Thyroxine Requirements Research Articles

Abstract #1405611: A Case Regarding Severe Hypothyroidism Which Complicated to De Novo Nephrotic Syndrome (Minimal Change Disease)

Hypothyroidism is a condition of an under-reactive thyroid. More prevalent in women, 10% exhibit some degree of thyroid insufficiency. It has numerous metabolic effects and may have an impact on renal physiology and worsening kidney function. Hypothyroidism was cited in certain case studies as a contributing factor to minimal change disease, which we will be highlighting here. We report a case of an 82-year-old female with PMH of graves’ disease status post left thyroidectomy in 2009 and was started on Levothyroxine, reported non-compliance, presented to the emergency department with a complaint of generalized edema mostly lower extremities that is progressively worsening over 2 weeks along with foamy urine. Unremarkable physical exam except for 2+ lower extremity pitting edema. On lab, high thyroid stimulating hormone (TSH) was 65.2 ulU/ml, normal Free Thyroxin (FT4) and low Free Triiodothyronine (FT3) 0.4 pg/ml, Serum Creatinine is 4.35 mg/dl, Urinalysis shows >500 protein, urine protein/Cr was 3, hypoalbuminemia and hyperlipidemia were present. A Glomerulopathy workup was initiated. She was admitted for further testing. Autoimmune kidney diseases were ruled out and a renal biopsy was performed, the specimen revealed Minimal change disease. She was started on Prednisone 60 mg daily and Levothyroxine 125 mcg. Three weeks later, patient showed a good response to therapy with an improvement of symptoms and repeated creatinine was 3.8. Hypothyroidism can be caused by partial or total thyroidectomy. As a highly lipophilic substance, Thyroxine binds to receptors that are expressed in cells all over the body to exhibit its physiological action. In patients with thyroidectomy, exogenous levothyroxine is the thyroid hormone supply to the body. Not having enough supply, can alter kidney function by affecting vascular resistance, re-absorptive process, and renal blood flow. It can also affect the RAAS system, beta-adrenergic receptors, and dopaminergic activation of the renal tubular cells. Gradual worsening of kidney function leads to an increase in the loss of free and bound thyroid hormones and eventually increases thyroxine requirement. GFR is reversibly reduced (by about 40%) in more than 55% of adults with hypothyroidism. Thyroxine treatment is effective by reducing edema, capillary permeability of albumin, and plasma colloid osmotic pressure. Proteinuria can sometimes be reversible by prompt initiation of thyroxine treatment. Also, the severity of symptoms plays a role in recovery. More research is needed to determine the relationship between hypothyroidism and nephrotic syndrome as only a few isolated occurrences were reported in the literature.

Levothyroxine Absorption Test - Results and Follow Up of Patients from a Single Center.

Treating primary hypothyroidism with appropriate weight-based dosing is usually straightforward. When supraphysiologic doses of thyroxine are required, it is important to know the reason behind the increased requirement. When compliance with medication is assured and when there are no drug interactions resulting in increased thyroxine requirements, a levothyroxine absorption test (LT4AT) could be performed to diagnose the coexistence of malabsorption. This was a single-center, retrospective chart review. Patients who had undergone LT4AT between 2018 and 2020 with a complete evaluation and follow-up records were reviewed. LT4AT and further evaluation (if necessary) were standardized, and details until the last review were obtained. In all, 11 patients had complete records and follow-up details. The median age (range) of the cohort was 24 years (19 to 46), and the duration of hypothyroidism was 8 years (4 to 24). Seven had low absorption (<60%) in LT4AT of which two each had celiac disease and Helicobacter pylori infection; one had autoimmune gastritis, and in two the reasons of malabsorption was not known. The median follow-up duration was 13 months. Nine of 11 (81%) achieved euthyroid state with/without thyroxine dose reduction on follow-up. A high proportion of patients requiring supraphysiological doses of levothyroxine had occult malabsorptive states, some of which were curable. Even in those with pseudo-malabsorption, LT4AT helped in reinforcing compliance and thereby thyroxine dose reduction.

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

PurposeDespite 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 methodsAmong 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.ResultsThyroxine 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.ConclusionThe 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

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.

The diagnosis and management of central hypothyroidism in 2018.

Central hypothyrodism (CeH) is a hypothyroid state caused by an insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland. Several advancements, including the recent publication of expert guidelines for CeH diagnosis and management, have been made in recent years thus increasing the clinical awareness on this condition. Here, we reviewed the recent advancements and give expert opinions on critical issues. Indeed, CeH can be the consequence of various disorders affecting either the pituitary gland or the hypothalamus. Recent data enlarged the list of candidate genes for heritable CeH and a genetic origin may be the underlying cause for CeH discovered in pediatric or even adult patients without apparent pituitary lesions. This raises the doubt that the frequency of CeH may be underestimated. CeH is most frequently diagnosed as a consequence of the biochemical assessments in patients with hypothalamic/pituitary lesions. In contrast with primary hypothyroidism, low FT4 with low/normal TSH levels are the biochemical hallmark of CeH, and adequate thyroid hormone replacement leads to the suppression of residual TSH secretion. Thus, CeH often represents a clinical challenge because physicians cannot rely on the use of the ‘reflex TSH strategy’ for screening or therapy monitoring. Nevertheless, in contrast with general assumption, the finding of normal TSH levels may indicate thyroxine under-replacement in CeH patients. The clinical management of CeH is further complicated by the combination with multiple pituitary deficiencies, as the introduction of sex steroids or GH replacements may uncover latent forms of CeH or increase the thyroxine requirements.

Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study.

Thyroxine (T4) requirement after total thyroidectomy for differentiated thyroid carcinoma (DTC) is a debated issue. As most of the studies in the area have been retrospective and/or performed with heterogeneous therapeutic approaches, we designed our study to determine T4 requirement in the same patients and treatment settings, before and after total thyroidectomy. This was a longitudinal study including 23 goitrous patients treated with T4 in an individually tailored fashion. All patients exhibited a stable TSH (median TSH = 0.28 mU/l) at a stable T4 dose for at least 1 year before surgery (median T4 dose = 1.50 μg/kg per day). The patients underwent total thyroidectomy based on cancer suspicion or compressive symptoms. Eventually diagnosed as having DTC (pT1b-pT2N0) and following surgical and radiometabolic treatment, they were treated with the same pre-surgical doses of T4. Three months after surgery,using the same pre-surgical dose, median TSH increased up to 5.38 mU/l (P<0.0001) and so the T4 dose had to be increased (median T4 dose = 1.95 μg/kg per day; +30%; P < 0.0001). Once divided by patients' age, we observed that, after thyroidectomy and maintaining the same pre-surgical dose, serum TSH significantly increased both in younger and in older patients (median TSH = 4.57 and 6.11 mU/l respectively). Serum TSH was restored to the pre-surgical level by increasing the dose up to 1.95 and 1.77 μg/kg per day (+25 and +21%) respectively. Following the same treatment regimen, a thyroidectomized patient requires one-third higher therapeutic T4 dose than before surgery. Despite this increase, the dose of T4 needed in our patients remains significantly lower than that previously described in athyreotic patients.

Abstract #1257: Cost Effective Evaluation of a Patient with Rapidly Increasing Thyroxine Requirements

Abstract #1257: Cost Effective Evaluation of a Patient with Rapidly Increasing Thyroxine Requirements

PMM.75 Maternal Hypothyroidism in Pregnancy

Maternal hypothyroidism complicates 2-5% of pregnancies. Thyroxine (T₄) replacement is known to improve obstetric outcomes (rates of miscarriage, premature labour and low birth weight), although there is no evidence that...

Laparoscopic Sleeve Gastrectomy Leads to Reduction in Thyroxine Requirement in Morbidly Obese Patients With Hypothyroidism

The impact of laparoscopic sleeve gastrectomy (LSG) on various co-morbidities including type II diabetes mellitus, hypertension, and sleep apnea is well established. However, its effect on hypothyroidism has not been given due attention evidenced by the scant literature on the subject. The purpose of this report is to assess the change in thyroxine (T4) requirement in morbidly obese patients with clinical hypothyroidism after LSG. We conducted a retrospective review of morbidly obese patients on T4 replacement therapy for clinical hypothyroidism who underwent LSG from August 2009 to July 2012 at our institution. Of the 200 patients who underwent LSG during this period, 21 (10.5 %) were on T4 replacement therapy preoperatively for clinical hypothyroidism. Two patients were lost to follow-up. The remaining 19 patients were categorized into two groups. Group 1 comprised 13 patients with decreased T4 requirements after LSG. Group 2 comprised six patients in whom the T4 dose remained unaltered. The mean change in T4 requirement in group 1 was 42.07 % (12-100 %). Group 1 patients had a significantly higher mean preoperative body mass index (48.7 vs. 43.0 kg/m(2); p = 0.03) than the group 2 patients. There was a significant correlation between the percentage excess weight loss and the percentage change in T4 requirement in group 1 (r = 0.607, p = 0.028). Sleeve gastrectomy has a favorable impact on hypothyroid status as seen by a reduction in T4 requirement in the majority of morbidly obese patients with overt hypothyroidism.

50 Years Ago in The Journal of Pediatrics: Fetal Hypothyroidism: I. Effects of Hypothyroidism on Neural Development; II. Fetal versus Maternal Contributions to Fetal Thyroxine Requirements; III. Clinical Implications

50 Years Ago in The Journal of Pediatrics: Fetal Hypothyroidism: I. Effects of Hypothyroidism on Neural Development; II. Fetal versus Maternal Contributions to Fetal Thyroxine Requirements; III. Clinical Implications

English

Thyroid disease is particularly common in women of child bearing age. It is estimated that 2.5% of all pregnant women have some degree of hypothyroidism (1, 2). Thyroid disorders are the second are the second most common endocrine disorders found in pregnancy. Maternal complications of untreated hypothyroidism include microcytic anaemia, placental abruption, preeclampsia, postpartum haemorrhage, cardiac dysfunction and miscarriage (3). Fetal or neonatal complications include prematurity, low birth weight, congenital anomalies, stillbirth and poor neuropsychological development (1). In particular, as fetal thyroid cannot concentrate iodine until 10-12 weeks of gestation. Therefore before this time, the mother must provide for all the fetus' thyroxine (T4) requirements. This study focuses on thyroid screening in first trimester of pregnancy (1). OBJECTIVE: The aim of the study was to determine the incidence of hypothyroidism and hyperthyroidism in pregnancy during the first trimester. With the evidence provided by these results, we have studied if thyroid screening should be made as a routine screening in pregnancy. Materials and methods: Total 400 pregnant women were screened for thyroid functions during the first trimester of pregnancy using FT3, FT4 and TSH as criteria. RESULTS: Increased prevalence of thyroid with increasing age. Abnormal thyroid profile seen in patients with recurrent abortions. CONCLUSION: Mandatory to screen to include the thyroid screening in the first trimester antenatal

Long Term Efficacy Of Iron Chelation Therapy With Deferasirox On Endocrine Function In Thalassemia Major

Although the heart and liver have traditionally been the organs of interest for iron-related complications in Thalassemia Major (TM), endocrine disorders are common and carry significant morbidity. This is thought to result from iron accumulation in multiple organs functioning as part of endocrine systems. Deferasirox chelation therapy is well tolerated in TM and reduces iron burden effectively in the heart and liver. The impact of deferasirox on endocrine parameters remains unclear. The aim of this study was to examine the long-term efficacy of deferasirox for both the prevention of endocrine dysfunction in patients free of endocrine complications, and in improving endocrine parameters in those with pre-existing endocrine disorders.This was a multicentre retrospective cohort study of TM patients over 2 years of age receiving chelation treatment with once daily oral deferasirox monotherapy. Data on relevant clinical and laboratory parameters, including glycaemia, bone mineral density (BMD) z-scores, and testing of the pituitary, gonadal, thyroid and adrenal axes were collected at baseline and follow-up. Dosing regimens were titrated according to standard practice and only patients treated for at least 3 years were included in the present analysis. Data are presented as mean with standard deviation unless otherwise stated. Statistical comparisons were made using paired t-tests for continuous data, and chi-square test or Fisher's exact test to compare categorical data distributions.A total of 72 patients (69% female) with a mean age 26 ± 15 years were included. Mean duration of exposure to deferasirox was 6.9 ± 2.7 years with a mean daily dose of 25 ± 5 mg/kg. Myocardial T2* significantly increased from baseline to follow up (29.30 ± 10.29ms vs. 33.5 ± 13.06ms, P=0.01), signifying effective removal of iron from the heart. Among patients free of thyroid dysfunction at baseline, we observed no significant difference in mean TSH (2.10 ± 1.00 mi/u/ml vs. 2.28 ± 1.06 mi/u/ml, P=0.23 ), FT4 (6.89 ± 4.50 ng/ml vs. 7.10 ± 4.71 ng/ml, P=0.34) or FT3 (2.87 ± 1.16 pg/ml vs. 3.00 ± 0.58 pg/ml, P=0.35) during the study period. Of 9 patients with biochemical hypothyroidism at baseline, including 4 receiving thyroxine, we observed no significant change in thyroid function tests or thyroxine requirements. Two new incidences of subclinical hypothyroidism were noted. Among patients free of diabetes mellitus at baseline, we observed no significant variation in blood glucose measurements (pooled over 3 consecutive readings) at the end of treatment (88.62 ± 10.53 mg/dl vs. 88.36 ± 9.35 mg/dl, P=0.83). There was 1 incidence of type 2 diabetes during the study period. No significant difference was seen in blood sugar control or insulin requirements between baseline and end of treatment in patients with type 1 diabetes. Excluding normal pre-pubertal paediatric patients, there was no significant increase in the prevalence of hypogonadism between baseline and the end of study, 21 patients (38%) vs. 24 (44%) were diagnosed with hypogonadism respectively (P=0.56). Biochemical indices of bone metabolism showed no significant difference in calcium levels or vitamin D from baseline to follow up. BMD was improved from baseline to follow-up, with normal Z scores in 7 (20%) patients, 20 (57%) osteopenic, and 8 (23%) osteoporotic, compared with 7 (20%), 24 (69%), and 4 (11%) at end of treatment, respectively. Adverse effects were infrequent and of low grade, effecting 7 (9.7%) patients.Endocrine disorders are common sequelae of iron overload in patients with TM, and follow an insidious course of progressive dysfunction. We report infrequent development and progression of endocrine abnormalities, and significant improvement in bone density in TM patients treated with deferasirox over a 7-year follow-up period. In comparison with the incidence of complications from other studies of TM, deferasirox appears effective in reducing risk of developing endocrine disorders. Increasing myocardial T2* values confirmed effective removal of iron from the heart. Although multiple biological pathways are likely responsible, reduction in global iron alleviating siderosis of endocrine organs may be responsible for preserved function and bone mineral metabolism. Our study suggests that chelation therapy with deferasirox may prevent endocrine complications in patients with TM and prevent progression in those with established abnormalities Disclosures:Silverio:Novartis: Consultancy, Research Funding.

Thyroid disorders in pregnancy

Thyroid disorders are common in pregnancy and the most common disorder is subclinical hypothyroidism. Due to the complex hormonal changes during pregnancy, it is important to remember that thyroxine requirements are higher in pregnancy. According to recent American Thyroid Association (ATA) guidelines, the recommended reference ranges for TSH are 0.1 to 2.5 mIU/L in the first trimester, 0.2 to 3.0 mIU/L in the second trimester, and 0.3 to 3.0 mIU/L in the third trimester. Maternal hypothyroidism is an easily treatable condition that has been associated with increased risk of low birth weight, fetal distress, and impaired neuropsychological development. Hyperthyroidism in pregnancy is less common as conception is a problem. Majority of them are due to Graves’ disease, though gestational hyperthyroidism is to be excluded. Preferred drug is propylthiouracil (PTU) with the target to maintain free T4 in upper normal range. Doses can be reduced in third trimester due to the immune-suppressant effects of pregnancy. Early and effective treatment of thyroid disorder ensures a safe pregnancy with minimal maternal and neonatal complications.

Permanent and transient congenital hypothyroidism in preterm infants

Transient fluctuations in thyroid function are well recognized in preterm infants. We wanted to assess TSH variation in babies with transient and permanent congenital hypothyroidism (CHT). Whole bloodspot TSH data in preterm infants (<35 weeks; 2005-2010) were assessed, and infants with bloodspot TSH values >6 mU/L identified. Permanent CHT was defined as a requirement for thyroxine beyond 3 years of age. A first TSH sample was obtained from 5518 infants (median gestational age, 32 w; range, 22-35), with a second sample obtained from 5134 infants (median gestational age, 32 w; range, 22-35). Five infants had raised TSH concentrations on both occasions. Three of the five infants had a serum TSH >80 mU/L on second screen but two came off thyroxine beyond 3 years of age. All preterm babies with permanent or transient hypothyroidism were detected by the first TSH cut-off of 6 mU/L. Only one infant with a birth weight <1500 g remains on thyroxine treatment beyond 2 years of age. The incidence of permanent CHT in preterm infants is similar to term infants. Profound abnormalities of thyroid function can occur in preterm babies with transient hypothyroidism but both categories of hypothyroidism can be detected by a 'once-only' TSH screening strategy with a relatively low cut-off.

In subclinical hypothyroidism, thyroxine (T4) requirement may increase in early pregnancy resulting from gonadotropin stimulation

Increased estradiol (E2) may augment thyroxine-binding globulin (TBG) synthesis and thus raise T4 dose requirement in hypothyroid women undergoing ovarian stimulation. We hypothesized that this would be reflected in increased serum TSH and decreased free T4 (fT4) after stimulation and in early pregnancy. Prior studies have been conflicting.

Predicting thyroxine requirements following total thyroidectomy

Optimal thyroxine replacement following total thyroidectomy is critical to avoid symptoms of hypothyroidism. The aim of this study was to determine the best formula to determine the initiated replacement dose of levothyroxine immediately following total thyroidectomy. Prospective study. All patients were initiated on 100 μg levothyroxine and titrated to within the reference range for TSH and free T4. Correlations to height, weight, age, lean body mass (LBM), body surface area (BSA) and body mass index (BMI) were calculated. One hundred consecutive adult patients underwent total thyroidectomy for non-malignant disease. Comparison between three methods of levothyroxine dose prediction, aiming for a levothyroxine dose correct to within 25 μg of actual dose required. Correlations were seen between levothyroxine dose and patient age (r=-0.346, P<0.01), bodyweight (r=0.296, P<0.01), LBM (r=0.312, P<0.01), BSA (r=0.319, P<0.01) and BMI (r=0.172, P<0.05). A regression equation was calculated (predicted levothyroxine dose=[0·943 × bodyweight] + [-1.165 × age] + 125.8), simplified to (levothyroxine dose= bodyweight - age + 125) pragmatically. Initiating patients empirically on 100 μg post-operatively showed that 40% of patients achieved target within 25 μg of their required dose; this increased to 59% when using a weight-only dose calculation (1.6 μg/kg) and to 72% using the simplified regression equation. A simple calculated regression equation gives a more accurate prediction of initiated levothyroxine dose following total thyroidectomy, reducing the need for outpatient attendance for dose titration.

Predicting Thyroxine Requirements After Total Thyroidectomy

Free accessAbstractFirst published online August 2010Predicting Thyroxine Requirements After Total ThyroidectomyDipan Mistry, MB, ChB, FRCS, presenter, Stephen Atkin, MD, PhD, […], Helen Atkinson, MBBS, and James England, MB, ChB, FRCS+1-1View all authors and affiliationsVolume 143, Issue 2_supplhttps://doi.org/10.1016/j.otohns.2010.06.377

Prediction of LT4 Replacement Dose to Achieve Euthyroidism in Subjects Undergoing Total Thyroidectomy for Benign Thyroid Disorders

Total thyroidectomy is becoming the preferred choice of treatment in patients with benign disorders of the thyroid gland; hence, an optimal method of replacing thyroxine is essential to avoid the ill effects of over- and under-replacement of thyroxine in such patients. We analyzed three methods of thyroxine replacement: replacement per kilogram of lean body mass (LBM) (2.5 mcg/kg LBM per day), per kilogram of body weight (1.6 mcg/kg body weight per day), and empirical replacement of thyroxine. The thyroxine requirement in thyroidectomized patients was 2.04 mcg/kg per day, with an increasing requirement of thyroxine with increments of weight. On multivariate analysis we found that the thyroxine requirement was strongly correlated both with body surface area (BSA) and with body weight. On subsequent correlation testing, we found that BSA was more strongly associated than weight with the thyroxine requirement. Patients undergoing total thyroidectomy may require higher doses of thyroxine to achieve euthyroidism when compared to patients with similar anthropometric parameters having primary hypothyroidism. The method of replacing thyroxine based on LBM is the ideal method, but replacement based on fixed-dose regimens could be a good method if the body weight is taken into consideration.

Systematic review: Heliocobacter pylori infection and impaired drug absorption

Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

Hypothyroidism in pregnancy: pre‐pregnancy thyroid status influences gestational thyroxine requirements

There is considerable uncertainty about the management of hypothyroidism in pregnancy. Our aim was to establish the pattern of thyroxine dose adjustment needed and to determine the clinical reasons for these changes and the contributory factors. Of 89 pregnancies, thyroxine dose was unchanged in 50, increased (by a mean of 38 micrograms) in 34, and decreased in 5. Twenty-three percent of women who were tested in the first trimester needed an immediate increase in thyroxine. One-quarter (26%) of the women who needed a gestational increase in thyroxine dose had had a recent pre-pregnancy increase in thyroxine requirement (compared with 0% in women on static dose in pregnancy, P < 0.001). Furthermore, they did not require a decrease in thyroxine dose postpartum, suggesting a long-term need for more thyroxine rather than a transient gestational effect. None of the women who had stable doses of thyroxine during pregnancy had required recent pre-pregnancy changes in dose or needed postnatal changes. Inadequate pre-pregnancy control of thyroid function is associated with a need to increase thyroxine dosage during pregnancy.