Transient hyperthyroidism after withdrawal of antithyroid drugs in patients with Graves' disease

The development of silent thyroiditis in patients with a history of Graves' disease is common, especially in the postpartum period. We describe herein patients with Graves' disease who developed transient hyperthyroidism but not silent thyroiditis after withdrawal of antithyroid drug (ATD). If such patients are diagnosed as recurrence of Graves' disease, they may receive ATD or radioiodine therapy unnecessarily. We investigated the characteristics of these patients to prevent unnecessary therapy. We retrospectively studied 22 patients with Graves' disease who showed transient thyrotoxicosis after withdrawal of ATD. Two of 22 patients were male and the mean ages (+/- SD) were 33.7 +/- 12.6 yr. We observed these patients for 28.5 +/- 12.8 (mean +/- SD; range 12-53) months after transient thyrotoxicosis, and measured TSH, FT4, and TSH binding inhibitor immunoglobulin in sera. Radioiodine uptake was measured in 6 of them. The radioiodine uptake in the 4 patients was not suppressed (27.5%, 28.0%, 32.7%, 38.1%). These uptake levels indicate that their thyrotoxicosis was not caused by silent thyroiditis. Most of the 22 patients became euthyroid within 6 months. This study suggests a new therapeutic option as follows: in the case of young patients with mild thyrotoxicosis after withdrawal of ATD, physicians should follow them up for one month without medication unless they have unbearable symptoms or complications.     

Usefulness of the 2nd generation assay for anti-TSH receptor antibodies to differentiate relapse of Graves' thyrotoxicosis from development of painless thyroiditis after antithyroid drug treatment for Graves' disease

After antithyroid drug (ATD) treatment for Graves' disease, either a relapse of Graves' thyrotoxicosis or painless thyroiditis can develop. It is important to differentiate these two types of thyrotoxicosis because of the difference in required therapy. However, differentiation of thyrotoxicosis is usually difficult without radioactive iodine uptake (RAIU) which is not available in general practice. We investigated the clinical usefulness of the 2nd generation assay for anti-TSH receptor antibodies (TRAb) to differentiate these two types of thyrotoxicosis after ATD treatment for Graves' disease. We recruited 26 patients who developed thyrotoxicosis after ATD treatment for Graves' disease. These patients once became negative for TRAb and seemed to be in remission after ATD treatment. Upon development of thyrotoxicosis after ATD treatment, TSH, free T4, free T3 and TRAb were measured. TRAb were measured by the 2nd generation assay using recombinant human TSH receptors instead of porcine TSH receptors. Fourteen patients relapsed into Graves' thyrotoxicosis and 12 patients developed painless thyroiditis. Twelve (85.7%) of 14 patients with relapse of Graves' thyrotoxicosis were positive for TRAb. Eleven (91.7%) of 12 patients with development of painless thyroiditis after ATD treatment for Graves' disease were negative for TRAb. Levels of TRAb were significantly different between patients with relapse of Graves' thyrotoxicosis (4.86 +/- 6.45 IU/L) and those with painless thyroiditis (0.62 +/- 0.61 IU/L) (P<0.001). The 2nd generation assay for TRAb was useful to differentiate relapse of Graves' thyrotoxicosis from development of painless thyroiditis in patients who seemed to be in remission after ATD treatment for Graves' disease.     

Ratio of serum free triiodothyronine to free thyroxine in Graves' hyperthyroidism and thyrotoxicosis caused by painless thyroiditis

The serum T3 to T4 ratio is a useful indicator for differentiating destruction-induced thyrotoxicosis from Graves' thyrotoxicosis. However, the usefulness of the serum free T3 (FT3) to free T4 (FT4) ratio is controversial. We therefore systematically evaluated the usefulness of this ratio, based on measurements made using two widely available commercial kits in two hospitals. Eighty-two untreated patients with thyrotoxicosis (48 patients with Graves' disease and 34 patients with painless thyroiditis) were examined in Kuma Hospital, and 218 patients (126 with Graves' disease and 92 with painless thyroiditis) and 66 normal controls were examined in Ito Hospital. The FT3 and FT4 values, as well as the FT3/FT4 ratios, were significantly higher in the patients with Graves' disease than in those with painless thyroiditis in both hospitals, but considerable overlap between the two disorders was observed. Receiver operating characteristic (ROC) curves for the FT3 and FT4 values and the FT3/FT4 ratios of patients with Graves' disease and those with painless thyroiditis seen in both hospitals were prepared, and the area under the curves (AUC), the cut-off points for discriminating Graves' disease from painless thyroiditis, the sensitivity, and the specificity were calculated. AUC and sensitivity of the FT(3)/FT(4) ratio were smaller than those of FT(3) and FT(4) in both hospitals. The patients treated at Ito hospital were then divided into 4 groups according to their FT4 levels (A: < or =2.3, B: >2.3 approximately < or =3.9, C: 3.9 approximately < or =5.4, D: >5.4 ng/dl), and the AUC, cut-off points, sensitivity, and specificity of the FT(3)/FT(4) ratios were calculated. The AUC and sensitivity of each group increased with the FT4 levels (AUC: 57.8%, 72.1%, 91.1%, and 93.4%, respectively; sensitivity: 62.6%, 50.0%, 77.8%, and 97.0%, respectively). The means +/- SE of the FT3/FT4 ratio in the Graves' disease groups were 3.1 +/- 0.22, 3.1 +/- 0.09, 3.2 +/- 0.06, and 3.1 +/- 0.07, respectively, versus 2.9 +/- 0.1, 2.6 +/- 0.07, 2.5 +/- 0.12, and 2.3 +/- 0.15, respectively, in the painless thyroiditis groups. In the painless thyroiditis patients, the difference in the FT3/FT4 ratio between group A and group D was significant (p<0.05). Thus, the FT3/FT4 ratio in patients with Graves' disease likely remains unchanged as the FT4 level rises, whereas this ratio decreases as the FT4 level rises in patients with painless thyroiditis. In conclusion, the FT3/FT4 ratios of patients with painless thyroiditis overlapped with those of patients with Graves' disease. However, this ratio was useful for differentiating between these two disorders when the FT4 values were high.     

Simple and practical parameters for differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis

OBJECTIVE: Differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis is important for selection of therapy. It is, however, often difficult to make this distinction without measurement of radioactive iodine uptake. We searched for simple and practical parameters that might allow differentiation between the two entities. PATIENTS: One hundred and eleven untreated patients with thyrotoxicosis (69 Graves' disease, 21 painless thyroiditis, 21 subacute thyroiditis) and 45 normal controls were examined. MEASUREMENTS: Serum levels of free T4 (FT4) and free T3 (FT3) were measured by radioimmunoassay, and anti-TSH receptor antibodies (TBII) were measured by radioreceptor assay. Peripheral leucocyte counts and the percentages of eosinophils and monocytes were measured using an automated leucocyte differential system. RESULTS: Peripheral eosinophils were significantly higher in Graves' disease (3.54 +/- 4.18%, P < 0.05) and lower in subacute thyroiditis (1.08 +/- 1.03%, P < 0.001) than in normal controls (2.26 +/- 1.33%). Peripheral monocytes were significantly higher in painless thyroiditis (6.87 +/- 2.85%, P < 0.01) than that in normal controls (4.63 +/- 2.14%). In comparison between groups, FT3 was higher with Graves' disease (20.55 +/- 10.29 pmol/l) than both painless thyroiditis (11.59 +/- 8.22 pmol/l, P < 0.001) and subacute thyroiditis (15.27 +/- 8.63 pmol/l, P < 0.05). The eosinophil to monocyte (Eo/Mo) ratio, FT3/FT4 ratio and Eo/Mo ratio multiplied by FT3 (pmol/ml) (Eo/Mo.FT3) were calculated and compared in these three disease groups. The Eo/Mo ratio, FT3/FT4 ratio and Eo/Mo.FT3 were significantly higher in patients with Graves' thyrotoxicosis (0.782 +/- 0.759, 0.399 +/- 0.089, 16.7 +/- 23.5 pmol/l, respectively) than in those with painless thyroiditis (0.259 +/- 0.157, 0.304 +/- 0.072, 2.43 +/- 1.49 pmol/l, respectively) and subacute thyroiditis (0.234 +/- 0.241, 0.335 +/- 0.057, 2.98 +/- 3.51 pmol/l, respectively). Twenty-two of 24 (91.7%) thyrotoxic patients with Eo/Mo < 0.2 had destruction-induced thyrotoxicosis (painless or subacute thyroiditis). Twenty-two of 28 (78.6%) thyrotoxic patients with FT3/FT4 < 0.3 had destruction-induced thyrotoxicosis. Thirty-six of 42 (85.7%) thyrotoxic patients with Eo/Mo.FT3 < 4.5 had destruction-induced thyrotoxicosis. The Eo/Mo ratio, FT3/FT4 ratio and Eo/Mo.FT3 were found to be similarly useful for differentiation between the two types of thyrotoxicosis. All thyrotoxic patients with TBII > or = 20% had Graves' disease and 76.4% of patients with TBII < 20% had destruction-induced thyrotoxicosis. CONCLUSION: The Eo/Mo ratio, FT3/FT4 ratio, and Eo/Mo.FT3 are simple, practical parameters and were as effective as TBII for differentiation of destruction-induced thyrotoxicosis (painless or subacute thyroiditis) from Graves' thyrotoxicosis. Eo/Mo < 0.2 and/or Eo/Mo.FT3 < 4.5 in untreated thyrotoxic patients are laboratory signals of destruction-induced thyrotoxicosis, and if these are determined, the radioactive iodine uptake test can be omitted for differential diagnosis of these two types of thyrotoxicosis.     

Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease

OBJECTIVE: Differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis is important for selection of proper therapy. It is, however, often difficult to make this distinction without measurement of radioactive iodine uptake. We investigated the possibility that assessment of thyroid blood flow would allow differentiation between the two entities. PATIENTS AND MEASUREMENTS: One hundred and fourteen untreated patients with thyrotoxicosis (56 Graves' disease, 28 painless thyroiditis, 30 subacute thyroiditis) and 25 normal controls were examined. Serum levels of freeT4 (FT4), freeT3 (FT3) and TSH were measured by chemiluminescent immunoassay, and anti-TSH receptor antibodies (TSH-binding inhibitory immunoglobulin, TBII) were measured by enzyme-linked immunosorbent assay. Thyroid volume and blood flow (TBF) were measured quantitatively by ultrasonography. RESULTS: TBF was significantly higher in Graves' disease (mean +/- 1SD: 14.9 +/- 6.4%, P < 0.0001) than in painless thyroiditis (0.8 +/- 0.5%), subacute thyroiditis (0.9 +/- 0.7%) and in normal controls (0.8 +/- 0.5%). All patients with Graves' disease had TBF values of more than 4% and all patients with painless thyroiditis and subacute thyroiditis had TBF values less than 4%. TBF values significantly correlated with values of radioactive iodine uptake (RAIU) either at 3 h (r = 0.492, P < 0.01) or 24 h (r = 0.762, P < 0.001) within the Graves' disease and painless thyroiditis groups. There was no relationship between TBF values and thyroid volumes or values of TBII in the Graves' disease group. All patients with Graves' disease had positive TBII of 15% or more. Three of 28 patients with painless thyroiditis and one of 30 patients with subacute thyroiditis had positive TBII. CONCLUSION: TBF was quantitatively measured by power Doppler ultrasonography and was more effective than TBII for differentiation between destruction-induced thyrotoxicosis (painless or subacute thyroiditis) and Graves' thyrotoxicosis. TBF values of less than 4% in untreated thyrotoxic patients are laboratory signals of destruction-induced thyrotoxicosis and if these are determined, the radioactive iodine uptake test can be omitted for differential diagnosis of these two types of thyrotoxicosis.     

Hashimoto's Thyroiditis Presenting as Acute Painful Thyroiditis and as a Manifestation of an Immune Reconstitution Inflammatory Syndrome in a Human Immunodeficiency Virus-Seropositive Patient

Background: An immune reconstitution inflammatory syndrome (IRIS) may complicate immune restoration following start of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. The occurrence of Graves' disease in the setting of an IRIS is well recognized. We hereby report a case of Hashimoto's thyroiditis, presenting as an acute painful thyroiditis, and as a complication of IRIS. Summary: A painful acute thyroiditis with thyrotoxicosis occurred in a 37-year-old HIV-infected woman 10 months after initiation of ART. This thyroiditis was associated with the appearance of a high titer of anti-thyroid peroxidase (anti-TPO) antibodies and was followed by persistent hypothyroidism, requiring thyroxine replacement therapy. Conclusions: Hashimoto's thyroiditis may present as an acute thyroiditis with thyrotoxicosis in HIV-infected patients after initiation of ART. Clinicians caring for HIV-infected patients should be aware of this possible association.     

Measurement of red blood cell zinc concentration with Zn-test kit: discrimination between hyperthyroid Graves' disease and transient thyrotoxicosis.

We have previously reported in patients with hyperthyroidism that the red blood cell (RBC) zinc (Zn) concentration reflects the mean thyroid hormone concentration over the preceding months. In the present study, the concentration of RBC Zn was measured by a simple and easy method with a Zn-test Wako kit. Within-run and between-run precision were 1.4% and 1.3%, respectively. The relationship between RBC concentration and dilution was linear. The average recovery was 103%. A good correlation (r=0.97) was obtained between this method and atomic absorption spectrophotometry. The mean concentration of RBC Zn in 39 euthyroid controls was 12.6 +/- 1.3 mg/l, ranging from 10.4 to 15.1 mg/l. The RBC Zn concentrations in 38 patients with Graves' disease, in 10 patients with silent thyroiditis and in 3 patients with gestational thyrotoxicosis were 7.3 +/- 1.6 (3.2-9.8), 12.0 +/- 1.6 (9.5-14.2) and 11.8 +/- 1.7 (10.5-13.7) mg/l, respectively. The concentration of RBC Zn was able to differentiate hyperthyroid Graves' disease from transient thyrotoxicosis except in 1 case and was a better index than TSH-binding inhibitory immunoglobulin. These results indicate that measuring RBC Zn with the Zinc-test Wako kit is very useful in differentiating hyperthyroid Graves' disease from transient thyrotoxicosis.     

Serial changes in liver function tests in patients with thyrotoxicosis induced by Graves' disease and painless thyroiditis.

CONTEXT: When the liver function tests are aggravated after starting antithyroid drugs (ATDs) in Graves' hyperthyroidism, discontinuation of ATDs is generally considered. However, a question arises whether such aggravation constitutes an adverse effect of the drugs or not. OBJECTIVE: The aim of this study was to clarify the influence of thyrotoxicosis on liver function tests, comparing the results with those in thyrotoxicosis induced by painless thyroiditis. DESIGN: We prospectively studied liver biochemical tests in 30 patients with Graves' disease and in 27 patients with painless thyroiditis. MAIN OUTCOMES: Twenty-three (76.7%) untreated Graves' disease patients and 14 (51.9%) untreated painless thyroiditis patients were found to have at least one liver function test abnormality. One month after starting ATD therapy in patients with Graves' disease, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations from initial values were observed in 16 (53.3%). Similar elevations of AST and ALT from initial values at 1 month were observed in 10 (37.0%) and 7 (25.9%) patients with painless thyroiditis, respectively. Alkaline phosphatase (ALP) increased gradually after starting ATD therapy and maintained an elevated value for 3-5 months in Graves' disease. In painless thyroiditis, ALP also increased gradually, similarly to that in Graves' disease, but changes were mild. Elevation of ALT after 1 month of ATD therapy in Graves' disease was significantly higher in patients whose estimated disease duration was 6 months or more compared to those with duration of less than 6 months. Elevated AST and ALT at 1 month after ATD therapy decreased to normal ranges, even though patients were receiving the same ATDs in Graves' disease. CONCLUSION: Similar serial changes in liver function tests in both Graves' disease and painless thyroiditis strongly suggest that increases of AST and ALT after starting ATD therapy may not be due to ATD side effects but may be induced by changes in thyroid function.     

Interferon-alpha-induced hyperthyroidism: a three-stage evolution from silent thyroiditis towards Graves' disease

Autoimmune thyroid disease is a common side-effect of interferon-alpha (IFN-alpha) treatment of viral hepatitis C. We have described three patients with hepatitis C for whom IFN-alpha and ribavirin were prescribed and who developed two successive phases of silent thyroiditis followed by hyperthryroidism relapse due to Graves' disease. These three men had no known history of familial or personal thyroid disease. Destructive thyrotoxicosis appeared 4-6 months after starting IFN-alpha, followed by Graves' hyperthyroidism within 8 to 11 months. The thyrotropin (TSH) level was normal before IFN-alpha was started. The diagnosis of destructive thyroiditis was confirmed by anti-TSH receptor antibody (TSHRAb) negativity and the absence of radionuclide ((123)I or (99)Tc) uptake on thyroid scintiscans. Eight to eleven months after starting treatment, TSHRAb positivity and intense scintigraphic uptake confirmed the appearance of Graves' disease. IFN-alpha was continued in only one patient. Hence, hyperthyroidism induced by IFN-alpha could correspond to the first phase of silent thyroiditis, to Graves' disease or to the succession of both. Rigorous diagnostic procedures with repeated scintiscans and TSHRAb titering are necessary to avoid a false diagnosis and inappropriate therapy.     

Hodgkin's disease and hyperthyroidism

In recent years we have had the occasion to observe hyperthyroidism in 6 patients with Hodgkin's disease. All patients had received Mantlefield irradiation and were disease-free when hyperthyroidism appeared. Hyperthyroidism allows three different pictures to be distinguished: 1 case report of Graves' disease without ophthalmopathy, 1 case report of Hashimoto's thyroiditis corresponding to a particular form called hashitoxicosis, and 4 case reports of atypical silent thyroiditis. Reports concerning case studies of postirradiation Graves' disease or Hashimoto's thyroiditis during Hodgkin's disease are only to be found exceptionally. Atypical silent thyroiditis was recently individualized, but no postirradiation case studies have been reported. It is suggested that these 6 cases represent a radiation-induced immune thyroid disease: physiopathology and predisposing factors are discussed.     

Thyroid ultrasonography related to clinical and laboratory findings in patients with silent thyroiditis.

We summarized the clinical course of 10 patients with silent thyroiditis and evaluated the clinical usefulness of ultrasonography, in combination with clinical and laboratory findings, for the differentiation from Graves' disease. Serum T3 and T4 were increased in all cases, and the ratio of T3/T4 (ng/micrograms) was 17.8 +/- 3.6 (SD). But in 3 of 10 patients the ratio was greater that 20. TSH receptor antibody (TRAb) and thyroid stimulating antibody (TSAb) were negative in all cases. The estimated thyroid volume by ultrasonography was 18.4 +/- 5.5 ml, which was slightly increased but significantly lower than those in Graves' disease (p less than 0.05). The internal texture of the thyroid showed a decreased echogenicity with a mean echo level of 70.4 +/- 15.4. There was a weak positive correlation between the echo level at the onset of thyrotoxicosis and the lowest T3 level during the clinical course (p less than 0.05). It is suggested that ultrasonography gives a useful information to the diagnosis and outcome of patients with silent thyroiditis.     

Four cases of Graves' disease which developed after painful Hashimoto's thyroiditis

We report four cases of Graves' disease that developed after painful Hashimoto's thyroiditis. All were middle-aged women, who had high titers of anti-thyroid antibodies and thyrotoxicosis at the onset of painful Hashimoto's thyroiditis. After 2 to 7 years, they developed Graves' disease with positive antibody against the thyrotropin receptor. Their clinical courses of Graves' disease went favorably due to the treatment with antithyroid drug or radioactive iodine therapy. Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis and is one form of destructive thyroiditis. Thyroid damage due to painful Hashimoto's thyroiditis may be associated with the development of Graves' disease.     

Epidemiology of subtypes of hypothyroidism in Denmark

OBJECTIVE: Studies of hypothyroidism are often based on referred patients, and limited information is available on the incidence rates of subtypes of hypothyroidism in the general population. We therefore studied incidences of subtypes of primary, overt hypothyroidism in a Danish population cohort and compared incidences in two subcohorts with different levels of iodine intake. DESIGN: A prospective population-based study, monitoring a well-defined cohort representative of the Danish population. METHODS: The Danish Investigation of Iodine Intake and Thyroid Diseases registry of hyper- and hypothyroidism was established as part of the monitoring of the iodine fortification of salt in Denmark. A computer-based system linked to laboratory databases identified all patients diagnosed with new, biochemically overt hypothyroidism in populations living in Aalborg (moderate iodine deficiency, n = 311,102) and Copenhagen (mild iodine deficiency, n = 227,632). We subsequently evaluated all identified patients to verify incident thyroid disease, and subclassified hypothyroidism into nosological types. RESULTS: During a 4-year period (2,027,208 person-years) 685 new cases of overt hypothyroidism were diagnosed in the cohort; the incidence rate was 32.8 per 100,000 person-years (standardised to the Danish population). Nosological types of hypothyroidism were: spontaneous (presumably autoimmune) 84.4%, post-partum 4.7%, amiodarone-associated 4.0%, subacute thyroiditis 1.8%, previous radiation or surgery 1.8%, congenital 1.6% and lithium-associated 1.6%. Crude incidence rates were 29.0 around Aalborg and 40.6 in an area of Copenhagen. The higher incidence rate of hypothyroidism in the area with higher iodine intake was caused solely by more cases of spontaneous (presumably autoimmune) hypothyroidism, whereas the incidence of non-spontaneous hypothyroidism (all types combined) was significantly lower in the area with higher iodine intake. CONCLUSION: In a population-based study we observed a higher incidence of hypothyroidism with higher iodine intake. This was due solely to the entity of spontaneous hypothyroidism. The occurrence of overt hypothyroidism was relatively low in Denmark.     

Treatment of post-partum thyrotoxicosis

Thyrotoxicosis occurs more frequently during the post-partum period than at other times in women of childbearing age. Graves' disease and post-partum thyroiditis are two major causes of thyrotoxicosis in this period. The major task lies in differentiation of these two diseases in the post-partum period; since throtoxicosis caused by post-partum thyroiditis usually does not require treatment. The radioiodine uptake is elevated or normal in Graves' disease and low in post-partum thyroiditis, and TSH-receptor antibodies are positive in Graves' and negative in post-partum thyroiditis. Post-partum thyrotoxicosis due to Graves' disease may be treated with radioiodine but it requires radiation safety measurements for infant and is contraindicated if the mother is breast-feeding. Antithyroid drugs are the mainstay of the treatment of post-partum thyrotoxicosis. Recent investigations conclude that neither propylthiouracil nor methimazole cause any alterations in thyroid function and physical and mental development of infants breast-fed by lactating thyrotoxic mothers, and both can be safely administered in moderately high doses during lactation.     

Serum ratio of triiodothyronine to thyroxine, and thyroxine-binding globulin and calcitonin concentrations in Graves' disease and destruction-induced thyrotoxicosis

The serum ratios of T3 to T4, and T4-binding globulin (TBG) and calcitonin concentrations were studied in cases of thyrotoxic Graves' disease and destruction-induced thyrotoxicosis. In 272 patients with Graves' disease, 209 of 240 (87%) untreated patients without complications had high T3 to T4 ratios (nanograms per micrograms) of more than 20. Six of 32 (19%) patients with Graves' disease who had complications (15 with pregnancy, 14 with increased TBG, and 3 with conditions associated with a low T3 syndrome) had high T3 to T4 ratios. Eleven of 74 (15%) patients with destruction-induced thyrotoxicosis (24 with subacute thyroiditis, 39 with postpartum transient thyrotoxicosis, and 11 with spontaneous transient thyrotoxicosis) had high T3 to T4 ratios. Patients who had serum T4 levels of more than 30 micrograms/dl and/or T3 levels of more than 800 ng/dl had Graves' disease. There was no significant correlation between the T3 to T4 ratio and activities of thyroid-stimulating immunoglobulins in thyrotoxic patients with Graves' disease who had no complications. The average serum levels of TBG in destruction-induced thyrotoxicosis and thyrotoxic Graves' disease were 20.7 +/- 4.3 micrograms/ml (mean +/- SD; n = 22), and 19.9 +/- 4.0 (n = 41), respectively, which were significantly lower than that in healthy subjects (22.7 +/- 4.4 micrograms/ml; n = 165), but there was no difference between the values in the two groups of thyrotoxicosis patients. The average serum level of calcitonin in destruction-induced thyrotoxicosis patients was 96.7 +/- 66.7 pg/ml (n = 21), which was significantly (P less than 0.05) higher than the values in patients with thyrotoxic Graves' disease (62.0 +/- 44.7 pg/ml; n = 26) and in healthy subjects (63.9 +/- 31.2 pg/ml; n = 29), but the difference in values in the two groups of thyrotoxicosis was not clinically useful because of considerable overlap of individual values. The T3 to T4 ratio is a simple and helpful index for the differentiation of the two types of thyrotoxicosis. A T3 to T4 ratio less than 20 in thyrotoxic patients before therapy is a laboratory signal of destruction-induced thyrotoxicosis or Graves' disease with complications, but final differentiation should be confirmed by measuring radioactive iodine uptake.     

Thyroid vascularity and blood flow are not dependent on serum thyroid hormone levels: studies in vivo by color flow doppler sonography

OBJECTIVE: Thyroid blood flow is greatly enhanced in untreated Graves' disease, but it is not known whether it is due to thyroid hormone excess or to thyroid hyperstimulation by TSH-receptor antibody. To address this issue in vivo patients with different thyroid disorders were submitted to color flow doppler sonography (CFDS). SUBJECTS AND METHODS: We investigated 24 normal subjects, and 78 patients with untreated hyperthyroidism (49 with Graves' hyperthyroidism, 24 with toxic adenoma, and 5 patients with TSH-secreting pituitary adenoma (TSHoma)), 19 patients with thyrotoxicosis (7 with thyrotoxicosis factitia, and 12 with subacute thyroiditis), 37 euthyroid patients with goitrous Hashimoto's thyroiditis, and 21 untreated hypothyroid patients with Hashimoto's thyroiditis. RESULTS: Normal subjects had CFDS pattern 0 (absent or minimal intraparenchimal spots) and mean intraparenchimal peak systolic velocity (PSV) of 4.8+/-1.2cm/s. Patients with spontaneous hyperthyroidism due to Graves' disease, TSHoma, and toxic adenoma had significantly increased PSV (P<0.0001, P=0.0004, P<0.0001 respectively vs controls) and CFDS pattern. Patients with Graves' disease had CFDS pattern II (mild increase of color flow doppler signal) in 10 (20%) and pattern III (marked increase) in 39 cases (80%). Mean PSV was 15+/-3cm/s. Patients with toxic adenoma had CFDS pattern I (presence of parenchymal blood flow with patchy uneven distribution) in 2 (8%), pattern II in 16 (70%) and pattern III in 5 (22%). Mean PSV was 11+/-2.4cm/s. Patients with TSHoma showed CFDS pattern I in one case (20%) and pattern II in 4 (80%). Mean PSV was 14.8+/-4.2cm/s. Patients with thyrotoxicosis had normal PSV (4.2+/-1. 1cm/s in subacute thyroiditis, 4+/-0.8cm/s in thyrotoxicosis factitia, P=not significant vs controls) and CFDS pattern 0. Untreated euthyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern 0, and mean PSV (4.3+/-0.9cm/s; P=not significant vs controls). Untreated hypothyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern I in 14 cases (67%), pattern II in 4 (19%) and pattern 0 in 3 (14%) and mean PSV (5.6+/-1. 4cm/s) was higher than that of controls (P=0.026). CONCLUSIONS: An increase in both intrathyroidal vascularity and blood velocity was observed in patients with spontaneous hyperthyroidism but not in thyrotoxicosis due to either ingestion of thyroid hormones or to a thyroidal destructive process. The slightly increased vascularity and blood velocity observed in patients with hypothyroid Hashimoto's thyroiditis suggests that thyroid stimulation by either TSH-receptor antibody or TSH is responsible for the increased thyroid blood flow.     

Increased serum concentration of interleukin-12 in patients with silent thyroiditis and Graves' disease.

We previously reported that interleukin-5 (IL-5), secreted from Th2 cells, was increased in patients with Graves' disease, but not in patients with silent thyroiditis. In this study, we investigated serum levels of interleukin-12 (IL-12) in order to examine the role of Th1-type immune response in the pathogenesis of autoimmune thyroid diseases. Serum levels of IL-12 were determined by a highly sensitive sandwich enzyme-linked immunosorbent assay in 68 patients with Hashimoto's thyroiditis (26 of whom had silent thyroiditis), 74 patients with Graves' disease, 8 patients with subacute thyroiditis, and 27 normal controls. Serum levels of IL-12 in thyrotoxic patients with silent thyroiditis (385.2 +/- 164.5 pg/mL, mean +/- SD), and in thyrotoxic patients with Graves' disease (343.6 +/- 163.8 pg/mL) were significantly increased compared with serum levels in normal subjects (163.9 +/- 66.8 pg/mL, p < 0.0001, p < 0.0001, respectively) or in thyrotoxic patients with subacute thyroiditis (241.9 +/- 46.5 pg/mL, p < 0.01, < 0.05, respectively). The ratio of IL-12 to IL-5 in thyrotoxic patients with silent thyroiditis (64.2 +/- 39.7) was significantly higher than that in normal controls (33.7 +/- 13.3, p < 0.01) or in thyrotoxic patients with Graves' disease (40.6 +/- 36.0, p < 0.05). These data suggest that Th1-type immune response is predominant in silent thyroiditis, and that not only Th2-type immune response but also Th1-type immune response is important in the pathogenesis of Graves' disease.     

Lithium-associated thyrotoxicosis

Primary hypothyroidism developed in a 57-year-old woman treated for eight years with lithium carbonate for manic-depressive illness, and nine months later she became thyrotoxic. Although autoimmune disease appeared to be responsible, lithium was suspected to play a contributory role in both phases of her illness. This is the first reported case of hyperthyroidism following hypothyroidism in a lithium-treated patient. The 24 reported cases of lithium-associated thyrotoxicosis and the possible mechanisms that may explain this poorly understood phenomenon are also reviewed.     

Epidemiologic relation between HIV and invasive pneumococcal disease in San Francisco County, California

BACKGROUND: Patients with AIDS have a high incidence of invasive pneumococcal disease, but no population-based data are available on secular trends or rates of this disease in specific demographic groups. OBJECTIVE: To compare clinical characteristics, rates, and trends of pneumococcal disease in HIV-infected and non-HIV-infected persons. DESIGN: Population-based laboratory surveillance and chart review. SETTING: All of the 13 microbiology laboratories in San Francisco County, California. PATIENTS: Persons who had a sterile site culture that was positive for Streptococcus pneumoniae between October 1994 and June 1997. MEASUREMENTS: Stratified incidence rates and adjusted rate ratios, serotyping of isolates, and comparison of secular trends and rates according to census tract by Poisson regression. RESULTS: Persons infected with HIV accounted for 54.2% of 399 patients 18 to 64 years of age who had pneumococcal disease. The incidence of pneumococcal disease per 100 000 person-years was 35.0 cases overall and 802.9 cases in patients with AIDS. Compared with persons who were not known to be HIV-infected, the rate ratio for patients with AIDS was 46:0 (95% CI, 36.0 to 58.9); 55.2% of cases were attributable to HIV. In HIV-infected patients, 82.5% of isolates were serotypes that are included in the pneumococcal polysaccharide vaccine. The incidence of pneumococcal disease in black patients with AIDS (2384.6 cases per 100 000 person-years) was 5.4 times that in nonblack patients with AIDS. Rates by census tract were inversely associated with income (P < 0.001), During the study period, the incidence of pneumococcal disease decreased from 10.6 cases per 1000 person-years to 4.2 cases per 1000 person-years in patients with AIDS (P = 0.004, Poisson regression). CONCLUSIONS: In a community with a high prevalence of HIV infection, much of the burden of pneumococcal disease was attributable to AIDS. High incidence rates were seen in young adults and especially in black persons. Efforts to increase pneumococcal vaccination rates should target HIV-infected adults, particularly those living in poor urban areas.     

Graves' disease with unusual histological findings

We reported three cases of Graves' disease which showed unusual histological findings featuring solid follicles, multinucleated giant cells and diffuse infiltration of histiocytes as well as lymphocytes in the whole section of the resected thyroid. Characteristics of these three cases were as follows: (1) Clinically, longer duration of the disease and exophthalmos were their prevailing findings. (2) On laboratory data, antimicrosomal antibody showed extremely high titers with 100,000 to 400,000. (3) Their operative findings were different from ordinary Graves' goiters in that colors of the goiter were yellow-red or gray-red, surface was rough and coarse, consistency was firm, and adhesions with the adjacent connective tissue were noted. (4) Postoperative clinical outcome was quite similar to that of ordinary Graves' patients. From these findings, these three cases were considered to be different from either so-called Hashitoxicosis or silent thyroiditis or Graves' disease with granulomatous foci, and it was suggested that these three cases might be a subgroup of Graves' disease or another hyperthyroidism than ordinary Graves' disease. Further accumulation and analysis of such cases will be necessary in order to answer this question.