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Postpartum thyroiditis.

Postpartum thyroiditis (PPT) is a syndrome of transient thyroid dysfunction occurring in the first postpartum year. A thyrotoxic phase may be brief and unnoticed before a more long-lasting hypothyroid phase occurs. The incidence is variably reported, ranging from 1.9% to 16.7%, perhaps reflecting racial or geographical differences in the distribution of genetic or environmental risk factors such as the titre of thyroid antibodies and the dietary intake of iodine. The syndrome is an autoimmune disorder, strongly associated with the presence of thyroid microsomal antibody in serum. The thyrotoxic phase may be distinguished from Graves' disease by the finding of low, rather than high, uptake of radioactive iodine or technetium in the thyroid. Screening may be valuable in women with other autoimmune disorders such as Type 1 diabetes mellitus. Treatment should be tailored to the symptoms. Significant thyrotoxic problems should be managed with beta-blocking agents, but severe hypothyroid symptoms should be treated with the short-term replacement thyroxine. A small proportion of affected women will remain permanently hypothyroid. There is also a significant risk of recurrent disease after a subsequent pregnancy.

Female↗

Postpartum proptosis with ophthalmopathy.

BACKGROUND: Postpartum thyroid disease presents in two forms: postpartum thyroiditis (PPT) and postpartum Graves' disease (PPGD). CASE REPORT: A case of postpartum thyroid dysfunction with ophthalmopathy is presented. DISCUSSION: In women diagnosed with Graves' disease during the ages of 20 to 35 years, 66% have a postpartum onset; women with a previous history of Graves' disease frequently relapse in the postpartum period. Additionally, up to 25 to 30% of postpartum women can develop permanent hypothyroidism from postpartum thyroiditis. The signs and symptoms of PPT and PPGD may be indefinite after delivery and often go undiagnosed. Because complications can be significant and may become irreversible, proper diagnosis and timely treatment is important.

Adult↗

Inhibition of thyrotropin-induced adenosine 3'5'-monophosphate increase by immunoglobulins from patients with primary myxedema.

Immunoglobulin G (IgG) fractions prepared from the serum of 18 patients with primary myxedema, 9 patients with goitrous Hashimoto's thyroiditis, and 14 normal controls were tested for their ability to alter TSH stimulation of cAMP production in cultured human thyroid cells and the binding of TSH to its receptor. When compared with the cAMP increase induced by 0.1 mU/ml bovine TSH in the presence of normal IgG, cAMP accumulation was significantly inhibited (P less than 0.005) by the addition of IgG from patients with primary myxedema. TSH-induced cAMP accumulation was not affected by IgG from patients with goitrous thyroiditis. IgG from patients with primary myxedema also inhibited the cAMP increase induced by thyroid-stimulating immunoglobulins, but not against the increase induced by prostaglandin E1. None of the IgG tested affected the basal level of cAMP. Two potent inhibitory IgG were strongly positive for TSH-binding inhibitor immunoglobulins. Excluding these, no significant correlation was found between the thyroid stimulation-blocking activity and the TSH-binding inhibitory activity. These data suggest the presence of at least two different types of antibodies in primary myxedema which block adenylate cyclase stimulation by TSH and might be responsible for thyroid dysfunction and atrophy.

Adenylyl Cyclase Inhibitors↗

[Congenital transient hypothyroidism: characteristics of children identified at Newborn Screening Program of the State of Minas Gerais, Brazil].

Early diagnosis and treatment of congenital hypothyroidism are the main goals of the neonatal screening programs. A retrospective analysis was carried out to assess the characteristics and etiologies of congenital transient hypothyroidism (CTH) in the Newborn Screening Program of the State of Minas Gerais, Brazil. To reach a diagnosis of CTH, altered screening and serum confirmatory T4 and TSH tests and normal serum free T4 and TSH at 4 and 8 weeks after the withdrawal of levothyroxine were used. We studied 21 children with CTH who represented 4.23% of the whole group with detected hypothyroidism and followed them up in the Screening Program. These patients received LT4 therapy for a variable period of one month to three years. Serum confirmatory TSH levels varied from 10.4 to 583.4 microUI/mL. Maternal antibodies, TRAB and anti-TPO, were associated to CTH in two children and iodine overload in one of them. We concluded that CTH is an important component in neonatal screening and hormonal treatment during the first months of the life is essential. The TSH initial levels are not relevant to determine whether the thyroid dysfunction is transient or permanent.

Autoantibodies↗

[Thyroid diseases and myasthenia gravis].

In a group of 304 myasthenic patients 15 cases with thyropathies were reported: nine with hyperthyroidism, one with hypothyroidism and five with nontoxic goiter. Four patients presented diffuse simple goiter and one a multinodular goiter with normal thyroid function. No patient came from an endemic goiter region, not even familial goiter. The prevalence and influence of hyperthyroidism on myasthenic symptomatology were studied. Our findings suggest that there is no clinical correlation between both myasthenia symptomatology and thyroid dysfunction, neither significant influence on myasthenic symptoms when the endocrine disorders improve.

Adolescent↗

The risk factor for development of thyroid disease during interferon-alpha therapy for chronic hepatitis C.

OBJECTIVES: To determine the risk factors for the development of thyroid diseases during interferon-alpha therapy, we analyzed the patients with chronic hepatitis C who were treated with interferon-alpha. METHODS: One hundred nine patients with chronic hepatitis C (77 men and 32 women, ages 20-72 yr) were treated with interferon-alpha (alpha, 48; alpha 2a, 38; alpha 2b, 23) for 14-40 wk. Thyroid function tests and seven autoantibodies were assessed at the beginning and end of interferon-alpha therapy, and every other month. A logistic multiple regression model was used in the statistical analysis of risk factors for development of thyroid diseases. RESULTS: Among the 106 patients with normal pretreatment thyroid function tests, nine patients (three men and six women, ages 33-62 yr) developed thyroid diseases. However, among three patients with abnormal thyroid function tests, exacerbation of thyroid disease was not observed during interferon-alpha therapy. Logistic multiple regression model revealed that positivity for microsome antibody was a significant risk factor for the development of thyroid disease (p < 0.0001, chi 2 = 20.18). Actually, compared to patients without microsome antibody at the beginning of therapy, the incidence of thyroid diseases in the patients with pretreatment microsome antibody was very high: 3.3% (3/99) versus 60% (6/10), respectively. Six patients developed hyperthyroidism and three patients developed hypothyroidism. The patients with hyperthyroidism had atypical clinical features. CONCLUSION: Our study revealed that positivity for microsome antibody at the beginning of interferon-alpha therapy is a risk factor for thyroid dysfunction.

Adult↗

[6-sulfatoxymelatonin in women with secondary amenorrhea].

We evaluated the overnight urinary excretion of 6-sulfatoxymelatonin in a group of 347 women (range: 18-69 years). 26 women (range 20-29 years) with normogonadotrophic, hypoestrogenemic amenorrhoea (WHO II) were selected and compared with a group of 26 women menstruating normally (range: 19-30 years) with respect to urinary 6-sulfatoxymelatonin excretion, serum 17 beta-estradiol levels and response to the thyroid releasing hormone (TRH) test. Patients with hyperprolactinemia, hyperandrogenemia, thyroid dysfunction and weight problems were excluded. 6-sulfatoxymelatonin was found to be significantly higher in the amenorrhoeic women than in the controls (p < 0.000001). In the amenorrhoeic patients a statistically significant inverse correlation was found between serum 17 beta-estradiol levels and urinary 6-sulfatoxymelatonin excretion. A positive correlation was obtained between the thyroid stimulation hormone (TSH) value measured at 20 minutes after stimulation and 6-sulfatoxymelatonin excretion. Further clinical research in this field is required to evaluate its clinical impact, especially in patients with secondary amenorrhea.

Adolescent↗

The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E.

OBJECTIVE: Although lipid abnormalities are well described in hypothyroidism, effects on apolipoproteins are less well understood. The aim of this study was to examine the effects of thyroid dysfunction on plasma lipids and apolipoproteins. DESIGN: A prospective study of lipids and apolipoproteins before and after treatment of hypothyroidism and hyperthyroidism. PATIENTS: Eighteen patients with hypothyroidism and 5 patients with hyperthyroidism were included. MEASUREMENTS: Plasma cholesterol, triglycerides, HDL cholesterol, apo AI, apo AII, and apo E were measured before and after treatment of the thyroid abnormality. RESULTS: Total and HDL cholesterol, apo AI and apo E decreased with treatment of hypothyroidism, while triglycerides and apo AII levels were unchanged. The total/HDL cholesterol and LDL/HDL cholesterol ratios also decreased with treatment of hypothyroidism. In contrast, treatment of hyperthyroidism was associated with an increase in total and HDL cholesterol, and apo AI. Triglycerides, apo AII and Apo E were unchanged by treatment of hyperthyroidism. The total/HDL cholesterol and the LDL/HDL cholesterol ratios increased with treatment of hyperthyroidism. CONCLUSIONS: Hypothyroidism and hyperthyroidism have opposite effects on plasma lipids and apolipoproteins. In hypothyroidism, total and HDL cholesterol, total/HDL cholesterol ratio, apo AI and apo E are elevated. The increase in apo AI without a concomitant increase in apo AII suggests selective elevation of HDL2. In contrast, hyperthyroidism is associated with decreased total and HDL cholesterol, total/HDL cholesterol ratio, and apo AI levels. These effects are reversible with treatment of the underlying thyroid disorder.

Adult↗

Cross-sectional and longitudinal study of the pituitary-thyroid axis in patients with thalassaemia major.

OBJECTIVE AND DESIGN: Thyroid dysfunction is known to occur frequently in thalassaemia major, but its prevalence and severity varies in different cohorts, and the long-term natural history is poorly described. We evaluated the pituitary/thyroid axis in thalassaemia major patients in a cross-sectional study and correlated abnormalities with indices of iron overload. Furthermore, the course of thyroid disease in thalassaemia major patients was assessed in a 15-year longitudinal study. PATIENTS AND MEASUREMENTS: Cross-sectional study: pituitary-thyroid axis function was examined in 37 patients (22 F, 15 M; aged 10-39 years, mean +/- SE = 21 +/- 1.4) out of a total of 43 who attended the Haematology and Endocrinology Clinics of Hadassah Hospital on a regular basis. The mean pretransfusion Hb level was 85 +/- 20 g/l, and all patients except one were treated with desferrioxamine (DF, mean +/- SE dose 20.2 +/- 2.6 mg/kg/day). Twenty-two had hypogonadotrophic hypogonadism (HH). Longitudinal study: 21 thalassaemia major patients were evaluated with TRH tests in 1976 and again in 1985. Fourteen of these and another eight were evaluated in both 1985 and 1991. RESULTS: Cross-sectional study: no patient had any clinical signs or symptoms of hypothyroidism; however, one had abnormally low T4, borderline low FT4 and normal T3 levels associated with an exaggerated TSH response to TRH consistent with mild hypothyroidism. This patient did not have a previous TRH test, but serial basal determinations over 7 years revealed a progressive decrease in thyroid function. Thirty-six patients had thyroid hormone levels within the normal range. Nine of these (24.3%) had only an exaggerated TSH response to TRH whereas seven others (19%) also had borderline elevated basal TSH levels. TSH response to TRH was not correlated with age, serum ferritin or liver function tests (ALT or GGT). Longitudinal study: mean TSH response to TRH decreased (P < 0.002), and mean T3 levels increased (P < 0.001) between 1975 and 1985. These findings are probably related to the initiation of DF treatment in 1981. During the last 6 years, four patients with previously normal TSH responses to TRH developed elevated peak TSH levels. Mean T3 concentrations decreased and TSH response to TRH increased significantly (P < 0.001 for both). CONCLUSIONS: (1) In this patient group the thyroid pituitary axis is less sensitive than the gonadal axis to iron-induced damage; only one out of 37 patients developed mild uncompensated hypothyroidism. (2) As opposed to the gonadal axis, the thyroid gland appears to fail before the central components of the axis. (3) Abnormal thyroid function may be reversible in the early stages. (4) Progression is variable, and it may take years to progress from normal to uncompensated hypothyroidism.

Adolescent↗

HLA-DR factors associated with postpartum hypothyroidism: an early manifestation of Hashimoto's thyroiditis?

Thirty-three Danish women selected from a prospective study of postpartum thyroiditis were HLA-DR typed. All women had positive titers of antimicrosomal antibodies, and 20 women developed thyroid dysfunction after delivery. DR5 and the phenotype 4.5 were significantly increased in the whole group (p less than 0.001) and strongly associated to hypothyroidism (p less than 0.01), whereas DR3 was insignificantly increased in thyrotoxic women. It is concluded that postpartum hypothyroidism is an autoimmune disorder and may be an early manifestation of Hashimoto's thyroiditis.

Female↗

Circulating thyroid antibodies and thyroid function studies in children and adolescents with insulin-dependent diabetes mellitus.

Significant high titres (1:400-1:25,600) of circulating thyroid microsomal antibodies (MCHA) were found in the sera of 5 out of 59 non-ketoacidotic, insulin-dependent diabetic (IDDM) patients (mean age 14.5 years). Among these five patients (four females, one male), all of whom were over 11 years, two also had thyroglobulin antibodies. Increased thyrotropin (TSH) response to TRH was found in 3/5 MCHA positive patients and in 3/54 without circulating MCHA. Serum thyroxine (T4) and free T4 (FT4) average values were significantly lower (P less than 0.01 and P less than 0.001) in diabetics (7.1 +/- 1.8 micrograms/dl and 10.2 +/- 3.1 pg/ml, means +/- SD) as compared to normal sex and age matched controls (8.9 +/- 1.9 micrograms/dl and 12.2 +/- 2.2 pg/ml, respectively). T4 and FT4 values were inversely related to the duration of the disease. Subnormal T4 values were found in six (five females and one male) patients, four of whom had subnormal FT4 values. No patient had low triiodothyronine (T3) and high reverse T3 (rT3) values, i.e. none displayed the biochemical pattern of the 'low T3 syndrome' described with ketoacidotic status. This indicates also a satisfactory compensation of IDDM in all the patients. At the time of study no patient (including also those with circulating MCHA and TGHA and with TSH hyper-response to TRH) showed either thyroid size enlargement or clinical features of thyroid dysfunction including impaired growth and bone age retardation.

Adolescent↗

Thyroid function screening of psychiatric inpatient admissions: a worthwhile procedure?

A thyroid function screening programme of admissions to a general psychiatric service was established. Over a 22-week period 588 patients were admitted and thyroid function tests were performed on 336, a screening rate of 57.1%. Initial investigation showed that 21.3% had a total thyroxine outside the range 75-130 nmol/l. On further investigation only 9 patients (1 thyrotoxic, 8 hypothyroid) had confirmed thyroid disease. In 7 of the 9 patients the disease had been clinically suspected. Thus the screening programme identified only 2 unsuspected cases of thyroid dysfunction and we conclude that this level of detection does not warrant a formal screening programme.

Adult↗

Thyrotropin-releasing hormone stimulation test to assess thyroid function in severely sick cats.

Basal serum thyroxine (T4) concentration and the thyrotropin-releasing hormone (TRH) stimulation test were used to assess thyroid function in 36 critically ill cats examined between July 1996 and October 1998. Of the 36 cats. hyperthyroidism (as underlying or complicating disease) was suspected in 22 based on clinical signs, palpable thyroid nodules, and abnormal thyroid gland histology (study group). Hyperthyroidism was not suspected in the remaining 14 cats, which served as the control group. Based on serum T4 concentrations, suppression of thyroid function was documented in 14 (64%) cats of the study group and in 10 (71%) cats of the control group. The TRH stimulation test revealed an increase in serum T4 of less than 50% of the baseline concentration in 18 (82%) cats of the study group, and in 6 (43%) cats of the control group. In conclusion, based on the results of serum T4 determinations and the TRH stimulation tests, it was not possible to differentiate between cats with clinical and histologic evidence of thyroid dysfunction (hyperthyroidism) and cats with severe nonthyroidal illnesses.

Animals↗

Growth hormone secretion in Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is a multisystem defect characterized by obesity, hypogenitalism and short stature for genetic background. Low GH serum levels have been found in patients with PWS and were related to a hypothalamic-pituitary dysfunction. We studied spontaneous nocturnal GH secretion and GH-response to provocative tests in five patients affected by PWS. We observed in three of them (Group A) abnormally low GH and IGF-1 serum levels. In the other two patients (Group B) GH secretion and IGF-1 serum levels were normal. In all patients no thyroid dysfunction was observed. These data might suggest the presence of two different subgroups of patients affected by PWS, from an endocrinological point of view. An abnormally low GH secretion would be evident only in a subgroup of patients, which appears to be normal in the remaining patients. This casistic is small in number, but if our data will be confirmed by more extensive studies it may be possible to identify a specific population of PWS patients who could benefit from recombinant GH-therapy.

Adolescent↗

Down syndrome and thyroid function in adults.

Thyroid function has been studied in 11 middle-aged and elderly subjects with proven Down syndrome. Unequivaocal biochemical evidence of hypothyroidism was found in 6, and of thyrotoxicosis in 1. It is concluded that, in contrast to the situation in children with Down syndrome, thyroid dysfunction is exceedingly common in adults with the syndrome.

Adult↗

Thyroid ultrasound versus antithyroid peroxidase antibody determination: a cohort study of four hundred fifty-one subjects.

Autoimmune thyroiditis is mirrored by a hypoechoic ultrasound pattern. We determined diagnostic precision of thyroid sonography compared to that of anti-thyroid peroxidase antibody (TPOAb) concentration. Ambulatory patients with unknown thyroid status (n = 451; 407 female, ages 44 +/- 16 years; 45 male, ages 50 +/- 14 years) excluding those with suspected hyperthyroidism or on drugs known to cause hypothyroidism were recruited consecutively. Subjects were recruited from a specialized thyroid outpatient unit with higher frequencies of thyroid disorders than in the general population. Before determination of thyroid function and TPOAb concentration thyroid volume (normal values: women < 12 mL, men < 14 mL) and echogenicity (grade 1 = normal: similar to submandibular gland, hyperechoic to neck muscles; grade 2: hypoechoic to submandibular gland, hyperechoic to neck muscles, grade 3: iso-/hypoechoic to neck muscles) were determined. Positive predictive value of grade 3 pattern for detection of autoimmune thyroiditis was 94% (with overt hypothyroidism) and 96% (with any degree of hypothyroidism), that of grade 2 or 3 85% and 87%, respectively. Negative predictive value of grade 1 pattern for detection of euthyroid TPOAb negative subjects was 91%. Goiter was present in 31% and 21% of TPOAb postive and negative subjects, respectively, while 11% and 15% had an atrophic thyroid gland (p = not significant [n.s.]). Given a high intraobserver and interobserver agreement abnormal thyroid ultrasound patterns were highly indicative of autoimmune thyroiditis and allowed the detection of thyroid dysfunction with 96% probability.

Adolescent↗

Antenatal diagnosis and treatment of fetal hypothyroidism. A report of two cases.

Fetal goiter in the presence of maternal Graves' disease can signify either hyperthyroidism or hypothyroidism in the fetus. Two patients with Graves' disease taking propylthiouracil were found to have a fetal goiter on a prenatal sonogram. Fetal blood sampling identified hypothyroidism in both instances. Administration of intraamniotic thyroxine resulted in rapid resolution of the goiter, normalization of subsequent fetal thyroid studies, and delivery of a euthyroid fetus. Cordocentesis allows accurate diagnosis and follow-up of fetal thyroid dysfunction and prompt initiation of appropriate therapy.

Adult↗

The assessment of risk to acquired hypothyroidism from exposure to PCBs: a study among Akwesasne Mohawk women.

PCBs are a family of 209 chemical compounds, each of which consists of two benzene rings and 1 to 10 chlorine atoms. Their long-term stability and dispersion into the environment and the food chain have caused concern about their impact on humans and the environment. Native American communities are believed to be at particularly high risk of such exposure since they typically are more dependent than other populations on local fish and game as a food source. We have evidence for a significant excess in incidence and prevalence of hypothyroidism among Mohawks, particularly older women, as compared to other populations. The goal of the current project is to compare serum PCB concentrations to indicators of thyroid function in controls and patients with demonstrated thyroid dysfunction. Studies on experimental animals (rats) have shown significant depression of circulating levels of T4 and moderate reductions in levels of T3 after exposure to PCBs. We are conducting a retrospective observational case-control study. The participants are Mohawk women 30 years of age and older. Controls are participants in an ongoing environmental epidemiology study, whose thyroid hormone tests show a normal function. Our study aims to investigate the association between long-term exposure to PCBs and acquired hypothyroidism, to identify the critical exposure routes and to develop and apply toxic equivalents for thyroid disease for the various PCB congeners. PCB exposure is assessed by ultra-trace, congener-specific determination in blood specimen using GC/ECD. The study is currently ongoing. We have analyzed 46 samples of cases and 75 samples of controls.

Adult↗