Percutaneous ethanol injection of thyroglossal duct cysts.

OBJECTIVE: To report the results of treating 3 patients with a thyroglossal duct cyst by percutaneous ethanol injection and compare the outcome with the results of treatment in 17 patients with thyroid cysts. METHODS: The details of the ultrasound-guided injection procedure and the clinical course of the patients are presented, along with review of the literature pertaining to alcohol ablation for thyroglossal duct cysts. RESULTS: Percutaneous ethanol injection was successful in only 1 of 3 patients with thyroglossal duct cysts, in whom the diagnosis was confirmed by ultrasonography, during a 2-year period. During the same 2-year interval, 17 patients with a thyroid cyst received similar treatment. Ablation of the thyroid cyst was successful in all 17 patients, only 1 of whom required a second ethanol injection procedure. CONCLUSION: Percutaneous ethanol injection does not seem to be as effective in treating thyroglossal duct cysts as in treating thyroid cysts. If the presence of a malignant lesion can be excluded, percutaneous ethanol injection may be considered a secondary treatment in patients with thyroglossal duct cysts who cannot undergo a surgical procedure.

American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules.

Thyroid nodules are common and are frequently benign. Current data suggest that the prevalence of palpable thyroid nodules is 3% to 7% in North America; the prevalence is as high as 50% based on ultrasonography (US) or autopsy data. The introduction of sensitive thyrotropin (thyroid-stimulating hormone or TSH) assays, the widespread application of fine-needle aspiration (FNA) biopsy, and the availability of high-resolution US have substantially improved the management of thyroid nodules. This document was prepared as a collaborative effort between the American Association of Clinical Endocrinologists (AACE) and the Associazione Medici Endocrinologi (AME). Most Task Force members are members of AACE. We have used the AACE protocol for clinical practice guidelines, with rating of available evidence, linking the guidelines to the strength of recommendations. Key observations include the following. Although most patients with thyroid nodules are asymptomatic, occasionally patients complain of dysphagia, dysphonia, pressure, pain, or symptoms of hyperthyroidism or hypothyroidism. Absence of symptoms does not rule out a malignant lesion; thus, it is important to review risk factors for malignant disease. Thyroid US should not be performed as a screening test. All patients with a palpable thyroid nodule, however, should undergo US examination. US-guided FNA (US-FNA) is recommended for nodules > or = 10 mm; US-FNA is suggested for nodules < 10 mm only if clinical information or US features are suspicious. Thyroid FNA is reliable and safe, and smears should be interpreted by an experienced pathologist. Patients with benign thyroid nodules should undergo follow-up, and malignant or suspicious nodules should be treated surgically. A radioisotope scan of the thyroid is useful if the TSH level is low or suppressed. Measurement of serum TSH is the best initial laboratory test of thyroid function and should be followed by measurement of free thyroxine if the TSH value is low and of thyroid peroxidase antibody if the TSH value is high. Percutaneous ethanol injection is useful in the treatment of cystic thyroid lesions; large,symptomatic goiters may be treated surgically or with radioiodine. Routine measurement of serum calcitonin is not recommended. Suggestions for thyroid nodule management during pregnancy are presented. We believe that these guidelines will be useful to clinical endocrinologists, endocrine surgeons, pediatricians, and internists whose practices include management of patients with thyroid disorders. These guidelines are thorough and practical, and they offer reasoned and balanced recommendations based on the best available evidence.

Erythropoietin decreases cytotoxicity and nitric oxide formation induced by inflammatory stimuli in rat oligodendrocytes.

In the present study, we investigated whether erythropoietin (Epo) has a protective effect against cytotoxicity induced by interferon-gamma (IFN-gamma ) and lipopolysaccharide (LPS) in primary rat oligodendrocyte cultures. The possible modulatory effect of erythropoietin on inducible nitric oxide synthase (iNOS) mRNA expression and nitrite production were also analyzed. Erythropoietin exerted a significant protective effect against IFN-gamma and LPS-induced oligodendrocyte injury as determined by lactate dehydrogenase assay. Treatment with erythropoietin inhibited the expression of iNOS mRNA and nitrite production resulting from proinflammatory stimulation by IFN-gamma and LPS. These results suggest that erythropoietin has protective effects against inflammatory oligodendrocyte injury in vitro and may play a protective role in neurological disorders characterized by oligodendrocyte death, such as multiple sclerosis.

Erythropoietin attenuates lipopolysaccharide-induced splenic and thymic apoptosis in rats.

Apoptosis of lymphoid tissues during sepsis is well documented and linked to the pathobiology of organ failure and death. In this study, we evaluated the effect of a single dose of recombinant erythropoietin (EPO) on thymic and splenic apoptosis in an endotoxic sepsis model. Young male Wistar rats were divided into 3 groups and administered intraperitoneally (IP) either normal saline; lipopolysaccharide (LPS) 10 mg/kg; or EPO (5000 U/kg) 30 min before lipopolysaccharide. Six hours following LPS administration animals were sacrificed. Apoptosis was assessed by hematoxylin-eosin staining, terminal deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling (TUNEL), and caspase-3 immunostaining. When compared with animals given LPS, animals pretreated with EPO displayed reduced splenic and thymic TUNEL positivity of 44+/-3 (p<0.05) and 143+/-4 (p<0.05) nuclei per high power field (hpf), respectively. Caspase-3 positivity was also significantly reduced in the spleen and thymus, with 31+/-4 (p<0.05) and 93+/-3 (p<0.05) positive stained nuclei per hpf, respectively. Serum nitrite levels were elevated in animals given lipopolysaccharide. Pretreatment with EPO attenuated the increase in nitrite levels; however, this did not reach statistical significance. We conclude that a single dose of recombinant erythropoietin can reduce thymic and splenic apoptosis associated with lipopolysaccharide administration.

What is the risk of pyelonephritis due to desmopressin in rats with cystitis?

The risk of pyelonephritis in children with asymptomatic cystitis or bacteriuria, using desmopressin for primary nonpoliuric nocturnal enuresis, is not known. The aim of this study was to study whether there is a risk of pyelonephritis in rats with cystitis using desmopressin. Wistar rats (n = 28) were divided into four groups of cystitis (groups I-IV). DDAVP (2 microg daily) and saline (0.5 ml daily) were injected intramuscularly for 7 days in groups II and IV and groups I and III, respectively. The urinalysis, urine culture, and 24-h urinary volume (UV(24)) were assessed for all rats on days 1, 3, 5, and 7. In groups III and IV these studies were also performed on days 14, 21, and 28. Serum creatinine was determined on day 7 in all rats and on day 28 in groups III and IV. Groups I and II and groups III and IV were killed at the end of days 7 and 28, respectively. Kidneys and urinary bladders were graded subjectively for inflammation and fibrosis. Inflammation and fibrosis scores in kidney and bladder tissues were not different between DDAVP or saline-injected rats in cystitis groups at weeks 1 and 4. No fibrosis was found in any of the urinary bladders on histological examination. Ascendant pyelonephritis was detected in each of the four rats in DDAVP-administered and saline-administered cystitis groups. The histopathologic scores of the renal tissue with pyelonephritis showed no correlation with the daily urine volume, the positive test results for urine leukocyte esterase with dipstick test, the urine culture results for E. coli based on colony-forming unit per milliliter, or serum creatinine levels in cystitis groups. It was found that the administration of DDAVP to cystitis groups did not increase the risk of ascendant pyelonephritis.

Selective apoptotic behaviour of bovine herpesvirus 1 in an epithelial-like microenvironment.

Apoptosis seems to play an important role in the pathogenic profile of bovine herpesvirus 1 (BHV-1) infection. Nitric oxide (NO) is also important as a signal molecule. In this study, apoptosis was selectively induced in HEp-2 cells in the early stage [1-3 h postinfection (PI)] of BHV-1 multiplication, and this apoptotic process was realised through the caspase-8, and partially through the caspase-3, pathway. BHV-1 infection inhibited staurosporine- (SS-) induced apoptosis only if the SS was added at 6 h PI. The results of this study showed that the 'NO-apoptosis' relation was realised through the caspase-8 pathway ('outer membrane receptor' pathway) at a later stage of infection in apoptosis induced by BHV-1 + SS. Our previous report (Yazici et al., 2004) and this study together showed that BHV-1 might induce and inhibit cell-type-specific pathways of apoptosis.

Study of programmed cell death in bovine herpesvirus 1 infected MDBK cells and the possible role of nitric oxide in this process.

Bovine herpesvirus 1 (BHV-1) is the aetiological agent of many disease types and may predispose infected animals, possibly through immunosuppression, to secondary bacterial infections. Immunosuppression may directly be associated with the induction of programmed cell death (PCD) in some virus-infected cells. Nitric oxide (NO) has an important mediating role against fungal, bacterial, protozoal, viral pathogens and tumours. BHV-1 induced apoptosis between 0.5-3 h postinfection (PI) in MDBK cells; however, between 3 and 6 h PI the PCD response was found to be decreased. It was interesting to see that BHV-I inhibited staurosporin-induced PCD after 1 h. These results showed similarities with those obtained from herpes simplex type I infections in human epithelial cells. PCD response decreased 1 h following caspase-3 inhibitor applications, whereas NO response increased 3 h following infection in the presence of caspase-8 and -9 inhibitory peptides. In conclusion, BHV-1 inhibited the staurosporin-induced apoptotic response and also the NO response. We propose that this inhibition is caspase-3 dependent.

Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and multinodular goiters.

OBJECTIVE: To describe various techniques for performing ultrasound-guided fine-needle aspiration (FNA) biopsy of thyroid nodules, with the intent of shortening the learning curve for physicians with interest in this new procedure. METHODS: General principles and details of biopsy techniques and equipment are reviewed, and personal experience and preferences are described. RESULTS: Real-time ultrasound guidance has technically refined the FNA biopsy technique by decreasing the number of inadequate biopsy specimens and increasing both the specificity and the sensitivity of this procedure. In addition to being cost-effective, well tolerated, and expedient, ultrasound-guided FNA biopsy has emerged as the most accurate method for evaluation of thyroid nodules. The success of the procedure depends on the experience of the person using these techniques. CONCLUSION: For provision of optimal evaluation and management of thyroid nodules, endocrinologists should develop expertise in ultrasound-guided FNA biopsy and understand its advantages over conventional FNA biopsy.

Significance of radioiodine uptake at 72 hours versus 24 hours after pretreatment with recombinant human thyrotropin for enhancement of radioiodine therapy in patients with symptomatic nontoxic or toxic multinodular goiter.

OBJECTIVE: To report the effects of pretreatment with recombinant human thyrotropin (rhTSH) on radioiodine uptake (RAIU) and subsequent radioiodine therapy in 30 patients with symptomatic nontoxic or toxic multinodular goiter. METHODS: Patients received a single injection of rhTSH (0.1 mg in 21 and 0.3 mg in 9 patients). Thyroid function tests were performed before and 72 hours after rhTSH administration. Both 4-hour and 24-hour RAIU studies were done after rhTSH administration and repeated at 48 to 52 hours and at 72 hours, respectively. Then all patients were treated with 30 mCi of 131 I. RESULTS: All study patients experienced symptomatic relief by 1 to 2 months. In addition to the previously reported twofold increase over the baseline RAIU at 24 hours, we found that a second 24-hour RAIU showed a further twofold increase (quadrupling of the RAIU over baseline) at 72 hours after administration of 0.1 mg of rhTSH (from 22% to 43%; P<0.001) and 0.3 mg of rhTSH (from 16% to 37%; P = 0.002), with no significant difference between doses on the RAIU at 24 hours or at 72 hours. Additionally, the RAIU value at 4 hours and 52 hours after administration of 0.1 mg and 0.3 mg of rhTSH revealed a fourfold increase for each dose--from 7% to 28% (P<0.001) and from 5% to 21% (P = 0.002), respectively. CONCLUSION: In patients with symptomatic toxic or nontoxic multinodular goiter, 0.1 mg and 0.3 mg of rhTSH were equally efficacious at inducing a quadrupling of the low or low-normal baseline RAIU values at 72 hours after injection. Subsequent radioiodine therapy alleviated compressive and thyrotoxic symptoms in all 30 treated patients. Future studies should help determine doses of rhTSH and radioiodine therapy that are optimal in iodine-sufficient and insufficient regions of the world.

New applications of thyroid and parathyroid ultrasound.

In the past decade ultrasound has become an essential part of the examination of the thyroid patient. Sonography of the thyroid has been integrated with the history and physical exam and other thyroid tests (especially needle biopsy) to provide valuable information that has improved patient care. Advances in technology and engineering including high-resolution phased-array transducers, color flow and power Doppler have provided much more detail and information regarding thyroid and neck morphology making diagnosis more accurate. This has expanded the use of ultrasound and resulted in development of new ultrasound applications for both the diagnosis and therapy of thyroid and parathyroid disorders. Ultrasound guidance for needle biopsy of thyroid nodules has become routine. It is now being used to confirm the ultrasound diagnosis of parathyroid adenoma by measuring parathyroid hormone obtained with the needle placed in the lesion under ultrasound guidance. Likewise, non-palpable lymph nodes in the neck discovered by ultrasound and suspected of having metastatic carcinoma can be easily biopsied using ultrasound. The material can be submitted for both cytology and peptide analysis to confirm the diagnosis replacing more expensive imaging. Using these same ultrasound guidance techniques, several groups of investigators have developed methods of therapeutic ablation of tissue by chemical or physical means. This may result in an alternative to surgery for certain thyroid, parathyroid, and lymph node lesions.

The American College of Endocrinology and Endocrine University.

Subspecialty training in endocrinology depends in part on local expertise, with fellows having "hands-on" experience in some areas but only "book knowledge" in others. To provide more uniform training in new technologies, The American College of Endocrinology developed Endocrine University, which provides on-site didactic and interactive sessions on thyroid ultrasound, bone densitometry, and other topics over 6 to 7 days. The inaugural event in 2002 was attended by 137 fellows. A second conference in 2003 had capacity attendance of 143. A third course is scheduled for 2004. Fellows pay a token registration fee; the College provides grants to defray the cost of registration, travel, etc. Financial support comes from the College and industry, with plans for an endowment to sustain the program. Fellows value the educational sessions and also the unique opportunity to meet and visit with their peers. This innovative program can serve as a model for other specialties.

Detection of recurrent papillary thyroid carcinoma by thyroglobulin assessment in the needle washout after fine-needle aspiration of suspicious lymph nodes.

To evaluate an efficient method of surveillance of low-risk patients with thyroid cancer, ultrasound was performed on 74 postoperative patients being followed for stage I and II papillary carcinoma. All patients were clinically free of cancer 1-43 years after a total thyroidectomy, and were screened with ultrasound and thyroglobulin (Tg) measurement while taking thyroid hormone suppression. Ultrasound revealed findings suspicious of recurrent disease in the lymph nodes of the neck in 21 patients. An ultrasound-guided fine-needle aspiration (FNA) to obtain material for cytology and Tg analysis was done on these 21 patients, 7 of whom tested positive for Tg in their needle washout. Only 3 of the 7 had detectable Tg in their serum, and only 5 of the 7 had positive cytology. Ultrasound (with FNA-Tg analysis of needle washout of suspicious lymph nodes) is proposed as an effective and efficient method of surveillance in these low-risk patients. Presence of Tg in the needle washout proved to be more sensitive than cytology in diagnosing cancer in the lymph nodes and was not affected by positive anti-Tg antibodies in the serum.

The inversely proportional relation between nitric oxide and lipid peroxidation in atherosclerotic plaque formation in human.

It is known that in the presence of oxygen radicals, anti-atherogenic nitric oxide is converted into pro-atherogenic products, which increase lipid peroxidation. In this study, plaque-free atherosclerotic tissues (n=26), atherosclerotic plaques (n=26) and fetal tissues (n=2; as control) were evaluated. High nitrite, but low malondialdehyde, levels in non-atherosclerotic tissues may show the protective role of nitric oxide from atherosclerosis. In plaque-developed tissues nitrite levels were three times, and lipid peroxidation levels were 10 times, higher than non-plaque developed tissues. In the atherosclerotic plaque forming process, the role of nitric oxide can be discovered according to the lipid peroxidation of tissues. In conclusion, the results of this study show an inversely proportional relation between pro- and anti-atherogenic effects of nitric oxide in the pathogenesis of atherosclerotic vascular diseases.

Utility of recombinant human thyrotropin for augmentation of radioiodine uptake and treatment of nontoxic and toxic multinodular goiters.

OBJECTIVE: To report our results in treating 16 patients with low radioiodine uptake (RAIU) multinodular goiter who had obstructive symptoms or suppressed thyroid-stimulating hormone (TSH or thyrotropin), indicating mild hyperthyroidism. METHODS: Six patients were treated with 0.3 mg of recombinant human thyrotropin (rhTSH) followed by 30 mCi of (131)I 72 hours later. Ten patients were treated with 0.9 mg of rhTSH followed by 30 mCi of (131)I 24 hours later. RESULTS: Of the 16 treated patients, all 10 with compressive symptoms and both patients with weight loss had remission or improvement, as did 1 of 2 patients with atrial fibrillation. All patients with suppressed TSH had a return to normal levels or became hypothyroid. During the next 3 to 7 months, estimated gland size reduction was 30 to 40%. Three of the 6 patients who received 0.3 mg of rhTSH and 6 of the 10 patients who received 0.9 mg of rhTSH, in conjunction with (131)I therapy, ultimately had TSH levels indicative of hypothyroidism. Mild radiation thyroiditis developed in only one patient, and no other side effects occurred. CONCLUSION: The 0.3-mg dose of rhTSH seemed to be as efficacious as the 0.9-mg dose. The greater than fourfold increase in RAIU at 72 hours after administration of rhTSH in our study is more than twofold higher than the 24-hour RAIU results previously reported in normal subjects and in patients with multinodular goiter. These findings have implications for future expanded studies and alternative dosing regimens in treating patients with both multinodular goiter and subclinical hyperthyroidism.