Long-term follow-up of patients with papillary and follicular thyroid cancer: a prospective study on 715 patients.

PURPOSE: This prospective study evaluated the recurrence rate in 715 patients with differentiated thyroid cancer who had no evidence of persistent disease after total thyroidectomy and lymph node dissection in 94% of them followed up by radioiodine ablation (30-100 mCi) and assessed the predictive value of the initial thyroglobulin (Tg) levels for detecting recurrence, both during levothyroxine (LT4) treatment and after TSH stimulation. PATIENTS AND METHODS: Patients had Tg determinations performed at 3 months on LT4 treatment (Tg1) and at 9-12 months after stimulation by either thyroid hormone withdrawal or recombinant human TSH (Tg2); the Access kit was used (functional sensitivity of 0.11 ng/ml); they had undetectable anti-Tg antibodies. Patients were followed up annually. Predictive values were calculated by comparing Tg levels (Tg1 and Tg2) and the outcome in terms of recurrence. RESULTS: During the median follow-up of 6.2 yr, 32 patients had a recurrence. Assuming a cutoff level for Tg1 at 0.27 ng/ml, Tg1 sensitivity and specificity reached 72 and 86%, respectively, whereas predictive positive and negative values were 20 and 99%, respectively. With a cutoff level for Tg2 at 1.4 ng/ml, sensitivity and specificity reached 78 and 90%, respectively, whereas positive and negative predictive values were 26 and 99%, respectively. CONCLUSION: This large prospective cohort of patients presented a low rate of recurrence. Initial Tg measurements allow to predict long-term recurrence with an excellent specificity. Stimulated Tg determination presented a slightly higher sensitivity than Tg determination on LT4. TSH stimulation may be avoided when Tg measured 3 months after ablation is less than 0.27 ng/ml during LT4 treatment.

Epidemiology, clinical presentation, treatment and prognosis of a regional series of 26 anaplastic thyroid carcinomas (ATC). Comparison with the literature.

OBJECTIVE: The aim of this study is to retrospectively describe the epidemiological and clinical features, therapeutic modalities, prognostic factors and survival figures in a population of patients with anaplastic thyroid carcinoma (ATC) observed in Auvergne, France. We compared these data with those in the literature. MATERIAL AND METHODS: The analysis was conducted based on a computer database containing a regional register recorded by health professionals treating ATC. RESULTS: Of the 1500 cancers observed over 16 years, 26 were identified as ATC. The male/female ratio was 1/2.7 and the average age: 72.1; 76.9% of the cases had thyroid medical history, average tumor size at diagnosis was 7.35 cm with N1 in the course of illness in 61.5% of cases, M1 in 34.6% of cases. Surgery was performed in 84.6% of cases, radiotherapy in 53.8% and chemotherapy in 19.2%. The average survival was 9 months, the survival median: 4 months. CONCLUSION: Our results show that, in univariate analysis, age above 75, capsular invasion, lymph nodes metastasis, tumor residue after surgery and lack of multimodal treatment (particularly radiotherapy in patients without tumor residue) are factors of poor prognosis. In a multivariate analysis only age above 75, followed by node invasion, capsular invasion, and finally female gender are factors of poor prognosis.

Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients.

BACKGROUND: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease. AIM: The goal of the study is to compare the diagnostic values of seven methods for serum Tg measurement for detecting recurrent disease both during L-T4 treatment and after TSH stimulation. METHODS: Thyroid cancer patients who had no evidence of persistent disease after initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on L-T4 treatment (Tg1) and then at 9-12 months after withdrawal or recombinant human TSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the clinical status of the patient at the end of follow-up. RESULTS: Thirty recurrences were detected among 944 patients. A control 131I total body scan had a low sensitivity, a low specificity, and a low clinical impact. Assuming a common cutoff for all Tg assays at 0.9 ng/ml, sensitivity ranged from 19-40% and 68-76% and specificity ranged from 92-97% and 81-91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2-0.3 ng/ml, sensitivity was 54-63% and specificity was 89% for Tg1. Using the two methods with a lowest functional sensitivity at 0.02 and 0.11 ng/ml resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods, using an optimized functional sensitivity according to receiver operating characteristic curves at 0.22 and 0.27 ng/ml resulted in a sensitivity at 65% and specificity at 85-87% for Tg1. CONCLUSION: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation. Serum Tg determination obtained after TSH stimulation still permits a more reliable assessment of cure and patient's reassurance.

The meaning and predictivity of Hürthle cells in fine needle aspiration cytology for thyroid nodular disease.

AIMS: The significance of Hürthle cells in thyroid nodule fine needle aspiration cytology (FNAC) samples remains uncertain. This study aims to clarify the meaning and the predictivity of this kind of cells. METHODS: One hundred and ten patients with Hürthle cells in FNAC of thyroid nodules were reviewed. Histopathology was correlated with cytological findings. RESULTS: The density of Hürthle cells in FNACs ranged from 20 to 100%. Eighty-nine patients had benign nodular disease (Hürthle cell or follicular adenoma), and 21 patients had malignant tumours. The presence of more than 50% Hürthle cells in FNAC correlated with benign or malignant Hürthle cell neoplasm. Hürthle cell carcinomas displayed more than 90% Hürthle cells in FNAC. CONCLUSIONS: Surgery is indicated for all nodular lesions with more than 50% Hürthle cells in FNAC.

Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism.

We have examined insulin action on glucose metabolism in six hypothyroid patients before and after regular thyroid hormone treatment, and in six healthy volunteers before and after transient induction of moderate hyperthyroidism. Insulin was infused under euglycaemic and eukalaemic clamps. An appropriate amino acid infusion was used to blunt insulin-induced decreases in amino acid levels. Glucose kinetics were assessed using a primed continuous infusion of [6,6-(2)H(2)]glucose. The results showed that basal plasma insulin and glucose levels (i.e. before infusion) were similar in each case. Despite similar insulin infusion rates, the plateau value of insulin was lower after thyroid treatment in both hypothyroid patients and healthy volunteers. The rate of exogenous glucose needed to maintain plasma glucose at a steady-state level was increased by thyroid hormone in hypothyroid patients (P <0.05), but not in healthy volunteers. Thyroid treatment resulted in a significant increase in basal glucose disposal in both groups (P <0.05). Insulin, in conjunction with glucose and amino acids, significantly stimulated glucose disposal (P <0.05) under all conditions. The incremental increase in glucose disposal after infusion tended to be higher following thyroid hormone treatment, but this was not statistically significant. However, the ratio of the incremental increase in glucose disposal to the increase in plasma insulin was significantly improved after thyroid hormone treatment in hypothyroid patients (P <0.05). It was also increased in healthy volunteers, but not significantly. We conclude that thyroid hormones improve the ability of insulin to stimulate glucose disposal related to insulinaemia. This phenomenon may be highly sensitive, because it was only apparent at low thyroid hormone levels.

Response of leucine metabolism to hyperinsulinemia in hypothyroid patients before and after thyroxine replacement.

We have investigated the effect of hypothyroidism and insulin on protein metabolism in humans. Six hypothyroid patients were studied in a postabsorptive state before and after 5 months of regular treatment for hypothyroidism (153 +/- 17 microg/day of L-T4). The effect of insulin was assessed under hyperinsulinemic euglycemic and eukalemic conditions. Insulin was infused for 140 min at 0.0063 +/- 0.0002 nmol/kg x min. An amino acid infusion was used to blunt insulin-induced hypoaminoacidemia. Whole body protein turnover was measured using L-[1-13C] leucine. When compared to L-T4-induced subclinical thyrotoxic state, hypothyroidism induced a significant decrease (P < 0.05) in leucine endogenous appearance rate (a reflection of proteolysis; 0.89 +/- 0.09 vs. 1.33 +/- 0.05 micromol/kg x min), oxidation (0.19 +/- 0.02 vs. 0.25 +/- 0.03 micromol/kg x min), and nonoxidative disposal (a reflection of protein synthesis; 0.87 +/- 0.11 vs. 1.30 +/- 0.05 micromol/ kg x min). Insulin lowered proteolysis during both the subclinical thyrotoxic and hypothyroid states. Hypothyroidism impaired the antiproteolytic effects of insulin. Thyroid hormones are, therefore, essential for the normal antiproteolytic action of insulin.

[Epidemiologic characteristics of 336 thyroid cancers observed in the Auvergne region]. / Caractéristiques épidémiologiques de 336 cancers de la thyroïde observés en région Auvergne.

Patients treated and followed for thyroid cancer by a multidisciplinary group were studied between 1989 and 1993, 336 patients living in the French region Auvergne underwent total or partial thyroidectomy for thyroid carcinoma. The sex ratio was 4.3 and the median age was 52 (14-57) and 49 (17-83) in females and males respectively. Papillary carcinoma was the most common form: 76.5 of all thyroid tumors. The incidence of occult thyroid cancer was 17.4%; tumor size was smaller than for intranodular cancer (p < 0.00001). Tumor size at diagnosis of patients who died was higher than in patient who survived (p < 0.0001) and changed with histological type. It decreased between 1989 and 1993 (p < 0.01). 73% of the patients were asymptomatic before surgery, 23% described a rapid growth of their nodule. Clinically, 43.9% of the patients had a single nodule, 83% of these nodules were suspect because of their hardness. Median follow-up was 2.8 years. 279 patients are living and well, 28 were lost to follow-up and 39 died. There were 30 (8.93%) deaths due to thyroid carcinoma. In our study, significant prognostic factors for death were age at diagnosis (p < 0.0001), histological type (p < 0.0001) and nodular size (p < 0.01).

Hyperthyroidism without elevated levels of thyroxine and triiodothyronine in a patient with pulmonary tuberculosis.

We have reported a case of toxic thyroid adenoma with low T3 and low T4 syndrome in a patient who received antituberculous drugs for active pulmonary tuberculosis. Search for thyroid-hormone-binding antibodies was negative. Thyroid lobectomy was done and histologic examination confirmed toxic thyroid adenoma; two months after operation the patient was clinically and biologically euthyroid. During the course of a severe nonthyroidal illness, normal thyroid hormone levels must be regarded as an indicator of hyperthyroidism. In addition, we believe that rifampin has a significant effect on thyroid function tests and results of thyroid physiology.

[Prolonged hyperthyroidism and recurrent atrio-ventricular block]. / Hyperthyroïdie prolongée et bloc auriculo-ventriculaire récidivant.

The authors report the case of a patient with hyperthyroidism who had three episodes of grade 2 and 3 atrio-ventricular block over a 6-year period. After he recovered from hyperthyroidism, the atrio-ventricular conduction returned to normal and remained so throughout a 5-year follow-up. A grade 1 atrio-ventricular block is found in 6 to 8 p. 100 of hyperthyroid patients, but grade 2 and 3 blocks are rare in such patients. Case reports in which thyrotoxicosis alone seemed to be responsible for disorders of conduction are exceptional; frequently, other factors likely to induce such disorders were present. In 90 p. 100 of the cases hyperthyroidism was due to Graves' disease; it lasted for more than one year and thyrotoxicosis was often severe. These facts suggest the possibility of a thyrotoxic myocarditis and/or an autoimmune focal myocarditis. Although rare, atrio-ventricular block in hyperthyroid subjects is a possibility that warrants electrocardiographic monitoring, notably when negative dromotropic drugs are prescribed.

[Myxedema coma with hypervasopressinism. 2 cases]. / Coma myxoedémateux avec hypervasopressinisme. Deux observations.

Hyponatremia is usual during myxedema coma. Hereafter we report two cases with increased plasma arginine vasopressin (AVP). Patients were admitted because of hypothyroid coma. In each case, there was an hyponatremia with normal urine sodium and low serum osmolality. Renal function was normal. On hormonal results, primary hypothyroidism was evident. Plasma AVP was increased. The plasma cortisol of one patient was high. Immediate therapy associated: water restriction, hypertonic saline infusion, furosemide, oral thyroid hormones with low doses. On the fourth day, conscience improved obviously. Natremia and plasma AVP went back to normal state before returning to euthyroid state. Patients went on improving along with normalizing thyroid status. Hyponatremia can be a serious sign of hypothyroidism. In case of myxedema coma with hyponatremia, clinical improvement seems to be related to fast correction of water and electrolyte disturbances and we prefer to give low doses of thyroid hormones at first. The hyponatremia and increased plasma AVP mechanisms are complex. However, in each of these cases, plasma AVP come back to normal before returning to euthyroid state. In one case, high plasma cortisol level rules out adrenal insufficiency as causal mechanism of electrolyte disorders.

[Lipoatrophic diabetes with acanthosis nigricans. Prolonged blood glucose normalization by continuous infusion of insulin]. / Diabète lipoatrophique avec acanthosis nigricans. Normalisation glycémique prolongée par infusion continue d'insuline.

Insulin resistance is a permanent feature of lipoatrophic diabetes, the resistance being almost regularly stubborn. We report the case of a 23-year old unmarried woman with generalized lipoatrophy and Acanthosis nigricans. Seven years after a diabetes resistant to all treatments was diagnosed, blood glucose levels were permanently around 25 mmol/l. Multiple and severe micro- and macroangiopathies were present. Partial resistance to insulin was demonstrated. This resistance could not be explained by abnormalities in anti-insulin hormones nor by a decrease in the number or affinity of insulin receptors, which suggested an intracellular abnormality below membrane receptors. Sustained control of glycaemia at a normal level was achieved by continuous infusion of insulin in high doses. It would appear that optimum insulin therapy using an insulin pump would offer hopes of therapeutic success in this particular form of insulin resistance.