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PubMed2002

Focus on primary care. Thyroid function and dysfunction in women.

UNLABELLED: All forms of thyroid disease are more common in women. The reason for this gender predilection has not been entirely elucidated but may relate to the closely intertwined relationship between thyroid function and the female reproductive axis. Thyroid dysfunction influences both menstrual function and fertility, likely through changes in sex hormone levels, gonadotropin release, and possibly ovarian function. Similarly, alterations in reproductive physiology can modulate thyroid function. In such settings as pregnancy, when sex hormone levels fluctuate markedly, variations in thyroid function occur frequently. For the clinician, understanding when such alterations require intervention is critical. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the abnormalities of the female reproductive axis associated with both hypo- and hyperthyroidism, to summarize how female sex hormones affect thyroid function, and to explain the effects of pregnancy on thyroid conditions.

Female↗
PubMed1996

Chronology of Graves' ophthalmopathy in an incidence cohort.

PURPOSE: To determine the chronologic characteristics of Graves' ophthalmopathy in an incidence cohort of 120 patients. METHODS: We reviewed the community medical records of 120 patients residing in Olmsted County, Minnesota, in whom Graves' ophthalmopathy had been diagnosed between 1976 and 1990. RESULTS: Median age at the time of diagnosis of Graves' ophthalmopathy was 43 years; the minimum and maximum ages were 8 and 88 years, respectively. Among 108 patients with hyperthyroidism, ophthalmopathy was diagnosed in the six-month interval preceding the diagnosis of thyroid dysfunction in 20 patients (18.5%); ophthalmopathy was concurrent with the diagnosis of hyperthyroidism in 22 patients (20.3%); and ophthalmopathy developed in the six-month interval after thyroid diagnosis in 24 patients (22.2%). Ophthalmopathy was diagnosed more than six months before the diagnosis of hyperthyroidism in only four additional patients (3.7%), whereas ocular changes developed six months or more after thyroid disease in the remaining 38 patients (35.2%). There was no significant seasonal variation in the diagnosis of either thyroid dysfunction or ophthalmopathy. Treatment of hyperthyroidism with iodine-131 did not appear to influence the course of Graves' ophthalmopathy. CONCLUSIONS: There is a strong temporal relationship between the thyroid and eye manifestations of Graves' disease. The diagnosis of Graves' ophthalmopathy tends to follow the diagnosis of hyperthyroidism. Treatment with iodine-131 does not appear to influence the course of Graves' ophthalmopathy. Although both childhood Graves' disease and Graves' ophthalmopathy are uncommon, ophthalmopathy occurs at all ages.

Adolescent↗
PubMed1999

Thyroid function during pregnancy.

BACKGROUND: This Case Conference reviews the normal changes in thyroid activity that occur during pregnancy and the proper use of laboratory tests for the diagnosis of thyroid dysfunction in the pregnant patient. CASE: A woman in the 18th week of pregnancy presented with tachycardia, increased blood pressure, severe vomiting, increased total and free thyroid hormone concentrations, a thyroid-stimulating hormone (TSH) concentration within the reference interval, and an increased human chorionic gonadotropin (hCG) beta-subunit concentration. ISSUES: During pregnancy, normal thyroid activity undergoes significant changes, including a two- to threefold increase in thyroxine-binding globulin concentrations, a 30-100% increase in total triiodothyronine and thyroxine concentrations, increased serum thyroglobulin, and increased renal iodide clearance. Furthermore, hCG has mild thyroid stimulating activity. Pregnancy produces an overall increase in thyroid activity, which allows the healthy individual to remain in a net euthyroid state. However, both hyper- and hypothyroidism can occur in pregnant patients. In addition, two pregnancy-specific conditions, hyperemesis gravidarum and gestational trophoblastic disease, can lead to clinical hyperthyroidism. The normal changes in thyroid activity and the association of pregnancy with conditions that can cause hyperthyroidism necessitates careful interpretation of thyroid function tests during pregnancy. CONCLUSION: Assessment of thyroid function during pregnancy should be done with a careful clinical evaluation of the patient's symptoms as well as measurement of TSH and free, not total, thyroid hormones. Measurement of thyroid autoantibodies may also be useful in selected cases to detect maternal Graves disease or Hashimoto thyroiditis and to assess risk of fetal or neonatal consequences of maternal thyroid dysfunction.

Adult↗
PubMed1984

[Free thyroxine estimation for screening of hyper- and hypothyroidism in an adult population].

Serum free thyroxine (FT4) was determined in 1,114 adults (male 239, female 875) in a periodic health evaluation in 1980 to detect unsuspected thyroid dysfunction, especially hyper- and hypothyroidism. The participants were dwelling in two towns of Miyagi prefecture. Beside FT4, serum T4 and T3 were also determined by radioimmunoassay. If thyroid dysfunction was suspected, further detailed examinations such as TRH-test (500 micrograms i.v.), radioimmunologic determinations of serum TSH and TBG, resin-sponge T3-uptake, 24-hr thyroid radioiodine 131I-uptake, radioiodine thyroid scan and anti-thyroid antibodies were performed. There were 3 patients with hyperthyroidism (0.27%), 4 with hypothyroidism (0.36%), 3 taking thyroid medication (2; Hashimoto's disease, 1; goiter), 3 on estrogen administration, 4 with Hashimoto's disease and 1 with goiter. Excluding these 18 patients, FT4, T4 and T3 values in 1,096 euthyroid subjects, 236 males and 860 females, were 1.1 +/- 0.3 (mean +/- S.D.), 1.1 +/- 0.3 and 1.0 +/- 0.3 ng/100 ml, 8.9 +/- 1.5, 8.8 +/- 1.6 and 9.0 +/- 1.5 micrograms/100 ml, and 122 +/- 33, 125 +/- 26 and 122 +/- 35 ng/100 ml, respectively. Serum FT4, T4 and T3 showed the distribution of logarithmic normal probability. The 95% normal range for free T4 was 0.60 to 1.80 ng/100 ml, total T4 6.0 to 11.8 micrograms/100 ml, and T3 84 to 176 ng/100 ml, respectively. Out of 1,114 subjects examined, the cases to be reexamined for the higher serum concentration than normal were 26 in FT4, 35 in T4 and 27 in T3, respectively. And the cases for lower values were 28 in FT4, 31 in T4 and 24 in T3, respectively. Serum FT4 values in the subjects during the administration of estrogens were within the normal range. FT4 and T4 were low in four patients with hypothyroidism, but two of them showed normal T3 values. Determinations of serum FT4, total T4 and total T3 were all useful for the screening of hyperthyroidism. But serum FT4 was the most reliable of the three. Determination of either serum FT4 or total T4 was suitable for the screening of hypothyroidism, but serum total T3 measurement did not cover all patients with hypothyroidism.

Adult↗
PubMedDate not supplied

Thyroid function in the elderly.

Thyroid dysfunction is common in older individuals, yet the diagnosis is often complicated by atypical clinical presentations and difficulty in interpretation of laboratory tests. An understanding of the alterations in thyroid function occurring normally as a consequence of the aging process is necessary for correct laboratory diagnosis of thyroid dysfunction in the elderly. There are subtle alterations in hypothalamic and pituitary function but normal feedback control of TSH secretion persists. In the thyroid itself, morphologic changes develop with age, but have little impact on thyroid hormone economy. Thyroidal secretion of thyroxine decreases, but parallels the decrease in thyroxine degradation rate, resulting in unaltered plasma thyroxine levels. Decreased peripheral conversion of thyroxine to triiodothyronine causes a fall in triiodothyronine concentrations. Nonthyroidal illnesses in the elderly may perturb the laboratory assessment of thyroid function by producing isolated high or low thyroxine levels in euthyroid individuals.

Adult↗
PubMed2005

Outcomes of pregnancy complicated by thyroid disease.

AIMS: To perform a case note review of pregnancies complicated by thyroid dysfunction to determine management and therapeutic intervention in relation to pregnancy outcome. METHODS: A retrospective case note analysis of 81 ongoing pregnancies in 70 pregnant women with a history of thyroid dysfunction over a period of 5 years at the Glasgow Royal Maternity Hospital (GRMH), Glasgow, Scotland, United Kingdom. The results of thyroid function tests and whether a change in treatment was instituted were recorded. Thyroid function was assessed by standard laboratory reference ranges for free thyroxine (FT4) and thyroid stimulating hormone (TSH) in all trimesters. Other parameters were also noted. RESULTS: Medication levels needed to be increased in the hypothyroid group (45%), and decreased (38%) in the hyperthyroid group. CONCLUSION: Pregnancy outcome was good in majority of cases given appropriate replacement therapy for stated reference values.

Antithyroid Agents↗
PubMed2000

Thyroid function in children with perinatal human immunodeficiency virus type 1 infection.

OBJECTIVE: To study thyroid function in children with perinatal HIV-1 infection retrospectively and determine whether thyroid abnormalities are correlated with clinical condition, disease progression, immunological impairment, and viral load. STUDY DESIGN AND SETTING: Total (TT4) and free (FT4) thyroxine, total (TT3) and free (FT3) triiodothyronine, reverse triiodothyronine (rT3), thyrotropin (TSH), thyroglobulin (TG), and thyroid binding globulin (TBG) were measured twice in 56 children with perinatal human immunodeficiency virus type 1 (HIV-1) infection. Median age at first determination was 13.5 (range: 0.03-127.0) months; median age at second determination was 66.2 (range 3.42-147.4) months. Antithyroglobulin, antimicrosomal, thyroid peroxidase, and thyrotropin receptor antibodies were also evaluated. Fifty-three healthy children were selected as controls. RESULTS: TT3, TT4, FT4, and TG were significantly reduced and rT3, TBG, and TSH increased in children with HIV-1 infection when compared with controls. Thyroid dysfunction correlated with severe immunosuppression and high viral load early in life preceded the onset of the disease and worsened over time. Autoantibodies were negative in all children with HIV-1 infection in all determinations. CONCLUSION: Thyroid abnormalities are observed early in the course of perinatal HIV-1 infection; thyroid dysfunction is particularly pronounced in children with severe immunosuppression and high viral load. Modifications of thyroid function precede worsening of clinical course in HIV-1 infected children.

CD4 Lymphocyte Count↗
PubMedDate not supplied

Prevalence of abnormal thyroid function tests in a Down's syndrome population.

As thyroid function has been documented to be of a higher prevalence in individuals with Down's syndrome, a study was set up to assess the thyroid status of these individuals. Thyroid function tests (T.F.T.s) were initially reviewed on 100 individuals with Down's syndrome in the community and on 36 individuals who were residentially based. Abnormal T.F.T.s were then reviewed 3 yr later. In total sample of 136, initially 13 percent [n = 18] of individuals with Down's syndrome had abnormal T.F.T.s, 5 percent [n = 7] were established cases of thyroid disease and 8 percent [n = 11] were newly identified cases who had abnormal T.F.T.s. Three yr later 6.5 percent [n = 9] of the group who had had abnormal T.F.T.s continued to have abnormal T.F.T.s, 5 percent [n = 7] had thyroid disease and 1.5 percent [n = 2] still had biochemical evidence of thyroid dysfunction. There was a statistically significant increase in abnormal T.F.T.s in the residential sample compared to the community sample on both occasions. The incidence of thyroid dysfunction has been found to increase with age, particularly over the age of 40, however in this study the majority were under the age of 40 with an age range between 28.3 yr and 33.8 yr. The results in this study, coupled with the variability of T.F.T.s over time, highlights the need for regular monitoring of the thyroid status of individuals with Down's syndrome.

Adolescent↗
PubMed1990

Endocrine disorders following treatment of childhood brain tumours.

We have studied the long-term endocrine effects of treatment on 144 children treated for brain tumours. All received cranial irradiation, 86 also received spinal irradiation and 34 chemotherapy. Almost all patients (140 of 144) had evidence of growth hormone insufficiency. Treatment with growth hormone was effective in maintaining normal growth but could not restore a deficit incurred by delay in instituting treatment. The effect of spinal irradiation on spinal growth was not corrected by growth hormone. As spinal growth makes the major contribution to the pubertal growth spurt and limb length the major contribution to childhood growth, treatment with GH will have maximal effect on leg length if instituted before the onset of puberty. Primary thyroid dysfunction was found in 11 of 47 children (23%) treated with craniospinal irradiation but in none treated with cranial irradiation alone. The incidence rose to 69% of 29 children treated with spinal irradiation and chemotherapy and to 50% of four children treated with cranial irradiation and chemotherapy. This effect of chemotherapy has not previously been reported and was detected by us through measurement of serum TSH concentration. Primary thyroid dysfunction requires treatment with thyroxine to prevent increasing the risk of secondary thyroid tumours. Seven of 20 girls (35%) treated with spinal irradiation had primary ovarian dysfunction as determined by raised gonadotrophin levels. Chemotherapy increased this, but not significantly. Three of 15 boys (20%) treated with chemotherapy had primary testicular dysfunction. Gonadotrophin deficiency occurred in seven boys. Four of 90 children had deficiency of cortisol secretion in response to hypoglycaemia. These results confirm the requirement for long-term follow-up of children treated for brain tumours from the endocrine point of view. Anticipation of hormone deficiencies and replacement treatment can improve the quality of life of survivors.

Adolescent↗
PubMed2004

High leptin levels in women developing postpartum thyroiditis.

BACKGROUND: There is experimental evidence that leptin is required for the development of T helper 1 (Th1)-mediated autoimmune diseases. However, to our knowledge, there are no studies demonstrating such a role in human autoimmune thyroid disease. OBJECTIVE: In the present study we have retrospectively examined patients developing postpartum thyroiditis (PPT), as a model of autoimmune disease, for changes in serum leptin levels during the postpartum period. MATERIALS AND METHODS: The study group included 61 women in the first month postpartum who were positive for thyroid peroxidase antibodies (TPOAb+ve). Twenty TPOAb-negative (-ve), age and body mass index (BMI)-matched, postpartum women were enrolled as the control group. All subjects were evaluated for BMI, serum leptin values, thyroid function [serum free-triiodiothyronine (FT3), free-thyroxine (FT4), thyrotropin (TSH)] and autoimmunity [TPOAb levels and complement activity index (C3 index)] at 4, 12, 16, 20 and 24 weeks' postpartum. During the postpartum period, 32 of 61 TPOAb+ve women (52.4%) showed one or more episodes of thyroid dysfunction (PPTD group), whereas the remaining 29 TPOAb+ve women remained euthyroid throughout the study period (PPTE group). None of the control group developed thyroid dysfunction. RESULTS: Four weeks postpartum, TPOAb+ve women showed higher serum leptin values than TPOAb-ve women, despite comparable BMI. At this time, PPTE and PPTD patients showed no significant differences in leptin levels or leptin/BMI ratio. Throughout the postpartum period, PPTD patients maintained significantly higher leptin values and leptin/BMI ratio compared to the healthy women. In PPTE women, however, a significant reduction in leptin levels and leptin/BMI ratio was seen at 12 weeks' postpartum. This decrease was transient and correlated negatively with the variation in C3 index at the same time. No significant correlation was found between serum leptin variations and FT4 or TSH levels. CONCLUSIONS: This study has demonstrated that women developing postpartum thyroiditis have higher leptin values compared to the healthy women. The higher levels were maintained for 6 months postpartum. This result would suggest an involvement of leptin in the pathogenesis of postpartum thyroid disease, although further studies are needed to characterize the reciprocal effects of leptin, immune system and thyroid hormones during the course of this disease.

Adult↗
PubMed2000

Measurement of anti-thyroglobulin and anti-thyroid peroxidase antibodies using highly sensitive radioimmunoassay: an effective method for detecting asymptomatic focal lymphocytic thyroiditis in the elderly.

Subclinical thyroiditis or thyroid dysfunction is relatively common in the elderly. To estimate the effectiveness of measurement of serum levels of anti-thyroglobulin and anti-microsomal or thyroid peroxidase antibodies for detecting focal lymphocytic thyroiditis (FLT) in the elderly, we examined the relationships between antibody titer and postmortem histological finding of the thyroid gland in 180 consecutive autopsies (69 women and 111 men) over 60 years of age without any overt clinical thyroid or collagen diseases. FLT was found in 25 cases (13.9%) with female predominance (21.7% in female vs. 9.0% in male). Measurements of serum levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies by radioimmunoassay (TgAb and TPOAb, respectively) were compared with the measurements of anti-thyroglobulin and anti-microsomal antibodies by a hemagglutination technique (TGHA and MCHA, respectively), using sera from 25 patients with FLT and age- and sex-matched 51 patients without FLT. Among 25 cases with FLT, TgAb and TPOAb were positive in 17 (68%) and 12 (48%), respectively. There was a close relationship between degree of FLT and serum level of TgAb or TPOAb (P<0.0001). On the other hand, TGHA and MCHA were positive only in 8 (32%) and 10 (40%), respectively. TgAb and TPOAb were more sensitive than TGHA (68% vs. 32%, P<0.05) and MCHA (48% vs. 40%) to detect FLT. Positive findings in either TgAb or TPOAb significantly improved sensitivity (76%) compared with that of TGHA or MCHA (44%) (P<0.05). Specificities of combined measurements of TgAb and TPOAb (90%) were not significantly different from those of TGHA and MCHA (100%). These findings indicate that TgAb is a more sensitive method for detecting FLT and that its diagnostic sensitivity for FLT increases by using it in combination with TPOAb. Therefore, in the elderly without clinically or biochemically overt thyroid dysfunction, positive TgAb and/or TPOAb could imply presence of FLT, and their titers might reflect degree of inflammation.

Aged↗
PubMed2004

The relation of Graves' ophthalmopathy to circulating thyroid hormone status.

AIM: The risk factors and epidemiological data for Graves' ophthalmopathy with and without abnormal circulating thyroid levels were examined to determine the relation of thyroid dysfunction to ophthalmopathy. METHODS: The authors retrospectively evaluated 482 patients seen with Graves' ophthalmopathy. Of these, 413 were classified as having abnormal levels of circulating thyroid hormone (ALTH) and 69 as having normal levels of circulating thyroid hormone (NLTH). RESULTS: Patients in the NLTH group, compared to the ALTH group, were older on average (56 (SD 13.5) v 52 (15.4)) and had a higher age adjusted body mass index (26.1 (0.8) v 23.4 (0.3)). In addition, a higher percentage of NLTH patients had hypercholesterolaemia. Those in the ALTH group were more likely to be female (76% v 51%), to have a family history of thyroid problems, and to have had eye surgery. CONCLUSION: NLTH and ALTH appear to differ from each other in terms of risk factors and epidemiological characteristics. Additionally, thyroid dysfunction seems to be associated with a more severe ophthalmopathy compared to the euthyroid state.

Adult↗
PubMed2006

Experimental confirmation by Sir Victor Horsley of the relationship between thyroid gland dysfunction and myxedema.

Whereas Sir Victor Horsley is well known for his many contributions to neurosurgery, this is not the case for his treatments for both myxedema and cretinism. Horsley's research on thyroid physiology was concentrated in the years 1884-1890, while he was director of the Brown Institute for Animals. Based upon experimentation with dogs and monkeys as well as some human patients, Horsley demonstrated conclusively that removal of the thyroid gland produced tremors, rigidity, and paralysis, which he attributed to changes in lower motor centers. Furthermore, the development of imbecility suggested that thyroid excision produced deficits in higher cortical functioning. Horsley showed that it was possible to alleviate temporarily some of the psychological and physiological symptoms of both myxedema and cretinism using transplanted thyroid tissue. Several of Horsley's students, most notably George Murray, continued and extended his work by examining other ways in which myxedema and cretinism could be treated (e.g., by injecting an extract of thyroid tissue).

Animals↗
PubMed2004

Thyroid toxicants: assessing reproductive health effects.

A thyroid toxicant workshop sponsored by the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction convened on 28-29 April 2003 in Alexandria, Virginia. The purpose of this workshop was to examine and discuss chemical-induced thyroid dysfunction in experimental animals and the relevance of reproductive and developmental effects observed for prediction of adverse effects in humans. Presentations highlighted and compared reproductive and developmental effects of thyroid hormones in humans and rodents. Rodent models of thyroid system dysfunction were presented. Animal testing protocols were reviewed, taking into account protocol designs that allow extrapolation to possible human health effects. Potential screening methods to assess toxicant-induced thyroid dysfunction were outlined, and postnatal bioassays of thyroid-related effects were discussed.

Animals↗
PubMed2003

The pathogenic role of anti-thyroglobulin antibody on pregnancy: evidence from an active immunization model in mice.

BACKGROUND: The presence of antibodies to thyroglobulin (Tg) is associated with fetal loss even in the absence of thyroid dysfunction. The aim of this study was to examine whether active immunization with Tg could elicit anti-Tg autoantibodies and reproductive failure without interfering with thyroid function. METHODS: BALB/c mice that were immunized with human Tg in complete Freund's adjuvant (CFA) or injected with only CFA were studied for the development of antibodies to Tg, T4, dsDNA, ssDNA and cardiolipin. Total T4, free T4 and thyroid-stimulating hormone (TSH) levels were also assessed before and during pregnancy. Percentages of resorbed fetuses (the equivalent to human missed abortion) were compared and autoantibody presence on the placentae and fetuses was examined. RESULTS: Following immunization, high levels of anti-Tg were observed in mice immunized with Tg, compared with mice injected with CFA [0.83 +/- 0.23 versus 0.012 +/- 0.016 respectively; mean +/- SD optical density (OD) at 405 nm; P < 0.001]. The specificity of binding to Tg was confirmed by competition assay. Although total T4 levels were increased in comparison with control mice, this was associated with the presence of antibodies to T4. Indeed, free T4 levels and TSH were similar to control mice. Mice were killed after 14 days of pregnancy. The thyroid function and the histology of the thyroid glands were normal. Increased fetal wastage was found among the Tg-immunized mice compared with the CFA-injected mice (P = 0.04), with lower fetal and placental weights (fetal weights: 194 +/- 4 mg versus 240 +/- 6 mg; placental weights: 105 +/- 2 mg versus 130 +/- 3; P < 0.001 for both). Antibodies to Tg were demonstrated only on the placentae of Tg-immunized mice. CONCLUSION: Immunization with Tg results in the production of Tg antibodies and fetal resorption. These effects occur in the absence of thyroid dysfunction.

Animals↗