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In a group of 48 highly selected patients, thyroid surgery was performed on an outpatient basis. It was found to be a safe, cost-effective procedure, convenient for both the patient and the surgeon. Economic factors, although definitely a consideration, were not the compelling reason to perform thyroidectomy in this manner.
The role of thyroid ablation following thyroidectomy for invasive follicular cancer remains controversial. The use of iodine 131 (131I) ablation as adjuvant therapy may facilitate follow-up of patients in whom serum thyroglobulin levels and 131I total body scans are used to detect metastatic disease. It is uncertain if 131I ablation improves survival of patients with follicular thyroid cancer. Thus, the purpose of this study was to determine if survival is enhanced following ablation, with particular reference to those patients with minimally invasive cancer. Between the years 1955 to 1988, 142 patients with invasive thyroid follicular cancer were treated at the British Columbia Cancer Agency, of whom 71 had minimal invasion and no extrathyroidal extension of tumor. In this group of patients, 46 underwent hormone suppression only, 17 had ablation, and 8 had neither. The average follow-up was 9 years and extended beyond 15 years in many patients. Data were entered in a mainframe computer, and Kaplan-Meier survival analysis was used, comparing crude survival, disease-specific survival, and disease-free survival. There was no significant difference between groups. In patients with follicular thyroid cancer and capsular invasion only, 131I ablation does not improve survival compared with patients treated with thyroid hormone suppression only.
The role of thyroid hormones in the maintenance of juvenile refractoriness was studied in the red-legged partridge hybrid, Alectoris graeca chukar. Juvenile partridges, maintained on long (20L:4D) daylengths from hatch, were radiothyroidectomized at 6 1/2 weeks of age, and after 2 weeks were either held on long days or transferred to short (8L:16D) daylengths. Short-day thyroidectomized birds showed no evidence of gonadal growth 18 weeks after thyroidectomy, and neither did euthyroid controls on either short or long daylengths. Thyroidectomized birds held on long daylengths did show significant gonadal growth at this point. Further treatment with low levels of thyroxine (10 micrograms/bird) led to even greater testicular development in long-day thyroidectomized birds, but had no effect on the gonads of short-day thyroidectomized or euthyroid birds.
Experience with 17 children in one kindred with familial medullary carcinoma of the thyroid and pheochromocytoma has demonstrated the utility and validity of periodic provocative testing by calcium infusion or pentagastrin injection in the identification of children with early medullary carcinoma of the thyroid or its premalignant precursor, C-cell hyperplasia. In these 17 patients with two consecutive elevations of calcitonin levels greater than 0.55 ng/ml after stimulation all but one have had MTC or CCH at operation. Total thyroidectomy has been well tolerated and can be performed with an acceptably low incidence of complications in this group of patients.
Radiothyroidectomy protected against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity in rats as assessed by the spleen anti-SRBC plaque-forming cell assay. Thyroxine (T4) replacement therapy partially reversed the effects of thyroidectomy on T4 and triiodothyronine (T3) serum levels, body weight and immune function as well as restored TCDD-induced immunotoxicity. Thus, hypothyroidism induced by TCDD exposure can be viewed as a protective response of the organism to reduce the insult caused by TCDD.
The sequential changes in serum thyroglobulin (Tg), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3) and thyrotropin (TSH) were evaluated in ten patients on whom partial thyroidectomy for nontoxic nodular goiter had been performed. These changes were compared with those in ten patients who underwent upper abdominal surgery (cholecystectomy) under similar anesthesia, and whose calorie and fluid intake was similar until at least 48 hours after surgery. In agreement with previous reports, marked elevations in serum Tg that reached peak concentration (660 to 1350 ng/mL) at one or two hours after the thyroid incision (mean +/- SD; 787 +/- 304.0 ng/mL and 839 +/- 345.7 ng/mL, respectively) were observed. On the other hand, the significant but minimal increases in serum T4 and FT4 were observed at 24 hours (P less than .001 and P less than .001, respectively), 48 hours (P less than .01 and P less than .001, respectively), and 72 hours (P less than .01 and P less than .01, respectively) after the thyroid incision compared with the level just prior to the thyroid incision. Similarly, serum T3 also increased significantly at 6 to 168 hours after the thyroid incision (P less than .01, P less than .05, P less than .05, P less than .05, and P less than .05, respectively). These increases in serum T4, FT4 and T3 were not observed in the cholecystectomy patients. The mean serum TSH levels at 24 to 72 hours after thyroid incision and those at 6 to 48 hours after the abdominal incision were significantly decreased compared with those before thyroid and abdominal incision, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipoprotein(a) [Lp(a)], a lipoprotein that structurally resembles low-density lipoprotein (LDL), contains apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apo B). There exists a close inverse correlation between serum concentrations of LDL or apo B and concentrations of thyroid hormone in patients with thyroid disease, probably due to a change in LDL receptor activity. To clarify the relations between thyroid hormone and Lp(a), we measured serum Lp(a) levels in 13 hyperthyroid subjects before treatment (stage H), during the euthyroid stage induced immediately before performing a subtotal thyroidectomy (stage E), and during the hypothyroid stage observed transiently after the operation (stage L). The mean serum concentration of Lp(a) increased significantly (P = .01) from 9.4 mg/dL in stage H to 26.8 in stage L through the level of 15.5 mg/dL in stage E. There was no significant difference between the mean serum concentration of Lp(a) in these patients in stage E and healthy controls (14.2 mg/dL). There was a low but statistically significant negative correlation between the Lp(a) level and the serum free thyroxine (fT4) concentration (r = .31, P < .05). The results suggest that thyroid hormone is a potent modulator of Lp(a) metabolism.
A patient with bilateral, insidiously developing enlargement of the parotid glands that started 1 year after a total thyroidectomy and ablative radioiodine therapy (200 mCi I131) for papillary carcinoma is presented. The patient displayed prolonged periods of hypothyroidism accompanied by hypercholesterolinemia, notwithstanding hormone replacement therapy. Three years after surgery, parotid and lacrimal gland functions were reduced and fatty degeneration of the parotid parenchyma was demonstrated histologically. The submandibular and sublingual glands were preserved. It is suggested that the hormonal and metabolic derangements are responsible for the glandular dysfunction, rather than a direct effect of iodine on the glands.
Chemical thyroidectomy effectively protected athyroid rats from mortality during 45 days after dosing with 100 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg, whereas 70 to 80% of nonthyroidectomized-euthyroid and thyroidectomized-T4 (thyroxine)-maintained-euthyroid rats died within the same period of time. There was a significant decrease in body weight of all TCDD-treated groups compared to vehicle controls. However, body weight loss was much slower in thyroidectomized-athyroid (congruent to 1 g/day) than in nonthyroidectomized-euthyroid or in thyroidectomized-T4-euthyroid (congruent to 8 g/day) rats. TCDD significantly reduced feed intake in nonthyroidectomized-euthyroid and thyroidectomized-T4-euthyroid rats, but no altered feed consumption was observable in thyroidectomized-athyroid animals. These data indicate that thyroid hormone(s) play(s) an important role in mediating the toxicity of TCDD.
We received the clinical and pathologic features of 22 cases of papillary carcinoma of the thyroid that invaded the trachea and were treated by thyroidectomy and airway resection with or without reconstructive surgery over an interval of 16 years. We studied the fine relationships between lamina propria and lymphatics in the region between the isthmus of the thyroid and the trachea. The manner of invasion of papillary carcinoma of the thyroid was by blunt dissection along blood vessels and collagen fibers oriented perpendicularly to the tracheal lumen between cartilaginous rings. Although lymph node metastases were found in 14 patients (64%), we observed lymphangitic tumor in the tracheal mucosa in only three patients (14%). We devised a staging system for papillary carcinoma of the thyroid based on the extent of invasion of the trachea. Of the 11 patients with stage I, II, or III disease, none of six (0%) followed for 5 years died of thyroid cancer in the 5-year observation period; one patient in this group died later of thyroid cancer. Of the 11 patients with stage IV disease, five of seven (71%) followed for 5 years died of thyroid cancer in the 5-year observation period; one additional patient in this group died later of thyroid cancer.
The changes produced on the whole dendritic morphology of layer III cortical pyramidal neurons by neonatal hypothyroidism, induced in rats by thyroidectomy at 10 days of age (T), as well as those changes related to ageing, have been studied in rats at 40 and 80 days of age. For these purposes, the dendritic structure of these neurons was defined by a set of 10 variables whose measurements were analyzed using multivariate methods. The effect of tyroxine (T4) substitution therapies applied to T rats between 12-40 and 30-80 days of age has been further investigated with the same mathematical methodology. The results obtained from the analyses performed show that hypothyroidism affects both the apical tuft and the basal dendritic arborization of these neurons. The observed damage was similar: a decrease of the total length of the dendritic segments of the apical tuft and the basal arborization. This change, however, was detected in these two different subregions with a different timing. These results seem to reinforce our findings concerning the selective effect of T on different sites of these neurons. On the other hand, 3 morphological changes have been revealed regarding the development of the pyramidal neuron studied: (1) the total length of the apical tuft dendritic segments increases from 40 to 80 days of age; (2) the total length of the basal dendritic segments decreases from 40 to 80 days of age; and (3) the perimeter of the cell body decreases from 40 to 80 days of age. Finally, the results obtained did not allow us to detect any recovery of the damage induced by T, as a consequence of the T4 substitution therapies applied.
This work was undertaken to study the action exerted by thyroid hormones on mitochondria. By day 6 after thyroidectomy, the respective activities of two inner-membrane enzymes--succinate and beta-hydroxybutyrate cytochrome c reductases--had already dropped by 32 and 50%, whereas, in the outer membrane, the activity of rotenone-insensitive NADH-cytochrome c reductase did not change significantly. The decrease in the activity of the inner-membrane enzymes closely followed the disappearance of T3 and T4 from serum. 10 h after administration of 25 micrograms/100 g T3 to thyroidectomized rats, the activity of succinate and beta-hydroxybutyrate cytochrome c reductases and the oxygen consumption rate with succinate or beta-hydroxybutyrate were significantly increased, while, in the outer membrane, the activity of monoamine oxidase and rotenone-insensitive NADH-cytochrome c reductase remained unchanged. In the thyroidectomized rat, L-[3H]leucine incorporation in vivo is diminished in all the liver mitochondrial proteins, and especially in two constituents of MW 19 000 and 28 000. The radioactivity of these two components is also decreased in the normal rat treated with chloramphenicol, a specific inhibitor of mitochondrial protein synthesis. L-[14C]leucine incorporation in isolated liver mitochondria was significantly increased in the thyroidectomized rat, 10 h after T3 treatment. Thus, thyroid hormones have an early and preferential action on the mitochondrial protein synthesizing system and on the inner-membrane enzyme activities.
Modifications of tRNAs in various physiological or experimental conditions are well documented. We have compared isoacceptor tRNAs extracted from target organs (heart and liver) from thyroidectomized rats to those of control animals. Nine liver aminoacyl-tRNAs and eight heart aminoacyl-tRNAs from thyroidectomized and control rats were analysed by RPC-5 chromatography. Quantitative differences were demonstrated in the relative proportions of the various liver tRNA isoacceptors for glycine, lysine, methionine, phenylalanine and serine and of the heart isoacceptor tRNAs for glycine, lysine, methionine, phenylalanine and valine. A qualitative variation was noted only for tRNATyr from the heart and liver of thyroidectomized rats. Isoacceptor tRNAs were obtained at a high resolution using a two-dimensional polyacrylamide gel electrophoresis. Isoacceptor tRNAs corresponding to 14 amino acids for the liver and 12 amino acids for the heart were identified. Although for most of the tRNAs examined the number of isoacceptors remained unchanged, the number of spots corresponding to tRNAGlu and tRNAHis from the liver and tRNAAla from the heart was different after thyroidectomy. Furthermore the change in electrophoretic behaviour of tRNATyr from the liver of thyroidectomized rats suggests a structural modification of one of the isoacceptors in relation to the change in thyroid status. Thus, thyroid hormones appear to induce some modification of the isoacceptor tRNAs in their target organs.
To examine thyroid hormone regulation of c-erbA alpha 2 mRNA expression in the parvo-cellular region of the paraventricular nucleus of the rat hypothalamus (pPVN), quantitative in situ hybridization was performed using 3H-labeled probe complementary to c-erbA alpha 2 mRNA. Thyroidectomy induced a significant increase in the number of silver grains overlying the cytoplasm in the pPVN relative to sham-operated controls. This effect was prevented by daily injection of thyroxine. These results indicate that hypothyroidism induced an increase in cellular c-erbA alpha 2 mRNA level in the pPVN.
1. Experimental models of diabetes are increasingly used for the investigation of cardiovascular complications as well as other complications due to diabetes mellitus. However, animal models have been used in relatively few studies on the myocardial alpha 1-adrenergic responses. Hence, this report describes the effect of alloxan-induced diabetes and insulin-treatment on the alpha 1-adrenergic responses of the isolated rat atria. 2. Alloxan-induced diabetes caused an increase in the alpha 1-adrenergic responses assessed in isolated spontaneously beating rat atria. Both pD2 and alpha E values for phenylephrine, an alpha 1-adrenergic agonist were increased in atria from rats with alloxan diabetes. 3. Insulin treatment (4 IU/kg/day, s.c.) for 10 days normalized the changes in diabetic rat atria. pD2 and alpha E values for phenylephrine were slightly lower than those from control rats. Serum levels of thyroid hormones returned to normal following insulin treatment as well. 4. The effect of insulin on the increased alpha 1-adrenergic responses of rat atria due to alloxan diabetes seems to be related to thyroid hormone metabolism, since thyroidectomy also changed the atrial parameters measured. 5. The finding obtained in this study suggest that experimentally-induced diabetes increases alpha 1-adrenergic sensitivity of the rat atria possibly due to an increased receptor affinity, but these changes can be reversed with insulin treatment.
The effects of congenital hypothyroidism in the late gestation ovine fetus include changes in serotonin concentrations in specific brain areas. To investigate possible ontogenic patterns of changes in 5-HT receptor function, we studied the binding characteristics of [3H]5-HT in the midbrain, hypothalamus and cerebral cortex in the late gestation ovine fetus and young lamb. We compared the binding characteristics of control fetuses to those of thyroidectomized fetuses, with or without thyroxine replacement therapy. In each of the areas examined, age-dependent changes in the receptor density (Bmax) for [3H]5-HT was observed. In cerebral cortex, Bmax was constant from 120 days gestation through the early neonatal period and increased significantly only at 25-30 days after birth. In hypothalamus, [3H]5-HT binding density decreased late in gestation (140-145 days) with a return after birth to values comparable to those at 120-125 and 130-135 days gestation. The midbrain also exhibited a significant age-dependent pattern of altered receptor density with a decrease in the 130-135 and 140-145 day gestational age groups compared to both younger and older lambs. In contrast, the affinity constant (Kd) for [3H]5-HT did not change over the ages evaluated in cerebral cortex or hypothalamus. In the midbrain, however, there was a significant increase in Kd at 1-5 days after birth compared to all other age groups. The ability of fetal thyroidectomy, with or without thyroxine replacement therapy, to alter patterns of [3H]5-HT binding was also tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Oligonucleotide probes were designed to sequences of the rat alpha 1B- and alpha 2B-adrenergic receptor mRNA and used for in situ hybridization histochemistry on tissue sections of kidneys from control and thyroidectomized rats. Both alpha 1B- and alpha 2B-receptor mRNA labelling was demonstrated in proximal tubule cells in the outer stripe of the outer medulla, with tubular rays radiating into the cortex. Thyroidectomy induced a more than 4-fold increase in mRNA for the alpha 1B-receptor in the kidney, whereas no change in alpha 2B-receptor mRNA levels could be demonstrated in thyroidectomized rats as compared to control animals. The results suggest that thyroid hormone plays an important role in regulating expression of alpha 1B-receptors in renal tubule cells.
One theoretical limit of video-assisted thyroidectomy (VAT) was the supposed necessity of general anesthesia. Herein we describe a technique for VAT performed under locoregional anesthesia. Eligibility criteria were small thyroid nodules (<2 cm) in small or normal thyroid glands (thyroid volume < or =20 mL), no previous neck surgery or irradiation, and patient motivation for local anesthesia. VAT using locoregional anesthesia was performed under a superficial cervical block. During the procedure, the patients were completely awake and able to speak with members of the surgical team. Intraoperative and postoperative pain, as evaluated by a visual analogue scale, was usually negligible. No complications occurred. Mean postoperative stay was 26 hours. All of the patients were completely satisfied with the cosmetic result, the procedure, and the surgical outcome. VAT is also feasible and safe under local anesthesia. We are optimistic about the future of this approach, which opens a new frontier for minimally invasive procedures in thyroid surgery.