Thyroid carcinoma associated with squamous cell carcinoma of the head and neck: Which policy?

BACKGROUND: Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (HNSCC) is unusual. The clinical management of thyroid cancer in such cases has been debated. METHODS: Between 1975 and 2004, we collected 33 cases. The associated thyroid carcinoma was diagnosed either during or as a consequence of surgery planned as head and neck cancer treatment. RESULTS: The associated thyroid carcinoma was never seen to recur. Five-year overall survival was 41%. Disease-free survival after 40 and 66 months was 11.1% and 5.6%, respectively. CONCLUSIONS: We consider the treatment of thyroid cancer to be complete when the thyroid gland, either with or without lymph nodes, has been included in the specimen obtained during surgery for HNSCC. In the group of cases in which associated thyroid carcinoma was only found within the neck lymph nodes and the thyroid gland has not been treated, we discourage further surgical treatment or radioactive iodine therapy.     

Iatrogenic thyrotoxicosis. Causal circumstances, pathophysiology and principles of treatment. Review of the literature

Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones. In most instances, thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis may also result from a variety of conditions other than thyroid hyperfunction. The present report focuses on the etiologies, pathophysiology and treatment of iatrogenic thyrotoxicosis. Iatrogenic thyrotoxicosis may be caused by 1) subacute thyroiditis (a result of lymphocytic infiltration, cellular injury, trauma or radiation) with release of preformed hormones into circulation, 2) excessive ingestion of thyroid hormones ("thyrotoxicosis factitia"), 3) iodine-induced hyperthyroidism (radiological contrast agents, topical antiseptics or other medications). Among these causes of iatrogenic thyrotoxicosis, that induced by the iodine overload and cytotoxicity associated with amiodarone represents a significant challenge. Successful management of amiodarone-induced thyrotoxicosis requires close cooperation between endocrinologists and endocrine surgeons. Surgical treatment may have a leading yet often underestimated role in view of the potential life-threatening severity of this disease, whereas others kinds of iatrogenic thyrotoxicosis are usually treated conservatively.     

Thyroid disease and thyroid surgery

Thyroid disease remains very common. Knowledge of the implications of these diseases is essential for all anaesthetists as these patients are frequently encountered and may be at risk of complications at any stage, preoperatively, intraoperatively or postoperatively. This article focuses on disorders of thyroid function and their management, thyroid malignancy, surgery of the thyroid gland and the perioperative anaesthetic management of patients undergoing thyroidectomy.     

Thyroid disease and thyroid surgery

Thyroid disease remains very common. Knowledge of the implications of these diseases is essential for all anaesthetists as these patients are frequently encountered and may be at risk of complications at any stage, preoperatively, intraoperatively or postoperatively. This article focuses on disorders of thyroid function and their management, thyroid malignancy, surgery of the thyroid gland and the perioperative anaesthetic management of patients undergoing thyroidectomy.     

Physiology of the pituitary, thyroid and adrenal glands

The pituitary gland is made of clusters of cells producing specific hormones that control growth (growth hormones, GH), thyroid function (TH), adrenal function (ACTH), gonadal function (FSH and LH). In addition, the neurons that join the posterior pituitary (neurohypophysis) secrete vasopressin - the antidiuretic hormone involved in maintaining water balance.The negative feedback loop is the basic mechanism to control the regulation of all endocrine glands. Hypothalamic peptides - releasing hormones (e.g. TRH, CRH) reach the hypophysis via the portal venous system and induce the secretion of specific stimulating hormones (e.g. TSH, ACTH) that drive the end-target endocrine cells to secrete hormones (e.g. thyroid hormones - T3 and T4 or adrenal hormones - cortisol, DHEAS). The plasma levels of these circulating hormones inhibit the pituitary (short feedback) or the hypothalamus (long feedback) and limit the further release of releasing- and stimulating- hormones.The effects of circulating hormones on different tissues are mediated via specific receptors on the cell membrane (e.g. vasopressin receptors), in the cytoplasm (steroid receptor for cortisol) or in the nucleus (e.g. thyroid hormone receptors). Understanding the physiological effects of peripheral hormones helps understanding the mechanisms by which clinical signs and symptoms developed in diseases characterised by excessive hormone secretion (e.g. thyrotoxicosis, Cushing syndrome, phaeochromocytomas) or lack of hormone secretion (e.g. diabetes insipidus).     

Iatrogenic Thyrotoxicosis: Causal Circumstances, Pathophysiology, and Principles of Treatment—Review of the Literature

Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones. In most instances thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis may also result from a variety of conditions other than thyroid hyperfunction. The present report focuses on the etiologies, pathophysiology, and treatment of iatrogenic thyrotoxicosis. Iatrogenic thyrotoxicosis may be caused by (1) subacute thyroiditis (a result of lymphocytic infiltration, cellular injury, trauma, irradiation) with release of preformed hormones into circulation; (2) excessive ingestion of thyroid hormones (“thyrotoxicosis factitia”); (3) iodine-induced hyperthyroidism (radiologic contrast agents, topical antiseptics, other medications). Among these causes of iatrogenic thyrotoxicosis, that induced by the iodine overload and cytotoxicity associated with amiodarone represents a significant challenge. Successful management of amiodarone-induced thyrotoxicosis requires close cooperation between endocrinologists and endocrine surgeons. Surgical treatment may have a leading yet often underestimated role in view of the potential life-threatening severity of this disease, whereas others kinds of iatrogenic thyrotoxicosis are usually treated conservatively.     

Thyroid function after bone marrow transplantation: possible association between immune-mediated thyrotoxicosis and hypothyroidism

BACKGROUND: Thyroid dysfunction after bone marrow transplantation (BMT) has been investigated in many studies, and most posttransplant thyroid disorders are now recognized as a late complication of transplantation. However, these studies mainly focused on late thyroid function after BMT, and we have little information on early changes of thyroid function after BMT. METHODS: We prospectively investigated thyroid function in 57 patients receiving BMT. Serum thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels were determined at least monthly in the first 3 months, once between 3 and 12 months and once in the second year after BMT. RESULTS: During the first 6 months after BMT, 24 and 7 patients were diagnosed as having euthyroid sick syndrome (ETS) and thyrotoxicosis, respectively. Of the 52 patients alive 1 year after transplantation, 9 patients were still diagnosed as having ETS, and 8 patients developed hypothyroidism. Patients with thyrotoxicosis showed similar characteristics, and the high incidence of thyrotoxicosis after BMT is a novel finding. The median for the onset of thyrotoxicosis was day 111 after transplantation. Thyrotoxicosis was transient in all of the patients, but in seven patients hypothyroidism followed, the median onset at 12 months after BMT. Serum thyroglobulin levels were elevated in five patients, and antibodies autoreactive to the thyroid gland were detected in seven patients. CONCLUSIONS: Thyrotoxicosis may be a distinct clinical entity of thyroid dysfunction after BMT and may serve to predict the development of hypothyroidism. Immune-mediated thyroid injury may contribute to the development of posttransplant hypothyroidism.     

甲状腺癌规范化诊治理念更新及其意义

近年来我国甲状腺癌发病率呈现增高的趋势,众多临床工作者都在积极探索诊断和治疗方法的创新,寻求更符合国情的诊治体系。2009年美国甲状腺学会（ATA）指南及2012年《中国甲状腺结节和分化型甲状腺癌指南》的出台,使我国甲状腺癌的诊治逐渐规范,诊治理念也随之发生变化。2014年ATA年会及将于2015年初发布的新版ATA指南,将甲状腺癌诊断方法由单纯使用超声发展为影像定位-细胞病理-分子靶标多层次早期诊断体系。治疗理念也由模糊的手术指证升级为更加依赖精确的疾病分期和风险分层,使甲状腺手术、淋巴结清扫方式更加有章可循。更多的学者不仅关注于提高甲状腺癌病人存活率,减少肿瘤残留或者复发、转移等伴随症状发病风险,而且更加关心低风险甲状腺癌病人尽量保留腺体功能,避免不必要的治疗。     

Thyroid gland volume and serum concentrations of thyroid hormones in chronic renal failure

Thyroid gland volume, ultrasonically determined, and thyroid function were investigated in 40 patients with chronic renal failure (33 of these on hemodialysis) and 40 sex-, age- and weight-matched healthy controls. None had thyroid autoantibodies or a clinically detectable goiter. The median thyroid gland volume was significantly elevated in the uremic patients: 24 ml (range 8-43 ml) compared with the healthy controls 17 ml (range 10-22 ml) (p less than 0.005). The serum concentrations of thyroxine (T4), triiodothyronine (T3), free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were significantly decreased in uremic subjects compared with the controls. The serum concentration of thyrotropin did not differ significantly between patients and controls. None of the thyroid function variables correlated with thyroid gland volume. In conclusion, thyroid gland volume was increased in patients with chronic renal failure. The alterations in thyroid hormone concentrations could, however, not explain this finding.     

86例肿块型桥本病的外科治疗体会

目的总结肿块型桥本病的外科治疗经验。方法回顾性分析1990年1月~2005年12月收治的86例肿块型桥本病的手术治疗情况。结果86例均经手术治疗,术后病理均证实为桥本病。并发甲状腺癌9.3%(8/86)。双侧甲状腺次全或近全切除术后均出现甲状腺功能减退(下称甲减)。结论术中发现甲状腺质脆、水肿较甚,剖面呈新鲜肉芽样改变,特别是与颈前肌群有粘连、伴发甲减或峡部、锥体叶明显肥厚者,应高度怀疑桥本病。重视术中所见和快速切片,既要力求切除所有可疑结节,以免遗漏小癌灶,又要避免盲目切除过多的甲状腺组织。     

Manejo anestésico de una tormenta tiroidea en un paciente afecto de ataxia de Friederich. A propósito de un caso

A 26-year-old patient with Friederich's ataxia with hypertrophic obstructive cardiomyopathy undergoing a total thyroidectomy due to persistent amiodarone-induced thyrotoxicosis (despite high doses of antithyroid drugs and corticosteroids), presented an intraoperative episode suggestive of thyroid storm.Thyroid storm is an endocrine emergency that is associated with high morbimortality. Early diagnosis and treatment, which is of vital importance to improve survival. Treatment includes: symptomatic treatment, treatment of cardiovascular, neurological, and/or hepatic manifestations and thyrotoxicosis, measures to suppress or avoid triggering stimuli, and definitive treatment.     

雌激素及其受体与甲状腺疾病

临床上各种甲状腺疾病发病率女性均高于男性,流行病学数据表明,雌激素与甲状腺疾病的发生有关,研究发现甲状腺疾病组织表达雌激素受体,并且雌激素通过其受体介导不同的分子机制参与甲状腺良恶性疾病的发生,从而可以部分地解释甲状腺疾病的性别差异。     

Management of the thyroid nodule

Thyroid nodules are common and a frequent reason for referral to secondary care. Clinical assessment and investigation should aim to address the possibility of malignancy, functional status of the thyroid and compressive symptoms. A combination of neck ultrasound and fine needle aspiration cytology (FNAC) can usually help establish a plan of management, allowing conservative management of most patients, and surgical treatment for those with suspected or confirmed thyroid cancer. The limitations of FNAC include a relatively high rate of inadequate/non-diagnostic samples, and the inability of cytology to distinguish between benign and malignant follicular neoplasms. Surgery may therefore be required to establish the diagnosis in patients with indeterminate nodules, in addition to its role in treatment for compressive symptoms or thyrotoxicosis.     

Management of the thyroid nodule

Thyroid nodules are common, and a frequent reason for referral to secondary care. Clinical assessment and investigation should aim to address: functional status of the thyroid; exclusion of malignancy; and the presence of other symptoms (e.g. tracheal or oesophageal compression). A combination of neck ultrasound and fine-needle aspiration cytology (FNAC) can usually help establish a plan of management, allowing conservative management of most patients, and surgical treatment for those with suspected or confirmed thyroid cancer. The limitations of FNAC include a relatively high rate of inadequate/non-diagnostic samples, and the inability of cytology to distinguish between benign and malignant follicular neoplasms. Surgery may therefore be required to establish the diagnosis in patients with indeterminate nodules, in addition to its role in treatment for compressive symptoms or thyrotoxicosis.     

Thyroid disrupting chemicals: mechanisms and mixtures

Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis or change circulating or tissue concentrations of THs. For THs, homeostasis is defined as the normal range of THs and TSH in circulation and tissues. TDCs include a wide range chemical structures that act through a variety of mechanisms. Concern about TDCs has increased because of the critical role that thyroid hormones play in brain development. A major uncertainty regarding the endocrine disrupting potential of environmental xenobiotics is the potential for additive, antagonistic or synergistic effects following exposure to mixtures. In addition, there are a number of uncertainties in both interpretation and extrapolation of results from studies of TDC mixtures. Extrapolation of data from laboratory animals to humans is tempered by uncertainty in how the mechanism(s)-of-action of the TDCs may differ between species. The variety of mechanisms by which TDCs alter thyroid homeostasis also yields a difficulty in determining at what level of biological organization to cumulate effects. Should it be at the molecular level, which could be chemical class specific or at the level of a downstream consequence (e.g. circulating hormone levels, brain biochemistry and behaviour) which would be mechanism-independent? To date, the limited data from TDC mixture studies suggest that dose addition is reasonably accurate in predicting the effects on serum T4 concentrations. Assessing the health risks of thyroid disruption by environmental xenobiotics will need to include an improved understanding of how divergent mechanisms alter THs and consequent adverse impacts on nervous system development.     

Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation.

Hypothyroidism in children causes developmental abnormalities in bone and growth arrest, while thyrotoxicosis accelerates growth rate and advances bone age. To determine the effects of thyroid hormones on endochondral bone formation, we examined epiphyseal growth plates in control, hypothyroid, thyrotoxic, and hypothyroid-thyroxine (hypo-T4)-treated rats. Hypothyroid growth plates were grossly disorganized, contained an abnormal matrix rich in heparan sulfate, and hypertrophic chondrocyte differentiation failed to progress. These effects correlated with the absence of collagen X expression and increased parathyroid hormone-related protein (PTHrP) messenger RNA (mRNA) expression. In thyrotoxic growth plates, histology essentially was normal but PTHrP receptor (PTHrP-R) mRNA was undetectable. PTHrP is a potent inhibitor of hypertrophic chondrocyte differentiation that acts in a negative feedback loop with the secreted factor Indian hedgehog (Ihh) to regulate endochondral bone formation. Thyroid hormone receptor alpha1(TRalpha1), TRalpha2, and TRbeta1 proteins were localized to reserve zone progenitor cells and proliferating chondrocytes in euthyroid rat cartilage; regions in which PTHrP and PTHrP-R expression were affected by thyroid status. Thus, dysregulated Ihh/PTHrP feedback loop activity may be a key mechanism that underlies growth disorders in childhood thyroid disease.     

Thyrotoxicosis and thyroiditis

Thyrotoxicosis is a common presentation of thyroid disease. The commonest cause is Graves’ disease. The clinical features including goitre, eye disease, causes and diagnosis of thyrotoxicosis are discussed. Treatment strategies of Graves’ disease include anti-thyroid drugs, radioiodine and thyroidectomy. It is important to adequately prepare patients prior to surgery to reduce the possibility of thyroid storm. The preferred surgical procedure today is a total thyroidectomy, although historically subtotal thyroidectomy was performed. Less common but relevant surgical causes of thyrotoxicosis are also discussed.Thyroiditis (thyroid inflammation) has a variety of causes. Hashimoto's thyroiditis may present with a transient thyrotoxicosis or long term hypothyroidism. Surgery is rarely required. Subacute thyroiditis thought to be secondary to a viral infection can cause a short-term yet marked thyrotoxicosis due to thyroid damage. Other causes such as amiodarone-induced thyrotoxicosis can be more difficult to manage due to the underlying heart disease and may require thyroidectomy.     

Thyrotoxicosis and pregnancy. An analysis of 43 pregnancies in 42 thyrotoxic mothers

During the period 1965-1976, 43 pregnancies in 42 thyrotoxic mothers were seen. Thirty-nine pregnancies in 38 patients were analyzed further. Twenty-six patients (27 pregnancies) were treated with antithyroid agents with (9) or without (17) supplemental thyroid hormone therapy and 5 were subjected to subtotal thyroidectomy. In these groups spontaneous abortion occurred in 4 patients (12.5%), prematurity in 3 (9.4%) and perinatal death in one whereas 25 pregnancies ended at term (78%). Two pairs of twins were born and the number of live children in these 32 pregnancies was 29. Hypothyroidism developed in one patient after operation. Thyroid crisis occurred at delivery in one patient in whom the antithyroid therapy was interrupted before labour. Seven patients were not treated with specific antithyroid therapy. In this group there was one twinbirth, one premature birth, one stillbirth and one child died shortly after birth. Thyroid crises developed at delivery in two mothers. The authors use subtotal thyroidectomy if usual indications for operation are present and antithyroid therapy when the thyroid gland is small and diffuse. Beta-receptor blocking agents are recommended only as adjuncts to the antithyroid therapy. A close surveillance of the patients and the free thyroid hormone level during therapy is important and after thyroidectomy treatment with thyroid hormone is recommended until after delivery.     

A report of four cases of thyroid cancer occurring in thyrotoxicosis and review of the literature

Four cases of thyroid carcinoma occurring in 140 cases of Graves’ disease are presented herein. A standard workup of the patients was done to establish hyperthyroidism and all cases of cancer were diagnosed on receipt of histopathology. There were three cases of papillary carcinoma and one case of follicular carcinoma with one cancer being encountered in the ‘cold’ area of the thyrotoxic gland. The incidence of malignancy in thyrotoxicosis, however, was not found to be higher than that in other thyroid disorders.     

改进法甲状腺叶切除术（附360例报告）

【摘要】 目的 探讨以避开喉上神经、显露喉返神经和保留甲状旁腺的改进法甲状腺叶切除术为主体的甲状腺手术的可行性。方法 对2004年12月至2009年6月广东省人民医院普通外科完成的360例改进法甲状腺叶切除术为主体的甲状腺手术的全部临床资料进行回顾性分析。结果 在根治病变的基础上,共完成360例411侧改进法甲状腺叶切除术为主体的甲状腺手术,最大限度地保留了甲状腺功能,喉返神经显露率达100％,共保留甲状旁腺543个（平均每侧腺叶1.32个）,术后无一例出现喉上神经、喉返神经和甲状旁腺损伤相关并发症。结论 改进法甲状腺腺叶切除术为主体的甲状腺手术能最大限度保留甲状腺功能、降低手术相关并发症发生率、减少术后复发。