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

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 >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<0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p<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 (<60 years) required more T4 than those in the respective control group (1.61 vs. 1.27 μg/kg weight/day; +27%; p < 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

TAILORING THYROXINE TREATMENT: USEFULNESS OF SOFTGEL PREPARATION IN PATIENTS WITH IMPAIRED GASTRIC PH

Background: Patients with gastric disorders (H.Pylori related gastritis, gastric atrophy, using proton pump inhibitors) require high dose of thyroxine (T4). Gastric pH has been suggested as critical factor for both dissolution and bioavailability of thyroxine. Softgel thyroxine preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet T4 preparation. Clinical studies suggest a better performance of softgel T4 preparation in treating patients with or without T4 malabsorption. Aim: To analyze whether, in vivo, the better efficacy of softgel preparation may be related to the pH variations of gastric juice. Methods: We enrolled 28 hypothyroid patients treated, for at least 2 years, with a stable dose of tablet T4 (median = 1.65 μg/kg/day) showing a consistent and stable TSH values (mU/l). All patients warranted to take T4 in fasting conditions waiting at least one hour before eating or drinking. All of these patients underwent endoscopy for either dyspepsia or follow up of gastric disorders. Gastric juice has been sampled during endoscopy to measure gastric pH. These patients switched to softgel T4 preparation, titrated to obtain individual serum TSH values as above. Results: Mean gastric juice pH in the whole sample was 2.87 and, based on this value, patients were subdivided in two groups: Group A (n = 20) with a mean pH of 1.69 and Group B (n = 8) showing a mean pH of 5.81, that mirrors a defined reduced gastric acid production. The pH values well correlated with the dose of T4 in both groups (p = 0.0329 and 0.0023). Following the switch to softgel, T4 requirement was the same in 19 out of 20 (95%) of patients with normal pH. On the contrary in 7 out of 8 (88%, p < 0.0001; PPV 95%, Likelihood ratio = 7.6) patients with high gastric pH the requirement of T4 in softgel formulation was significantly reduced. The median reduction in these latter patients was from 1.98 to 1.67 μg/kg/day (–19%). Conclusions: These data indicate that the dose of both tablet and softgel thyroxine correlates with gastric pH and, in hypothyroid patients with disorders or conditions impairing gastric acid secretion, softgel T4 preparation should be the preferred therapeutic choice

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

Occurrence and Risk Factors for Autoimmune Thyroid Disease in Patients with Atrophic Body Gastritis

Purpose: To investigate the occurrence of and risk factors for autoimmune thyroid disease in atrophic body gastritis patients. Methods: Cross-sectional study on 401 consecutive outpatients with atrophic body gastritis. Diagnostic work-up of thyroid disease was completed in 319 atrophic body gastritis patients (225 women, median age 55.5 years [range 17-95 years]). Data on anagraphics, lifestyle, family history, and biochemical and histological items were obtained at baseline, and associations between atrophic body gastritis and autoimmune and nonautoimmune thyroid diseases were explored through descriptive statistics and logistic regression analyses. Results: Of the 319 atrophic body gastritis patients, 169 (53%) had an associated thyroid disorder, and 89 (52.7%) of these were unaware of it. The thyroid disease was autoimmune in 128 patients (75.7%) and nonautoimmune in 41 patients. Logistic regression showed that risk factors for having autoimmune thyroid disease in atrophic body gastritis patients were female sex (odds ratio [OR] 5.6, 95% confidence interval [CI], 2.6-12.1), presence of parietal cell antibodies (OR 2.5, 95% CI, 1.1-5.5), and presence of metaplastic atrophy (OR 2.2, 95% CI, 1.0-5.0). Conclusions: Autoimmune thyroid disease and atrophic body gastritis occur in a closely linked fashion, suggesting that atrophic body gastritis patients should be investigated for an occult autoimmune thyroid disease, in particular women and those with positive parietal cell antibodies. © 2008 Elsevier Inc. All rights reserved

Increased interleukin-4-positive lymphocytes in patients with Hashimoto's thyroiditis and concurrent non-endocrine autoimmune disorders

A prevalent T helper type 1 (Th1) subset of lymphocytes has been described in Hashimoto's thyroiditis (HT), but whether a similar polarizationmay characterize HT when associated with non-endocrine autoimmune disorders (NEAD) is not known. The aim of the present study was to analyse the intracellular Th1 and Th2 distinctive cytokines in patients with isolated HT or associated with non-endocrine autoimmune disorders. Intracellular cytokine expression was assessed in peripheral blood lymphocytes (PBL) of 68 out-patients (females = 55; males = 13; median age = 36 years) with HT : 33 had isolated HT and 35 had a concurrent NEAD. The percentage of interferon (IFN)-gamma and interleukin (IL)-2 Th1- and IL-4 Th2-positive cells was measured by flow cytometric analysis. We found an increased percentage of IL-2-positive cells in all patients, without differences between patients with isolated HT or associated with NEAD. IFN-gamma(+) cells were also increased in both groups, but the median percentage of those with isolated HT was lower than in patients with HT+NEAD (19.0 versus 29.9%; P = 0.0082). An increased number of IL-4-positive cells was observed in three of 33 (9.1%) patients with isolated HT and in 25 of 35 patients with NEAD [71%; P &lt; 0.0001; relative risk (RR) = 3.18]. The median values of IL-4(+) cells (HT = 5.0% versus HT + NEAD = 16.8%) confirmed this large difference (P &lt; 0.0001). A clear-cut increase of IL-4(+) lymphocytes characterizes patients with autoimmune thyroiditis who have associated non-endocrine autoimmune disorders. These findings may represent an initial tool to detect patients with autoimmune thyroiditis in which additional non-endocrine autoimmune disorders may be awaited