Daily requirement of softgel thyroxine is independent from gastric juice pH.

Background: Softgel 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. Methods: Twenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 µg/kg/day) and with stable thyroid stimulating hormone (TSH) values on target (<0.8-2.5> 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. Results: Upon 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 ρ =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman's ρ =1.952; p = 0.3194). Conclusions: These 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.

Levothyroxine treatment and gastric juice pH in humans: the proof of concept.

PURPOSE: Despite the absorption of oral thyroxine (T4) occurs in the small bowel, several patients with gastric disorders show an increased need for T4. In vitro evidence suggested that medium pH variations interfere with T4 dissolution. This study was aimed at finding the proof of concept of a direct relationship between the minimal effective dose of T4 and the actual gastric juice pH. PATIENTS AND METHODS: Among 311 consecutively thyroxine-treated patients, 61 bearing Hashimoto's thyroiditis (52 F/9 M; median age = 51 years) who complained persistent dyspepsia and/or upper abdominal symptoms following a noninvasive workup for gastrointestinal disorders, underwent EGDS with multiple biopsies and gastric juice pH measurement. All patients accepted to take thyroxine in fasting conditions, abstaining from eating or drinking for one hour. RESULTS: Thyroxine requirement increased along with the rising gastric pH (ρ = 0.4229; p = 0.0007). A multivariate analysis revealed that gastric pH was, beside body mass index, the far more important independent variable in determining the effective dose of T4 (p = 0.001). The ROC curve revealed that the pH threshold for an increased thyroxine requirement was at 2.28, being the AUC by 78%. Subdividing patients by the histologic findings, it appeared a significant increase (p = 0.0025) along with the progressive damage of gastric mucosa. CONCLUSION: The in vivo measurement of gastric pH highlighted its key role in determining the minimal effective dose of oral T4 and may explain the interference of food, of some drugs and gut disorders on levothyroxine treatment.

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 RPL in patients with HT isolated or accompanied with non-endocrine autoimmune diseases. Methods: This is a retrospective observational cohort study with a 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 (odds ratio = 2.78 [95% confidence interval 1.70-4.57]; p < 0.0001). On subdivision, this difference was still evident in euthyroid patients (p < 0.0001), while it disappeared in hypothyroid women (p = 0.21). The 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 out of 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 poly-autoimmunity.

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.

Infundibuloneurohypophysitis associated with autoimmune thrombocytopenia and chiasmal syndrome: a case report.

Lymphocytic hypophysitis is an uncommon autoimmune disease. It may involve the adenohypophysis, neurohypophysis and pituitary stalk. It is most often encountered in pregnant women. Its diagnosis and management pose a significant challenge, as its clinical manifestation and appearance in imaging studies are difficult to distinguish from more common lesion of the sellar region (e.g., pituitary adenomas). We present the case of a 42-year-old man who presented with a chiasmatic syndrome, diabetes insipidus and hypopituitarism. Brain MRI documented a sellar lesion with suprasellar extension and optic chiasm dislocation. He underwent an endoscopic endonasal transsphenoidal resection of the mass. Histopathological examination revealed a lymphocytic hypophysitis. Visual symptoms improved dramatically postoperatively with permanent diabetes insipidus and panhypopituitarism. We discuss the indication for surgical resection in patients with inflammatory lesions extending to the suprasellar region associated with visual impairment.

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.

Parathyroid reimplantation with PR-FaST technique in unselected patients during thyroidectomy. A case series with long term follow up confirming graft vitality and parathormone production.

INTRODUCTION: Parathyroid damage or unintentional excision still affect thyroid surgery and may cause permanent hypoparathyroidism. The only way to recover the excised or ischemic gland functionality is still reimplantation. Many sites of reimplantation have been described, each of one showing both advantages and drawbacks. The aim of this study is to verify results of a new procedure called PR-FaST: Parathyroid Reimplantation in Forearm Subcutaneous Tissue, in a series of unselected patients after long-term follow-up. MATERIALS AND METHODS: From January 2013 to October 2015, 296 consecutive total thyroidectomies have been performed) to treat both benign and malignant thyroid diseases. in 42 cases (14.1%), due to an insufficient blood supply or accidental removal, one parathyroid gland was reimplanted with the PR-FaST technique. Post-operative evaluation was carried out by: total serum calcium (Ca), magnesium (Mg) and phosphorus (P) analysis in the 1st and 2nd postoperative days; Ca, Mg, P and serum iPTH from both arms analysis one week after surgery; Ca and iPTH measurement from both arms 1 months, 3, 6 and 12 months after surgery. RESULTS: We observed transient hypocalcemia requiring calcium replacement therapy in 5 on 42 (11.9%) patients submitted to PR-FaST. No case of permanent hypoparathyroidism was reported. At 1 week after surgery, only 20 patients (47.6%) showed graft vitality, while the number of patients showing graft vitality arised to 33 (79%) after 1 month and to 39 (92.8%) after three and six months. At 1 year 38 (90.5%) patients showed good graft functionality. Considering levels of serum iPTH from both arms, we observed that in case of graft functionality, samples from reimplanted arm revealed in almost all cases values at least 2-3 folds higher than in non reimplanted arm. CONCLUSIONS: Results from this prospective evaluation suggest that PR-FaST is a safe and effective procedure, with potential advantages when compared to other techniques of parathyroid reimplantation, that are mainly the possibility to evaluate graft functionality in the follow-up and the easy and well reproducible technique. Furthermore, it can be applied, when needed, to potentially all patients undergoing thyroidectomy.

Parathyroid Reimplantation in Forearm Subcutaneous Tissue During Thyroidectomy: A Simple and Effective Way to Avoid Hypoparathyroidism.

INTRODUCTION: Parathyroid autotransplantation plays an important role in preventing hypoparathyroidism following thyroidectomy. The preferred reimplantation site is still the sternocleidomastoid muscle, but this approach does not permit to check graft vitality postoperatively. The authors report the first prospective evaluation of normal parathyroid gland reimplantation in forearm subcutaneous tissue (using the same technique proposed during parathyroidectomy for hyperplasia) in case of devascularized or inadvertently removed glands during thyroid surgery. MATERIALS AND METHODS: From January 2013 to August 2014, we performed 348 consecutive thyroidectomies for various disease, both benign and malignant. In 25 cases, due to inadvertent parathyroid removal or evidence of insufficient blood supply, we removed and fragmented the gland into 0.5-1 mm slices (one for frozen section) and reimplanted it into two subcutaneous pockets on the non-dominant forearm. After surgery we checked grafted gland function by evaluation of serum parathormone gradient between reimplanted versus non-reimplanted arm (considering significant a ratio of 1.5 or more), at 1 week, 1 and 3 months after surgery. RESULTS: We observed recovery of reimplanted graft function in 48, 88 and 96% of patients respectively at 1 week, 1 and 3 months after surgery. All patients showed normal parathormone levels in peripheral blood (non-reimplanted arm). In one case we observed post-operative wound hematoma on graft-site. This patient showed no graft functionality in post-operative period (even at 3 months follow-up). CONCLUSIONS: Parathyroid gland reimplantation in forearm subcutaneous tissue during thyroid surgery is a safe, easy and effective procedure; furthermore, it allows a good control of graft functionality and would allow an easy grafted gland removal if needed.

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.

Thyroxine softgel capsule in patients with gastric-related T4 malabsorption.

The key role of an intact gastric acid secretion for subsequent intestinal T4 absorption is supported by an increased requirement of thyroxine in patients with gastric disorders. A better pH-related dissolution profile has been described in vitro for softgel T4 preparation than for T4 tablets. Our study was aimed at comparing softgel and tablet T4 requirements in patients with gastric disorders. A total of 37 patients with gastric-related T4 malabsorption were enrolled, but only 31 (28F/3M; median age = 50 years; median T4 dose = 2.04 µg/kg/day) completed the study. All patients were in long-lasting treatment (>2 years) with the same dose of T4 tablets when treatment was switched to a lower dose of softgel T4 capsules (-17 %; p = 0.0002). Assessment of serum FT4 and TSH was carried out at baseline and after 3, 6, 12, and 18 months after the treatment switch. In more than 2/3 of patients (good-responders n = 21), despite the reduced dose of T4, median TSH values were similar at each time point (p = 0.3934) with no change in FT4 levels. In the remaining patients (poor-responders n = 10), TSH levels were significantly higher at each time point than at baseline (p < 0.0001). To note, in five of them intestinal comorbidity was subsequently detected. Comorbidity associated with poor-responders status was the only significant predictor in multivariate analysis (OR = 11.333). Doses of softgel T4 capsules lower than T4 tablet preparation are required to maintain the therapeutic goal in 2/3 of patients with impaired gastric acid secretion.

Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine.

CONTEXT: An increased need for T4 has been described in patients with different gastrointestinal disorders. However, there is a lack of systematic studies assessing the need for T4 in hypothyroid patients with lactose intolerance, a widespread and often occult disorder. OBJECTIVE: The objective of the study was to assess the replacement T4 dose required in hypothyroid patients with lactose intolerance. DESIGN: This was a cohort study. SETTING: The study was conducted at an outpatient endocrinology unit in a University Hospital. PATIENTS: The replacement T4 dose has been analyzed, from 2009 to 2012, in 34 hypothyroid patients due to Hashimoto's thyroiditis and lactose intolerance and being noncompliant with a lactose-free diet. MAIN OUTCOME MEASURE: An individually tailored T4 dose was measured. RESULTS: In all patients with isolated Hashimoto's thyroiditis, target TSH (median TSH 1.02 mU/L) was obtained at a median T4 dose of 1.31 µg/kg/d. In patients with lactose intolerance, only five of 34 patients reached the desired TSH (median TSH 0.83 mU/L) with a similar T4 dose (1.29 µg/kg/d). In the remaining 29 patients, the T4 dose was progressively increased and the target TSH (median TSH 1.21 mU/L) was attained at a median T4 dose of 1.81 µg/kg/d (+38%, P < .0001). In six of these patients, other gastrointestinal disorders were diagnosed, and their median T4 requirement was higher (2.04 µg/kg/d; +55%; P = .0032). In the remaining 23 patients with isolated lactose intolerance, a median T4 dose of 1.72 µg/kg/d (+31% P < .0001) has been required to attain pharmacological thyroid homeostasis. CONCLUSIONS: These findings show that lactose intolerance significantly increased the need for oral T4 in hypothyroid patients.

Atypical celiac disease as cause of increased need for thyroxine: a systematic study.

OBJECTIVE: Replacement T4 dose in hypothyroid patients bearing both chronic autoimmune thyroiditis and atypical celiac disease (CD) has been analyzed. DESIGN: Replacement T4 dose has been analyzed in 35 hypothyroid patients with Hashimoto's thyroiditis (HT) and atypical CD, as defined by the American Gastroenterological Association. We have evaluated the ability of the same dose of T4 to reach target TSH in 21 patients before and during gluten-free diet (GFD). In the remaining 14 patients, noncompliant with GFD, we analyzed replacement T4 dose and compared it with that in a similar group consisting of 68 patients with hypothyroid HT but no evidence of celiac sprue or other conditions interfering with T4 absorption. RESULTS: In patients with isolated HT, the desired serum TSH (median=1.02 mU/liter) was reached in all patients after 5±2 months of treatment at a median T4 dose of 1.31 µg/kg·d. After a similar period and dose of T4, higher levels of TSH (median=4.20 mU/liter) were observed in patients with HT and CD. In 21 CD patients, target TSH (median TSH=1.25 mU/liter) has been attained after 11±3 months of GFD without increasing T4 dose (1.32 µg/kg·d). In the remaining 14 patients, who were noncompliant with GFD, target TSH has also been achieved but at a higher T4 dose (median=1.96 µg/kg·d; +49%; P=0.0002) than in hypothyroid patients without CD. CONCLUSIONS: Atypical CD increases the need for T4. The effect was reversed by GFD or by increasing T4 dose. Malabsorption of T4 may provide the opportunity to detect CD that was overlooked until the patients were put under T4 therapy.

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.

Chronic unexplained anaemia in isolated autoimmune thyroid disease or associated with autoimmune related disorders.

OBJECTIVE: The prevalence of chronic unexplained anaemia was analysed in patients with autoimmune thyroid disease (ATD). DESIGN: The presence of chronic unexplained anaemia, defined as anaemia not related to evident or occult bleeding and/or to erythropoietic disorders, was retrospectively assessed and compared in patients with nonautoimmune thyroid disease (NATD) and in patients with ATD. SUBJECTS AND MEASUREMENTS: Biochemical and morphological parameters of anaemia were investigated and characterized in 1643 consecutive Caucasian outpatients with thyroid disease. In 991 patients, thyroid disease had a nonautoimmune origin. ATD was diagnosed in 652 patients (71 had Graves' disease and 581 had Hashimoto's thyroiditis and its variants). In 145 patients ATD was associated with other autoimmune disorders. RESULTS: The presence of chronic unexplained anaemia was diagnosed in 123 patients (7.5%). Forty-eight had a thalassaemic trait, representing 2.9% of the whole sample. A true chronic unexplained anaemia was recorded in 75/1643 (4.6%). The occurrence of unexplained anaemia was similar in patients with NATD (1.9%) and in those with isolated ATD (2.96%; P = NS) but increased in patients with ATD and autoimmune related disorders (ARD) compared to patients with isolated ATD and/or with NATD (28.3%; both P < 0.0001; RR = 9.56 and 14.75, respectively). Chronic unexplained anaemia was virtually absent in hyperthyroid patients and was more prevalent in hypothyroid than in euthyroid patients with ATD (P = 0.0047; RR = 2.104). CONCLUSIONS: These results indicate that the increased frequency of chronic anaemia in patients with ATD is essentially due to the presence of concomitant autoimmune gastrointestinal diseases.

[Oral thyroxine treatment: towards an individually tailored dose]. / La terapia tiroxinica: dall'empirismo al dosaggio individualizzato.

Sodium levothyroxine is one of the most prescribed drugs all over the world. Oral thyroxine treatment is often used lifelong and the search for optimal daily dose may be a challenge for the physician. Patient age and compliance to prescribed regimen are in fact relevant features to achieve therapeutic goal. Also, the absorption of thyroxine is not a linear function of the ingested dose being sensitive to several interferences. Inaccurate administration modality, thyroxine interaction with different drugs, pregnancy, and malabsorption are all possible causes of increased need for thyroxine. Important and simple evidences are now available to improve the accuracy of drug administration and optimize the treatment. In fact, recent evidence pointed out the role of gastric acid secretion on the subsequent intestinal absorption of thyroxine in relation with the timing of food ingestion as well as with pH impairment associated to frequent gastric disorders like Helicobacter pylori infection and gastric atrophy.

Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis.

BACKGROUND: Malabsorption of thyroxine has been described in patients treated with drugs that modify an acidic environment. We determined whether there is an increased need for thyroxine in patients with euthyroid multinodular goiter and impaired secretion of gastric acid. METHODS: We assessed the dose of thyroxine required to obtain a low level of thyrotropin (0.05 to 0.20 mU per liter) in 248 patients with multinodular goiter. Of these 248 patients, 53 also had Helicobacter pylori-related gastritis and 60 had atrophic gastritis of the body of the stomach (31 with evidence of H. pylori infection and 29 without such evidence). The reference group comprised 135 patients with multinodular goiter and no gastric disorders. In addition, variation in the level of serum thyrotropin was prospectively studied in 11 patients treated with thyroxine before and after H. pylori infection and both before and during treatment with omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux. RESULTS: The daily requirement of thyroxine was higher (by 22 to 34 percent) in patients with H. pylori-related gastritis, atrophic gastritis, or both conditions than in the reference group. In prospective studies, the occurrence of H. pylori infection in the 11 patients treated with thyroxine led to an increase in the level of serum thyrotropin (P=0.002), an effect that was nearly reversed on eradication of H. pylori infection. In a similar way, omeprazole treatment was associated with an increase in the level of serum thyrotropin in all 10 patients treated with thyroxine, an effect that was reversed by an increase in the thyroxine dose by 37 percent. CONCLUSIONS: Patients with impaired acid secretion require an increased dose of thyroxine, suggesting that normal gastric acid secretion is necessary for effective absorption of oral thyroxine.