Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves’ Disease

Background@#Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease. @*Methods@#Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy. @*Results@#The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months. @*Conclusion@#Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq

BACKGROUND: After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of 131I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis. METHODS: Total 636 patients who received 131I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS. RESULTS: In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts. CONCLUSION: Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Clinical Characteristics and Prognosis of Differentiated Thyroid Carcinoma with Small Foci of Anaplastic Transformation

BACKGROUND AND OBJECTIVES: Anaplastic thyroid carcinoma (ATC) is commonly related with concurrent differentiated thyroid carcinoma (DTC). We aimed to examine the clinicopathologic characteristics, prognosis and gene expression of DTC with anaplastic foci. MATERIALS AND METHODS: Eighteen patients with DTC with anaplastic foci were enrolled in this study. To compare the clinicopathologic characteristics and prognosis of anaplastic foci subjects with conventional ATC or DTC, we additionally included 12 ATC and 1030 DTC patients who diagnosed during same period. Immunohistochemistry was performed to check the gene expression in anaplastic foci and DTC component. RESULTS: In anaplastic foci group, tumor size was larger (2.5±1.3 vs. 1.2±0.9 cm, p=0.001), distant metastasis was more frequent (11.1 vs. 0%, p=0.000) and 1-year survival rate was low (88.9 vs. 100%, p=0.000) than DTC group. In contrast, compared with ATC group, anaplastic foci group showed younger age at diagnosis (50±16 vs. 63±18 years, p=0.039), smaller tumor size (2.5±1.3 vs. 3.8±1.4 cm, p=0.027), less distant metastasis (11.1 vs. 41.7%, p=0.084) and longer 1-year survival rate (88.9 vs. 25.0%, p=0.001). Expression of p53 protein was observed in 100% of anaplastic foci, ATC and 12.5% of papillary thyroid carcinoma component. CONCLUSION: DTC with foci of anaplastic transformation has a worse prognosis than DTC, but a better prognosis than ATC. Our results support that DTC with anaplastic foci was intermediate state from DTC to ATC.

Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: retrospective analysis of Korean multicenter data

BACKGROUND/AIMS: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine-sufficient areas. In this study we evaluated the clinical behavior, prognostic factors and treatment outcomes of FTC and HCC in Korea. METHODS: This multicenter study included 483 patients with FTC and 80 patients with HCC who underwent an initial surgery between 1995 and 2006 in one of the four tertiary referral hospitals in Korea. We evaluated clinicopathological factors associated with distant metastases and recurrence during a median of 6 years of follow-up. RESULTS: HCC patients were significantly older (49 years vs. 43 years; p < 0.001) and had more lymphovascular invasions (22% vs. 14%; p = 0.03) compared with FTC patients. Distant metastases were confirmed in 40 patients (8%) in the FTC group and in two patients (3%) in the HCC group (p = 0.07). Distant metastases were significantly associated with older age, widely invasive cancer and extrathyroidal invasion. Only 14 patients (3%) had recurrent disease and there was no significant difference between FTC and HCC groups (p = 0.38). Recurrence was associated with larger tumor size and cervical lymph node metastasis. CONCLUSIONS: HCC patients were older and had more lymphovascular invasions than FTC patients. However, FTC and HCC patients had similar initial clinicopathological features. Older age, wide invasiveness and extrathyroidal invasion were independent risk factors for predicting distant metastases in FTC and HCC patients.

Revised Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer / 대한이비인후과학회지

No abstract available.

Clinical Characteristics of Langerhans Cell Histiocytosis with Hypothalamo-Pituitary Involvement

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that involves a clonal proliferation of Langerhans cells. LCH has a predilection for hypothalamo-pituitary axis (HPA) dysfunction, and this leads to diabetes insipidus (DI) and/or anterior pituitary dysfunction. Here, we describe the endocrine dysfunction and clinical characteristics of adult patients with LCH and we analyzed the differences between an adult-onset type and a childhood-onset type. METHODS: The data was obtained from a retrospective chart review of the patients with LCH that involved the HPA and who attended Seoul National University Hospital. The patients were classified into the adult-onset type (age at the time of diagnosis > or = 16) and the childhood-onset type (age at the time of diagnosis < or = 15). RESULTS: Ten patients (9 males and 1 female) were diagnosed with LCH involving the HPA. Five patients were classified as an adultonset type and the other five patients were classified as a childhood-onset type. The median follow-up duration was 6 (3-12) years for the adult-onset type and 16 (15-22) years for the childhood-onset type. All the patients presented with DI as the initial manifestation of HPA involvement. Four adult-onset patients and three childhood-onset patients had a multi-system disease. Panhypopituitarism developed in three adult-onset patients and in one childhood-onset patient. The pituitary lesion of the three adult-onset patients had spread to the brain during the follow-up duration. In contrast, the pituitary lesion of the other two adult-onset patients without panhypopituitarism and all the childhood-onset patients had not changed. CONCLUSION: DI was the initial presentation symptom of HPA involvement. Anterior pituitary hormone deficiency followed in some patients. Compared with the childhood-onset patients, the adult-onset patients were more likely to have panhypopituitarism and a poor prognosis.

Association of the Parathyroid Adenoma Volume and the Biochemical Parameters in Primary Hyperparathyroidism

BACKGROUND: The objective of this study is to demonstrate the relationship between the volume of a parathyroid adenoma and the preoperative biochemical parameters in patients undergoing surgery for primary hyperparathyroidism. METHODS: The medical records of 68 patients who underwent a parathyroidectomy for a single parathyroid adenoma were retrospectively reviewed. The volume of the adenoma was estimated using its measured size and a mathematical formula. The correlation between the volume of the parathyroid adenoma and the preoperative laboratory data was assessed. RESULTS: There were no correlations between the estimated volume of the adenoma and the serum calcium, alkaline phosphatase and parathyroid hormone levels. However, the volume of the adenoma was associated with the preoperative level of serum phosphorus. After excluding 5 adenomas with cystic degeneration, a positive correlation was noted between the adenoma volume and the preoperative levels of alkaline phosphatase and parathyroid hormone. CONCLUSION: The preoperative serum levels of calcium, alkaline phosphatase and parathyroid hormone are of limited use to predict the volume of the parathyroid adenoma in patients with a single parathyroid adenoma. We suggest that the absence of a correlation between the volume of the adenoma and the biochemical parameters can be attributed to the cystic degeneration of the adenomas.

Effect of Thyroid Hormone to the Expression of Bile Salt Export Pump

BACKGROUND: Bile acids were important for the regulation of cholesterol homeostasis. Thyroid hormone increased the expression of CYP7A1 (cholesterol 7alpha-hydroxylase), catalyzing the first step in the biosynthesis of bile acids. However, the effect of thyroid hormone on bile acid export has not been previously assessed. The principal objective of this study is to evaluate the effects of thyroid hormone on the bile salt export pump (BSEP). METHODS: Thyroid hormone, T3 (1 mg/g) was administered to male mice via intraperitoneal injection. After 6 hours and 5 days of T3 treatment, we measured serum total and LDL cholesterol and hepatobiliary bile acid concentrations. We assessed the changes associated with bile acid synthesis and transport. In order to evaluate the direct effect of thyroid hormone, we assessed the changes in the levels of BSEP protein after T3 administration in human hepatoma cells. RESULTS: Serum total and LDL cholesterol were reduced and hepatobiliary bile acid concentrations were increased following T3 treatment. Expressions of Cyp7a1 and BSEP mRNA were increased following T3 treatment. The levels of the BSEP protein in the mouse liver as well as in the human hepatoma cells were increased after T3 treatment. CONCLUSION: Thyroid hormone can regulate LDL cholesterol metabolism. It increases bile acid synthesis and the excretion of bile acids via increased BSEP expression.

Malignancy Rate in Sonographically Suspicious Thyroid Nodules of Less than a Centimeter in Size Does Not Decrease with Decreasing Size

We evaluated the malignancy and nondiagnostic rates using fine needle aspiration cytology (FNAC) results in thyroid nodules smaller than 1 cm according to the subdivided size. We retrospectively reviewed the medical records of all subjects underwent FNAC from 2003 to 2009 in our hospital, and 2,756 patients of subcentimeter thyroid nodules with one or more suspicious sonographic features and 7,105 with nodule sized 1 cm or more were included. The malignancy rate was higher in those subcentimeter nodules with suspicious sonographic findings than the nodule sized 1cm or more (19.7% vs 7.8%, P < 0.001). We grouped the nodules based on size with mm interval and observed that the malignancy rate did not decrease but the nondiagnostic results increased its size decrement. When we divided the subjects arbitrarily into a 5 mm or smaller and a 6-9 mm sized group, nondiagnostic cytology findings were reported more frequently in the smaller group (24.3% vs 18.1%, P = 0.001), while the rate of "malignant" was similar (18.3% vs 15.5%, P = 0.123) and the rate of "suspicious for malignancy" was higher (6.8% vs 2.9%, P < 0.001). Therefore when we decide to perform FNAC or not in subcentimeter-sized nodules, we should consider sonographic findings and other clinical risk factors but not the nodular size itself.

Subclinical Hypothyroidism has Little Influences on Muscle Mass or Strength in Elderly People

Sarcopenia, the age-related decline in muscle mass, affects the muscle strength and muscle quality, and these changes decrease functional capacity. The prevalence of thyroid dysfunction increases with age, and changes in thyroid hormone level lead to neuromuscular deficits. We investigated the effects of subclinical hypothyroidism on the muscle mass, strength or quality in elderly people. One thousand one hundred eighteen subjects aged > or =65 yr were randomly selected from a local population and classified into a euthyroid (280 men and 358 women), subclinically hypothyroid (61 men and 75 women), or overtly hypothyroid (7 men and 16 women) group. Although women with subclinical hypothyroidism had a higher prevalence of sarcopenia, defined according to the ratio of appendicular skeletal muscle mass to the square of height, muscle mass, strength or quality did not differ in relation to thyroid status in men or in women. Multivariate analysis including age, diabetes, hypertension, acute coronary event, alcohol, smoking, presence of pain, physical activity score, and lipid profile, showed that thyroid-stimulating hormone level was not associated with muscle mass, strength or quality. In conclusion, subclinical hypothyroidism has little influences on muscle mass, strength or quality, and may not be associated with sarcopenia.

Endothelial Function is Not Changed during Short-Term Withdrawal of Thyroxine in Patients with Differentiated Thyroid Cancer and Low Cardiovascular Risk

PURPOSE: The incidence of differentiated thyroid cancer is increasing in young adults and females in Korea. Some of them experience short-term hypothyroidism in preparation for radioiodine (RAI) therapy, which can have a deleterious effect on the cardiovascular system. However, it is not clear if short-term hypothyroidism induces endothelial dysfunction in patients with low cardiovascular risk. Therefore, the aim of this study was to investigate whether short-term hypothyroidism is associated with endothelial dysfunction in patients with low cardiovascular risk. MATERIALS AND METHODS: To evaluate the effect of short-term hypothyroidism on endothelial function in this group, we recruited fifteen female patients with low cardiovascular risk. We analyzed clinical, biochemical, and cardiovascular parameters at four time points: the last day on levothyroxine (LT4) at their usual thyroid-stimulating hormone (TSH)-suppressive doses (P1), 7 days (P2) & 4 weeks (P3) after withdrawal of LT4, and 8 weeks (P4) after replacement of the previous dose of LT4. A high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual nitroglycerin. RESULTS: During short-term hypothyroidism (P3), serum concentrations of total cholesterol and low-density lipoprotein (LDL)-cholesterol were increased (p < 0.001 for each period). In spite of having worsened lipid states, serum high sensitivity C-reactive protein or flow-mediated vasodilatation, which is one of the surrogate markers of the endothelial function, did not change during short-term hypothyroidism. CONCLUSION: Short-term hypothyroidism induced worsening of metabolic parameters, but not enough to induce the endothelial dysfunction in patients with low cardiovascular risk.

Revised Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Thyroid Cancer

No abstract available.

The clinical characteristics of hypothyroidism after sunitinib treatment in a Korean population / 대한내과학회지

BACKGROUND/AIMS: Hypothyroidism is a common side effect induced by sunitinib. Studies have suggested that sunitinib induces destructive thyroiditis or inhibits iodine uptake by the thyroid or anti-thyroid peroxidase activity. Therefore, the amount of iodine intake will also influence the incidence and clinical characteristics of hypothyroidism after sunitinib treatment. We evaluated the incidence and clinical characteristics of hypothyroidism after sunitinib treatment in Korea, an area where iodine is abundant. METHODS: Between November 2005 and July 2007, 25 patients who had thyroid hormone levels measured during or after sunitinib treatment were included. Of the 25 patients, 13 had thyroid function tests (TFT) because they had symptoms suggesting hypothyroidism and 12 underwent TFT independent of symptoms for screening. RESULTS: All 13 patients who had symptoms suggesting hypothyroidism were hypothyroid (9 overt, 4 subclinical), 6 of 12 patients who had TFT independent of symptoms were hypothyroid (2 overt, 4 subclinical), and two had thyrotoxicosis. Of the 19 hypothyroid patients, the 11 overt hypothyroid patients took longer for a diagnosis of TSH elevation (44.5 vs. 14.8 weeks, p<0.05) and had a greater cumulative sunitinib dose (8050+/-3211 vs. 3718+/-1961 mg, p<0.05) compared with the subclinically hypothyroid patients. At the point of detecting TSH elevation, the TSH level correlated with the period and cumulative dose of sunitinib. CONCLUSIONS: The anticipated incidence of sunitinib-induced hypothyroidism is more than 50%. Compared with previous studies performed in other areas, the iodine intake did not affect the incidence of sunitinib-induced hypothyroidism.

Diagnostic Benefit of Thyroglobulin Measurement in Fine-Needle Aspiration for Diagnosing Metastatic Cervical Lymph Nodes from Papillary Thyroid Cancer: Correlations with US Features

OBJECTIVE: Our goals were to determine the added value of fine-needle aspiration biopsy (FNAB)-thyroglobulin (Tg) measurements over FNAB-cytology alone for diagnosing metastatic nodes, and to determine whether the ultrasound features of lymph nodes can be used to identify lymph nodes that may benefit from FNAB-Tg measurement in patients with papillary thyroid cancer. MATERIALS AND METHODS: We retrospectively evaluated 76 surgically proven cervical lymph nodes. Twenty-nine patients were awaiting surgery and 18 patients had undergone thyroid surgery for papillary thyroid cancer. Ultrasound-guided FNAB and Tg measurements were performed and the ultrasound features were evaluated. RESULTS: The accuracies, sensitivities, and specificities of FNAB-cytology, FNAB-Tg, and combined FNAB-Tg/cytology were 90%, 80%, and 100%; 92%, 95%, and 90%; and 93%, 96%, and 90%, respectively. The diagnostic sensitivity of FNAB-Tg for metastatic nodes was significantly higher than that of FNAB-cytology (p = 0.011). Furthermore, combined FNAB-Tg/cytology significantly increased sensitivity (p = 0.002) and accuracy (p = 0.03) as compared with FNAB-cytology. CONCLUSION: Combined FNAB-Tg/cytology is significantly more sensitive and accurate at detecting metastatic nodes than FNAB-cytology alone. FNAB-Tg was better at diagnosing metastases in small lymph nodes.

Analysis of the markers related with relapse after withdrawal of antithyroid drug in patients with Graves' disease / 대한내과학회지

BACKGROUND: Graves' disease is an organ-specific autoimmune disease that is characterized by thyrotoxicosis, and this is caused by TSH receptor stimulating autoantibody. Antithyroid drugs have been a mainstay of treatment for Graves' patients. Unfortunately, over 50% of patients relapse after their first antithyroid drug treatment and the likelihood of remission cannot be foreseen. Some HLA genes are associated with disease susceptibility, but the association between HLA genes and relapse after drug withdrawal is unclear. In this study, we investigated the association between the HLA genes and the clinical parameters for predicting the clinical outcome of Graves' disease patients. METHODS: We enrolled the patients (n=191) with Graves' disease who were treated by antithyroid drug and who had previously undergone studies for their genetic susceptibility (HLA-DQB1, -DRB1). The success group included patients who maintained a euthyroid state for at least 12 months after withdrawal of drugs. The failure group was defined as the patients who relapsed within 1 year after discontinuation of drug or who could not discontinue their antithyroid drug treatment within 24 months. RESULTS: The rate of treatment failure was 75.4%. There was no significant association between the clinical outcome and the HLA genotyping. The genes that were associated with susceptibility to Graves' disease showed no association with the outcome. A few clinical parameters, such as male patients, severe thyrotoxicosis and high TSH-binding inhibitory immunoglobulin value were related to treatment failure. CONCLUSIONS: Genetic markers such as HLA-DQB1 and DRB1 can not be used, instead of the clinical parameters, to predict relapse after drug withdrawal.

Diagnostic Value of Galectin-3, HBME-1, Cytokeratin 19, High Molecular Weight Cytokeratin, Cyclin D1 and p27(kip1) in the Differential Diagnosis of Thyroid Nodules

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.

Microarray Analysis of Thyroid Stimulating Hormone, Insulin-Like Growth Factor-1, and Insulin-Induced Gene Expression in FRTL-5 Thyroid Cells

To determine which genes are regulated by thyroid stimulating hormone (thyrotropin, TSH), insulin and insulin-like growth factor-1 (IGF-1) in the rat thyroid, we used the microarray technology and observed the changes in gene expression. The expressions of genes for bone morphogenetic protein 6, the glucagon receptor, and cyclin D1 were increased by both TSH and IGF-1; for cytochrome P450, 2c37, the expression was decreased by both. Genes for cholecystokinin, glucuronidase, beta, demethyl-Q 7, and cytochrome c oxidase, subunit VIIIa, were up-regulated; the genes for ribosomal protein L37 and ribosomal protein L4 were down-regulated by TSH and insulin. However, there was no gene observed to be regulated by all three: TSH, IGF-1, and insulin molecules studied. These findings suggest that TSH, IGF-1, and insulin stimulate different signal pathways, which can interact with one another to regulate the proliferation of thyrocytes, and thereby provide additional influence on the process of cellular proliferation.

Clinical Characteristics of Poorly Differentiated Carcinoma of the Thyroid and Comparison of Its Survival to the Tall Cell and Columnar Cell Variants of Papillary Carcinoma / 대한내분비학회지

BACKGROUND: Poorly differentiated carcinoma (PDC) of the thyroid includes tall and columnar cell variants (TCV) of the papillary carcinoma as well as the thyroid carcinoma with trabecular, insular and solid (TIS) growth patterns. There have been a few clinical studies on the PDC of the thyroid. We evaluated the clinical characteristics and the outcome of the PDC. METHODS: We investigated the clinicopathologic features of the thyroid carcinoma with TIS growth patterns (n = 46) and TCV of the papillary carcinoma (n = 14). We investigated the clinical features of ten patients diagnosed as PDC of the thyroid who had been undergone thyroidectomy for well differentiated carcinoma previously and compared these outcome with those of patients primarily diagnosed as PDC of the thyroid (n = 60). RESULTS: The clinical course of the thyroid carcinoma with TIS growth patterns was slightly more aggressive than that of TCV of the papillary carcinoma. However, disease-specific survivals of both cancers were not significantly different. Disease-specific survival was independently correlated with the presence of distant metastasis at diagnosis and high dose radioiodine therapy. The clinical features and outcome of the patients with PDC detected at recurred sites after operation for well-differentiated carcinoma were more aggressive than those diagnosed as PDC of the thyroid. CONCLUSION: The prognosis of the thyroid carcinoma with TIS growth patterns and TCV of the papillary carcinoma were similar. The PDC which was detected after thyroidectomy for well-differentiated carcinoma had worse prognosis than primarily diagnosed as PDC of the thyroid.

A case of papillary thyroid carcinoma arising from sacrococcygeal teratoma / 대한내과학회지

35-year-old female presented with recurrent spinal mass that was resected. Pathologic examination revealed mature teratoma consisting of thyroid follicles, fibroadipose tissue, and mature bony particles. And in this teratoma, focal area of papillary thyroid carcinoma component arising from the normal thyroid follicles were observed. This finding was clearly distinguished from metastasis from thyroid or from other sites. The patients underwent evaluation of thyroid gland, and there was a 1.2 x 1.1 x 2 cm sized nodule. It was well-margined, round, mixed and hyperechoic by sonographic evaluation, and its aspirates contained benign-looking follicular cells only. The patient refused further evaluation or treatment about thyroid cancer, and was discharged. To date, there are only one case of thyroid carcinoma arising from a sacrococcygeal mass containing thyroid tissue components alone (Thyroid 2004:14:548-552). We believe that this patient is a very rare case of thyroid cancer primarily arising from teratoma due to malignant transformation of its thyroid tissue component.

High-Dose Hook Effect in Patients with Macroprolactinoma / 대한내분비학회지

BACKGROUND: Large amounts of antigen may produce false low values on immunoradiometric assays due to the so-called high-dose hook effect. The physicians' awareness of the possibility of the "high-dose hook effect" will prevent preoperative misdiagnosis. The study was designed to identify the frequency and clinical features of patients with pituitary macroadenomas in whom a high-dose PRL hook effect was documented. METHODS: Our retrospective study involved 42 patients with non-functioning pituitary adenomas (tumor diameter >30mm) who underwent transsphenoidal microsurgery from between Jan 1999 to Aug 2004, and 6 patients with non-functioning pituitary adenoma(tumor diameter>30mm) were selected for prospective study from Sep 2003 to Feb 2004. Our retrospective study also involved 13 patients with macroprolactinoma for the comparison of the clinical features. RESULTS: 1) The presence of a high-dose hook effect was retrospectively suggested when the PRL levels increased in 4 out of the 42 patients with non- functioning adenomas(tumor diameter >30mm) after surgery. Post-operative immunohistochemical staining of their pituitary specimens revealed the tumors to be prolactinoma. 2) Prospectively, dilution testing of the specimens obtained before surgery was done in the 6 patients, and one patient presented with a case of the hook effect. The patient's prolactin level was measured at 53.1ng/mL before dilution and this was increased up to 22,600ng/mL upon the 1:1000 dilution. 3) Conclusively, the hook effect was seen in 5 of the 48 patients(10.4%) with non-functioning pituitary adenoma(tumor diameter >30mm) 4) Compared with other 2 patient groups(the macroprolactinoma(N=13) group, and the non-functioning pituitary tumor(N=43) group), the high-dose PRL hook effect is more likely to be observed in male patients with large pituitary tumors. CONCLUSION: In order to avoid the high-dose hook effect, PRL should be assayed at 1:100~1:200 or even higher dilutions of serum from all patients(and especially the male patients) with large pituitary tumors