Changes in cardiac function at rest before and after treatment in primary hypothyroidism.

The aim of the present study was to investigate in hypothyroid patients the reversibility of the prolongation of electromechanical delay and of the impairment of early diastolic relaxation as measured by radionuclide ventriculography after restoration of euthyroidism. We also evaluated Doppler echocardiography in relation to scintigraphic findings. Twenty-six consecutive hypothyroid patients were studied at diagnosis and after treatment. The time to peak ejection decreased (161 +/- 6 vs 145 +/- 5 ms; p = 0.03) without changes in global systolic function (ejection fraction). The peak filling rate was reversible as well: 2.6 +/- 0.1 versus 3.0 +/- 0.2 end-diastolic volume/s; p = 0.003. No significant changes in systolic and diastolic cardiac function or ventricular geometry were detected by Doppler echocardiography. However, subanalysis of profoundly hypothyroid patients (free T4 < 4.5 pmol/L, n = 8) revealed a decrease in the septal wall thickness (9.9 +/- 0.7 vs 8.3 +/- 0.4 mm, p = 0.01) and increases in early peak transmitral inflow velocity (53 +/- 4 vs 65 +/- 4 cm/s, p = 0.03), as well as left ventricular end-diastolic diameter (4.8 +/- 0.1 vs 5.1 +/- 0.2 cm, p < 0.05) after treatment. Thus, in primary hypothyroidism, a subtle reversible prolongation of contraction without major changes in global systolic function and a decrease in early active relaxation is observed by radionuclide ventriculography. Echocardiography shows changes only in severely hypothyroid patients.

Cardiac function at rest in hypothyroidism evaluated by equilibrium radionuclide angiography.

OBJECTIVE: Previous studies have suggested that hypothyroidism affects both systolic and diastolic cardiac function. We have applied equilibrium radionuclide angiography to the study of heart function at rest in hypothyroidism. DESIGN: A prospective study, evaluating cardiac function at rest in primary hypothyroidism. METHODS: Cardiac function was studied by means of equilibrium radionuclide angiography. Screening echo-Doppler examinations were performed on each patient. PATIENTS: Twenty-six consecutive untreated hypothyroid patients without clinical or echocardiographic cardiac disease and 20 healthy matched controls. RESULTS: Between patients and controls, the time to peak emptying rate (161 +/- 6 msec vs. 144 +/- 6 msec, P < 0.05) and the time to peak filling rate (188 +/- 6 msec vs. 170 +/- 5 msec, P < 0.05), were the only discriminatory parameters. In hypothyroid patients, a trend towards a decrease in diastolic cardiac function, expressed as peak filling rate, was observed: 2.6 +/- 0.1 End Diastolic Volume (EDV)/s vs. 3.0 +/- 0.1 EDV/s, P = 0.06. Within the hypothyroid patient group, the time to peak emptying rate was more prolonged in patients with lower free thyroxine levels (R = -0.60, F = 13.5, P < 0.001). Peak filling rate was decreased in patients with lower free thyroxine levels (R = 0.51, F = 8.4, P < 0.01) whereas the time to peak filling rate was more prolonged (R = -0.62, F = 15, P < 0.001). CONCLUSION: In a large group of consecutive patients presenting with primary hypothyroidism, even in the absence of clinical cardiac disease and echocardiographic abnormalities, clear changes in myocardial performance at rest were observed. The most obvious effect of thyroid hormone deficiency on the heart was a lengthening of both systolic and early diastolic time characteristics. Diastolic rather than systolic cardiac function was influenced by hypothyroidism.

Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients.

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.

Acute L-triiodothyronine administration potentiates inotropic responses to beta-adrenergic stimulation in the isolated perfused rat heart.

OBJECTIVE: Acute inotropic effects of triiodothyronine (T3) have been reported, employing both in vivo experimental animal models and in vitro isolated heart perfusions. However, the mechanisms responsible for these acute inotropic effects remain unclear. The aim of this study, therefore, was to delineate the role of the beta-adrenergic receptor system in these acute responses. METHODS: The hearts from both euthyroid and hypothyroid (treated with 0.05% PTU in drinking water) male Sprague-Dawley rats were used in 5 experimental study protocols. Hearts from euthyroid rats were perfused with buffer containing either T3(10(-7) M) or control while continuously recording left ventricular function for 10 min ('acute effects'). Two-hour perfusions ('subacute effects') and cardiac responses following increasing doses of isoproterenol (10(-10) to 10(-6) M) in the presence or absence of T3-containing buffer (acute interaction) were also determined. In hypothyroid rats, the subacute responses and the acute interactions were investigated. RESULTS: In the presence of T3, an acute, significant potentiation of the inotropic responses following beta-adrenergic stimulation with isoproterenol was observed in both rat cohorts, which was more pronounced in hearts from euthyroid rats. An acute (< 40 s), but transient (79 +/- 8 s), direct inotropic response was observed in hearts from euthyroid rats. No cardiac responses were seen during a 2-h perfusion in hearts from either euthyroid or hypothyroid rats. CONCLUSIONS: The acute inotropic effects of T3 in non-ischemic myocardium probably result from an acute interaction between T3 and catecholamines rather than through a direct inotropic effect of T3 alone.

Sucralfate causes malabsorption of L-thyroxine.

PURPOSE: To determine if sucralfate causes malabsorption of L-thyroxine. PATIENTS AND METHODS: Five healthy volunteers ingested L-thyroxine, 1,000 micrograms, administered orally (1) without sucralfate, (2) with sucralfate, 1 g, and (3) 8 hours after sucralfate, 2 g. The amount of L-thyroxine absorbed was calculated from the peak increase in serum T4 levels within 6 hours of hormone ingestion multiplied by the volume of distribution for the hormone. RESULTS: Peak absorption of L-thyroxine in the absence of sucralfate was 796 micrograms (95% confidence interval (CI): 515-1,074 micrograms). Coadministration of sucralfate, 1 g, with L-thyroxine reduced thyroid hormone absorption to 225 micrograms (95% CI: 151-299 micrograms) (P = 0.0029 compared with control). Peak hormone absorption was delayed 2 hours by simultaneous sucralfate ingestion. Separation of administered L-thyroxine and sucralfate doses by 8 hours returned hormone absorption to control values. Maximum T3 levels did not differ, regardless of drug regimen, but suppression of thyroid-stimulating hormone (TSH) by L-thyroxine was reduced by coadministration of sucralfate. CONCLUSIONS: Sucralfate causes malabsorption of L-thyroxine, presumably by intraluminal binding of hormone.

Clinical utility of posttreatment radioiodine scans in the management of patients with thyroid carcinoma.

A retrospective comparison was performed of whole body scans obtained before and after 143 131I treatments in 93 patients with thyroid carcinoma. Pretreatment scans were performed with 74-185 megabecquerel 131I, and posttreatment scans were performed 5-12 days after dosing with 1.1-7.4 GBq. In 38 (27%) treatment cycles, the results of posttreatment and pretreatment scans differed. Only 14 (10%) posttreatment scans detected new locations of metastatic disease. Seventeen posttreatment scans demonstrated metastatic locations that were already known from previous studies but not seen on the pretreatment scan. Among parameters evaluated (including demographic and histological characteristics), only the combination of age at diagnosis less than 45 yr and history of previous 131I therapy contributed to the likelihood of a new finding on posttreatment scan (relative risk, 3.8). Five of the 14 new posttreatment scan findings were subsequently corroborated by other radiographic studies or thyroglobulin elevations, all in patients with extrathyroidal extension of the primary tumor. Seven (5%) posttreatment scans were unable to detect a focus of uptake seen on the corresponding pretreatment scan. In conclusion, posttreatment scans were most likely to reveal clinically important new information in young patients who had previously received 131I therapy. In older patients and those without previous 131I therapy, posttreatment scans rarely yielded new information that would potentially alter the patient's prognosis.

Follicular variant of papillary thyroid carcinoma. A clinicopathologic study.

BACKGROUND: A retrospective clinicopathologic study was performed to identify the influence of diagnostic and therapeutic procedures on the outcomes of patients with the follicular variant of papillary thyroid carcinoma (FVPTC). METHODS: The results of 37 patients with FVPTC were compared with those of 37 randomly selected patients with papillary carcinoma and 22 patients with follicular carcinoma. Diagnostic, therapeutic, and follow-up data were obtained by review of clinical and histologic materials. RESULTS: Median follow-up was approximately 3 years in all groups. Fine-needle aspiration had a sensitivity of 75% for FVPTC, which was similar to that for papillary carcinoma. Frozen section evaluation had a sensitivity of only 27% for FVPTC but 94% for papillary carcinoma and 44% for follicular carcinoma. All patients for whom the fine-needle aspiration specimen contained cytologic features of papillary carcinoma and frozen section suggested a follicular lesion proved to have FVPTC: Consequently, hemithyroidectomy was performed three times more often among patients with FVPTC than among those with papillary carcinoma. FVPTC tumors were modestly, but significantly, smaller than papillary carcinoma tumors (1.2 versus 1.6 cm). Metastases to cervical lymph nodes occurred least often in patients with FVPTC and usually were detected within 3 months of diagnosis. The frequency of distant metastases within this limited period of follow-up did not differ between FVPTC and papillary carcinoma. CONCLUSIONS: Fine-needle aspiration appears to be superior to frozen section for identification of FVPTC, although the number of aspirations performed was limited. Greater use of aspiration may permit more appropriate surgical management of this disease. Local and distant metastases of FVPTC do not occur more often than do those of papillary carcinoma.