thyroid scan with radioactive iodine (I131) uptake (RAIU). Results: The percentage of confirmed thyroid functional autonomy was 319/490, being significantly higher in group 3 than in groups 1 and 2 (81.5 vs 64.7 vs 52.6%; chi-square P < 0.0001). However, the diagnosis with non-conventional approach was made at a significant earlier age (P < 0.0001). Cardiac arrhythmias as well as atrial fibrillation were similarly detected by conventional and non-conventional approaches (chi-square test: P = 0.2537; P = 0.8425). Conclusions: The hyper-responsiveness to thyroxine treatment should induce the suspicion of thyroid functional autonomy at an early stage, allowing to detect autonomous functioning areas in apparently euthyroid patients

L'impatto delle patologie gastrointestinali sul trattamento tiroxinico

Negli ultimi anni l’approccio alla terapia tiroxinica è mutato da una condizione di empirismo posologico a una fine calibrazione che consente di prevederne un dosaggio individualizzato. Il mancato raggiungimento del target terapeutico in corso di terapia con levotiroxina può derivare non solo da un inadeguato rapporto medico-paziente o dall’interazione con altri farmaci, ma anche e soprattutto dalla presenza di patologie gastrointestinali concomitanti, frequentemente occulte. La terapia tiroxinica diviene così, oltre che strumento terapeutico, un possibile strumento diagnostico

A case report of thyroid carcinoma confined to ovary and concurrently occult in the thyroid. Is conservative treatment always advised?

Introduction: Struma ovarii is an ovarian teratoma, represented in more than 50% by thyroid tissue. Five percent of struma ovarii cases have been proven to be malignant and, as in the thyroid gland, papillary thyroid carcinoma is the most common histotype arising in struma ovarii. Because of the unusual occurrence of this tumor, its management and follow-up after pelvic surgery is still controversial. Usually, total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii, while these procedures are still controversial in non-metastatic thyroid cancer arising in struma ovarii. Case Presentation: We report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii. After pelvic surgery, thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered. The patient underwent total thyroidectomy and histological examination showed a papillary carcinoma. Radioiodine-ablation of residual thyroid tissue was performed and levothyroxine mildly-suppressive treatment was started. Conclusions: A more aggressive treatment should not be denied for malignant struma ovarii without any evidence, even when apparently confined into the ovary. However, in selected cases, aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow-up

Daily requirement of softgel thyroxine is independent from gastric juice pH

BackgroundSoftgel levothyroxine (LT4) preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet LT4 preparation. Clinical studies suggested a better performance of softgel LT4 preparation in patients with gastric disorders but whether this finding is related to gastric juice pH variation in vivo is not known. MethodsTwenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 mu g/kg/day) and with stable thyroid stimulating hormone (TSH) values on target ( mU/l) have been shifted to softgel LT4 preparation. The dose of softgel LT4 has been titrated to obtain a similar individual serum TSH value. All subjects followed a specific treatment schedule, taking LT4 in fasting condition and then abstaining from eating or drinking for at least 1 hour. Owing to the presence of long-lasting dyspepsia or of already known gastric disorders, all patients underwent endoscopy, upon informed consent. Gastric juice has been collected during endoscopy to measure gastric pH. Then we plotted the dose of LT4 with the gastric pH obtained in vivo, before and after the switch tablet/softgel preparation in all patients. ResultsUpon the switch tablet/softgel preparation, the therapeutic LT4 dose was very slightly reduced (-6%) in the whole sample. However, the individual variations revealed the existence of two populations, one without any dose reduction (A) and the other showing a dose reduction &gt;20% (B). Upon matching with the actual gastric pH, patients with normal pH (A: n=17; 14F/3M, median 1.52) no showed a lower softgel LT4 requirement. Instead, among patients with reduced gastric acid production (B: n=11; 10F/1M, median pH 5.02) the vast majority (10/11; 91%, p&lt;0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p&lt;0.0001). Interestingly, the dose of LT4 in tablet correlated with pH value (Spearman's rho =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman's rho =1.952; p = 0.3194). ConclusionsThese findings provide evidence that softgel LT4 preparation is independent from the actual gastric pH in humans and may represent a significant therapeutic option in patients with increased LT4 requirement, owed to disorders impairing the gastric acidic output

Ulcerative Colitis as a Novel Cause of Increased Need for Levothyroxine

Background: Thyroxine absorption takes place at the small intestine level and several disorders affecting this intestinal tract lead to thyroxine malabsorption. An increased need for thyroxine has also been observed in gastric disorders due to variations in drug dissolution and/or in its ionization status. Ulcerative colitis (UC) is an inflammatory bowel disease that has been postulated as a potential cause of the increased need for thyroxine, but there is a lack of evidence on this topic. This study is aimed at measuring the thyroxine requirement in hypothyroid patients with UC.Patients and Methods: Among 8,573 patients with thyroid disorders consecutively seen in our referral center from 2010 to 2017, we identified 34 patients with a definite diagnosis of UC. Thirteen of them were hypothyroid (12 F/1 M; median age = 53 years), bearing UC during the remission phase and in need for thyroxine treatment, thus representing the study group. The dose of T4 required by UC patients has been compared to the one observed in 51 similarly treated age- and weight-matched patients, compliant with treatment and clearly devoid of any gastrointestinal and /or pharmacological interference.Results: To reach the target serum TSH, the dose of thyroxine had to be increased in twelve out of thirteen (92%) hypothyroid patients with ulcerative colitis. The median thyroxine dose required by UC patients was 1.54 μg/kg weight/day, that is 26% higher than the control patients, to reach a similar TSH (1.23 μg/kg weight/day; p = 0.0002). Since half of our study group consisted of patients aged over 60 years old, we analyzed the effect of age on the subdivision in two classes. Six out of seven (86%) adult patients (&lt;60 years) required more T4 than those in the respective control group (1.61 vs. 1.27 μg/kg weight/day; +27%; p &lt; 0.0001). An increased dose (+17%; p = 0.0026) but to a lesser extent, was also observed in all patients over 60 years, as compared to the control group.Conclusions: In almost all hypothyroid patients with UC, the therapeutic dose of thyroxine is increased. Therefore, ulcerative colitis, even during clinical remission, should be included among the gastrointestinal causes of an increased need for oral thyroxine

THYROXINE TREATMENT IN OVERWEIGHT AND OBESE HYPOTHYROID PATIENTS

Objective: Levothyroxine (LT4) is used by almost 13 million patients in USA and in the same country it has been estimated that 35% of subjects are obese. Oral thyroxine has a narrow therapeutic index and the dose must be tailored on the patient to avoid the over- or under-treatment and the related side effects. Studies on this subject were mostly carried out in thyroidectomized patients and/or in non standardized treatment schedule. Our study was aimed at investigating LT4 daily requirement in overweight or obese patients taking T4 in a tightly controlled fashion. Methods: Upon the exclusion of patients non-compliant and/or using drugs and/or with diagnosed gastrointestinal disorders, 60 overweight/obese hypothyroid patients with Hashimoto’s thyroiditis (55 F/5 M; median age = 44 ys) represented the study group. They were subdivided in: 26 overweight (O), 17 class I obese (C-I), 10 class II obese (C-II), 7 class III obese (C-III). Thirtyfive (34 F/1 M; median age = 40 ys) age-matched patients with normal BMI (35 kg/m2; n = 17) (–12%; p = 0.023). Conclusion: Daily T4 requirement is similar in normal and overweight patients while all classes of obese patients show a progressively reduced need for T4 requirement

TH17 AND REGULATORY B CELLS PROFILE IN PATIENTS WITH HASHIMOTO‘S THYROIDITIS ASSOCIATED WITH SYSTEMIC SCLEROSIS

Objectives: Hashimoto’s thyroiditis (HT) is highly prevalent in women with systemic sclerosis (SSc). HT is characterized by a Th17/Th1 polarization and an increased number of B regulatory (Breg) cells. Previous studies described an increased amount of naïve B cells with a decrease of memory B cells in isolated SSc. The aim of the study has been to characterize Th17 and Breg cell subsets in patients with HT associated with SSc. Methods: A total of 49 patients (44W/5M; mean age: 48 years) were selected: of these, 19 (17W/2M) had isolated HT and 12 patients (11W/1M) had SSc; seven of these latter also had Hashimoto’s thyroiditis (SSc+HT). Eighteen healthy donors (HD) (16W/2M) represented the reference group. Freshly PBMCs were assessed by FACS to characterize Th17 and Breg lymphocytes phenotypes. Moreover, activated Breg (IL-10+) have been measured upon stimulation with CpG oligonucleotide. Result: Mean percentage of Th17+ lymphocytes was 2.4±1.7% in isolated HT and significantly lower when associated with SSc (0.9±0.9%;p=0.0109). Breg cells (CD24hi CD38hi) were increased in patients affected by SSc, both isolated (4.6±2.9%) or associated with HT (4.6±3.2%), as compared to both patients with isolated HT (2.4±0.9%) and HD (2.0±0.7%; p=0.033). Following stimulation, the percentage of Breg cells was significantly higher in patients with SSc (13.6±5.6%) and SSc+HT (10.4% ± 4.9) than in HD (p<0.001 and p=0.0002) and isolated HT (p=0.0027 and p=0.0008). However, despite this increase, the cells producing IL-10 were lower in patients with SSc and SSc+HT (0.5±0.4% and 0.8±1.2%) than in HD (2.4±1.1% p=0.0231 and p=0.0015) and in isolated HT (3.9±1.8%; p=0.012 and p=0.0008). Conclusions: In patients with HT and SSc there was a reduction of Th17 and an increased percentage of Breg cells, but a clear reduction of IL-10+ Breg, as compared with those in isolated HT patients

RECURRENT PREGNANCY LOSS IN WOMEN WITH HASHIMOTO'S THYROIDITIS WITH CONCURRENT NON-ENDOCRINE AUTOIMMUNE DISORDERS

BACKGROUND: An increased rate of recurrent miscarriage has been described in patients with autoimmune thyroid disease. However, there is a lack of studies that assess the rate of recurrent pregnancy loss (RPL) in patients with Hashimoto's thyroiditis (HT) isolated or with concurrent non-endocrine autoimmune disorders (NEAD). The objective of the study was to assess the rate of recurrent pregnancy loss in patients with HT isolated or accompanied with non-endocrine autoimmune diseases. METHODS: This is a retrospective observational cohort study with systematic review of the NEAD with concurrent HT in an outpatient Endocrinology Unit at a University Hospital. Among the 3480 consecutively examined women with HT, 87 patients met the criteria of RPL and represented the study group. Sixty-five of them had isolated HT and 22 women had HT+NEAD. RESULTS: The rate of RPL in women with HT was 2.1% versus 5.64% observed in women with HT+NEAD (OR=2.78, 95%CI=1.70-4.57; p&lt;0.0001). Upon subdivision, this difference was still evident in euthyroid patients (p&lt;0.0001), while it disappeared in hypothyroid women (p=0.21). RPL did not correlate with the autoantibody concentrations nor in women with isolated HT nor in those with HT+NEAD. The presence of antiphospholipid syndrome (APS) explained RPL in 3/22 (14%) patients with HT+NEAD, the remaining being related to different autoimmune disorders. Interestingly, even subtracting the patients with APS, RPL was more frequent in patients with poly-autoimmunity than in patients with isolated HT (p=0.0013). CONCLUSIONS: The co-presence of NEAD is correlated with a higher risk of RPL in women with HT. The association with APS may explain only a fraction of RPL rate in patients with polyautoimmunity