Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development?

Women with antibodies against the enzyme thyroid peroxidase [TPO-Ab; formerly microsomal antibodies (MsAb)] are at particular risk for developing postpartum thyroid dysfunction; the latter is significantly associated with postpartum depression. Although the negative effect of postpartum maternal depression on child development is well documented, the consequences of elevated titers of TPO-Ab during pregnancy and subsequent postpartum thyroid dysfunction on child development are not known. In a prospective study of a cohort of 293 pregnant women, the occurrence of TPO-Ab during gestation, thyroid dysfunction, and depression was investigated. Five years after delivery, child development was assessed in 230 children of the original cohort using the Dutch translation of the McCarthy Scales of Children's Abilities. Children of women with TPO-Ab during late gestation (n = 19, with normal thyroid function) had significantly lower scores (by t test) on the McCarthy Scales of Children's Abilities than antibody-negative women. The difference on the General Cognitive Scale, which reflects IQ scores, was substantial (10.5 points; t = 2.8; P = 0.005). After correction for possibly confounding variables, maternal TPO-Ab during gestation was found to be the most important factor related to the scores on the General Cognitive Scale (odds ratio = 10.5; 95% confidence interval = 3-34; P = 0.003). We conclude that children of pregnant women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired development.

Androgen turnover during marathon running.

The purpose of the study was to investigate the effect of prolonged physical stress on peripheral androgen turnover. Venous blood samples were taken from 18 athletes 24 h before finishing a competitive marathon run and directly after running the race. Serum cortisol, testosterone (T), dehydroepiandrosteronesulfate (DHEAS), sex hormone binding globulin (SHBG), and 5 alpha-androstane- 3 alpha, 17 beta-diolglucuronide (3 alpha-AdiolG) were determined and corrected for hemoconcentration. Marathon running caused a rise in serum cortisol concentration in all athletes. Furthermore, a significant (P < 0.01) rise in serum T and T-index (index of free T) was observed. The significant (P < 0.01) rise in serum DHEAS concentration, a mainly adrenal cortical androgen, pointed toward a stimulation of the adrenal cortex or a reduced hepatic metabolic clearance rate. Finally, 3 alpha-AdiolG, an androgen metabolite exclusively formed in peripheral tissues, was increased in the sera of all athletes. These results suggest that marathon running leads to increased concentrations of serum adrenal and gonadal androgens. The simultaneously increased 3 alpha-AdiolG levels may be caused by increased androgen turnover in peripheral tissues containing 5 alpha-reductase.

Microsomal antibodies during gestation in relation to postpartum thyroid dysfunction and depression.

RATIONALE: Microsomal antibodies have been related to postpartum thyroid dysfunction and postpartum depression. OBJECTIVES: To detect the value of microsomal antibodies during gestation in a random population, as a risk factor for thyroid dysfunction and depression during the postpartum period. MAIN FINDINGS: The presence of microsomal antibodies was investigated in a random population of 293 women at 32 weeks' gestation. At the same time, postpartum thyroid function was assessed repeatedly in all women every six weeks up to 34 weeks' postpartum. Postpartum thyroid dysfunction, defined as the presence of abnormal TSH, in combination with abnormal fT4 and/or fT3 values, occurred in 21 women (7.2%) during the postpartum period. Depression was assessed using the Research Diagnostic Criteria without knowing the results of biochemical thyroid function tests. At 32 weeks' gestation there were 27 (9.2%) women with elevated microsomal antibody titres. Compared with microsomal-antibody negative women at 32 weeks' gestation, these women had an RR of 20 for developing postpartum thyroid dysfunction and an RR of 1.7 for developing postpartum depression. CONCLUSIONS: Women with elevated microsomal antibody titres during gestation are particularly at risk for postpartum thyroid dysfunction, but only have a slightly increased risk for postpartum depression.

[Incidence of postpartum thyroid function disorders in The Netherlands]. / Vóórkomen van postpartale schildklierfunctiestoornissen in Nederland.

In a longitudinal study the incidence of postpartum thyroid dysfunction in the Netherlands was investigated in an unselected open population. There were 293 women who were screened by repeated assessments of thyroid function until 34 weeks postpartum at 6-week intervals. Thyroid dysfunction was defined as abnormal TSH values accompanied by abnormal FT4 and (or) FT3 values. The frequency of postpartum thyroid dysfunction was 7.2% (n = 21). Most of the thyroid dysfunction occurred between 16 and 28 weeks postpartum. There were five women with subclinical thyroid dysfunction: abnormal TSH values with complementary FT4 and (or) FT3 changes within normal limits. Four of them showed (marked) increase in antimicrosomal antibody titres. With the inclusion of the five women the frequency rose to 8.9%. These data appear representative for the Netherlands as a whole, suggesting that every year 14,000 women suffer from (transient) postpartum thyroid dysfunction.

Androstanediolglucuronide: a parameter for peripheral androgen activity before and during therapy with cyproterone acetate.

Serum 5 alpha-androstane-3 alpha,17 beta-diolglucuronide (3 alpha-AdiolG) levels were measured and the degree of hirsutism was scored in female outpatients complaining of excessive hair growth before and during treatment with cyproterone acetate. In a group of 16 patients with idiopathic hirsutism and in a group of 9 patients with either polycystic ovary syndrome and hirsutism or 21-hydroxylase deficiency and hirsutism, the serum 3 alpha-AdiolG levels were significantly increased (p less than 0.01) as compared with the serum 3 alpha-AdiolG level in a control group of 13 apparently healthy women: 3 alpha-AdiolG levels, median (range), being 5.3 (2.3-7.8) nmol/l, 8.5 (4.1-10.4) nmol/l, and 2.9 (1.5-5.2) nmol/l, respectively. In contrast to a previous report, no correlation was found between the serum 3 alpha-AdiolG levels and the Quetelet Index (N = 18, R = 0.42, p greater than 0.05), indicating an apparent ineffectiveness of the excessive androgen turnover in fat tissue. The use of the anti-androgen drug cyproterone acetate alone or in combination with ethinylestradiol in reverse sequential therapy did lower the 3 alpha-AdiolG levels significantly (p less than 0.01) together with a significant decrease (p less than 0.01) in hirsutism score. From the results of this study we therefore conclude that 3 alpha-AdiolG can be used as a parameter for peripheral androgen action before and during treatment with anti-androgens.

Treatment of amiodarone induced hyperthyroidism with potassium perchlorate and methimazole during amiodarone treatment.

To exploit the antiarrhythmic effect of amiodarone when patients develop the side effect of thyrotoxicosis three patients with hyperthyroidism induced by amiodarone were given simultaneously 1 g potassium perchlorate a day for 40 days and a starting dose of 40 mg methimazole a day while they continued to take amiodarone. As hyperthyroidism might have recurred after potassium perchlorate treatment was stopped the dose of methimazole was not reduced until biochemical hypothyroidism (raised thyroid stimulating hormone concentrations) was achieved. The patients became euthyroid (free triiodothyronine concentration returned to normal values) in two to five weeks and hypothyroid in 10 to 14 weeks. One patient became euthyroid while taking 5 mg methimazole a day and 600 mg amiodarone weekly; the two others required substitution treatment with thyroxine sodium while taking 5 mg methimazole or 50 mg propylthiouracil (because of an allergic reaction to methimazole) and 2100 or 1400 mg amiodarone weekly. Hyperthyroidism induced by amiodarone may be treated with potassium perchlorate and methimazole given simultaneously while treatment with amiodarone is continued.