Arie Berghout

DETERMINANTS OF THYROID VOLUME AS MEASURED BY ULTRASONOGRAPHY IN HEALTHY ADULTS IN A NON‐IODINE DEFICIENT AREA

Thyroid volume was measured by ultrasonography in 50 healthy adults (25 males, 25 females, age 20‐70 years) living in the non‐iodine deficient area of Amsterdam. Thyroid volume was 10‐7 ± 4–6 ml (mean ± SD, range 2.7‐20.4 ml). No relation was found between thyroid volume and any of the following parameters: plasma TSH, T4, T3, thyroglobulin (Tg), urinary iodine excretion, tobacco and alcohol consumption. Thyroid volume in males (12.7 ± 4.4 ml) was greater than in females (8.7 ± 3.9 ml, p = 0.0014), but no sex difference was observed in the ratio of thyroid volume to body weight (males, 0.16 ± 005 ml/ kg; females 013 ± 0.06 ml/kg; NS). Thyroid volume was positively related to body weight, but not to age. We conclude that the sex difference in thyroid volume is due to the difference in body weight between males and females. Lean body mass is presumably the most important physiological determinant of thyroid size in subjects living in a non‐iodine deficient area.

Correlation between severity of thyroid dysfunction and renal function

Objective  Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively.

Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre

The efficacy of treatment with TSH-suppressive doses of L-thyroxine (T4, 2.5 micrograms/kg body weight daily) either alone or combined with carbimazole (CBZ, 40 mg daily) was studied in 78 patients with sporadic non-toxic goitre in a prospective placebo-controlled double-blind randomised clinical trial. Treatment was given for 9 months, with 9 months of follow-up. A response to treatment as measured by ultrasonography was found in 58% of the T4 group, in 35% of the T4/CBZ group, and in 5% of the placebo group. The mean (SEM) decrease of thyroid volume at 9 months in the responders was 25% (2). After discontinuation of treatment, thyroid volume increased in the responders and had returned to base-line values after 9 months of follow-up. In the placebo group mean thyroid volume had increased by 6% (4) at 4 months, 20% (7) at 9 months, and 27% (8) at 18 months. The findings show that untreated sporadic non-toxic goitre continues to increase in size; T4 is effective in the treatment of the disorder; and the addition of CBZ has no therapeutic advantage.

Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter

PURPOSE To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. PATIENTS AND METHODS A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid-stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay). RESULTS Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%. CONCLUSION The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function--related to increasing thyroid volume--during the natural history of this disorder.

Thyroid autoimmunity and abortion: a prospective study in women undergoing in vitro fertilization

OBJECTIVE To determine whether an association exists between the presence of thyroid peroxidase (TPO) antibodies before pregnancy and miscarriage in women without a history of habitual abortion. DESIGN Prospective study and nested case-control study. SETTING Inner-city teaching hospital. PATIENT(S) Four hundred eighty-nine women in an IVF program. INTERVENTION(S) In the prospective study, we measured levels of TPO antibodies and TSH. In the nested case-control study, we also measured levels of anticardiolipin antibodies. MAIN OUTCOME MEASURE Miscarriage. RESULT(S) One hundred seventy-three women were observed, of whom 31% (54/173) became pregnant. Pregnancy occurred in 48% (12/25) of the antibody-positive women and in 28% (42/148) of the antibody-negative women. Among those who became pregnant, miscarriage occurred in 33% (4/12) of TPO antibody-positive women and in 19% (8/42) of TPO antibody-negative women. The TSH level was abnormal (<0.2 microIU/mL) in only one of the TPO antibody-positive women who miscarried. The presence of anticardiolipin antibodies was not associated with miscarriage. CONCLUSION(S) No association was found between the presence of TPO antibodies before pregnancy and miscarriage in women without a history of habitual abortion. The presence of TPO antibodies did not adversely affect a womans chances of becoming pregnant.

Thyroid function and thyroid size in normal pregnant women living in an iodine replete area

OBJECTIVE The interpretation of the changes in thyroid hormone concentrations during normal pregnancy is a matter of debate involving, in some geographical regions, enhanced thyrold activity in early pregnancy and a hypothyroid state In the third trimester.

Irreversible gonadal damage in male survivors of pediatric Hodgkin's disease

Gonadal damage in adult patients after chemotherapy for Hodgkins disease is well documented, but data of patients treated before adulthood are scarce.

Effects of Evening vs Morning Levothyroxine Intake: A Randomized Double-blind Crossover Trial

BACKGROUND Levothyroxine sodium is widely prescribed to treat primary hypothyroidism. There is consensus that levothyroxine should be taken in the morning on an empty stomach. A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. To date, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed. METHODS To ascertain if levothyroxine intake at bedtime instead of in the morning improves thyroid hormone levels, a randomized double-blind crossover trial was performed between April 1, 2007, and November 30, 2008, among 105 consecutive patients with primary hypothyroidism at Maasstad Hospital Rotterdam in the Netherlands. Patients were instructed during 6 months to take 1 capsule in the morning and 1 capsule at bedtime (one containing levothyroxine and the other a placebo), with a switch after 3 months. Primary outcome measures were thyroid hormone levels; secondary outcome measures were creatinine and lipid levels, body mass index, heart rate, and quality of life. RESULTS Ninety patients completed the trial and were available for analysis. Compared with morning intake, direct treatment effects when levothyroxine was taken at bedtime were a decrease in thyrotropin level of 1.25 mIU/L (95% confidence interval [CI], 0.60-1.89 mIU/L; P < .001), an increase in free thyroxine level of 0.07 ng/dL (0.02-0.13 ng/dL; P = .01), and an increase in total triiodothyronine level of 6.5 ng/dL (0.9-12.1 ng/dL; P = .02) (to convert thyrotropin level to micrograms per liter, multiply by 1.0; free thyroxine level to picomoles per liter, multiply by 12.871; and total triiodothyronine level to nanomoles per liter, multiply by 0.0154). Secondary outcomes, including quality-of-life questionnaires (36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale, 20-Item Multidimensional Fatigue Inventory, and a symptoms questionnaire), showed no significant changes between morning vs bedtime intake of levothyroxine. CONCLUSIONS Levothyroxine taken at bedtime significantly improved thyroid hormone levels. Quality-of-life variables and plasma lipid levels showed no significant changes with bedtime vs morning intake. Clinicians should consider prescribing levothyroxine intake at bedtime. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN17436693 (NTR959).

THE VALUE OF THYROID VOLUME MEASURED BY ULTRASONOGRAPHY IN THE DIAGNOSIS OF GOITRE

Thyroid volume was measured by ultrasonography in 80 euthyroid patients with sporadic nontoxic goitre and in 50 healthy adults, all residing in non‐iodine deficient areas. All patients were referred because of complaints of goitre and had been diagnosed as cases of goitre by inspection and palpation. The thyroid volume in 15 patients with goitre (19%) was within the normal reference range (4.9–19.1 ml). Fourteen of the 15 patients had thyroid nodules larger (mean diameter 2.9 ± 1.1 cm) than those detected in nine of the healthy adults (mean diameter 0.8 ± 0.6 cm; P < 0.001). Thyroid size as estimated by inspection and palpation (grade OA to III according to Stanbury et al, 1974) was poorly related to thyroid volume measured by ultrasonography. In conclusion: (1) a thyroid volume within the normal reference range does not rule out the presence of nodular goitre; and (2) application of thyroid volume measurement by ultrasonography may prevent overestimation of goitre prevalence in epidemiological surveys.

Effects of evening vs morning thyroxine ingestion on serum thyroid hormone profiles in hypothyroid patients.

Objective   Standard drug information resources recommend that l‐thyroxine be taken half an hour before breakfast on an empty stomach, to prevent interference of its intestinal uptake by food or medication. We observed cases in which TSH levels improved markedly after changing the administration time of l‐thyroxine to the late evening. We therefore conducted a pilot‐study to investigate whether l‐thyroxine administration at bedtime improves TSH and thyroid hormones, and whether the circadian rhythm of TSH remains intact.