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.     

Erythrocyte carbonic anhydrase-I concentrations in patients with Graves' disease and subacute thyroiditis reflect integrated thyroid hormone levels over the previous few months

We have recently reported that in patients with hyperthyroidism, red blood cell (RBC) zinc (Zn), most of which is present as the metal of carbonic anhydrase-I isozyme (CAI), reflects a patient's integrated thyroid hormone level over the previous few months. In the present report the RBC CAI concentration was measured by RIA in 26 healthy controls, 25 patients with hyperthyroid Graves' disease, 5 patients with primary hypothyroidism, and 10 subjects with subacute thyroiditis with elevated thyroid hormone levels. The mean (+/- SD) RBC CAI concentration in euthyroid controls was 380 +/- 70 nmol/g hemoglobin (Hb), and the normal range defined as the mean +/- 2 SD, was 240-520 nmol/g Hb. The mean RBC CAI in Graves' disease was decreased (180 +/- 53 nmol/g Hb), and 22 patients (88%) had subnormal values. The mean RBC CAI concentrations in hypothyroidism and subacute thyroiditis were not different from the control values. After treatment with antithyroid drugs, both mean the plasma T4 and T3 levels in 11 Graves' patients became normal within 4 weeks, but the normalization of RBC CAI lagged behind by about 2 months. Furthermore, the highest correlation was observed between the RBC CAI and plasma T4 and T3 levels measured 8 weeks earlier. During prednisolone therapy the RBC CAI in patients with subacute thyroiditis remained at a normal level. These results suggest that 1) not only RBC Zn but also the RBC CAI concentration in patients with Graves' disease reflect the patient's mean thyroid hormone level over the preceding several months; and 2) in patients with subacute thyroiditis, elevation of plasma thyroid hormone concentrations is transient and causes little change in the RBC CAI concentration.     

The sonographical and functional sequelae of de Quervain's subacute thyroiditis: long-term follow-up

Fifty-three patients with subacute thyroiditis (SAT) were seen during the acute stage of the disease. HLA-Bw 35 was positive in 33 out of 39 tested patients. At first presentation, all examined patients (N = 23) had ultrasound abnormalities (generalized hypodensity, single or multiple hypodense areas). Serum T4 and/or T3 were increased in 24/52, free T4 in 11/23, and the TSH response to TRH was flat in 8/11 patients. Six of 12 in whom volumetry was performed had goitres. Thirty-seven patients were re-examined after a mean follow-up interval of 46.5 months. At this follow-up, serum T4, free T4 and T3 levels as well as the sonographically determined thyroid volume had decreased, but there was still abnormalities by ultrasound detected in 14/36 patients; 19.4% had focal sonolucent lesions, whereas the prevalence of such lesions was only 3.1% in asymptomatic controls. Three patients were subclinically hypothyroid at the follow-up, whereas all others were euthyroid. Patients with abnormal ultrasound findings were of the same age and had a similar thyroid size, but a slightly higher TSH and a significantly (P less than 0.02) lower free T4 than those with normal ultrasound findings. They also had a higher prevalence of thyroid autoantibodies in low titres. Serum thyroglobulin was elevated in more than half of the patients during the acute phase, but only in 1 out of 11 patients during follow-up. Thyroglobulin at the follow-up was not related to TSH, but there was a correlation with thyroid volume (r = 0.57).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum concentrations of osteocalcin in patients with hyperthyroidism, hypothyroidism and subacute thyroiditis.

Serum concentration of osteocalcin (OC) was measured in sera from untreated patients with Graves' disease, hypothyroidism due to Hashimoto's thyroiditis, and subacute thyroiditis. Serum concentration of OC in Graves' disease and hypothyroidism were 14.1 +/- 5.6 micrograms/L and 3.8 +/- 2.7 micrograms/L, respectively which were significantly different from that of healthy subjects (Graves' disease, p less than 0.001, hypothyroidism, p less than 0.01). Serum concentration of OC in patients with subacute thyroiditis was 8.0 +/- 3.5 micrograms/L which was not statistically different from age-matched normal controls. Serial measurement of serum OC for 24 mo in 15 patients with Graves' disease after initiation of antithyroid drugs disclosed that the decline of serum OC was obtained only 24 mo after antithyroid drug therapy. On the other hand, in hypothyroid patients, increased serum OC was observed after 1-2 months treatment of L-T4. Correlation coefficients between serum concentrations of OC and T3, T4, FT3 or FT4 in all the patients with thyroid disorders were 0.66, 0.51, 0.50 and 0.54, respectively, which were statistically significant (all, p less than 0.001). These results suggest that osteoblastic activity is enhanced in hyperthyroidism and suppressed in hypothyroidism. In hyperthyroid patients, despite of normalization of FT4 concentration in relatively short period (within 3-4 mo), it took 24 mo after initiation of antithyroid drugs for OC to normalize, suggesting not only thyroid hormone per se but also some unknown factor(s) participates in serum OC secretion. In contrast to thyrotoxic patients, rapid increase in serum OC after initiation of supplemental L-T4 treatment in hypothyroidism was observed, suggesting a direct effect of thyroid hormone on the osteoblasts in patients with hypothyroidism.     

Increased sensitivity to the inhibitory effect of excess iodide on thyroid function in patients with beta-thalassemia major and iron overload and the subsequent development of hypothyroidism

OBJECTIVE: Patients with beta-thalassemia frequently develop primary hypothyroidism and other endocrine disorders due to iron overload. We studied whether administration of excess iodide to patients with apparently normal thyroid function could uncover an underlying thyroid disease. DESIGN AND METHODS: Twenty-five patients, 10 prepubertal (mean age 11+/-3 years) and 15 adults (mean age 23+/-5 years) with normal thyroid hormone and TSH levels, a normal response of TSH to TRH and negative thyroid peroxidase antibodies received 20mg iodide three times daily for three weeks, and thyroid hormone and TSH levels were measured weekly during, and for three weeks after, iodide administration and every 3 months thereafter for the next 5 years. RESULTS: During iodide administration there was a significant decrease in thyroid hormone concentrations which remained within normal levels, and a significant increase in TSH concentrations which in 14 out of 25 (56%) patients reached the hypothyroid level. Baseline TSH values were higher in those patients who developed subclinical hypothyroidism (2.31+/-0.71mU/l vs 1. 34+/-0.64mU/l, P=0.0016). Subclinical hypothyroidism developed in 70% of prepubertal and in 47% of adult patients. Serum ferritin was elevated in all patients. Nine of the fourteen patients (64.3%) who developed subclinical hypothyroidism during iodide administration developed hypothyroidism during the 5-year follow-up compared with only one of the eleven patients with a normal response to iodide (P=0.004). CONCLUSIONS: Patients with beta-thalassemia should not be exposed to excess iodide due to increased sensitivity to its inhibitory effects on thyroid function. The susceptible individuals frequently develop permanent hypothyroidism in the following years.     

Assessment of thyroid function during the long course of Hashimoto's thyroiditis in children and adolescents

Context  The prognosis of Hashimoto's thyroiditis (HT) in children and adolescents is not well known and studies reporting long-term outcome of the disease are scarce.
Objective  To assess the thyroid hormone status during long-term follow-up and to establish the prognosis of children and adolescents with HT.
Patients  One hundred and twenty-nine patients with HT were re-evaluated for thyroid hormone status after a mean follow-up period of 50 months.
Results  Seventy-seven per cent of the euthyroid patients were still euthyroid, while 21·1% of these patients became hypothyroid at the time of re-evaluation. However, 69·5% of hypothyroid patients remained hypothyroid (overt or subclinical) and 30·5% recovered.
Conclusion  HT is a dynamic process. Thyroid functions can show variation during follow-up. Therefore, thyroid function tests should be repeated periodically to detect progression to hypothyroidism in initially euthyroid patients as well as reversibility of hypothyroidism.     

Studies of hypothyroidism in patients with high iodine intake

Twenty-two patients with spontaneously occurring primary hypothyroidism were studied to evaluate the spontaneous reversibility of the hypothyroid state. Twelve (54.5%) became euthyroid after restriction of iodine intake for 3 weeks (reversible type). In the remaining 10 patients, thyroid function did not improve with restriction of iodine alone, and thus, replacement therapy was required, (irreversible type). In the reversible type, 1) radioactive iodine uptake after 1 week of restricted iodine intake was higher than in the irreversible type [50.0 +/- 12.2% (+/- SD) vs. 4.3 +/- 3.2%; P less than 0.01], 2) the perchlorate discharge test was positive in 2 of 10 patients, and 3) the iodine-perchlorate discharge test, carried out in 7 of 8 patients with negative perchlorate discharge test, was positive in 6. Seven patients with the reversible type were given 25 mg iodine daily for 2-4 weeks; all became hypothyroid again. Two patients had a history of habitual ingestion of seaweed (25.4 and 43.1 mg iodine, respectively), but the remaining 10 patients ingested ordinary amounts of iodine (1-5 mg) daily. The patients with reversible hypothyroidism had focal lymphocytic thyroiditis changes in the thyroid biopsy specimen, whereas those with irreversible hypothyroidism had more severe destruction of the thyroid gland. These results indicate the existence of a reversible type of hypothyroidism sensitive to iodine restriction and characterized by relatively minor changes in lymphocytic thyroiditis histologically. Attention should be directed to this type of hypothyroidism, because thyroid function may revert to normal with iodine restriction alone.     

Results of subtotal thyroidectomy for Graves' disease.

The objective of this study was to find the factors responsible for hypothyroidism after subtotal thyroidectomy for Graves' disease. Two hundred five patients who were operated on from July 1989 to December 1997 were studied. The mean age of patients was 33.4+/-11.0 (mean +/- SD) years, and 175 (85.4%) were female. Patients were prepared with an antithyroid drug and Lugol's solution preoperatively. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyrotropin-binding immunoglobulins (TBII) antimicrosomal antibodies (AMA = 100x 4(M-1)), and antithyroglobulin antibodies (ATA = 100x4(T-1)) were measured 1 week before patients were operated on. Operations were performed according to the standard procedure with 2.5x1x1 cm of thyroid tissue remaining on each side before approximating the thyroid capsule and pretracheal fascia. Hypothyroidism was defined by patients with overt hypothyroidism in laboratory data, and or with T4 to maintain T3 and T4. Two hundred two patients were checked 3 months after being operated on. Latent hyperthyroidism was found in 22, euthyroidism in 55, latent hypothyroidism in 91, hypothyroidism in 34 (16.8%) and none were in overt hyperthyroidism. After a follow-up period of 26.9+/-15 (mean +/- SD) months, 199 patients were reevaluated. Overt hyperthyroidism was found in 2 patients, latent hyperthyroidism in 12, euthyroidism in 97, latent hypothyroidism in 72, and hypothyroidism in 16 (8%). Factors having possible effects on hypothyroidism after longterm follow-up were analyzed. Patient's age, gender, body surface, premedicative T3 and T4, preoperative ATA, and TBII, and the weight of removed thyroid had no effect on the occurrence of hypothyroidism. Preoperative AMA levels, and finding more than 10 lymphoid infiltrations per 10 low-power fields (x40) were significantly different between the hypothyroid and nonhypothyroid groups. A high level of preoperative AMA was the only factor independently causing overt hypothyroidism in the follow-up period. Patients with high preoperative AMA levels have a higher risk of hypothyroidism if only 2.5x1x1 cm remnants are left on each side.     

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.     

The incidence of thyroid stimulating blocking antibodies during the hypothyroid phase in patients with subacute thyroiditis.

The etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses. It has been suggested that nonimmune processes are involved in SAT patients who have negative autoantibody titers. The disease has a variable course; although it is self-limited in most cases, some patients develop transient hypothyroidism, and others do not during the recovery period. The present study was performed to evaluate the occurrence of TSH receptor antibody (TRAb), measured by RRA (TSH binding inhibitor), TRAb measured by stimulation assay (thyroid-stimulating antibody), and TRAb measured by blocking assay [TSH-blocking antibody (TSH-BAb)] activity in 68 patients with SAT who had negative autoantibody titers. The patients were divided into 2 groups: group I, 31 patients who developed hypothyroidism during the recovery period; and group II, 37 patients who remained euthyroid during recovery. Positive immunoglobulin activity occurred in about 20% of group I patients during follow-up, but in only 3% of group II patients. About 20% of group I patients developed positive TSH-BAb activity and were hypothyroid, requiring exogenous hormone therapy for 1.2-3.5 yr, whereas hypothyroidism was relatively transient in group I patients who had negative TSH-BAb activity (2-6 months). Although increased TSH-BAb activity may account for hypothyroidism in some patients with SAT, the precise mechanism for the development of transient hypothyroidism in SAT remains enigmatic.     

Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.     

Assessment of thyroid function in two hundred patients with beta-thalassemia major.

Despite improved hematologic care, multiendocrine dysfunction is a common complication of homozygous transfusion-dependent beta-thalassemia. In this study our goal was to estimate the prevalence of thyroid dysfunction in a large homogenous group of thalassemic patients. Two hundred patients with beta-thalassemia major (100 males and 100 females; mean age, 23.2 +/- 6.7 years; age range 11-43 years), regularly transfused and desferioxamine chelated, were randomly selected from a pool of approximately 800 patients with beta-thalassemia followed in our department. Thyroid function and iron-load status were evaluated by measurements of free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH), and serum ferritin levels. Of the subgroup of patients who proved to have normal thyroid hormone values, 26 (12 males, 14 females; mean age, 23.6 +/- 6.8 years; age range, 15-36 years) were randomly selected and underwent a standard TRH stimulation test. Thyroid dysfunction was defined as follows: overt hypothyroidism: low FT4 and/or FT3, increased TSH levels; subclinical hypothyroidism: normal FT4, FT3, increased TSH levels; exaggerated TSH response: normal FT4, FT3, normal basal TSH, deltaTSH > or = 21 microIU/mL (TSH levels measured prior and 30 minutes after intravenous TRH administration). Normal thyroid hormone values were found in 167 (83.5%) of the 200 patients studied. Eight (4%) of the remaining patients had overt hypothyroidisim, and 25 (12.5%) had subclinical hypothyroidism. Exaggerated TSH response to TRH was revealed in 7 of the 26 patients with normal hormone values tested (26.9%). Antithyroglobulin and anti-thyroid peroxidase (TPO) antibody titers were negative in 191 patients (95.5%). Mean ferritin levels in hypothyroid and euthyroid patients were 2707.66 +/- 1990.5 mg/L and 2902.9 +/- 1997.3 mg/L, respectively, (p = 0.61), indicating no correlation between ferritin levels and thyroid functional status. Mean ferritin levels in the patients who responded normally to TRH stimulation and in those who overresponded, were 2,586 +/- 1791 mg/L and 3,228 +/- 2473 mg/L, respectively (p = 0.46; NS). Thyroid failure is a rather rare endocrine complication in patients with beta-thalassemic from Greece. In our series, no case of central hypothyroidism was observed. No correlation was found between thyroid functional status and ferritin plasma levels. Approximately 1 of 5 beta-thalassemic patients with normal thyroid hormone values showed an exaggerated TSH response to TRH test. It is to be investigated how many of these patients will establish overt or subclinical hypothyroidism in the future.     

Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism

The clinical usefulness of thyroid ultrasonography in the evaluation of patients with autoimmune thyroiditis has been investigated. Thyroid ultrasonography was performed in 1184 consecutive patients attending our clinic, and the echo density of the thyroid parenchyma was evaluated with respect to that of normal thyroid tissue. Diffuse thyroid hypoechogenicity was found in 44 of 238 (18.5%) patients with autoimmune thyroiditis; the degree of hypoechogenicity was significantly correlated with the levels of circulating thyroid autoantibodies. Thyroid function was normal in all 194 patients with normal thyroid echogenicity, whereas hypothyroidism was found in 28 of 44 (63.6%) with reduced thyroid echogenicity. Included in this group were 8 patients, euthyroid at the first observation, who developed hypothyroidism over an 18-month follow-up period. None of the 133 patients with autoimmune thyroiditis and normal thyroid echogenicity followed for the same period of time became hypothyroid. Evidence of diffuse lymphocytic thyroiditis was obtained by histology after thyroidectomy (n = 10) or multiple fine needle aspiration cytology (n = 15) in 25 of the 44 patients with thyroid hypoechogenicity; on the other hand, focal thyroiditis was shown at histology in 8 patients who had normal thyroid echogenicity. In conclusion, diffuse low thyroid echogenicity was found in about 20% of patients with autoimmune thyroiditis. This echographic pattern is indicative of diffuse autoimmune involvement of the gland and is associated with or may predict the development of hypothyroidism.     

Thyroid function and thyroid autoimmunity independently modulate serum concentration of soluble interleukin 2 (IL-2) receptor (sIL-2R) in thyroid diseases

OBJECTIVE: The serum concentration of soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation. Increased circulating sIL-2R has been reported in untreated Graves' disease. This finding has been interpreted as the consequence of the autoimmune activation, but recent data suggest that sIL-2R is directly correlated to thyroid state. The aim of this study was to elucidate the respective roles of autoimmunity and thyroid function in modulating serum sIL-2R. DESIGN AND PATIENTS: sIL-2R was evaluated in 20 normal euthyroid subjects and in a large series of patients with autoimmune and non-autoimmune thyroid disorders in different functional state. MEASUREMENTS: sIL-2R was assayed by a solid-phase monoclonal antibody assisted ELISA method. RESULTS: Serum sIL-2R in normals was 461 +/- 186 U/ml (mean +/- SD). Increased sIL-2R was found in 61 hyperthyroid patients with Graves' disease (1610 +/- 962 U/ml, P < 0.0001) and in 23 with toxic adenoma (1121 +/- 598 U/ml, P < 0.0001). Restoration of euthyroidism lowered to normal sIL-2R in both groups. Serum sIL-2R was higher in euthyroid Graves' disease patients with active than in those with non-active ophthalmopathy. Decreased serum sIL-2R (228 +/- 93 U/ml, P < 0.0001) was found in 30 patients hypothyroid after total thyroidectomy. Highly variable circulating sIL-2R (range 100-1456 U/ml, mean +/- SD: 379 +/- 301 U/ml) was found in 49 patients with hypothyroid Hashimoto's thyroiditis (P = NS vs normals; P < 0.02 vs post-thyroidectomy hypothyroid patients). Treatment with L-thyroxine increased sIL-2R in all thyroidectomized and in the majority of Hashimoto's thyroiditis patients. In individual Hashimoto's thyroiditis patients (mostly with increased serum sIL-2R), L-thyroxine caused a decrease of circulating sIL-2R, sIL-2R was normal in 29 patients with euthyroid Hashimoto's thyroiditis. Both in Graves' disease and in Hashimoto's thyroiditis, no correlation was found between sIL-2R and anti-thyroglobulin, anti-thyroid peroxidase and anti-thyrotrophin-receptor autoantibodies. Highly significant positive correlation between serum thyroid hormones and sIL-2R was found in all study groups. CONCLUSIONS: In thyroid disorders thyroid hormones are the main regulator of serum sIL-2R concentration. The contribution of autoimmune activation may be detected only in some patients with autoimmune hypothyroidism, while in Graves' disease the role of the immune system is masked by the hyperthyroid state.     

The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid-stimulating antibodies in patients with silent thyroiditis

Silent (painless) thyroiditis has been recognized as a clinical entity for over a decade and is characterized by spontaneously resolving thyrotoxicosis. Its etiology is uncertain; however, a few reports have indicated the occurrence of TSH binding-inhibiting immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) in some of the patients. The present study was undertaken to evaluate thyroid function and the occurrence of TBII and TSAb and thyroid autoantibodies (antithyroglobulin and antimicrosomal) in 53 patients with silent thyroiditis during the course of their disease. The patients were divided into 2 major groups: I) those who developed transient hypothyroidism and II) those who did not. All patients initially had significantly increased concentrations of serum T4, free T4, and free T3, suppressed TSH levels, and decreased thyroid radioiodine uptake. TBII and TSAb were initially positive in 8 (15.1%) and 10 patients (18.9%), respectively. Forty patients were available for follow-up. TBII was positive in 6 of 24 (25.0%), and TSAb was positive in 8 of 24 (33.3%) of the patients who developed transient hypothyroidism during the course of their disease. Among the patients who did not become hypothyroid at any time, TBII was positive in only 2 of 16 (12.5%), and none of the patients became TSAb positive. The findings indicate that increased TSAb and TBII activity may be detected in patients with silent thyroiditis and, when present, are associated with transient hypothyroidism during the course of the disease.     

Grey-scale analysis allows a quantitative evaluation of thyroid echogenicity in the patients with Hashimoto's thyroiditis

OBJECTIVE: In the present study we have performed a grey-scale quantitative analysis of thyroid echogenicity in the patients affected by Hashimoto's thyroiditis (HT), obtaining a numerical estimate of the degree of hypoechogenicity associated with the appearance of thyroid dysfunction. MATERIALS AND METHODS: The study group included 89 patients with serum positivity for thyroglobulin (TgAb) and/or peroxidase (TPOAb) antibodies. Ultrasound (US) evaluation of thyroid gland and biochemical assay of serum thyrotropin (TSH), free-thyroxine (FT4) and free-triiodiothyronyne (FT3) were performed in all patients, and in 40 healthy subjects enrolled as control group. Thyroid echogenicity was compared with that of the surrounding neck muscles, using the grey-scale histogram analysis. The echogenicity was expressed in grey-scales (GWE). RESULTS: In HT patients, the mean of thyroid echogenicity was lower when compared to the normal thyroid (61.9 +/- 8.3 GWE vs. 71.9 +/- 3.1 GWE; P = 0.01). In all HT patients the lowest limit of thyroid echo distribution was in the echogenicity range of the surrounding muscle, the overlapping ranging between 3.4% and 95.0% (mean +/- SD 48.4 +/- 20.9%). The extension of like-muscle hypoechogenicity into the thyroid gland was significantly correlated with serum TSH values (r = 0.37; P < 0.001), serum FT4 values (r = -0.60; P < 0.001), and serum TPOAb values (r = 0.31; P = 0.004). Nobody was hypothyroid when the hypoechogenicity was less than 38.0%, whereas hypothyroidism occurred in all cases with hypoechogenicity of more than 68.9%. The receiving operating characteristic curve demonstrated that 48.3% was the best cut-off for identifying hypothyroid patients with sensitivity, specificity and diagnostic accuracy of 88.9%, 86.3% and 87.6%, respectively. CONCLUSIONS: In conclusion, the grey-scale quantitative analysis has provided a measure of thyroid hypoechogenicity associated with the appearance of hypothyroidism during the course of HT. The results of the present study would encourage the application of the computerized grey-scale analysis as complementary tool to US evaluation in the patients affected by HT.     

Transitory subclinical and permanent hypothyroidism in the course of subacute thyroiditis (de Quervain)

Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14 months (range 1-40), by monitoring thyroid hormone levels in basal condition, pituitary TSH reserve, antithyroglobulin (TgAb) and antimicrosomal antibodies ( MsAb ), in order to study the natural course of the disease and to characterize its intermediate phase. In the first phase the mean serum iodothyronine levels were within normal limits, nevertheless elevated T3 and T4 levels were detected in 34 (54%) and 20 (32%) patients, respectively. The next phase was characterized by normal serum iodothyronine levels; TRH stimulation test, however, showed a significant increase of pituitary TSH reserve in 35 (56%) patients. All parameters reverted gradually towards normal in all but 3 patients, who showed overt permanent hypothyroidism. TgAb and MsAb were positive in the early stage in 15 (24%) and 40 (64%) patients, respectively, disappearing at the end of the follow-up period in all but one patient; this particular patient belonged to the group of 3 patients affected with permanent hypothyroidism. Our data indicate that the onset of SAT is characterized by transient hyperthyroidism and that transient subclinical hypothyroidism characterizes the next phase. TRH stimulation test is required for the diagnosis of the latter and for the identification of the few who develop permanent hypothyroidism.     

Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto''s thyroiditis

OBJECTIVE: It has been postulated that a decrease in thyroid size can be achieved by thyroxine treatment in patients with goitrous Hashimoto's thyroiditis but no objective data are available. We have therefore investigated the influence of thyroxine treatment on ultrasonically determined thyroid size. We also measured serum antithyroid peroxidase antibodies. DESIGN: Consecutive patients with goitrous Hashimoto's thyroiditis was studied. PATIENTS: Thirteen women participated; all had goitrous thyroiditis. TREATMENT: To render them euthyroid thyroxine was given for 24 months. MEASUREMENTS: Thyroid size was measured ultrasonically and antithyroid peroxidase antibodies were measured using a commercial radioimmunological method. RESULT: Concomitant with the gradual increase in serum free thyroxine and free triiodothyronine index values and a fall in serum thyrotrophin level, a gradual decrease in thyroid volume from 50.4 +/- 6.8 ml (mean +/- SEM) to 34.1 +/- 5.7 ml (32%), P less than 0.001 was demonstrated. Antithyroid peroxidase antibodies were present in high concentrations in all subjects but the mean serum level was not significantly changed at 24 months after initiation of treatment. CONCLUSION: A clinically significant reduction in thyroid volume related to normalization of thyroid function but unrelated to changes in antithyroid peroxidase antibody can be achieved during L-thyroxine treatment of hypothyroid goitrous Hashimoto's thyroiditis.     

Follow-up study of thyroid stimulating-blocking antibodies in hypothyroid patients

It has been shown that hypothyroidism of some patients may be associated with increased activity of thyroid stimulating-blocking antibodies (TSBAb). The present study was undertaken to follow the course of thyroid blocking, stimulating immunoglobulins and TSH-binding inhibitor immunoglobulins (TBII) in six hypothyroid patients who had elevated TSBAb and were treated with T4. Four of the six had Graves' disease previously treated with antithyroidal drugs, one had Graves' disease treated with 131I and one had subacute thyroiditis and subsequently became hypothyroid. The patients were followed for 1-5 years. Blocking activity and TBII normalized in four of the six during T4 therapy, so T4 was discontinued and they remained euthyroid. These data indicate that it is important to monitor carefully thyroid function in hypothyroid patients treated with a fixed amount of T4 to avoid subclinical hyperthyroidism and its consequence, e.g. osteoporosis.