Coronary vasoreactivity in subjects with thyroid autoimmunity and subclinical hypothyroidism before and after supplementation with thyroxine.

BACKGROUND: The association of subclinical hypothyroidism (SCH) with increased risk for cardiovascular disease is still controversial. This study aimed to examine coronary vascular reactivity by positron emission tomography (PET) in asymptomatic patients with SCH before and after levothyroxine (LT4) supplementation. METHODS: Ten patients (7 women and 3 men; mean age 43±15 years) with untreated autoimmune SCH, defined by elevated levels of thyroid-stimulating hormone (mean TSH: 16.9±11.3 µU/mL), normal levels of free thyroxine (0.9±0.1 µg/mL), free triiodothyronine (3.2±0.4 pg/mL), and positive thyroid peroxidase antibodies were studied. Eight euthyroid subjects with similar low-risk cardiovascular risk profile served as controls. Myocardial blood flow (MBF) and coronary flow reserve (CFR) were quantitatively assessed with rest/stress N-13 ammonia PET at baseline and after 6 months of LT4 replacement therapy (given only to patients). RESULTS: At baseline, stress MBF and CFR corrected (c) for rate pressure product (RPP) and myocardial vascular resistance (MVR) during stress were significantly reduced in SCH compared with controls (stress MBF: 2.87±0.93 vs. 4.79±1.16 mL/g/min, p=0.003; CFR: 2.6±0.73 vs. 4.66±1.38, p=0.004; MVR: 40.14±18.76 vs. 20.47±6.24 mmHg/mL/min, p=0.02). Supplementation therapy with LT4 normalized TSH in all subjects and was associated with an increase in CFR (2.6±0.73 vs. 3.81±1.19, p=0.003) and with a tendency toward a decrease in MVR. Differences in CFR between SCH and controls were also seen after correction of resting MBF for RPP. CONCLUSIONS: In asymptomatic subjects with SCH due to thyroid autoimmunity, coronary microvascular function is impaired and improves after supplementation with LT4. This may partially explain the increased cardiovascular risk attributed to SCH.

Incidence and predictability of amiodarone-induced thyrotoxicosis and hypothyroidism.

OBJECTIVES: To determine the incidence and predictability of amiodarone-induced thyrotoxicosis (AIT) and hypothyroidism (AIH) in patients with cardiomyopathy. PATIENTS AND METHODS: A total of 72 patients (mean age 69 +/- 11 years) living in an area previously endemic for thyroid disease but with currently sufficient iodine intake were enrolled in this prospective study. All participants were treated with amiodarone for the first time. The course of thyroid function in patients with normal thyroid morphology and in those with goiter was monitored over a median follow-up period of eight months in 71 (98.6%) patients. RESULTS: Of 72 participants, 18 (25.0%) had a morphologically normal thyroid gland as evidenced by sonography. The prevalence of thyroid dysfunction before initiation of amiodarone was 37.6% (27 of 72) with almost equal distribution between hypothyroidism and hyperthyroidism (14 and 13 patients). After treatment with amiodarone, thyroid dysfunction was diagnosed in 56.8% (25 of 44) of the patients without preexisting dysfunction. Of these 25 patients, nine (36%) developed either subclinical or overt AIH and 16 (64.0%) developed either subclinical or overt AIT. Although 61.1% (44 of 72) had normal thyroid function before initiation of amiodarone, this number decreased to 26.7% (19 of 71, P < 0.001) after treatment. Factors such as (99m)Tc-pertechnetate scan uptake, thyroid autoimmunity, age, thyroid autonomy or abnormal thyroid morphology were not significantly associated with the development of thyroid dysfunction. CONCLUSIONS: Prevalence of thyroid dysfunction was high in elderly patients treated with amiodarone. Cases of AIT and AIH occurred in patients with and without preexisting thyroid disorders. Because of the high incidence of amiodarone-induced thyroid dysfunction, regular testing of thyroid function is mandatory during and following amiodarone treatment.

Bone lesion detection with carrier-added 99mTc-EDTMP in comparison with 99mTc-DPD.

An increased uptake of bone-seeking radiopharmaceuticals into malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. The tracers used in clinical routine for bone scanning are methylene-diphosphonate (MDP), dicarboxypropane-diphosphonate (DPD) and ethylenediaminetetramethylene-phosphonate (EDTMP). MDP and DPD are usually labelled with 99mTc for diagnostic use, whereas EDTMP is labelled with 153Sm for therapeutic purposes. This study aimed to compare, for the first time, bone scanning with an improved preparation of 99mTc-EDTMP (by the addition of rhenium) (carrier-added) with 99mTc-DPD. Twenty malignant bone lesions were investigated in 10 patients. The ratios of bone lesion to soft tissue (BL/ST) and of bone lesion to normal bone (BL/NB) were compared 3 h after the injection of either compound. Quantitative analysis demonstrated a significant (P<0.05) difference in BL/ST ratio in favour of 99mTc-DPD. The BL/NB ratio was not significantly different. Visual image analysis resulted in a clinically comparable interpretation of imaging studies with the use of 99mTc-DPD and carrier-added 99mTc-EDTMP. These preliminary data support the concept of carrier addition to increase bone uptake by the modification of the complex structure of 99mTc-EDTMP. However, any advantage over conventional 99mTc-based tracers for bone scintigraphy in clinical use needs to be demonstrated in controlled trials.

Radiation synovectomy with (166)Ho-ferric hydroxide: a first experience.

UNLABELLED: Radiation synovectomy (RS) is indicated when conventional pharmacologic treatment of chronic synovitis has not relieved its symptoms. The use of radionuclides that are bound to ferric hydroxide (FH) particles has been shown to be effective and safe for this procedure. (166)Ho-FH macroaggregates offer promising properties for RS but there is a lack of clinical data. We investigated the efficacy and safety of (166)Ho-FH in a prospective clinical trial in patients suffering from chronic synovitis. METHODS: Twenty-four intraarticular injections were performed in 22 patients receiving a mean activity of 1.11 GBq (range, 0.77-1.24 GBq) (166)Ho-FH. Blood activity measurements and monitoring of activity distribution were performed by whole-body gamma-camera imaging for control of leakage 3 and 24 h after injection of (166)Ho-FH. The patients were evaluated clinically before RS, 1 wk and 1 mo after the treatment, and thereafter in 3-mo intervals by assessing joint effusion, pannus, local pain, range of motion, and the patient's satisfaction. RESULTS: In 18 of 24 treatments, no leakage to nontarget organs was visible, whereas small amounts of activity could be detected in the local inguinal lymph nodes in 6 patients and to the lungs and to the liver in 1 patient (<0.1%). In all cases leakage to the lymph nodes was <1%. Leakage to the blood was negligible. Clinically, 17 patients (71%) exhibited a complete or partial response. CONCLUSION: RS with (166)Ho-FH was safe and effective in patients with chronic synovitis of different origin. Controlled clinical trials are necessary to evaluate the therapeutic efficacy and safety compared with the treatment with other radionuclides and glucocorticosteroids.