Multivariate analysis on factors affecting suppression of thyroid-stimulating hormone in treated congenital hypothyroidism

AIMS: To determine the factors which influence the suppression of thyroid-stimulating hormone (TSH) in infants with congenital hypothyroidism (CH) following treatment. METHODS: We examined retrospectively the patterns of thyroid function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH from screening. Patients were classified into 3 groups: athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH suppression was defined as plasma TSH concentration <6 mU/l. The factors affecting the suppression of TSH at 6 months and 1 year of age which were evaluated were: initial confirmatory plasma TSH, initial plasma thyroxine (T4), mean age of starting treatment with L-T4, dose of L-T4 at diagnosis, 6 weeks, 3 months and 6 months, and aetiology of the congenital hypothyroidism. Variables were then entered in a stepwise logistic regression model for TSH suppression at 6 months and 1 year of age. RESULTS: All infants had radionuclide scans prior to treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23). 58% of patients had persistently raised TSH at 6 months of age while 31% of patients had a persistently raised TSH at 1 year of age. There was a significant delay in the normalisation of plasma TSH in athyreosis and ectopia groups compared with dyshormonogenesis. Multiple regression analysis for TSH suppression at 6 months of age found plasma T4 levels and aetiology of CH as independent factors affecting the timing of TSH suppression. Aetiology of CH was the only independent factor affecting TSH suppression at 1 year of age. CONCLUSION: At 6 months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were independent factors affecting timing of TSH suppression. However, by 1 year of age, the aetiology of CH was the only independent factor affecting suppression of TSH.     

Galactorrhea in subclinical hypothyroidism

Galactorrhea was found in 5 patients with subclinical hypothyroidism. The galactorrhea consisted of the discharge of a few drops of milk only under pressure. Serum T4 was in the lower level of the normal range, but serum T3 was normal (T4: 6.3 +/- 1.2 micrograms/dl, T3: 113 +/- 7 ng/dl). Basal serum TSH and PRL were slightly increased only in 2 and 1 cases, respectively. The PRL responses to TRH stimulation were exaggerated in all cases, although the basal levels were normal. An enlarged pituitary gland was observed in 1 patient by means of CT scanning. All patients were treated by T4 replacement. In serial TRH tests during the T4 replacement therapy, the PRL response was still increased even when the TSH response was normalized. Galactorrhea disappeared when the patients were treated with an increased dose of T4 (150-200 micrograms/day). Recurrence of galactorrhea was not observed even though replacement dose of T4 was later decreased to 100 micrograms/day in 4 cases. In patients with galactorrhea of unknown origin, subclinical hypothyroidism should not be ruled out even when their serum T4, T3, TSH and PRL are in the normal range. The TRH stimulation test is necessary to detect an exaggerated PRL response, as the cause of the galactorrhea. To differentiate this from pituitary microadenoma, observation of the effects of T4 replacement therapy on galactorrhea is essential.     

Comparative effects of desiccated thyroid gland and sodium salt of L-thyroxine in the treatment of hypothyroidism

The studies comparing the actions of dried thyroid gland (Thyroideum-Polfa) with L-thyroxine sodium (L-T4) were carried out in 20 female patients with hypothyroidism, including 19 patients with the primary hypothyroidism and 1 patient with hypothyroidism secondary to pituitary deficiency. Administration of the dried thyroid gland did not normalize blood serum T4 an TSH in any patient. Normal serum T4 or even slightly increased was achieved in all patients treated with L-T4. Serum TSH was normalized in 17 patients with the primary hypothyroidism. The following conclusions have been drawn: 1. Dried thyroid gland (Thyroideum-Polfa) is ineffective in the treatment of hypothyroidism. 2. Serum TSH remains elevated despite normal serum T3 in cases of the primary hypothyroidism with decreased serum T4 levels. 3. Sodium salt of L-thyroxine should be used for the treatment of hypothyroidism. 1-Triiodothyronine sodium may be used as an adjuvant therapy.     

Blood-spotted filter paper measurements of thyroxine and thyroid-stimulating hormone in the follow-up of children with congenital hypothyroidism

Neonatal screening for congenital hypothyroidism using T4 and TSH measurements from blood-spotted filter paper is a well-established method. However, it has not been used to monitor T4 and TSH concentrations in the follow-up of these children. In 22 treated children with congenital hypothyroidism whom we follow up in our Clinic, T4 and TSH concentrations were concomitantly measured from venous blood and blood-spotted filter paper. There was a significant positive correlation between both T4 and TSH measurements from venous blood versus blood-spotted filter paper (r = 0.7, p = 0.001; r = 0.78, p less than 0.05). Filter paper T4 values above 7 micrograms/dl could exclude hypothyroxinemia in 98% of the specimens. When TSH values were above 10 microU/ml, it was confirmed in 94% of the specimens, and when they were above 20 microU/ml, it was confirmed in 97% of the specimens. Measurements of both filter paper T4 and filter paper TSH did not increase the reliability of the results obtained by examining the two hormones separately. We therefore suggest that filter paper T4 and/or TSH measurements have distinct advantages in monitoring the treatment of children with congenital hypothyroidism. It can be performed in the community, enabling assistance in the follow-up of children in remote areas who are unable to show up for serum tests. The results are obtained quickly and allow improved follow-up by providing useful information such as excluding hypothyroxinemia or suggesting the possibility of noncompliance, and by a psychological effect on parents. However, they cannot replace serum T4 and TSH measurements altogether.     

Therapeutic exploration of betulinic acid in chemically induced hypothyroidism

Hypothyroidism is a chronic condition characterized by abnormally low thyroid hormone production. The decreased serum level (>5.1 mIU/l) of thyroid-stimulating hormone (TSH) in blood indicates hypothyroidism. The study was an attempt to access the effect of betulinic acid on chemically induced hypothyroidism in female albino rats. Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as anticancer potential, by inhibiting topoisomerase. Hypothyroidism was induced in female albino rats using propylthiouracil (PTU) at a dose of 60 μg/kg body weight orally for 1 month. Induction of hypothyroidism was confirmed by increased TSH level. At the end of second month, blood was collected, centrifuged and serum was analyzed for TSH, T3, and T4 level and protocol was terminated by killing of animals. The animals exposed to PTU were treated with pure standard drug thyroxine at a dose of 10 μg/kg of body weight by oral route and the test drug betulinic acid 20 mg/kg by oral route through force feeding in their respective groups. Treatment was carried out for a period of 2 months. Group with PTU-induced hypothyroidism showed an elevation in serum TSH and reduction level, which was restored by the betulinic acid in treated female albino rats. Betulinic acid also reduced the damage caused in the thyroid tissues by PTU, thus minimizing the symptoms of hypothyroidism. Histopathological examinations of the thyroid tissue showed changes in the thyrocytes of PTU-treated group while thyroxine group showed normal thyroid follicles cell architecture and the group treated with betulinic acid also showed marked improvement in the follicles integrity which shows that betulinic acid has some protective activity. This study shows that the betulinic acid has thyroid-enhancing potential by lowering down the TSH levels and reducing the damage caused in the thyroid tissues, thus minimizing the symptoms of hypothyroidism when used anaphylactically in rats.     

Impaired serum thyrotropin response to hypothyroidism in mice with disruption of neuromedin B receptor

Neuromedin B (NB), a neuropeptide highly concentrated in pituitary, has been proposed to be an inhibitor of thyrotropin (TSH) secretion. Previous study showed that mice with disruption of neuromedin B receptor (NBR-KO) have higher TSH release in response to thyrotropin-releasing hormone (TRH), although TSH seems to have decreased bioactivity. Here we examined in NBR-KO mice the response of TSH to thyroid hormone (TH) deprivation, obtained by methimazole treatment, or excess, obtained by acute and chronic TH administration. In response to hypothyroidism NBR-KO mice exhibited a lower magnitude increase in serum TSH compared to wild-type (WT) mice (1.7 vs. 3.3-times increase compared to euthyroid values, respectively, P<0.001). One hour after a single T4 injection (0.4 microg/100 g BW), WT and NBR-KO hypothyroid mice presented similar degree of serum TSH reduction (54%, P<0.05). However, 3 h after T4 administration, WT mice presented serum TSH similar to hypothyroid baseline, while NBR-KO mice still had decreased serum TSH (30% reduced in comparison to hypothyroid baseline P<0.05). T3 treatment of euthyroid mice for 21 days, with progressively increasing doses, significantly reduced serum TSH similarly in WT and NBR-KO mice. Also, serum T4 exhibited the same degree of suppression in WT and NBR-KO. In conclusion, disruption of neuromedin B receptor did not interfere with the sensitivity of thyroid hormone-mediated suppression of TSH release, but impaired the ability of thyrotroph to increase serum TSH in hypothyroidism, which highlights the importance of NB in modulating the set point of the hypothalamus-pituitary-thyroid axis at hypothyroidism.     

Serum thyroglobulin concentration in patients with diabetes mellitus

The serum thyroglobulin (Tg) concentration was measured in 97 patients with diabetes mellitus (39 males, 58 females). Hyper Tg-nemia which exceeds the normal range (1.0-26.6 ng/ml) was observed in 10 patients (3 out of 21 cases treated with diet alone, 3 out of 50 cases treated with oral hypoglycemic agents, 4 out of 26 cases treated with insulin). There was no significant correlation between concentrations of serum Tg and triiodothyronine (T3), thyroxine (T4), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). However, a positive correlation was observed between serum concentrations of Tg and thyroid stimulating hormone (TSH). Patients with diabetes were divided into three groups according to the mode of treatment (Group I; diet alone, n = 21, Group II; oral hypoglycemic agents, n = 50, Group III; insulin, n = 26). No significant difference in the serum Tg concentration was observed among the three groups. They were also divided into two groups; normal Tg-nemia (Group A, n = 87) and hyper Tg-nemia (Group B, n = 10). There was no difference between levels of T3, T4, FPG, and HbA1c in the two groups. The serum TSH concentration measured by double antibody RIA and two site immunoradiometric assay in Group B was significantly higher than that in Group A. These results suggest that hyper Tg-nemia in patients with diabetes could be due to the increased TSH concentration which reflects latent subclinical primary hypothyroidism in them.     

Treatment of hypothyroidism with L-thyroxin]

To compare an efficacy of the galenic form of desiccated thyroid gland--Thyreoideum "Polfa" with the synthetic L-thyroxine (Eltroxin Glaxo) in the treatment of hypothyroidism 15 patients were investigated. In all 15 cases before and after treatment ECG and the serum concentrations of cholesterol, thyroxine (T4), triiodothyronine (T3) as well as thyrotropin (TSH) in response to TRH were performed. After the treatment with Thyreoideum "Polfa" in doses 0.2 to 0.6 mg/daily there were neither clinical improvement, normalization of ECG, the serum concentrations of cholesterol, T3, T4 nor TSH. However, after the L-thyroxine treatment (Eltroxin Glaxo) in doses 100 to 200 micrograms/daily the clinical signs of hypothyroidism disappeared in all 15 patients. In ECG the statistically significant increase in voltage of the R and T waves after L-thyroxine treatment were observed. Also a significant decrease in the serum concentration of cholesterol and an increase in T4 and T3 were found. The serum concentration of TSH in response to TRH after the L-thyroxine treatment significantly decreased. L-thyroxine appeared to be a very efficacious in the treatment either primary or secondary hypothyroidism.     

Rate of recalls in congenital hypothyroidism based upon a regional survey in Isfahan, Iran, using serum T4 and TSH analyses: comparison of two different recall methods

AIMS: To evaluate and compare the recall rate in congenital hypothyroidism screening project in Isfahan, first using an approach involving measures of both TSH and T4 and then using TSH alone. METHODS: From June 2002 to January 2005, serum TSH and T4 level of referred neonates were measured at 3rd to 7th day of birth through venous sampling. If neonates' serum TSH was >20 mIU/l or T4 was <6.5 microg/dl by the first protocol, or TSH was >20 mIU/l by the second protocol, they were recalled. TSH and T4 were measured using an immunoradiometric assay and radioimmunoassay, respectively. Neonates with TSH > 10 and T4 < 6.5 on their second measurement were considered as congenitally hypothyroid. RESULTS: Serum T4 and TSH of 29,425 neonates by first and 57,235 neonates by second recall approach were measured. Recall rate was higher in the first protocol (2.2% vs. 0.6%, p < 0.05). Most of the recalled neonates in the first protocol were recalled for low T4 level (p < 0.05). The prevalence of CH was 1 in 350 livebirths. CONCLUSION: Although the recall rate was in the acceptable range by either approach, the TSH alone protocol seems to be a more sensitive and practical approach with the least recall burden and considering the high prevalence of CH in our region merit adaptation of widespread screening for CH using TSH measurements from heel stab blood spotted on filter paper.     

Highly sensitive immunoradiometric assay for TSH and thyroid radioiodine uptake as predictors of thyroid suppression test

Suppression of TSH and thyroid radioiodine uptake by doses of either T4 or T3 were compared in 33 patients in whom Graves' thyrotoxicosis had been treated with thioamide drugs and the medication was discontinued for at least 4 months. Thyroidal radiodine uptake was suppressed in 19 patients and was not suppressed in the remaining 14 patients. Basal TSH levels before suppression were 2.07 microU/ml in the former, significantly exceeding those of the latter (0.91 microU/ml). A TSH level of at least 1.2 microU/ml before suppression is a good predictor of positive thyroid radioiodine suppression with a predictive value of 76%. A level lower than 0.7 microU/ml before suppression is a good predictor of negative thyroid radioiodine uptake suppression with a predictive value of 89%. The determination of TSH levels before the thyroid suppression test was helpful in predicting the result, but there were limitations. In the thyroid suppression test positive group, circulating T4 was depressed by doses of T3. In them, the magnitude of T4 depression correlated with the levels of thyroid radioiodine uptake before suppression. The levels of TSH correlated neither to changes in T4 nor to those in thyroid radioiodine uptake. This indicates that the thyroid glands which show high radioiodine uptake are sensitive to TSH and are also sensitive to suppression. The elevated sensitivity to TSH probably warrants the disappearance of abnormal thyroid stimulation more precisely.     

Growth,development, and reassessment of hypothyroid infants diagnosed by screening.

Thirty]six neonates in whom hypothyroidism was diagnosed after thyroid stimulating hormone screening were reassessed at 1 year. All had grown satisfactorily and the mental development scores were normal in all except two. Treatment was withdrawn in 32 and persistent hypothyroidism was confirmed in 31 cases. Thyroid stimulating hormone concentrations were raised in one-third of cases before the withdrawal of treatment and this was associated with generally lower concentrations of serum thyroxine (T4) and smaller doses of L-thyroxine than in those cases with normal concentrations of thyroid stimulating hormone. In treating congenital hypothyroidism, serum T4 concentrations should be monitored regularly and the dose of thyroxine adjusted to maintain serum T4 in the upper part of the reference range.     

甲功五项化学发光免疫分析的基质效应对临床测值的影响

目的:探索评价基质效应在化学发光免疫分析中对甲状腺功能五项指标的影响。方法:选取甲状腺功能五项高值血清,用10种基质牛血清、马血清、山羊血清、水解明胶、BSA、PBS、生理盐水、正常人血清、甲减人血清、甲亢人血清分别对T3、T4、FT3、FT4、TSH的高值血清进行倍比稀释,观察基质效应,另将10种基质用考马斯亮兰法检测蛋白含量,分析蛋白含量与基质效应的关系。结果:T3项目牛血清、水解明胶、BSA有明显基质效应;T4和FT3项目牛血清、水解明胶、BSA、PBS、生理盐水有明显基质效应;FT4项目牛血清、马血清、水解明胶、BSA、PBS、生理盐水有明显基质效应;TSH项目没有发现基质效应,正常人血清、甲减人血清和甲亢人血清对甲状腺功能五项无基质效应。检测结果显示蛋白含量多少与基质效应无关。结论:人血清基质是用于稀释样本,基质效应最小的液体,针对个体差异性进行的选择,稀释T3、T4、FT3、FT4高值血清选择甲减人血清,稀释TSH高值血清选择甲亢人血清,可以得到较为满意的结果。     

Thyroid function tests in children with congenital hypothyroidism on L-thyroxine treatment

The plasma levels of thyroxine (T4), triiodothyronine (T3), free T4 (FT4), free T3 (FT3), reverse T3 (rT3) and immunoradiometrically assayed thyrotropin (IRMA TSH) have been measured in 28 L-T4-treated children with congenital hypothyroidism as well as in a control group (group C). The patients were subdivided into 2 groups according to the nonsuppressed (group A) or suppressed (group B) TSH response to TSH-releasing hormone (TRH). Basal IRMA TSH correlated with the TSH increment after TRH and it was significantly lower in group B vs. groups A and C, while no difference was present between groups A and B in regard to T4, FT4 and rT3, all higher than in group C. FT3 levels were similar in the 3 groups. In children, as in adults, basal IRMA TSH seems to be a reliable index in monitoring overtreatment.     

Hyperresponsiveness of residual thyroid lobe of hemithyroidectomised rat to thyrotropin

The effects of hemithyroidectomy and thyrotropin administration on rat thyroid gland function were studied in adult male rats. Immediately after surgery or sham operation rats were treated daily with 0.12 IU of bovine thyrotropin (TSH) for 3 or 5 days. In control rats TSH dose applied resulted in an increase in serum T4 level at day 5 of experiment. Serum thyroxine concentration markedly decreased in sham operated and hemithyroidectomised rats, an effect observed at days 3 and 5 of experiment. TSH administration had no effect on serum T4 concentration in sham operated rats while in hemithyroidectomised animals such a treatment resulted in a marked increase in serum T4 level, a phenomenon observed in both time intervals studied. The reasons for hemithyroidectomy-induced hyperresponsiveness of rat thyroid residual lobe to thyrotropin are unknown.     

Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.     

Monitoring treatment of congenital hypothyroidism by highly sensitive immunoradiometric assay for thyroid stimulating hormone

To assess the clinical value of a sensitive immunoradiometric assay for TSH (IRMA-TSH), serum IRMA-TSH levels were compared with those of a radioimmunoassay (RIA-TSH) in twenty-eight patients with congenital hypothyroidism. Among 144 samples taken from them, 44 samples showed undetectable RIA-TSH, while only 10 samples were undetectable by IRMA-TSH. In two patients prospectively followed, RIA-TSH levels were undetectable when serum T3 and T4 were normal. IRMA-TSH levels, however, were detectable when serum T4 levels were elevated or normal. The basal RIA- and IRMA-TSH levels in 4 groups (22 patients) were compared and classified according to the TSH response to TRH. The RIA-TSH levels were undetectable in any in group 1 (n = 7; absent response) or group 2 (n = 5; low response). At the same time, IRMA-TSH levels were undetectable in only three patients in group 1. In group 3 (n = 16; normal response), RIA-TSH levels were undetectable in three, whereas IRMA-TSH levels were detectable in all. The IRMA- and RIA-TSH levels rose in all in group 4 (n = 15; exaggerated response). These results suggest that the serum basal IRMA-TSH levels indicate the responsiveness of TSH to TRH more accurately than basal serum RIA-TSH levels. Therefore, it was concluded that IRMA-TSH may obviate the need for a TRH test and simplify the evaluation of adequate dosage in patients with congenital hypothyroidism during thyroxine treatment.     

Iodide-induced hypothyroidism in a patient with anorexia nervosa

A 39-year-old woman who had been suffering from anorexia nervosa was found to have hypothyroidism. Serum T4, free T4, T3, free T3 and TSH were 3.19 micrograms/dl, 0.5 ng/dl, 15.3 ng/dl, 1.2 pg/ml and 162.1 microU/ml, respectively. On careful questioning, she was found to have taken an iodine-rich diet. The serum iodine concentration was 122 micrograms/dl (normal: 4-9 micrograms/dl) and urinary iodide excretion was 13.05 mg/day (normal: less than 2 mg). After withdrawal of the iodine-rich diet, her serum T4 gradually increased and TSH returned to the normal range. She was diagnosed as having iodide-induced hypothyroidism. However, no significant elevation of serum T3 or free T3 was observed. Serum T4, free T4, T3, free T3 and TSH were 7.85 micrograms/dl, 0.8 ng/dl, 13.6 ng/dl, 4.3 pg/ml and 6.02 microU/ml, respectively. The iodide-perchlorate discharge test result was negative. These findings suggest that there exists some unknown mechanism by which a patient with anorexia nervosa may be sensitive to excess iodide. Furthermore, it is of interest to note that in a recovery phase from the hypothyroid state, normalization of serum T4 rather than T3 is well-correlated to TSH secretion.     

Thyroxine replacement dose in patients with Hashimoto disease: a potential role for interleukin-6

OBJECTIVE: To investigate the potential association between serum inflammatory cytokine levels and thyroxine replacement dose in patients with Hashimoto disease. PATIENTS AND METHODS: The study included 40 patients (12 men) with a mean age of 56.52+/-6.12 years who had hypothyroidism due to Hashimoto disease. Serum interleukin-1b (IL-1b), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels, as well as TSH, T(3) and T(4) were measured (ELISA). RESULTS: Serum IL-6 showed a significant positive correlation both with total thyroxine replacement dose (r=0.551, p=0.001) and with dose per kilogram of body weight (r=0.482, p=0.002). There was also a significant negative linear correlation between serum IL6 and T(3) (r=-0.322, p=0.043), as well as between serum IL6 and T(3)/T(4) ratio (r=-0.332, p=0.036). A further significant (r=0.419, p=0.007) positive association was demonstrated between IL6 and TNF-alpha. However, no association was found between T(3) or T(3)/T(4) ratio and TNF-alpha or IL1b. CONCLUSIONS: In patients with Hashimoto disease serum IL-6 levels are positively associated with thyroxine replacement dose and negatively associated with T(3) and T(3)/T(4) ratio. These results are possibly attributable to the inhibitory effect of IL6 on deiodination of T(3) and imply a role for IL6 in determining thyroxine replacement dose among these patients.     

Effect of Proton Pump Inhibitors on Serum Thyroid-Stimulating Hormone Level in Euthyroid Patients Treated with Levothyroxine for Hypothyroidism

ObjectiveTo examine retrospectively the effect of proton pump inhibitors (PPIs) on thyrotropin (thyroid-stimulating hormone or TSH) values in patients with hypothyroidism and normal TSH levels receiving levothyroxine (LT₄) replacement therapy.MethodsThe data collection was done by retrospective review of electronic medical records from the period of December 2002 to August 2005 from patients with hypothyroidism who were receiving at least 25 μg of LT₄ replacement daily at Queens Hospital Center. The first 92 patients meeting all inclusion and exclusion criteria were included in the study. The study group (N = 37) patient data were collected by selecting euthyroid patients who had received stable LT₄ replacement for at least 6 months and in whom PPI therapy (lansoprazole) was later initiated. TSH levels were collected before and at least 2 months after the PPI treatment was started. The control group (N = 55) patient data were collected by reviewing TSH levels among euthyroid patients with a history of hypothyroidism receiving stable LT₄ therapy and not receiving a PPI during the period of data collection. The statistical analysis was done by comparing the mean change in TSH level in each group with use of the Student t test.ResultsIn the study group, the mean change in the TSH level from before to at least 2 months after initiation of PPI therapy, 0.69 ± 1.9 μIU/mL, was statistically significant (P = 0.035). In the control group, the mean change in the TSH level during the study period, 0.11 ± 1.06 μIU/mL, was not statistically significant (P = 0.45).ConclusionTo our best knowledge, this is the first study in humans with hypothyroidism demonstrating the effect of PPIs on serum TSH levels. PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT₄ replacement. Patients with hypothyroidism and normal TSH values during LT₄ replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT₄ dose. (Endocr Pract. 2007;13:345-349)