[Aging and endocrinologic tests].
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Postpartum thyroid dysfunction (PPTD) is a common autoimmune disorder. Type I diabetes mellitus (IDDM) is an autoimmune disease with a high incidence of concomitant autoimmune thyroid failure. We hypothesized that women with IDDM would have an increased incidence of PPTD. Women with IDDM in New York City, were followed prospectively during the second and third trimester of pregnancy and at 6 weeks, 3 months, 6 months, 9 months, and 1 yr postpartum. A long-term follow-up was performed at 31 months postpartum. Forty-one women with IDDM were recruited at their initial prenatal visit. Two women (4.8%) had thyroid function test abnormalities observed at screening, three (7.3%) had a spontaneous miscarriage, and eight (19.5%) women were noncompliant with follow-up. Twenty-eight women (68.2%) completed the study. Thyroid function tests and thyroid autoantibody determinations were obtained at all visits. PPTD was defined as a TSH greater than 5.0 or less than 0.2 mU/L in the postpartum period with documented normal thyroid function tests during pregnancy. The incidence of PPTD in women with IDDM was 25%. This is a 3-fold increase compared to a similar study by our group in a nondiabetic population. Forty-three percent of the women (3/7) who developed PPTD required treatment in the immediate postpartum period and at long-term follow-up. The remainder of the women with PPTD, as well as all women who did not develop PPTD were euthyroid at 31 months postpartum. Women with IDDM are at high risk for PPTD. We recommend that all women with IDDM be screened for thyroid hormonal abnormalities during pregnancy and at 3 months postpartum for postpartum thyroid dysfunction. Long-term follow-up did not reveal an increased incidence of hypothyroidism in women who did not require treatment in the first postpartum year.
Various thyroid parameters in liver disease which were morphologically diagnosed were measured, and their relationship to liver function was mainly studied. Serum T4 levels were elevated in acute hepatitis (AH), chronic persistent hepatitis (CPH) and chronic aggressive hepatitis (CAH) compared with in normal controls (C). Serum T3 levels were elevated in CAH and reduced in liver cirrhosis (LC). Serum reverse T3 (rT3) levels were elevated in AH and chronic liver diseases (CLD). T3/T4 ratios decreased in AH, CPH and CAH. RT3/T3 ratios increased in AH and CLD. Serum Free T3 (FT3) levels reduced in CLD in order of CPH, CAH and LC, and were low levels in AH with the same degree as LC. Moreover, serum FT3 levels revealed negative correlation with ICG-R15 and positive correlation with prothrombin time (PT) and serum albumin levels (Alb). Therefore serum FT3 level was considered to become a sensitive index of liver damage. Serum free T4 (FT4) levels did not change significantly in AH with high levels of transaminases and reduced in only LC. Therefore serum FT4 may become an index of severity of liver dysfunction. On the other hand, T3/T4 ratios and rT3/T3 ratios showed less correlation with liver function tests compared with free thyroid hormones.
Thyroid gland dysfunction is a relatively common clinical problem in elderly people and is associated with significant morbidity if left untreated. The clinical features of thyroid disease may be subtle, easily overlooked or misdiagnosed. Therefore, a high index of suspicion is necessary. If potentially serious sequelae are to be avoided, the selection and interpretation of thyroid function tests must be appropriate. It is particularly important to consider both the effect of concurrent illness and the effect of certain drugs on thyroid function tests. With recent methodological advances, thyroid function tests are now more reliable, though in certain situations they still need to be interpreted with caution. Once the diagnosis is established, the management of both hypothyroidism and hyperthyroidism is relatively simple and effective, though there are special considerations relating to elderly patients.
BACKGROUND: The appropriate use of specific thyroid function tests to detect thyroid dysfunction remains controversial; some experts recommend both a sensitive thyrotropin (sTSH) test and a free thyroxine (FT4) test, while others recommend an sTSH test alone. OBJECTIVE: To determine how often sTSH and FT4 tests are ordered simultaneously, how often the results are discordant, and under what circumstances a single test of thyroid function may be sufficient to rule out thyroid dysfunction. METHODS: Retrospective descriptive study of all sTSH and FT4 tests performed on adult outpatients during a 6-month period. If both sTSH and FT4 tests were performed on a single serum specimen, the results were classified as concordant (both tests indicating hypothyroidism, hyperthyroidism, or euthyroidism) or discordant. Chart review was performed on patients with normal sTSH results and abnormal FT4 results. RESULTS: A total of 6551 sTSH and 3518 FT4 tests were performed during the study period. Both sTSH and FT4 tests were ordered together on 3143 specimens (48% and 89% of the total number of sTSH and FT4 tests ordered, respectively) from 2629 patients. Of the sTSH results, 69.8% were within the normal range, and 92.7% of the FT4 results were normal. The concordance between sTSH and FT4 results was 74.3%. Among the 1835 specimens with normal sTSH results, FT4 level was low in 11 patients (0.6%; 95% confidence interval, 0.3%-0.9%) and high in 24 (1.3%; 95% confidence interval, 0.8%-1.8%). Chart review did not disclose any instances when an abnormal FT4 results contributed to the treatment of an individual with a normal sTSH result. CONCLUSIONS: The sTSH test alone, and not the combination of sTSH and FT4 tests, should be ordered in most outpatients. An FT4 test should not be routinely ordered if the sTSH result is normal; at our institution this approach would obviate the need for at least half of the FT4 tests performed each year.
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The classical signs and symptoms of hypothyroidism were reevaluated in the light of the modern laboratory tests for thyroid function. We analyzed 332 female subjects: 50 overt hypothyroid patients, 93 with subclinical hypothyroidism (SCH), 67 hypothyroid patients treated with T4, and 189 euthyroid subjects. The clinical score was defined as the sum of the 2 best discriminating signs and symptoms. Beside TSH and thyroid hormones, we measured parameters known to reflect tissue manifestations of hypothyroidism, such as ankle reflex relaxation time and total cholesterol. Classical signs of hypothyroidism were present only in patients with severe overt hypothyroidism with low T3, but were rare or absent in patients with normal T3 but low free T4 or in patients with SCH (normal thyroid hormones but elevated basal TSH; mean scores, 7.8 +/- 2.7 vs. 4.4 +/- 2.2 vs. 3.4 +/- 2.0; P < 0.001). Assessment of euthyroid subjects and T4-treated patients revealed very similar results (mean score, 1.6 +/- 1.6 vs. 2.1 +/- 1.5). In overt hypothyroid patients, the new score showed an excellent correlation with ankle reflex relaxation time and total cholesterol (r = 0.76 and r = 0.60; P < 0.0001), but no correlation with TSH (r = 0.01). The correlation with free T4 was r = -0.52 (P < 0.0004), and that with T3 was r = -0.56 (P < 0.0001). In SCH, the best correlation was found between the new score and free T4 (r = -0.41; P < 0.0001) and TSH (r = 0.35; P < 0.0005). Evaluation of symptoms and signs of hypothyroidism with the new score in addition to thyroid function testing is very useful for the individual assessment of thyroid failure and the monitoring of treatment.
Evaluation of thyroid hormone indices was performed in 138 children with newly diagnosed type 1 diabetes, with their siblings serving as controls. The DKA group consisted of 76 children who had diabetic ketoacidosis (DKA) at initial diagnosis. The non-DKA group consisted of 62 children and the control group of 35. The thyroid function tests of the patients were measured within 3 days of the initial diagnosis of diabetes and at least one follow-up test one month to two years after adequate treatment of diabetes. The DKA group had significantly lower levels of T3, T4, free T4 and FTI than did the other two groups (p < 0.0001, p < 0.0001, p < 0.0001, and p < 0.0001, respectively). T3 concentration was lower in non-DKA subjects than in controls (p = 0.0003), but the two groups did not significantly differ in terms of T4, free T4, and FTI. The TSH level did not differ among the three groups. We conclude that DKA changes thyroid function measurements. In the absence of true thyroid disease, abnormal thyroid function tests are reversible after institution of good diabetic control. We suggest that thyroid function tests should be restricted to those patients suspected of having thyroid disorders at the initial diagnosis of type 1 diabetes.
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Isocitrate dehydrogenase (ICDH) may be useful for differentiating centrilobular from periportal necrosis in rats with liver injury. In this study, we assessed the usefulness of ICDH as a marker of centrilobular necrosis in patients with hyperthyroidism. Isocitrate dehydrogenase and alanine aminotransferase (ALT) activities were measured in the plasma of 56 patients with hyperthyroidism, 16 patients with chronic viral hepatitis (CVH), and 17 controls. Isocitrate dehydrogenase levels were higher in patients with hyperthyroidism than in those with CVH or in the controls (p < 0.01 and p < 0.001, respectively), even though ALT levels were higher in patients with CVH than in patients with hyperthyroidism (p < 0.01). Isocitrate dehydrogenase/ALT ratios were also higher in patients with hyperthyroidism than in those with CVH (p < 0.0001). Isocitrate dehydrogenase correlated to ALT levels in patients with hyperthyroidism or CVH (p < 0.05). In a patient with hyperthyroidism, ICDH levels decreased progressively to normal, and the ALT level and thyroid function were normalized. Thus, the plasma ICDH or ICDH/ALT ratio might be useful for differentiating centrilobular from periportal necrosis and for monitoring the degree of hepatic necrosis in patients with hyperthyroidism.
Clinicians experience difficulty in correctly interpreting the results of in vitro thyroid function tests in the presence of abnormalities of thyrobinding proteins or when results are borderline. This difficulty has been largely resolved in our laboratory by three innovations. First, the borderline areas for each of three routine tests of thyroid function (total thyroxine, thyrobinding index, and free thyroxine index) were accurately determined. Second, the results from this routine profile of three tests were displayed pictorially so as to produce patterns characteristic of various diagnostic situations, including euthyroidism in the presence of abnormalities of thyrobinding proteins. Third, interpretive comments and, in the case of borderline patterns, suggested further testing procedures were added to the report. Clinicians find the reporting system helpful and respond when additional tests are suggested. The system, operated manually at first, was later computerized.
Endemic cretinism occurs in areas of severe iodine deficiency and is manifested by two major clinical patterns, myxedematous and neurological. The relationship between these types and the factors responsible for the clinical variability are not clear. We examined 69 endemic cretins, aged 4-52 yr, categorized clinically at the beginning of the study into the three traditional types of endemic cretins, myxedematous (n = 25), neurological (n = 15), and the mixed form (n = 29), from a previously unreported endemia in Qinghai Province, China. These patients underwent detailed endocrine and neurological examination, including intelligence assessment using the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales, audiometry (in a subset of 37 patients); thyroid function testing and thyroid ultrasonography; and radiology of the skull, hand, and hip. We found that categorization of the cretins into the conventional types did not reflect the pathophysiology of the condition, since an identical pattern and intensity of neurological, intellectual, and audiometric deficits were common to and equally present in all three types of endemic cretins regardless of their thyroid function. Gait disorder (in 99%) and pyramidal signs such as patellar hyper-reflexia (in 91%) were the most common neurological abnormalities. There was no difference in mean intelligence test scores among the three groups [overall mean intelligence score (Hiskey or Griffiths tests), 28.8 +/- 12.8 (SD)]. The differing clinical manifestations of cretinism could be explained by the length and severity of thyroid hormone deficiency. Myxedematous cretins were severely thyroid hormone deficient, and as a result sexually immature, dwarfed, and had retarded skeletal maturity. They had clinical and sonographic thyroid atrophy, rather than goiter. Although neurological cretins were euthyroid, linear growth arrest lines (demonstrated radiologically) in the long bones of these cretins suggested previous hypothyroidism. Furthermore, all cretins were growth retarded when compared with peers of similar age and race. Our data therefore suggest that the different clinical types of endemic cretinism are in fact the same disorder phenotypically modified by the length and severity of postnatal hypothyroidism. The neurological manifestations are interpreted as reflecting the effects of maternal and fetal hypothyroxinemia, secondary to severe iodine deficiency, on the developing nervous system.
OBJECTIVE: Postpartum thyroid dysfunction (PPTD) is an autoimmune disorder characterized by the development of transient hyperthyroidism and, more frequently, hypothyroidism (or both) during the first six months of the puerperal period. A variable incidence has been reported in part because of differences in the number of women studied, the frequency of thyroid assessment postpartum, diagnostic criteria and methodology. The aim of this study was to evaluate thyroid function, ultrasound images and titre of autoantibodies against thyroid antigens in a cohort of pregnant women who met the criteria of 'normal' thyroid gland structure on clinical examination and imaging and normal thyroid function tests without a significantly positive anti-thyroid peroxidase (TPO) antibody titre (i.e. < 100 U/ml) in the first trimester. DESIGN AND PATIENTS: Eight hundred nulliparous or multiparous (one to seven previous pregnancies) pregnant women (age 26.1 +/- 4.8 years, mean +/- SD), were submitted to clinical, laboratory and ultrasonographic examination in the first trimester of pregnancy. Among these forty-six patients were excluded because of thyroid dysfunction, ultrasound structural abnormalities or a positive anti-TPO antibody titre (> 100 U/ml). A total number of 754 women were available for further studies in the postpartum period. A relatively large number of these patients (386) were lost for follow-up either before or after delivery. MEASUREMENTS: A cohort of 368 puerperal women was followed up regularly at 3, 6, 12 and 24 months after delivery, with periodic thyroid function tests, random urine iodine measurements, assays for serum autoantibodies against thyroid antigens and imaging by ultrasound. RESULTS: The provisional diagnosis of PPTD was established in 78 out of 368 who had positive anti-TPO levels and ultrasonographic thyroid structural changes. Twenty-nine of these patients had a transient rise of anti-TPO autoantibodies characterizing an autoimmune reaction. These autoantibodies levels progressively declined or became negative. Moreover none of these patients had evidence for altered thyroid function during the 18-24 months of follow-up. The remaining 49 patients (13.3%) progressively developed thyroid function abnormalities (mainly hypothyroidism) indicating the presence of thyroid gland changes due to PPTD. Further follow-up studies indicated that at 18-24 months, 42 patients had serum levels of anti-TPO-Ab that were more elevated, as compared with the first year values. Predictive factors found during pregnancy for developing PPTD were: (1) relatively low levels of anti-TPO, between 60 and 100 U/ml (odds ratio 3.1 : 1), and (2) ultrasonographic thyroid structural changes in the first trimester (odds ratio 6.4 : 1). CONCLUSIONS: We conclude that the prevalence of postpartum thyroid dysfunction in our geographical area ranges from 6.7% to 13.3%, considering, respectively, all pregnant women that were examined (n = 754) or only the number of puerperal women actually followed-up (n = 368). A transient form of thyroid autoimmune reaction characterized by elevated serum levels of anti-TPO that progressively declined or disappeared was observed in 29 puerperal women. Sonographic structural and echogenicity changes in the thyroid gland and borderline positive anti-TPO levels (between 60 and 100 U/ml) during pregnancy were considered to be of predictive value for development of postpartum thyroid dysfunction.
Iodine is an important constituent of thyroid hormones and deficiency can lead to a range of problems depending on the degree and at what stage of life the deficiency occurs. We report a 10 day-old infant with a goitre, who presented with raised TSH on dried blood spot screening. It was observed that her mother also had a goitre. The mother was a vegan and, on dietary assessment, her iodine intake was extremely low. Both mother and infant had abnormal thyroid function tests. Mother was given Lugol's iodine and her thyroid function tests normalised. Her baby was initially prescribed thyroxine on the basis of the raised screening TSH. This was subsequently withdrawn at the age of 2 weeks, following a normal plasma TSH. Thyroid function tests remained normal and the goitre disappeared by the age of 2 months. Iodine deficiency is uncommon in the Western World. However the incidence may be rising in otherwise iodine replete areas, particularly in those who adhere to restrictive and unusual diets. In the case of pregnant mothers their unborn child's health is in danger. This report demonstrates the need to ascertain maternal diets early in antenatal care, and supplement if necessary to avoid risk to their own health and that of their offspring.
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We compared measurement of free thyroxin (fT4) and total thyroxin (tT4) in serum as a primary screening test of thyroid function, based solely on biochemical diagnostic classification. The normal 95% reference intervals for fT4 and tT4 were equated by probit transformation, which allowed us directly to compare the efficiency of the biochemical classification. fT4 showed a small but distinct advantage over tT4 in the diagnosis of hyperthyroidism, but narrowing the reference interval proportionally for fT4 and tT4 to improve the sensitivity of the screening test resulted in the loss of this advantage. No clear advantage of fT4 over tT4 for the initial diagnosis of hypothyroidism was found at any reference interval.
OBJECTIVES: To determine the prevalence of thyroid auto-antibodies in specimens sent to Parirenyatwa hospital laboratory for thyroid function testing and to compare the thyroid status of these patients with that of apparently healthy subjects. DESIGN: Cross sectional study. SETTING: Immunology and radio-immunoassay laboratories, Parirenyatwa hospital, Department of Chemical Pathology, and Blood Transfusion Services, Harare. SUBJECTS: 212 blood samples submitted for thyroid function testing and 230 blood samples from apparently healthy blood donors. MAIN OUTCOME MEASURES: Serum concentrations of free triiodothyronine (FT3), thyroxine (FT4), thyrotropin (TSH), and thyroid auto-antibodies; anti microsomal (M Ab) and antithyroglobulin (Ag Ab) antibodies. RESULTS: The hyperthyroid subjects had median serum TSH level of 0.027 mIU/L (Q1 = 0.006, Q3 = 0.052), median serum FT3 level of 15.895 pmol/L (Q1 = 10.563; Q3 = 30.111), and a median serum FT4 level of 45.513 pmol/L (Q1 = 30.256; Q3 = 63.910). The goitrous subjects had median serum TSH level of 0.390 mIU/L (Q1 = 0.157; Q3 = 0.745). The blood donor group had median TSH value of 0.724 mIU/L (Q1 = 0.471; Q3 = 1.170). (Normal ranges: TSH = 0.167 to 2.80) Amerlite TSH-30 diagnostic kit; FT3 = 3.4 to 7.2 pmol/L; FT4 = 11 to 24 pmol/L) Amelex-MAB diagnostic kits) Thirty nine percent of the hyperthyroid subjects had either positive M Ab or Tg Ab or both. None of the goitrous subjects and the blood donors tested positive for neither M Ab, nor Tg Ab. No significant difference was found between the blood donors and the goitrous subjects for serum FT4 (P = 0.51). However, significant differences were found between the goitrous, the blood donor and the hyperthyroid groups with regards to serum TSH, serum FT4, and serum FT3 levels (p = 0.001). CONCLUSION: Our findings indicate that the occurrence of thyroid auto-antibodies among the blood donors and the goitrous population was uncommon, but high in the hyperthyroid subjects. The increase of iodine intake through iodine prophylaxis could have had the side effects of iodine induced hyperthyroidism.