Association of Pro-apoptotic Bad Gene Expression Changes with Benign Thyroid Nodules.

BACKGROUND/AIM: This study aimed to investigate the role of the mitochondrial apoptotic pathway in benign thyroid nodules. MATERIALS AND METHODS: Paired samples of nodular and normal tissues were collected from 26 patients with nodular goiters undergoing thyroidectomy. Variable expression of Bcl-2, Bax and Bad genes were evaluated by quantitative PCR. RESULTS: Expression level of Bad gene in nodules was found to be significantly decreased compared to normal tissues (p=0.049). A positive correlation was observed between nodule size and Bad expression levels (correlation coefficient=0.563, p=0.004); and this correlation was stronger in hot nodules (n=18, correlation coefficient=0.689, p=0.003). No significant difference was observed between nodular and normal tissue expressions of Bax and Bcl-2. CONCLUSION: These results suggest that Bad expression correlates with the size of benign thyroid nodules and also its relatively lower expression in nodules, warrant further investigation.

Pendrin expression in nodular and non-nodular thyroid tissues.

INTRODUCTION: Different mechanisms for the expression of pendrin which is an apical iodide transporter have been reported in nodular thyroid tissues compared to normal thyroid. The aim of the present study was to determine the alterations of pendrin expression in nodular and surrounding non-nodular thyroid tissues and clarify the role of pendrin in the functional behaviour of nodular lesions. MATERIAL AND METHODS: Twenty-six nodular and paired non-nodular normal thyroid tissues were collected at the same centre. Patients were divided into two groups based on the function of the dominant thyroid nodule; hot nodules (n = 18) and cold nodules (n = 8). mRNA levels of pendrin were evaluated by quantitative RT-PCR. Pendrin protein expression was determined by immunohistochemical analysis. Results of dominant nodules were compared to non-nodular thyroid tissue of the same patient. RESULTS: No statistically significant difference was found with respect to qualitative and quantitative measurements of pendrin expression between hot and cold nodules. However, percent immunohistochemical staining of pendrin was significantly higher in both hot and cold nodules compared to non-nodular thyroid tissue of the same patients. RT-PCR revealed comparable mRNA levels of pendrin gene between hot nodules and corresponding normal thyroid tissues. However, in cold nodules, significantly decreased mRNA levels of pendrin were observed compared to normal thyroid tissue. mRNA levels of pendrin showed significant positive correlation with TSH in corresponding non-nodular thyroid tissues. CONCLUSIONS: The present study demonstrates that expression of pendrin could not be influenced by TSH in thyroid nodules and expression level of pendrin seems not to have an effect on nodule function.

The impact of age, vitamin D(3) level, and incidental parathyroidectomy on postoperative hypocalcemia after total or near total thyroidectomy.

BACKGROUND: Hypocalcemia caused by transient or definitive hypoparathyroidism is the most frequent complication after thyroidectomy. We aimed to compare the impact of incidental parathyroidectomy and serum vitamin D(3) level on postoperative hypocalcemia after total thyroidectomy (TT) or near total thyroidectomy (NTT). PATIENTS: Two hundred consecutive patients with nontoxic multinodular goiter treated by TT and NTT were included prospectively in the present study. Group 1 (n = 49) consisted of patients with a postoperative serum calcium level < or =8 mg/dL, and group 2 (n = 151) had a postoperative serum calcium level greater than 8 mg/dL. Patients were evaluated according to age, preoperative serum 25-hydroxy vitamin D (25-OHD) levels, postoperative serum calcium levels, incidental parathyroidectomy, and the type of thyroidectomy. RESULTS: Patients in group 1 (n = 49) were hypocalcemic, whereas patients in group 2 (n = 151) were normocalcemic. Preoperative serum 25-OHD levels in group 1 were significantly lower than in group 2 (P < .001). The incidence of hypoparathyroidism was significantly higher following TT (13.5%) than following NTT (2.5%) (P < .05). The risk for postoperative hypocalcemia was increased 25-fold for patients older than 50 years, 28-fold for patients with a preoperative serum 25-OHD level less than 15 ng/mL, and 71-fold for patients who underwent TT. Incidental parathyroidectomy did not have an impact on postoperative hypocalcemia. The highest risk of postoperative hypocalcemia was found in the patients with all of the above variables. CONCLUSIONS: Age, preoperative low serum 25-OHD, and TT are significantly associated with postoperative hypocalcemia. Patients with advanced age and low preoperative serum 25-OHD levels should be placed on calcium or vitamin D supplementation after TT to avoid postoperative hypocalcemia and decrease hospital stay.

Thyroid metastasis of endometrial carcinosarcoma associated with Graves' disease.

A 54-year-old woman who had undergone total abdominal hysterectomy and bilateral adnexial resection because of endometrial carcinosarcoma presented with thyrotoxicosis, rapidly enlarging neck mass, right cervical tenderness to the ears, palpitation, swelling and heat intolerance, 3 years after the operation. Her serum thyroid hormone levels confirmed hyperthyroidism. Triiodothyronine/thyroxine ratio was 18. The thyroid antibodies were markedly elevated. A thyroid scan showed a cold area corresponding to the thyroid nodule, with high radioiodine uptake in the remaining thyroid tissue. Antithyroid drugs were started to control the hyperthyroidism. In our patient, who had a history of malignancy, the rapidly enlarging neck mass was considered as metastasis to the thyroid gland. The patient underwent bilateral total thyroidectomy. Histopathological examination demonstrated findings compatible with Graves' disease on the left and a carcinosarcoma metastasis on the right thyroid lobe. We suggest that both destructive thyroiditis and Graves' disease contributed to our patient's thyrotoxicosis. Metastatic thyroid carcinoma and destructive thyroiditis should be considered in patients with rapidly enlarging neck mass and a prior history of visceral malignancy.

An unusual patient with hypercalciuria, recurrent nephrolithiasis, hypomagnesemia and G227R mutation of Paracellin-1. An unusual patient with hypercalciuria and hypomagnesemia unresponsive to thiazide diuretics.

A 19-year-old female patient with hypercalciuria and recurrent nephrolithiasis/urinary tract infection unresponsive to thiazide type diuretics is presented. The patient first experienced nephrolithiasis at the age of 4 years. Afterwards, recurrent passages of stones and urinary tract infection occurred. On diagnostic evaluation at the age of 19 years, she also had hypocitraturia and hypomagnesemia. Her serum calcium concentrations were near the lower limit of normal (8.5-8.8 mg/dl; normal range: 8.5-10.5), her serum magnesium concentrations were 1.15-1.24 mg/dl (normal range: 1.4-2.5) and urinary calcium excretion was 900 mg/24 h. PTH concentrations were increased (110-156 pg/ml; normal range: 10-65). We tried to treat the patient with hydrochlorothiazide at a dose of 50 mg/day. During treatment with thiazide diuretics, PTH concentration remained high and the patient had recurrent urinary tract infections and passages of stones. Serum magnesium concentration did not normalize even under the parenteral magnesium infusion. Her mother had a history of nephrolithiasis 20 years ago. Severe hypomagnesemia in association with hypercalciuria/urinary stones is reported as a rare autosomal recessive disorder caused by impaired reabsorption of magnesium and calcium in the thick assending limp of Henle's loop. Recent studies showed that mutations in the CLDN16 gene encoding paracellin-1 cause the disorder. In exon 4, a homozygous nucleotide exchange (G679C) was identified for the patient. This results in a point mutation at position Glycine227, which is replaced by an Arginine residue (G227R). The mother was heterozygous for this mutation. G227 is located in the fourth transmembrane domain and is highly conserved in the claudin gene family. This case indicates the pathogenetic role of paracellin-1 mutation in familial hypomagnesemia with hypercalciuria and nephrocalcinosis and further underlines the risk of stone formation in heterozygous mutation carriers.