Sandra Brogioni

Thyroid blood flow evaluation by color-flow doppler sonography distinguishes Graves’ disease from Hashimoto’s thyroiditis

Thyroid hypoechogenicity at ultrasound is a characteristic of autoimmune thyroid diseases, with an overlap of this echographic pattern in patients affected by Graves’ disease or Hashimoto’s thyroiditis. Aim of the present paper was to study the thyroid blood flow (TBF) by color-flow doppler (CFD) and peak systolic velocity (PSV) at the inferior thyroid artery in 37 Graves’ and 45 goitrous Hashimoto’s thyroiditis patients. CFD pattern was defined as normal (or type 0): TBF limited to peripheral thyroid arteries (PSV = 17.7±3 cm/sec, mean±SD); type I: TBF mildly increased; type II: TBF clearly increased; type III: TBF markedly increased. The CFD was in direct relationship to the PSV. Out of 18 patients with Graves’ disease and untreated active hyperthyroidism CFD pattern was type III in 17 and type II in 1. The PSV was 42.1±15 cm/sec. In 17 patients euthyroid under methimazole, the CFD pattern was type 0 in 3 (17%) type I in 5 (30%), type II in 5 (30%), type III in 4 (23%). In this group of Graves’ patients the PSV was 36±14 cm/sec. In two patients, hypothyroid after radioiodine treatment, the CFD pattern was type 0 in 1 and type I in 1. In the group of Hashimoto’s patients TBF was in no relationship with thyroid status or treatment and was type 0 in 22 (49%), type I in 20 (44%), type II in 3 (7%), while none had type III CFD pattern. Thyroid hypoechogenicity at ultrasound was present in 32/37 (86%) Graves’ and 41/45 (91%) Hashimoto’s patients. All the four patients with Hashimoto’s thyroiditis and normal thyroid ultrasound pattern had also a normal CFD pattern, while 4/5 patients with Graves’ disease and normal echographic pattern had an increased TBF. In conclusion, a diffusely increased thyroid blood flow is pathognomonic of untreated Graves’ disease and an abnormal CFD pattern identifies the majority of Graves’ patients with a normal thyroid ultrasound pattern. Thus, CFD sonography may be useful in distinguishing patients with Graves’ disease and Hashimoto’s thyroiditis having a similar thyroid echographic pattern at ultrasound.

Relationship of the increased serum interleukin-6 concentration to changes of thyroid function in nonthyroidal illness

Variations in the serum concentration of interleukin-6 (IL-6) have been reported concomitantly with thyroid dysfunction: increased serum IL-6 levels have been found in patients with thyroidal destructive processes, such as subacute thyroiditis, some forms of amiodarone-induced thyrotoxicosis, or after percutaneous ethanol injection into “hot” thyroid nodules, as a result of the cytokine release from the damaged thyrocyte. In addition, recent in vitro evidence suggests that IL-6 might account, at least in part, for changes of thyroid economy found in nonthyroidal illness (NTI). In this cross-sectional study we addressed this problem by measuring serum IL-6 levels in 71 patients with NTI, due to neoplasia(n=25), chronic liver disease (n=9), chronic renal failure (n=28), or other chronic nonthyroidal disorders (n=9). These patients had reduced mean serum total T3 (TT3) and free T3 (FT3) concentrations, normal total and free T4 levels, normal TSH values, and increased serum reverse T3 (rT3) concentration (with the exception of chronic renal failure patients, who had normal rT3 levels). Serum IL-6 concentration was increased above normal (i.e. >100 fmol/L) in almost all NTI patients, especially in those with low T3 values (median value: 258 fmol/L, range 73–3210, vs 152 fmol/L, range <12.5–460, in patients with normal TT3 values, p<0.001). Serum IL-6 values in NTI patients were negatively correlated with serum FT3 values (r=0.56, p<0.001), and positively correlated with serum rT3 values (r=0.78, p<0.001). The increased serum IL-6 levels might represent a systemic reaction to disease, possibly mediated by stimulation of IL-6 synthesis and release induced by other cytokines, such as IL-1 and tumor necrosis factor. Whether IL-6 is simply a marker of NTI or is responsible, at least in part, for abnormalities of thyroid function tests, as suggested by previous in vitro evidence, remains to be established.

The Prevalence of Elevated Serum C-Reactive Protein Levels in Inflammatory and Noninflammatory Thyroid Disease

C-reactive protein (CRP) levels have not been routinely used to diagnose thyroid disease, although many thyroid conditions involve inflammation. This study was intended to determine whether CRP levels could differentiate between inflammatory and noninflammatory thyroid conditions, especially between type II inflammatory amiodarone-induced thyrotoxicosis (AIT) and type I iodine-induced AIT. Serum high-sensitivity CRP levels were measured in 100 euthyroid controls (7 taking amiodarone) and 353 patients with one of the following thyroid conditions: AIT, subacute thyroiditis, toxic diffuse goiter, nodular goiter, Hashimotos thyroiditis, shortterm hypothyroidism, or postpartum thyroiditis. No patients with nontoxic multinodular goiter (n = 34), toxic nodular goiter (n = 23), or toxic diffuse goiter, either untreated (n = 49) or euthyroid while taking methimazole (n = 33), had positive CRP levels (>10 mg/L). The occurrence of positive CRP levels among patients with Hashimotos thyroiditis (n = 35), short-term hypothyroidism (n = 38), and postpartum thyroiditis (n = 70) did not differ significantly from controls. The occurrence of positive CRP values did not differ significantly between patients with type I and type II AIT and controls. Six of 7 patients (86%) with untreated subacute thyroiditis had positive CRP levels (p < 0.00001). These results indicate that there is only a limited role for measurement of CRP levels in the diagnosis of thyroid diseases other than subacute thyroiditis.

Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities and is believed to be due to increased thyroid hormone synthesis and release; Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone-induced destructive process of the thyroid. Management differs in the two forms of AIT, since Type 1 usually responds to combined thionamides and potassium perchlorate therapy, while Type 2 is generally responsive to glucocorticoids. Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and destructive phenomena, may require a combination of the two therapeutic regimens. In this cross-sectional prospective study, 55 consecutive untreated patients, whose AIT was subtyped according to clinical and biochemical criteria, were evaluated to assess the specificity of color flow doppler sonography (CFDS) and thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen patients (6 men, 10 women, age 66±13 yr), who had diffuse or nodular goiter with or without circulating thyroid autoantibodies, were classified as Type 1 AIT; 39 patients (27 men, 12 women, age 65±13 yr) with apparently normal thyroids were classified as Type 2 AIT. All Type 1 patients had normal or increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal or elevated thyroidal 3-h and 24-h RAIU values (range 6–37% and 10–58%, respectively), in spite of elevated values of urinary iodine excretion; the remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had low 3-h and 24-h RAIU values (range 1.1–3.0% and 0.9–4.0%, respectively). The latter patients, who were unresponsive to the combination of methimazole and potassium perchlorate, became euthyroid after the addition of glucocorticoids. Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4–3.7% and 0.2–3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU values (6% and 13%, respectively).In conclusion, CFDS can accurately distinguish between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus, assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and help in selecting the appropriate therapy. Finally, in long standing iodine sufficient areas, such as the United States, where the thyroid RAIU is consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and available method to differentiate between Type 1 and Type 2 AIT.

Increased serum interleukin-6 concentration in patients with subacute thyroiditis: relationship with concomitant changes in serum T4-binding globulin concentration

Interleukin-6 (IL-6) is the main media-tor of the acute phase response. Increased serum concentrations of the cytokine have been found in patients with nonthyroidal inflammatory disorders and infections. In 18 patients with subacute thyroiditis (SAT) evaluated within 1–2 weeks after the onset of the disease, serum IL-6 values, as assessed by an ELISA method having a limit of detection of 25 fmol/L, ranged 139.2–543.9 fmol/L (mean±SE, 287.2±28.2 fmol/L). These values were significantly higher than those of 25 normal healthy controls (mean±SE, 26.2±5.5 fmol/L, range <25-99.4), 18 of whom had serum IL-6 values below the detection limit. The increase in serum IL-6 levels in SAT patients appeared to be related to the inflammatory disorder and not to thyrotoxicosis, because 18 Graves’ disease patients and 13 patients with toxic adenoma or toxic multinodular goiter had significantly lower serum IL-6 concentrations (101.7+35.2 fmol/L, range <25–251, for Graves’ disease, 79.6±41.4 fmol/L, range <25–168.5, for toxic adenoma, p<0.001 vs SAT for both groups) despite the markedly higher levels of total and free thyroid hormones. Neither free T4 nor free T3 values were correlated with serum IL-6 levels both in SAT and Graves’ patients. Twelve SAT patients were reevaluated 3–4 months later, after remission of the disease and at least one month after glucocorticoid withdrawal. At the final observation, all SAT patients showed a normalization of IL-6 concentration, which was undetectable in 8/12 (meaniSE, 22.8±5.4 fmol/L, p<0.001 vs acute phase values). Mean serum TBG concentra-tion was reduced in SAT patients at the time of first observation (19.3+1.1 mg/L, p<0.001 us controls). While no correlation could be found between serum TBG and serum total or free thyroid hormone levels, serum TBG concentration was inversely correlated with serum IL-6 concentration (r=0.69, p<0.01). Remission of the disease was associated with a significant increase in mean serum TBG concentration to 24.3±1.1 mg/L (p<0.001 vs acute phase values). In conclusion, SAT is associated with an increased serum concentration of IL-6, which normalizes upon remission of the disease. The rise in serum IL-6 levels may at least in part account for the concomitant decrease in serum TBG concentration.

Measurement of serum free thyroid hormone concentrations: an essential tool for the diagnosis of thyroid dysfunction

Free thyroid hormones (free thyroxine, FT4, and free triiodothyronine, FT3) represent a more useful index of thyroid status than total thyroid hormones, because the latter are influenced by variations of thyroid hormone-binding proteins, especially T4-binding globulin (TBG). Thus, increased serum total T4 (TT4) and, in many instances, T3 (TT3) concentrations are encountered in euthyroid subjects with TBG excess, familial dysalbuminemic hyperthyroxinemia and transthyretin-associated hyperthyroxinemia, while decreased serum TT4 and TT3 levels are associated with TBG deficiency: under these circumstances, measurement of serum FT4 and FT3 levels correctly establishes the diagnosis of euthyroidism. In cases of suspected hyperthyroidism, a diagnostic strategy can be suggested based on serum FT3 (and TSH) measurement, since FT4 may occasionally be elevated, also in euthyroid subjects, e.g., in patients under chronic amiodarone or L-T4 treatment. When hypothyroidism is suspected, the most reliable test appears to be FT4 (together with TSH), because FT3 may still be normal in patients with subclinical or mild thyroid failure. In any case, it is essential that reliable free thyroid hormone assays be used, which are devoid of methodological limitations responsible for artifactual results under particular circumstances, such as thyroid hormone-binding protein abnormalities, pregnancy and nonthyroidal illness.

Continuation of Amiodarone Delays Restoration of Euthyroidism in Patients with Type 2 Amiodarone-Induced Thyrotoxicosis Treated with Prednisone: A Pilot Study

CONTEXT Type 2 amiodarone-induced thyrotoxicosis (AIT) is a destructive thyroiditis usually responsive to glucocorticoids. Whether continuation of amiodarone affects treatment outcome is unsettled. OBJECTIVE The objective of the study was to compare the outcome of glucocorticoid treatment in type 2 AIT patients who continued or withdrew amiodarone. DESIGN This was a matched retrospective cohort study. SETTING The study was conducted at a university center. PATIENTS Eighty-three consecutive patients with untreated type 2 AIT participated in the study. After matching with patients continuing amiodarone (AMIO-ON, n = 8), patients interrupting amiodarone were randomly selected in a 4:1 ratio (AMIO-OFF, n = 32). INTERVENTION All patients were treated with oral prednisone. Patients whose thyrotoxicosis recurred after glucocorticoid withdrawal were treated with a second course of prednisone. MAIN OUTCOME MEASURE Time and rate of cure were measured. RESULTS Median time to the first normalization of serum thyroid hormone levels did not significantly differ in AMIO-ON and AMIO-OFF patients (24 and 31 d, respectively; P = 0.326). Conversely, median time for stably restoring euthyroidism was 140 d in AMIO-ON patients and 47 d in AMIO-OFF patients (log rank, P = 0.011). In fact, AIT recurred in five of seven AMIO-ON patients (71.4%) and in only three of 32 AMIO-OFF patients (9.4%, P = 0.002), requiring readministration of prednisone. One AMIO-ON patient never reached thyroid hormone normalization during the study period. Factors associated with glucocorticoid failure were thyroid volume and amiodarone continuation. CONCLUSIONS Prednisone restores euthyroidism in most type 2 AIT patients, irrespective of amiodarone continuation or withdrawal. However, continuing amiodarone increases the recurrence rate of thyrotoxicosis, causing a delay in the stable restoration of euthyroidism and a longer exposure of the heart to thyroid hormone excess.

Improvement of intrinsic myocardial contractility and cardiac fibrosis degree in acromegalic patients treated with somatostatin analogues: a prospective study

Background Acromegalic patients have increased left ventricular (LV) mass (M) and impaired diastolic function.

Color flow doppler sonography in thyrotoxicosis factitia

Color flow doppler sonography (CFDS) is a powerful technique which displays tissue blood flow and vascularity. Hyperthyroidism due to Graves’ disease is characterized by variable degrees of increased blood flow at CFDS. The purpose of this study was to evaluate CFDS patterns in five women with thyrotoxicosis factitia, a condition due to surreptitious ingestion of excess thyroid hormone. Diagnosis was supported by the finding of elevated free thyroxine (FT4), ranging 24.2–67.6 pmol/L (normal values: 8.3–20.5), elevated free triiodothyronine (FT3), ranging 9.9–26.7 pmol/L (normal values: 3.8–8.4), undetectable thyrotropin (TSH), absent anti-thyroid antibodies, undetectable serum thyroglobulin (Tg) concentrations, very low/suppressed thyroidal radioiodine uptake and normal/low urinary iodine excretion. Moreover, all patients admitted thyroid hormone pills intake. All patients had normal thyroid volume and echogenicity at conventional sonography (mean estimated volume, 9.4 ml, range, 6–11 ml), and absent hypervascularity or minimal intrathyroidal vascular spots at CFDS. The peak systolic velocity (PSV) was at the lower limit of normal values (mean, 4 cm/sec, range 3–5 cm/sec). Twenty-six women with untreated Graves’ disease had an increase in the mean PSV, (mean 12.9 cm/sec, range 8–20, p<0.001) and diffuse hypervascularity. CFDS pattern in 24 normal women residing in the same area did not differ from that found in patients with thyrotoxicosis factitia. Thus, due to the nonthyroidal origin of excess thyroid hormone, CFDS showed absent hypervascularity and normal PSV in spite of a thyrotoxic status. These findings well correlate with the etiology of thyrotoxicosis factitia and may represent an additional, useful tool to confirm the diagnosis. For its easiness, rapidity (10 min) and noninvasive features, CFDS can be considered a first line test during office examination when thyrotoxicosis factitia is suspected.

Short- and long-term changes of quality of life in patients with acromegaly: Results from a prospective study

Quality of life (QoL) may be affected in acromegalic patients, although the role of disease activity is still unsettled. The aim of the study was to assess the QoL of acromegalic patients with a specific questionnaire (ACROQOL). ACROQOL was evaluated in a prospective study (at baseline, at 6 and 24 months) in 23 active untreated acromegalic patients. Control of acromegaly was defined by normal age-matched serum IGF-I concentrations. Patient groups were defined as controlled or uncontrolled at 6 months and at 24 months: controlled or uncontrolled during the entire study period (ACROCC or ACRONC, respectively) or uncontrolled at 6 months and controlled thereafter (ACROC). At 6 months, ACROQOL scores improved globally (from 54.3±21 to 65.1±19, p=0.04) as did subdomains and were inversely related to IGF-I variation (r=−0.50, p=0.052). At 24 months, ACROQOL improved globally (from 54.3±21 to 65.7±18.0, p=0.04) and this was also seen in the appearance subdomains; however, no correlation was revealed between variation of serum IGF-I concentrations and changes in ACROQOL total score (r=0.008, p=0.87). ACROQOL scores did not significantly change in ACRONC (p=0.310) and in ACROC (p=0.583), whereas it improved globally (from 42.1±22.1 to 58.8±16.04, p=0.021) and in psychological subdomains in ACROCC; however, it reflected the improvement occurred within the first 6 months of disease control. In conclusion, successful treatment, which normalizes disease activity, improves QoL in acromegaly in the short term. However, the lack of correlation between the ACROQOL score in the long term might suggest that factors other than serum IGF-I participate in the well-being of acromegalic patients; however, due to the small sample size, our results need to be confirmed in larger studies.