Jerzy Sowiński

The role of sonoelastography in acute, subacute and chronic thyroiditis - a novel application of the method

OBJECTIVE Reports on sonoelastography, which provide an objective estimation of tissue elasticity, are scarce in terms of thyroiditis. The aim of this study was to prospectively assess the applicability of sonoelastography in different types of thyroiditis. DESIGN The study assessed and compared the thyroid tissue stiffness in patients with acute thyroiditis (AT), subacute thyroiditis (SAT), and chronic autoimmune thyroiditis (CAT) with healthy control subjects (CS), followed up for 10 weeks. METHODS The study group consisted of two patients with AT, 18 patients with SAT, 18 patients with CAT, and 40 CS matched for age and gender. Sonoelastography was performed at baseline, at a 4-week follow-up during treatment, and at 10 weeks following diagnosis and treatment initiation. RESULTS Thyroid tissue stiffness was higher in SAT at baseline (214.26 ± 32.5 kPa) in comparison with values recorded at a 4-week follow-up (45.92 ± 17.4 kPa) and at 10 weeks following diagnosis and treatment initiation (21.65 ± 5.3 kPa, P < 0.0001). Baseline thyroid stiffness in SAT was higher than that found in CAT (36.15 ± 18.7 kPa, P < 0.0001) and CS (16.18 ± 5.4 kPa, P < 0.0001). In the remission of SAT, thyroid stiffness was lower than that found in CAT (P = 0.006), while it was higher than that in CS (P = 0.0008). No difference was observed between thyroid stiffness in SAT at 4-week follow-up and in CAT. Patients with CAT presented higher thyroid stiffness than CS (P < 0.0001), which was not influenced by L-thyroxine treatment. Thyroid stiffness in patients with AT was 216.6 and 241.9 kPa at baseline; after treatment, it decreased to 17.93 and 85.348 kPa respectively. CONCLUSIONS Sonoelastography may assist in the diagnosis and treatment monitoring of AT, SAT and CAT, as well as in the differentiation of the various types of thyroiditis.

Increased risk of thyroid pathology in patients with thyroid hemiagenesis: results of a large cohort case-control study

OBJECTIVE Thyroid hemiagenesis (THA) is an anomaly resulting from the developmental failure of one thyroid lobe. Etiopathogenesis, clinical significance, and management of patients in whom THA is diagnosed are still a matter of debate. The aim of the study is to provide the first systematic analysis of a large cohort of subjects with THA. DESIGN Forty patients with THA are described in comparison to a control group of 80 subjects with fully developed thyroid gland. METHODS Serum concentrations of thyrotropin (TSH), free thyroxine (FT(4)), free triiodothyronine (FT(3)), and thyroid autoantibodies were measured. In 37 patients, thyroid ultrasonography and Tc-99m thyroid scintiscan were performed, followed by fine-needle aspiration biopsy if indicated. The remaining archival three cases were diagnosed with the use of I-131 scintiscan under basal conditions and after TSH stimulation. RESULTS Patients with THA, while usually clinically euthyroid, presented with significantly higher levels of TSH and FT(3) as well as with higher FT(3)/FT(4) concentration in comparison to the control group. Furthermore, a higher incidence of associated functional, morphological, and autoimmune thyroid disorders in patients with THA was observed when compared to subjects with bilobate thyroid (P<0.05). CONCLUSIONS Our results revealed that individuals with THA are more likely to develop thyroid pathology. The observed high incidence of associated pathologies is presumably due to long-lasting TSH overstimulation. Therefore, THA diagnosis should be followed by systematic observation and adequate levothyroxine treatment in patients with elevated TSH level.

Influence of hormonal replacement therapy on the regional cerebral blood flow in postmenopausal women

OBJECTIVES The aim of this study was evaluation of the influence of hormonal replacement therapy (HRT) on the regional cerebral blood flow in postmenopausal women. METHODS The study group were 20 postmenopausal women, mean age 48.7 years (S.D. +/- 4.9 years). The control group were ten regularly menstruating women, mean age 32.6 years (S.D. +/- 13.2 years). In the studied group we measured the severity of climacteric syndrome with the use of Kupperman index and serum FSH and 17beta-estradiol level with the use of radioimmunological method. Cerebral blood flow was measured at rest using Single Photon Emission Computed Tomography (SPECT). Tracer accumulation evaluation was performed in three slices defined as: cerebellar slice, thalamic slice and ventricular slice, the reference region was delineated in the cerebellum. In ten women with an impairment in the cerebral blood flow at the beginning of the study all the tests were repeated after 12 months of HRT. RESULTS Before HRT mean value of the Kupperman index in the study group was 29.8 points (S.D. +/- 7.1 points); 17beta-estradiol 27 pg/ml (S.D. +/- 2 pg/ml); FSH 56 IU/l (S.D. +/- 49.5 IU/l); SPECT study revealed cerebral blood flow impairment in ten women. In all the studied slices cerebral blood flow was lower in the study group than in the controls. After 12 months of HRT the mean value of the Kupperman index in the study group was 13.2 points (S.D. +/- 2.1 points) (P < 0.05); 17beta-estradiol 44 pg/ml (S.D. +/- 25 pg/ml); FSH 36.4 IU/l (S.D. +/- 57.3 ng/ml); we found cerebral blood flow increase in all studied slices: right cerebellar slice: 5.2%; left cerebellar slice: 4.1%; right thalamic slice: 3.8%; left thalamic slice: 3.3%; right ventricular slice: 7.5%*; left ventricular slice: 6.7%* (* P < 0.05). CONCLUSIONS Cerebral blood flow is lower in the postmenopausal women than in regularly menstruating women. HRT increases regional cerebral blood flow and this improvement coexists with an increase of serum 17beta-estradiol level.

Thyroid hormones affect plasma ghrelin and obestatin levels.

Using radioimmunoassay, the effects of thyroid hormones on plasma total ghrelin (Gh) and obestatin (Ob) concentrations were evaluated in thyrotoxic patients with an excess of thyroid hormones and in hypothyroid patients lacking endogenous thyroid hormones. 24 patients with thyrotoxicosis, 25 hypothyroid patents after total thyreoidectomy performed due to thyroid cancer, and 17 control subjects were examined. Compared with the controls, the ghrelin and obestatin were elevated in hypothyroidism, while they were decreased in thyrotoxicosis. The plasma Gh and Ob levels differ depending on the thyroid function. In thyroid hormones deficiency, plasma Gh and Ob are increased, while in patients with excess of thyroid hormones, the levels of both Gh and Ob are definitely lower. Gh/Ob ratio is higher in hypothyroidism than in control subjects and thyrotoxic patients.

Leptin, Soluble Leptin Receptors, Free Leptin Index, and Their Relationship with Insulin Resistance and BMI: High Normal BMI is the Threshold for Serum Leptin Increase in Humans

Leptin binds to the soluble form of its receptor (sOB-R). Leptin and sOB-R balance (free leptin index, FLI) reflect leptin activity. Leptin correlates with obesity and insulin resistance, but it remains uncertain whether sOB-R and FLI also do the same. Therefore, the aim of this study was to measure serum leptin, sOB-R, and FLI, and evaluate their associations with BMI and insulin resistance. We studied 145 obese and 49 nonobese humans. Obesity was defined according to WHO (BMI >30 kg/m (2)). Results are given as: median and interquartile range, obese vs. nonobese, respectively. Leptin (ng/ml): 30.83, 37.27 vs. 8.31, 10.04; sOB-R (ng/ml): 17.62, 17.05 vs. 27.25, 11.30; FLI: 231.2, 310.0 vs. 30.85, 27.77; HOMA: 5.99, 6.64 vs. 3.92, 4.52; p<0.001 for all. Serum leptin, sOB-R, and FLI did not correlate with insulin resistance separately in obese and nonobese humans. Leptin and FLI, but not sOB-R, were associated with insulin resistance in obese and nonobese subjects examined together. Leptin, sOB-R and FLI differed between obese and nonobese humans, and, except sOB-R, correlated with BMI. In piecewise linear regression, BMI threshold where leptin increased was 24.6 (r=0.5969, p=0.00016 and <0.00001). Leptin and its free index, but not sOB-R, correlate with BMI only in a mixed obese and nonobese human cohort, and not in isolated obese or nonobese groups. Moreover, BMI threshold where leptin starts to increase is 24.6 kg/m (2), which is lower than the cutoff for overweight. Under the conditions, metabolic abnormalities may occur in parallel to much lower BMI levels as expected so far.

FOXE1 Polyalanine Tract Length Polymorphism in Patients with Thyroid Hemiagenesis and Subjects with Normal Thyroid

Background/Aims: Recent studies have pointed to the correlation between FOXE1 polyalanine tract (FOXE1-polyAla) length polymorphism and genetic susceptibility to thyroid dysgenesis causing congenital hypothyroidism. The objective of this study was a first assessment of the role of FOXE1-polyAla expansion in the genetic background of thyroid hemiagenesis (TH). Methods: The group studied consisted of 40 patients with TH, including 6 familial cases and a control group of 89 subjects with a normal thyroid. The polyAla tract and flanking sequence of FOXE1 was amplified using conventional PCR. Subsequently, capillary electrophoresis was performed to estimate the length of products. Results: A short variant of FOXE1-polyAla, containing 12 alanines, was present in 5 control subjects (5.6%), but was not found in TH. The incidence of longer variants (≧16 codons) of FOXE1-polyAla was significantly higher in patients with the familial form of TH in comparison to those with sporadic TH (p = 0.003) and controls (p = 0.005). Conclusions: There is high polymorphic variability of FOXE1-polyAla in both groups. Shorter variants of FOXE1-polyAla are underrepresented in subjects with familial TH. Therefore, FOXE1-polyAla tract expansion may contribute to the molecular background of familial but not sporadic forms of TH. Further studies are still required to confirm such findings.

Sonoelastography in de Quervain Thyroiditis

Sonoelastography is a novel technique, providing an objective estimation of tissue elasticity by measuring the degree of distortion under the application of an external force (1). Recent studies demonstrated exceptional utility of sonoelastography in preoperative evaluation of thyroid nodules because neoplastic transformation is often associated with decreased elasticity of a lesion (1– 4). However, a sonoelastographic picture of de Quervain thyroiditis (dQT) has not yet been described. Herewithin we report cases of dQT in two women, ages 36 and 42 yr, presenting with malaise, pain in the neck, and temperature up to 38 C. Conventional ultrasonography revealed a picture typical for dQT in the first patient, but only minimal changes in the second patient, whereas sonoelastography in both demonstrated markedly decreased elasticity of the affected area (Figs. 1 and 2). Patients were euthyroid (TSH was 0.29 and 0.57 IU/ml, respectively) and had an increased erythrocyte sedimentation rate (48 and 61 mm/h, respectively). The cytological diagnosis of the specimen obtained by fine-needle biopsy was consistent with dQT. Patients were treated with ibuprofen and prednisone, which resulted in total remission. To conclude, obtained results suggest that inflammatory infiltration of thyroid parenchyma in dQT causes decreased thyroid tissue elasticity. Sonoelastography might be useful in diagnosing dQT, selecting regions for biopsy in patients with minimal changes on conventional ultrasonography, as well as in differential diagnosis with Hashimoto’s thyroiditis. Moreover, the coexistence of dQT may affect interpretation of elasticity of concomitant thyroid nodules. Studies on larger groups are required to further assess the usefulness of elastographic evaluation in dQT.

Nicotinamide phosphorybosiltransferase overexpression in thyroid malignancies and its correlation with tumor stage and with survivin/survivin DEx3 expression

Nicotinamide phosphorybosiltransferase (NAMPT) plays an important role in the regulation of cellular growth, angiogenesis, and apoptosis in mammalian cells. NAMPT overexpression has been recently found in colorectal, breast, prostatic, gastric, esophageal, pancreatic cancers, and specific NAMPT inhibitors might be adjuvant therapeutic modalities. In this study, we analyzed NAMPT expression in 40 malignant and in 67 benign thyroid tissue samples using qPCR. We also investigated relationships between NAMPT expression and survivin/survivin splicing variants DEx3 and 2B expressions. NAMPT expression was significantly higher in thyroid cancers (P < 0.0001), and it was positively correlated with tumor stage (P = 0.0012; r = 0.493). NAMPT expression was significantly higher in tumors staged pT3 or pT4 (16 cases) than in tumors staged pT1 or pT2 (24 cases) (P = 0.0106). Metastases to the lymph nodes were found in 12 out of 40 cases, and NAMPT expression was higher in the metastatic group (P = 0.0258). Multifocality was not associated with higher NAMPT expression (P = 0.3451). NAMPT expression in thyroid cancers significantly correlated with survivin and with survivin splice variant DEx3 expressions (P < 0.0001; r = 0.624 and P = 0.0239; r = 0.357, respectively). There was no correlation between NAMPT and survivin 2B expressions (P = 0.3508). This is the first study demonstrating NAMPT overexpression in thyroid malignancies using quantitative RT-PCR. Moreover, it shows that NAMPT is upregulated in patients with more advanced tumor stage and metastatic disease which may prove to be clinically relevant. Further studies are needed to explain the role of NAMPT in thyroid cancer biology and the possible use of NAMPT inhibitors in thyroid cancer.

A cross‐sectional study of thyroid function in 66 patients with bipolar disorder receiving lithium for 10–44 years

An important side effect of lithium therapy is an influence on thyroid function. It is unclear whether there is a significant association between thyroid function and duration of lithium administration. The aim of the present cross‐sectional study was to measure levels of thyroid hormones and antibodies in patients with bipolar disorder receiving lithium for more than ten years.

Primary hyperthyroidism--diagnosis and treatment. Indications and contraindications for radioiodine therapy.

Isotope therapy is one of the methods used in primary hyperthyroidism. The therapy is based on short-range beta radiation emitted from radioactive iodine. Radioiodine administration must always be preceded by pharmacological normalization of thyroid function. Otherwise, post-radiation thyrocyte destruction and thyroid hormones release may lead to hyperthyroidism exacerbation. Indications for radioiodine therapy in Graves-Basedow disease include recurrent hyperthyroidism after thyrostatic treatment or thyroidectomy and side-effects observed during thyrostatic treatment. In toxic nodule, isotope therapy is the first choice therapy. Radioiodine is absorbed only in autonomous nodule. Therefore, it destroys only this area and does not damage the remaining thyroid tissue. In toxic goitre, radioiodine is used mostly in recurrent nodules. Absolute contraindications for radioiodine treatment are pregnancy and lactation. Relative contraindications are thyroid nodules suspected of malignancy and age under 15 years. In patients with thyroid nodules suspected of malignancy, radioiodine treatment may be applied as a preparation for surgery, if thyrostatic drugs are ineffective or contraindicated. In children, radioiodine therapy should be considered in recurrent toxic goitre and when thyrostatic drugs are ineffective. In patients with Graves-Basedow disease and thyroid-associated orbitopathy, radioiodine treatment may increase the inflammatory process and exacerbate the ophthalmological symptoms. However, thyroid-associated orbitopathy cannot be considered as a contraindication for isotope therapy. The potential carcinogenic properties of radioiodine, especially associated with tissues with high iodine uptake (thyroid, salivary glands, stomach, intestine, urinary tract, breast), have not been confirmed.