Toxic adenoma and papillary thyroid carcinoma in a patient with Graves' disease.

A case of a very rare association of toxic adenoma and papillary carcinoma with Graves' disease is presented. A 34-year-old woman developed Graves' disease with mild ophthalmopathy. An ultrasound revealed diffuse thyroid enlargement with a hypoechoic pattern and a hypoechoic nodule with regular edges of 1.6 cm in diameter at the lower pole of the left lobe. A thyroid 131I scintiscan showed a diffuse and homogeneous 131I distribution. The 131I uptake (RAIU) was elevated. One year later, while still on a low dose of methimazole, the patient had a recurrence of hyperthyroidism following an iodine load from a contrast agent. A further thyroid ultrasound confirmed the previously described pattern but showed a new hypoechoic nodule of 1.1 cm with irregular edges in the left lobe. A thyroid 131I scintiscan this time demonstrated a hyperactive area localised in the larger nodule and a lower diffuse uptake of the remaining tissue. Because of the worsening of the symptoms of hyperthyroidism, the patient had a left lobectomy. On histological examination, the larger nodule was well encapsulated and showed the characteristics of a hyperfunctioning follicular adenoma. The smaller nodule was a typically unencapsulated papillary carcinoma. Several other microfoci of papillary carcinoma were also found in the adjacent tissue. Completion of thyroidectomy was therefore performed, followed by 131I ablative therapy and thyroxine suppressive treatment. This observation suggests that the chronic abnormal stimulation of the thyroid gland by the thyroid-stimulating antibody (TSAb) may facilitate the neoplastic transformation of the thyrocytes in individuals with a critical genetic background.

[Atrial fibrillation and hyperthyroidism. The results of a retrospective study]. / Fibrillazione atriale ed ipertiroidismo. Risultati di uno studio retrospettivo.

BACKGROUND: To examine the prevalence of atrial fibrillation (AF) in cardiopathic patients with hyperthyroidism. METHODS: The data concerning the patients had been derived from registers of the Laboratory of Radioimmunoassay where cardiopathic patients' blood samples were referred from the Cardiology Unit to evaluate thyroid function, consecutively from January 1992 to December 1997. Of the 443 patients, 303 (68.4%) were classified as being euthyroid, 23 (5.2%) hypothyroid, 117 (26.4%) hyperthyroid. Thyroid function was diagnosed clinically and confirmed by serum TSH and free thyroid hormone (FT3, FT4), levels. RESULTS: Among hyperthyroid patients, the more frequent arrhythmia was AF (54.7%). After excluding from the study those hyperthyroid patients with rheumatic disease, hypertension, myocardial infarction, 37 hyperthyroid patients were selected; 18 (48.6%), (mean age 63.4 +/- 10.8 yrs), showed sinus rhythm and 19 (51.4%), (mean age 66.0 +/- 12.1 yrs), showed AF. FT3 and FT4 were higher in patients with AF than in those without AF, whereas TSH was not significantly different between the groups. Left ventricular (LV) mass index was significantly increased in hyperthyroid women with AF compared with hyperthyroid women without AF (109.80 +/- 22.33 g/m2 vs 84.50 +/- 6.20 g/m2; p < 0.005). A significant correlation was found between FT3 levels and LV mass index in the hyperthyroid women with and without AF (r = 0.77; p < 0.001). CONCLUSIONS: In this study the prevalence of AF is 51.4% in hyperthyroid patients. FT3 is higher in patients with AF than in those without AF. Finally, the correlation between FT3 and LV mass index suggests that cardiac hypertrophy is associated with thyroid hyperfunction.

Plasma endothelin-1 levels in patients with angina pectoris and normal coronary angiograms.

BACKGROUND: Some patients with typical angina and electrocardiographic evidence of ischemia have normal coronary angiograms. These patients have a reduced coronary flow reserve and abnormal endothelium-dependent vasodilator responses; this syndrome is known as microvascular angina. Among endothelium-derived peptides, endothelin-1 (ET-1) is a potent vasoconstrictor and an important modulator of microvascular function. METHODS: Plasma ET-1 was measured in 13 patients with typical angina, instrumental evidence of ischemia, and normal arteriograms and in 20 normal control subjects. RESULTS: Mean concentration of ET-1 was 2.89+/-1.24 pmol/L in patients with angina and normal angiograms and 1.99+/-0.81 pmol/L in normal control subjects (p < 0.02). Plasma levels of ET-1 values were significantly higher in patients with angina, positive exercise test results for ischemia, and normal coronary arteriograms compared with the group of patients with no clinical or instrumental evidence of ischemia. CONCLUSIONS: This is consistent with the hypothesis that in patients with microvascular angina, an endothelial dysfunction in the coronary vascular area caused by impaired endothelium-derived ET-1 could play an active role in the disease process.

Identification and characterization of a novel de novo mutation (L346V) in the thyroid hormone receptor beta gene in a family with generalized thyroid hormone resistance.

We have investigated an Italian family with generalized resistance to thyroid hormone (RTH), consisting of two individuals with elevated serum thyroid hormones (TH) and a non-suppressed TSH, together with unaffected family members, for a mutation in the thyroid hormone receptor beta gene (hTR beta). We have identified a single nucleotide substitution (1321 CTT to GTT) corresponding to a leucine to valine substitution at codon 346 (L346V) in the predicted protein. The index case and her affected child are heterozygous for the receptor defect, with normal sequence in unaffected family members. Furthermore, both parents of the index case were unaffected, suggesting that the mutation had arisen de novo. When expressed in vitro, the L346V mutant receptor showed a marked reduction in its affinity for tri-iodothyronine (T3), impaired ligand-dependent transactivation and potent dominant negative activity. Its functional impairment could not be alleviated, even at supraphysiological concentrations of T3, suggesting that the mutation might interfere with the intrinsic ligand-dependent transactivation function (AF-2) located in the hormone binding domain of hTR beta. Finally, the presence of the L346V mutation in the son of the propositus, who died from complications associated with congenital heart disease, raises the possibility that RTH might have contributed to the pathogenesis or severity of the latter.

Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease.

To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 nondiabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19 +/- 1.61 pmol/l in those with stable angina, 3.58 +/- 1.92 pmol/l in those with unstable angina, 4.24 +/- 2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64 +/- 2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92 +/- 0.73 pmol/l in those with stable angina, 4.35 +/- 1.67 pmol/l in those with unstable angina, 4.33 +/- 1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07 +/- 0.67 pmol/l; P < 0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P < 0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.