Absence of allelic imbalance involving EMSY, CAPN5, and PAK1 genes in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) accounts for 80% of all thyroid malignancies, and genetic alterations associated to its etiology remain largely unknown. Chromosomal band 11q13 seems to be one of the most frequently amplified regions in human cancer, providing several candidate genes that need detailed characterization. The aim of our study was to investigate the existence of allelic imbalance at EMSY, CAPN5, and PAK1, as candidate genes within 11q13.5-q14 region using a single nucleotide polymorphism-based analysis. We selected a panel of 9 polymorphisms that were analyzed in 41 thyroid carcinoma samples, their contralateral non-pathological tissue and 178 controls from the general population. We did not detect allelic imbalance at these loci in our series. However, we observed a difference in the EMSY-haplotype distribution among PTC patients when compared to controls (odds ratio=2.00; p=0.02). We conclude that 11q13.5-q14 is not imbalanced in PTC, but there is evidence suggesting that EMSY might be of relevance in PTC etiology.

[The risk factors and bone mineral density in women on long-term levothyroxine treatment]. / Factores de riesgo y densidad mineral ósea en mujeres en tratamiento prolongado con levotiroxina.

BACKGROUND: It is controversial if the long-term treatment with thyroid hormone given at substitutive or suppressive doses has a negative effect on bone metabolism. In previous reports the lack of ultrasensitive TSH assays and densitometers with adequate precision, and the heterogeneity of the patients analyzed could explain these discordant results. PATIENTS AND METHODS: We have assessed bone mineral density (BMD) in 43 premenopausal and 53 postmenopausal women, who underwent near total thyroidectomy and I-131 ablation due to differentiated thyroid cancer, that have been followed up (mean duration, 75.5 [43] months) with suppressive thyroid hormone treatment (mean dose, 170 [42] micrograms) in our hospital. Patients with history of hyperthyroidism were excluded. Lumbar BMD (L2-L4) and BMD in three different sites of hip were measured (dual X-ray densitometry) to determine the contribution of several clinical and risk factors associated with thyroid hormone therapy given to BMD. RESULTS: We have not found significant decrease in BMD at spine or hip when patients were compared with healthy, age and sex matched. Age (inverse correlation) and weight (direct correlation) were the variables mostly influencing BMD). Histologic type of thyroid neoplasia, doses of thyroid hormones, thyroid hormone levels and duration of follow-up, were not associated with changes in BMD. A decrease in calcium intake in postmenopausal and less physical activity in premenopausal women were related with a decreased lumbar BMD. CONCLUSIONS: During long-term treatment of female patients with thyroid hormones, other risk factors should be studied in order to prevent possible loss of bone mass.

Bone changes in pre- and postmenopausal women with thyroid cancer on levothyroxine therapy: evolution of axial and appendicular bone mass.

The effects of suppressive doses of levothyroxine (LT4) on bone mass are controversial. Our aim was to evaluate the effects on axial and appendicular bone mineral density (BMD) and bone metabolism of long-term LT4 suppressive therapy in women by means of cross-sectional and longitudinal studies, and also to assess the potential influence of menopausal status and LT4 dose. Seventy-six women (aged 47 +/- 13 years, 37 pre- and 39 postmenopausal) on suppressive therapy (67 +/- 34 months duration, mean LT4 dose 168 +/- 41 micrograms/day) from our Thyroid Cancer Unit without previous hyperthyroidism or concomitant hypoparathyroidism were studied. Serum TSH, T3 free T4, calcium, phosphorus, alkaline phosphatase, BGP, iPTH and urinary calcium (uCA) were measured. BMD was measured by dual-energy X-ray absorptiometry (DXA) at lumbar spine, femoral neck, Ward's triangle, ultradistal and distal third radius and expressed as a Z-score. In a subset of 27 women aged 46 +/- 15 years (14 pre- and 13 postmenopausal) a second densitometry scan was performed 27 +/- 5 months later. Patients on suppressive therapy showed a small reduction in BMD at the distal third radius (Z-score: -0.77 +/- 0.98; 95% confidence interval: -1.11, -0.44) without differences between pre- and postmenopausal women. Significant relations with the regimen of suppressive therapy and bone turnover markers were detected except at the lumbar spine. In the longitudinal study a significant although mild reduction in femoral neck BMD was found that correlated with prior T3 and iPTH. In conclusion, our data show a small detrimental effect of cautious LT4 suppressive therapy on bone mass assessed by DXA; it remains to be established whether this increases the prevalence of fractures.

[Cushing's syndrome associated with a metastatic medullary carcinoma of the thyroid. A report of 2 cases and a review of the literature]. / Síndrome de Cushing asociado a carcinoma medular de tiroides metastásico. Descripción de dos casos y revisión de la literatura.

An ectopic Cushing syndrome (CS) caused by a medullary thyroid carcinoma (MTC) is an exceptional observation. Two patients are here reported with metastatic MTC, who developed CS two years after the thyroid cancer was diagnosed. A review is also made of clinical and biochemical characteristics of cases with MTC associated with ectopic CS reported in the literature and it is concluded that the cortico-adrenal function in follow-up should be monitored in patients with this type of cancer.

RET/PTC oncogene activation is an early event in thyroid carcinogenesis.

RET/PTC oncogene activation occurs in about 20% of human thyroid papillary carcinomas. However, it is not known yet whether it is an early or late event in the process of thyroid carcinogenesis. Here we demonstrate, by using a combined immunohistochemical and reverse transcriptase-polymerase chain reaction based approach, that RET/PTC activation is present in 11 out of 26 occult thyroid papillary carcinomas analysed. Therefore, we conclude that it represents an early event in the process of thyroid cell transformation.

Both class I and class II HLA antigens are thyroid cancer susceptibility factors.

It has been established that HLA antigens are susceptibility factors for different cancers, including thyroid tumors. However, the diversity and sometimes weak and contradictory associations found have frequently led to the view that the HLA and tumorigenesis links might be the result of statistical errors. However, it has recently been established that it is indeed a currently complex and unexplained but real phenomenon, which may be crucial in preventing several types of cancer. In the present work we have found in a relatively large series of thyroid cancer patients (n = 161) that both HLA class I (B35) and class II (DR11) antigens are susceptibility factors only in the papillary tumor group of patients, B35 association p value is found at the limit of significance (pc(120) = 0.05); the follicular group did not show any HLA association, suggesting that the etiopathogenesis of each type of cancer is different. HLA-B35 and DR11 are not working together to induce tumorigenesis and each of them seems to confer susceptibility by using different pathways or by being markers of distinct neighboring susceptibility genes. DR4 has also been found in 86% (n = 6) of Hürthle cell carcinoma. No association has been found between HLA and disease activity. HLA mechanisms of association to cancer are discussed and a world-wide HLA/tumorigenic study is proposed to obtain a clear picture of the puzzling and controversial susceptibility markers found in different tumors and in different ethnic groups.

Spinal bone mass after long-term treatment with L-thyroxine in postmenopausal women with thyroid cancer and chronic lymphocytic thyroiditis.

This study investigated the effect of long-term treatment upon bone density with L-Thyroxine in postmenopausal women compared with untreated postmenopausal women with climacteric symptoms. We measured spinal bone density in three groups (n = 84) of postmenopausal women: (A) those treated with TSH-suppressive doses of L-Thyroxine for a medium of 5 years after removal of thyroid cancer; (B) those on L-Thyroxine treatment for a median of 9 years after being diagnosed with chronic lymphocytic thyroiditis (CLT); and (C) those with no thyroid disease or other known pathology and without any treatment. There were no differences in dietary calcium intake and daily activity between untreated and L-Thyroxine-treated women. Measurements of bone mineral density were performed at spine level L1-L4 using a dual X-ray densitometer and serum thyroid-stimulating hormone (TSH), thyroid hormones, and bone markers (serum osteocalcin, procollagen I, urinary calcium), and PTH levels were assayed and found to be within normal ranges. Women receiving L-Thyroxine after thyroid cancer had slightly higher FT4 levels compared with women who had CLT and lower TSH levels, with serum T4 and T3 levels normal and similar in both groups. No significant differences were found in spinal bone density after L-Thyroxine treatment between Groups A and B and compared with Group C. Bone loss according to 2 SD below reference standards (age and sex matched) was found in the 12.9% of L-Thyroxine-treated patients versus 22.6% of untreated women. No correlation was found between bone loss and thyroid hormone levels and duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Fine needle aspiration biopsy in the diagnosis of thyroid cancer and thyroid disease.

Fine needle aspiration biopsy (FNAB) performed for diffuse and nodular goiter in the past 5 years, was evaluated in 1399 cases. Surgery was performed on the basis of FNAB cytologic diagnosis that was positive or suggestive of malignancy and/or a suggestive clinical history. Surgery also was performed in cases of cold nodules with negative FNAB results that did not respond to 6 months of suppressive thyroxine therapy. A correlation of cytologic findings with histologic findings was possible in 415 patients who underwent surgery: the evaluation of FNAB results yielded better results when suspicious cytologic findings were considered to be positive (2.4% false-negative, 86.3% sensitivity) rather than negative (6.5% and 65.7%, respectively). FNAB has become a useful procedure in the study and diagnosis of thyroid diseases. It is a simple, rapid diagnostic procedure that may be used to expedite the management of malignant lesions.

Acromegaly and bronchial carcinoid. Effect of removal of the latter.

A patient with a long-standing history of bronchial carcinoid and acromegaly was studied. There was pituitary enlargement with an intrasellar mass (brain computed tomography scan), high basal GH levels, and abnormal GH and other pituitary hormones response to oral glucose and a combined test (LHRH, TRH, insulin). After resection of the bronchial carcinoid, basal GH was normal, GH was normally suppressed during OGTT, pituitary function was within expected normal range, and there was regression of the pituitary tumor together with clinical improvement. These data suggest that the patient's acromegaly was secondary to pituitary stimulation due to the bronchial carcinoid.