Bengt Hallengren

Pregnant Women on Thyroxine Substitution Are Often Dysregulated in Early Pregnancy

BACKGROUND Thyroid hormones are important for normal fetal development. Maternal hypothyroidism during early pregnancy is associated with impaired neuropsychological development of children and other adverse outcomes. The primary aim of this prospective study was to determine whether thyroxine-treated pregnant women with hypothyroidism are adequately thyroxine substituted in early pregnancy. A secondary aim was to determine if fetal loss differed between females with thyrotropin (TSH) values within and outside the reference range at their first TSH test, scheduled for 1-2 weeks after verification of pregnancy. METHODS This was a prospective open-labeled study. During the years 1997-2002, 119 consecutive pregnancies in 101 females with thyroid diseases were followed at the Department of Endocrinology, Malmö University Hospital. At the first visit, 63 patients, median age 30 years (range 17-45 years), were on thyroxine substitution therapy for hypothyroidism. In these patients 83% were in their first trimester at the time of the initial test. RESULTS Of the 63 patients on thyroxine substitution for hypothyroidism 32 (51%; Group A) patients had serum TSH values within the reference range at their initial test and 31 (49%; Group B) had serum TSH values outside the reference range. Twelve (19%) had TSH values of <0.40 mIU=L and 19 (30%) had TSH values of >4.0 mIU=l. The fetal loss was 2 of 32 (6%) in Group A compared to 9 of 31 (29%) in Group B ( p < 0.05). CONCLUSIONS In 49% of pregnant women on thyroxine substitution, serum TSH values were outside the reference range when first tested, generally in the first trimester. Fetal loss was significantly greater in pregnant women with abnormal TSH values compared to those with normal TSH values. Thyroid function in pregnant women on thyroxine substitution should be monitored early in pregnancy and carefully followed during pregnancy. The thyroxine dose should be increased as needed early in pregnancy to avoid hypothyroidism.

Slow Elimination of Glyburide in NIDDM Subjects

OBJECTIVE To determine the terminal elimination half-life of glyburide in non-insulin-dependent diabetes mellitus (NIDDM) subjects after cessation of long-term treatment. RESEARCH DESIGN AND METHODS Ten NIDDM patients (5 of each sex, 36-72 years old, without hepatic or renal disease) taking a median glyburide dose of 14 mg/day, who were to start insulin therapy because of sulfonylurea failure, were studied. Serum glyburide concentrations, measured by a newly developed selective and sensitive liquid chromatographic method, were followed from 10 to 48 h after the last glyburide dose. RESULTS Serum glyburide levels declined in three different phases, with a terminal 7-phase between 18 and 48 h having a mean ± SD half-life of 15.0 ± 6.7 h. Two patients had half-lives over 20 h. The half-life values did not correlate with fasting blood glucose, age, body weight, body mass index, or creatinine levels. The latter agrees with the assumption that glyburide is completely eliminated by metabolic transformation. Although longer than previously observed, the current half-life values are in accordance with clinical experience that glyburide is a long-acting sulfonylurea. CONCLUSIONS The elimination of glyburide in NIDDM subjects is slower than previously reported. The long half-life adds support to the use of a once-daily dosage of glyburide. It also justifies increased caution when using this sulfonylurea.

Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases

Abstract. Papadopoulos KI, Melander O, Orho‐Melander M, Groop LC, Carlsson M, Hallengren B (University of Lund, Malmö University Hospital, Malmö, Sweden). Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases. J Intern Med 2000; 247: 71–77.

Gender differences in GAD antibody – positive diabetes mellitus in relation to age at onset, C‐peptide and other endocrine autoimmune diseases

Females have an increased incidence of autoimmune diseases. However, no gender difference in the incidence of type 1 diabetes is found. The frequency of antibodies against glutamic acid decarboxylase (GADA) in diabetes mellitus depends on age at diagnosis and also gender. Several studies have shown that high GADA levels can predict future β‐cell failure and need for insulin treatment. The aim of this study was to investigate possible gender differences in relation to GADA levels, fasting plasma C‐peptide levels and frequency of other autoimmune endocrine diseases in GADA‐positive patients with different age at diabetes diagnosis.

Evidence of gastrointestinal immune reactivity in patients with sarcoidosis

Objectives.  The aim of the present study was to explore the frequency of clinical and serological manifestations of gastrointestinal immune reactivity in a large group of Swedish patients with sarcoidosis.

Comparative in vitro effects and in vivo kinetics of antithyroid drugs

SummaryThe in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole.The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole.Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.

Effects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetes

SUMMARY

Treatment with a thiazolidinedione increases eye protrusion in a subgroup of patients with type 2 diabetes.

Objective  Changes in eye protrusion in patients treated with pioglitazone.

PLASMA NORADRENALINE AND BLOOD PRESSURE IN HYPOTHYROID PATIENTS: EFFECT OF GRADUAL THYROXINE TREATMENT

High plasma noradrenaline (PNA) levels have been reported in hypothyroid patients and hypothyroidism has been associated with hypertension. To explore the relationship between PNA and blood pressure (BP) in hypothyroid patients, and the effects of gradual thyroxine replacement, a prospective study was performed comparing BP, heart rate (HR) and PNA in a normotensive and a hypertensive group of hypothyroid patients before and during gradual thyroxine substitution. Thyroxine treatment reduced the BP; the reduction in supine BP was greater in the hypertensive than in the normotensive group. HR increased similarly in both groups during treatment. PNA was elevated in the normotensive group before treatment and decreased gradually during thyroxine treatment. The hypertensive group had normal PNA levels. The present study indicates that normotensive, in contrast to hypertensive, hypothyroid patients have increased sympathetic nervous activity. Although the mechanism is unclear, thyroid replacement therapy can reverse hypertension in hypothyroid patients.

Influence of hyperthyroidism on the kinetics of methimazole, propranolol, metoprolol and atenolol

SummaryThe kinetic profiles of oral methimazole 40mg, propranolol 80mg, metoprolol 100mg and atenolol 100mg were compared in hyperthyroid patients both during the hyper-and euthyroid states. For methimazole, neither the peak concentration (Cmax), the time to reach peak concentration (tmax), the elimination half-life (t1/2) nor the area under the curve (AUC) value was affected by the hyperthyroid state. For propranolol and metoprolol, which undergo extensive presystemic clearance, the AUC values were lower (p<0.02) when the patients were hyperthyroid than when they had become euthyroid, but the t1/2s were not significantly altered. For atenolol, there were no significant kinetic differences between the hyperthyroid and euthyroid states. The findings are compatible with the assumption that hyperthyroidism does not affect the kinetics of methimazole or atenolol, but that it may enhance presystemic clearance of propranolol and metoprolol.