Can misdiagnosis in pre-operative FNAC of thyroid nodule influence surgical treatment?

BACKGROUND: Pre-operative cytology in thyroid disease remains the most appropriate diagnostic test for defining the nature of a thyroid nodule before surgical excision. MATERIALS AND METHODS: We selected the most recent 825 surgical thyroid procedures performed in our institution from January 2004 to June 2007; 776 were total thyroidectomies, 23 were lobe-isthmectomies, and 26 were radical neck dissections. We distributed the data based on pre-operative cytology. Each cytological diagnosis was compared to results obtained by definitive histology. Tumors were called incidentalomas if they consisted of a neoplastic focus with a low grade of aggressiveness, as demonstrated by dimension <5 mm, non-aggressive histological subtype. RESULTS: Of the 541 cases of benign disease, 417 were confirmed as benign. The other 124 cases are listed as follows: 29 follicular adenoma; 76 papillary carcinoma (35 found as incidentalomas), and 19 follicular carcinoma (3 incidentalomas). Cytology suggestive of papillary carcinoma was correct in 95.2% of cases (119/125). The 135 tumors termed "follicular neoplasm" were staged on pathology thus: 56 adenoma (41.4%), 26 carcinoma (19.2%), 13 (9.6%) absence of follicular proliferation, 38 (28.1%) papillary follicular variant, 2 (1.4%) undifferentiated cells. Medullary carcinomas were both confirmed. The "suspicious group" exhibited no malignancy on fine needle aspiration cytology (12 of 21; 57%). CONCLUSIONS: Cytology has good reliability in malignant lesions. Incidental tumors occurring in benign disease have little impact on clinical and surgical management; "follicular neoplasm" posed two problems - the impossibility of identifying the nature of the tumor, as well as the newer difficulty in distinguishing papillary follicular subtype.

Minimally invasive video-assisted thyroidectomy: the learning curve.

BACKGROUND: MIVAT (minimally invasive video-assisted thyroidectomy) is a recent technique that requires a learning curve. MATERIALS AND METHODS: From July 2005 to December 2006, we treated 100 from a total of 467 thyroidectomy patients with MIVAT. We divided the patients into 3 groups. The first 2 groups consisted of 25 patients each: group A (cases 1-25) and group B (26-50). We also divided patients into 2 groups based on our surgical experience: group A + B (cases 1-50) and group C (cases 51-100). RESULTS: The operative times for groups A and B were 101.7 and 84.6 min, respectively (p < 0.03); those for groups A + B and C were 91.07 and 63.06 min, respectively (p < 0.004). Complications of hypocalcemia were observed in 6 cases (4 in the first 50 cases and 2 in the second 50), and complications of nerve palsy were observed in 2 cases from group A. CONCLUSIONS: After 25 cases, we observed that the MIVAT procedure allows for a lower mean operative time and a reduction of complications.

[Medullary carcinoma of the thyroid gland]. / Il carcinoma midollare della tiroide.

We report the experience of the Institute of Surgical Pathology of the University of Parma on three patients with sporadic medullary thyroid carcinoma (MTC). MTC is a tumor of parafollicolor cells origin (C cells). The surgical excision of the thyroid tumor and cervical node metastases is potentially curative. The other therapeutic options are limited. Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN) related MTC. Genetic screening promises earlier and accurate diagnosis (RET gene mutations are found in MEN).

The effect of diltiazem, a calcium channel-blocking drug, on cardiac rate and rhythm in hyperthyroid patients.

Tachycardia and tachyarrhythmias are frequent in patients with thyrotoxicosis, especially in the elderly. Since myocardial calcium uptake is increased in thyrotoxic rats, the efficacy of the calcium channel-blocking drug diltiazem in decreasing heart rate and the incidence of arrhythmias was evaluated in 11 hyperthyroid patients. All patients were studied with a 24-hour Holter monitor prior to the beginning of sole diltiazem therapy (120 mg given every eight hours), on the tenth day of therapy, and five days after therapy was discontinued. Heart rate significantly decreased by 17% during diltiazem treatment (96.5 +/- 3.7 systoles/min vs 79.9 +/- 3.2 systoles/min [mean +/- SE]) and returned to baseline values five days after the therapy was discontinued (100.7 +/- 3.4 systoles/min). Similarly, the number of premature ventricular extrasystoles per hour was significantly decreased (18 +/- 7 vs 2 +/- 1). In three patients, asymptomatic bouts of supraventricular tachycardia, paroxysmal atrial fibrillation, or ventricular tachycardia disappeared during diltiazem therapy. These findings suggest that calcium-blocking drugs may be extremely useful as adjunctive therapy for thyrotoxicosis in the presence of angina, congestive failure, and tachyarrhythmias.

Graves' disease and thyroxine-binding globulin deficiency.

Thyroxine-binding globulin (TBG) deficiency has been frequently described in single patients and in many families. Most people with abnormal TBG concentrations are euthyroid. Cases of Graves' disease and TBG deficit have rarely been reported. We describe the case of a person with Graves' disease and TBG deficiency. Because of this condition, the patient had a misdiagnosis during part of his clinical history, and therefore underwent unnecessary therapy.

Comparison of methimazole, methimazole and sodium ipodate, and methimazole and saturated solution of potassium iodide in the early treatment of hyperthyroid Graves' disease.

We have evaluated three regimens for the rapid control (10 days' therapy) of thyrotoxicosis in hyperthyroid Graves' disease: methimazole (MMI, 40 mg/day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre-treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre-treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI + Na Ipodate-treated patients. The present findings suggest that the rapid control of hyperthyroid Graves' disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate-treated patients.

Cord blood iodothyronine and thyrotropin concentrations in newborns of mothers exposed to povidone iodine in the last trimester.

In the present study, we have evaluated thyroid function in neonates at delivery and in their mothers who used vaginal povidone-iodine (PVP-I) during the last trimester of pregnancy. Newborns and their mothers without a history of iodine exposure, admitted to the same department and residing in the same geographical area served as controls. Maternal serum thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and thyrotropin (TSH) concentrations at delivery were not significantly different between the two groups of pregnant women. Cord blood thyroid hormone concentrations in the newborns of iodine exposed mothers were not significantly different from those in control newborns. In contrast, cord blood TSH concentrations in the neonates of mothers exposed to PVP-I during the last trimester of pregnancy were significantly higher than values in control neonates (p less than 0.05). These data confirm that the fetal thyroid gland, even in the last trimester of pregnancy, does not adapt completely to the inhibitory action of iodine on thyroid hormone synthesis and/or release.

Dopaminergic regulation of fetal growth hormone (GH) secretion: study with maternal administration of bromocriptine.

To investigate the role of dopaminergic pathways on the control of growth hormone (GH) secretion, bromocriptine (BMC), a dopamine agonist drug, was orally administered at the dose of 5 mg to 46 pregnant women during labor whereas 41 received placebo. Maternal blood was obtained before drug administration and at delivery. Cord blood was obtained at delivery. Following the interval of time elapsed between BMC or placebo ingestion and parturition, maternal and cord blood samples were divided in 7 groups for statistical analysis. Cord blood GH resulted significantly higher than the corresponding maternal value (p less than 0.001). No significant change in GH values was observed nor in samples of mothers treated with BMC compared to mothers treated with placebo neither in cord blood samples of the corresponding neonates. These findings indicate that BMC administration does not modify GH secretion in the term fetus.

Goiter size and thyroid function in an endemic goiter area in northern Italy.

Thyroid function was studied in a large number of subjects residing in Varsi, a town in the province of Parma, Italy. In this area, endemic goiter associated with moderate iodine deficiency [59 +/- 3 (+/- SE) microgram iodine/g creatinine], as defined by WHO criteria, affects 65% of the population. Serum T4, T3, thyroglobulin (Tg), and TSH concentrations were measured by RIA in 1218 subjects. The TSH response to TRH was determined in 108 subjects selected randomly from the groups with different grades of goiter. No significant change in serum T4 concentrations was found in subjects with different grades of goiter. Serum T3 concentrations were higher in subjects with the larger goiters. Serum Tg concentration progressively increased, and serum TSH progressively decreased with increasing goiter size. The TSH response to TRH was diminished in subjects with larger goiters. The findings of decreasing serum TSH concentrations and blunted TSH responses to TRH as goiter size increased suggest the possibility of autonomous thyroid function in the larger goiters in subjects residing in this area of moderate iodine deficiency.

Effect of sodium ipodate and iodide on free T4 and free T3 concentrations in patients with Graves' disease.

Graves' hyperthyroid patients were treated daily for 10 days with 1 g sodium ipodate, a cholecystographic agent which exerts a blocking effect on the peripheral conversion of T4 to T3, or with 12 drops of saturated solution of potassium iodide (SSKI). Serum concentrations of free T4 (FT4) and free T3 (FT3) were measured before, during and 5 and 10 days after the administration of each drug. Sodium ipodate treatment induced a rapid decrement of serum FT4 concentrations which declined from 48.9 +/- 6.6 pg/ml to 26.0 +/- 2.7 pg/ml. In these patients serum FT3 concentrations declined from 12.4 +/- 2.0 pg/ml to 2.5 +/- 0.4 pg/ml. Ten days after sodium ipodate withdrawal, serum FT4 and FT3 concentrations returned to baseline values. In patients treated with SSKI serum FT4 concentrations declined from 51.1 +/- 8.8 pg/ml to 11.3 +/- 1.4 pg/ml and FT3 from 15.7 +/- 2 pg/ml to 2.6 +/- 0.3 pg/ml. Moreover, after therapy interruption serum free thyroid hormone concentrations returned to baseline values in these patients. Serum FT4 pattern during the study was not different between the two groups of subjects whereas serum FT3 concentrations were significantly lower in patients treated with sodium ipodate. These findings indicate that SSKI and sodium ipodate are effective in inducing a rapid decrement of serum free thyroid hormone concentrations. Therefore the employment of these drugs may be useful in the treatment of patients with thyroid storm and those undergoing thyroidectomy.

Human foetal prolactin but not thyrotropin secretion is decreased by bromocriptine.

In the adult, dopamine inhibits prolactin (Prl) secretion and less so thyrotropin (TSH) release. Little information is available concerning the role of dopaminergic stimuli in the regulation of TSH and Prl secretion in the term human foetus. The dopamine agonist, bromocriptine (5 mg), or placebo were randomly administered orally to 120 pregnant women during labour. Maternal and foetal cord blood was obtained at parturition and analyzed for Prl, TSH, T4, T3 and rT3 concentrations. Since the time of parturition is unpredictable, maternal and cord blood hormone values were grouped at intervals of time from the time of bromocriptine or placebo administration to delivery. Hormone values were compared between the bromocriptine and placebo groups by two-way analysis of variance (ANOVA). Bromocriptine markedly inhibited maternal serum Prl concentrations compared to values in the placebo treated women (P less than 0.001) and this decrease was more marked as the time interval between bromocriptine administration and delivery increased (P less than 0.001, regression analysis). Cord blood Prl was also significantly lower in newborns whose mothers received bromocriptine (P less than 0.001). Bromocriptine significantly inhibited maternal serum TSH concentrations as compared to values in women treated with placebo (P less than 0.006). In contrast, bromocriptine administration did not affect cord blood TSH concentrations. These findings suggest that bromocriptine crosses the term human placenta and suppresses foetal Prl secretion. In contrast to the small inhibition of TSH secretion in pregnant women, bromocriptine does not affect foetal TSH secretion suggesting that regulation of TSH secretion in the term foetus may not be under dopaminergic control.

Basal and glucose- and arginine-stimulated serum concentrations of insulin, C-peptide, and glucagon in hyperthyroid patients.

The effect of oral glucose and arginine infusion on plasma glucose, glucagon, serum insulin, and C-peptide concentrations was evaluated in 16 patients with hyperthyroid Graves' disease and in ten euthyroid age- and sex-matched normal subjects. Basal plasma glucose concentrations were significantly higher in the hyperthyroid patients, but the plasma glucose response following glucose and arginine administration was similar in the two groups. The insulin response was similar in the hyperthyroid and normal subjects after glucose administration and significantly lower during arginine infusion in the hyperthyroid patients. The serum C-peptide response to both glucose and arginine administration was markedly blunted in the hyperthyroid patients, and the plasma glucagon response to arginine infusion was decreased. These results suggest that pancreatic beta and alpha cell secretory function is impaired in hyperthyroidism as assessed by C-peptide and glucagon secretion following oral glucose administration and arginine infusion. The apparent discrepancy between C-peptide and insulin secretion in the hyperthyroid patients following glucose administration might be due to diminished hepatic extraction of insulin or enhanced metabolism of C-peptide.

Somatostatin inhibits the dermorphin-stimulated thyrotropin release in man.

We have studied the effect of the intravenous administration of somatostatin (SRIF) on the thyrotropin (TSH) response to intravenous dermorphin (D), a new potent opioid peptide, in 7 healthy men. D significantly increased the serum TSH concentration. SRIF administration prior to, during and after D completely prevented the D-induced rise in serum TSH. These results confirm that D stimulates TSH release in man and that this stimulatory effect can be prevented by SRIF.