Cyclooxygenase-2 expression and its association with thyroid lesions

Cyclooxygenase (COX), also known as prostaglandin H synthase, catalyses the formation of prostaglandins from arachidonic acid. It can be expressed in response to various stimuli, such as hormones, mitogens, cytokines, other inflammatory mediators and growth factors. The product of COX-2 activity has been implicated in carcinogenesis by promoting angiogenesis, inhibiting apoptosis, increasing cell invasion and stimulating cell proliferation. It has also been proved that the regular intake of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the risk of developing colon and breast cancers. Thus, it speaks for an important role of COX-2 in growth processes of various types of neoplasms. The connection between COX-2 activity and carcinogenesis has also been examined in human thyroid neoplasms. COX-2 overexpression has been reported in thyroid cancers and also in inflammatory conditions. In consequence there is significant interest whether COX-2 could be of importance as a molecular marker of malignancy in the case of thyroid carcinoma

Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids - early effect

<p>Abstract</p> <p>Introduction</p> <p>Radioiodine (¹³¹I) therapy is widely accepted as an essential part of therapeutic regimens in many cases of differentiated thyroid cancer. Radiation-induced oxidative damage to macromolecules is a well known phenomenon. Frequently examined process to evaluate oxidative damage to macromolecules is lipid peroxidation (LPO), resulting from oxidative damage to membrane lipids. The aim of the study was to examine serum LPO level in hypothyroid (after total thyroidectomy) cancer patients subjected to ablative activities of ¹³¹I.</p> <p>Materials and methods</p> <p>The study was carried out in 21 patients (18 females and 3 males, average age 52.4 ± 16.5 years) after total thyroidectomy for papillary (17 patients) or follicular (4 patients) thyroid carcinoma. Hypothyroidism was confirmed by increased TSH blood concentration (BRAHMS, Germany), measured before ¹³¹I therapy. Activity of 2.8 - 6.9 GBq of ¹³¹I was administered to the patients orally as sodium iodide (OBRI, Poland). Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO (LPO-586 kit, Calbiochem, USA), were measured in blood serum just before ¹³¹I administration (day "0") and on the days 1-4 after ¹³¹I therapy. Sera from 23 euthyroid patients served as controls. Correlations between LPO and TSH or ¹³¹I activity were calculated.</p> <p>Results</p> <p>Expectedly, serum LPO level, when measured before ¹³¹I therapy, was several times higher (p < 0.00001) in cancer patients than in healthy subjects, which is probably due to hypothyroidism caused by total thyroidectomy. However, we did not observe any differences between LPO levels after and before ¹³¹I therapy. LPO did not correlate with TSH concentration. In turn, negative correlation was found between ¹³¹I activity and LPO level on the day "2" after radioiodine treatment.</p> <p>Conclusions</p> <p>Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.</p

Effects of drugs on the efficacy of radioiodine (131|) therapy in hyperthyroid patients

The treatment of hyperthyroidism is targeted at reducing the production of thyroid hormones by inhibiting their synthesis or suppressing their release, as well as by controlling their influence on peripheral tissue (conservative therapy, medical treatment). Radical treatment includes surgical intervention to reduce the volume of thyroid tissue or damage of the mechanisms of thyroid hormone synthesis by radioiodine (131|) administration. Radioiodine (131|) is a reactor radionuclide, produced as a result of uranium decomposition and emission of β and γ radiation. The therapeutic effects of the isotope are obtained by the emission of β radiation. In the paper, the effects of administered drugs (antithyroid, glucocorticosteroids, lithium carbonate, inorganic iodine, β-blockers) on the final outcome of radioiodine therapy in patients with hyperthyroidism are discussed

Do IGF-I concentrations better reflect growth hormone (GH) action in children with short stature than the results of GH stimulating tests? Evidence from the simultaneous assessment of thyroid function

<p>Abstract</p> <p>Background</p> <p>The diagnosis of growth hormone (GH) deficiency (GHD) in short children seems unquestionable when both GH peak in stimulating tests (GHST) and IGF-I concentration are decreased. However, the discrepancies between the results of GHST and IGF-I secretion are observed. It seems purposeful to determine the significance of GHST and IGF-I assessment in diagnosing GHD. The relationship between GH secretion and thyroid function, as well as GH influence on the peripheral thyroxine (T₄) to triiodothyronine (T₃) deiodination, mediated by IGF-I, were identified. Thus, clear differences in thyroid function between GH-deficient and non-GH-deficient subjects should exist.</p> <p>Methods</p> <p>Analysis comprised 800 children (541 boys), age 11.6 ± 3.1 years (mean ± SD), with short stature, in whom two (2) standard GHST (with clonidine and with glucagon) were performed and IGF-I, free T₄(FT₄), free T₃(FT₃) and TSH serum concentrations were assessed. The patients were qualified to the following groups: GHD - decreased GH peak in GHST and IGF-I SDS (n = 81), ISS - normal GH peak and IGF-I SDS (n = 347), low GH - normal IGF-I SDS, and decreased GH peak (n = 212), low IGF - decreased IGF-I SDS, and normal GH peak (n = 160). The relationships among the results of particular tests were evaluated.</p> <p>Results</p> <p>In the groups with decreased IGF-I concentrations (GHD Group and low IGF Group), the more severe deficit of height was observed, together with higher TSH and FT₄but lower FT₃levels than in groups with normal IGF-I concentrations (ISS Group and low GH Group), independently of the results of GHST. TSH, FT₄and FT₃concentrations were - respectively - similar in two groups with decreased IGF-I secretion, as well as in two groups with normal IGF-I levels. Significant correlations were found between patients' height SDS and IGF-I SDS, between FT₃and IGF-I SDS (positive), and between FT₄and IGF-I SDS (negative), with no correlation between GH peak and any of the parameters analyzed.</p> <p>Conclusion</p> <p>The assessment of thyroid function in children with short stature provides the evidence that measurement of IGF-I concentration may be a procedure reliable at least to the some degree in diagnosing GHD as the results of GHST.</p

Limited usefulness of the test of spontaneous growth hormone (GH) nocturnal secretion as a screening procedure in diagnosing GH deficiency in children with short stature

[b]introduction and objective[/b]. In Poland, the assessment of nocturnal GH secretion has gained the status of screening test; however, this procedure is not included in international recommendations. The aim of the study was to assess the accuracy and predictive value of the test of nocturnal GH secretion as a screening procedure in diagnosing GHD, and to check the adequacy of the cut-off value for GH peak in this test on the level of 10 ng/ml. [b]materials and methods. [/b]The analysis comprised the data of 1,000 children with short stature. In all the patients, GH secretion was assessed in a screening test (after falling asleep) and in 2 stimulating tests (reference tests), with simultaneous assessment of IGF-I secretion before stimulating tests. The indices of screening test accuracy, likelihood ratios and predictive values were assessed. The cut-off level of GH peak after falling asleep, ensuring its 95% sensitivity, was calculated in ROC curve analysis. [b]results[/b]. Sensitivity of the screening test was 70.4%, while the specificity – 61.2%, positive likelihood ratio – 1.842, negative likelihood ratio – 0.482, positive predictive value – 0.462, negative predictive value – 0.812. The sensitivity of the test of GH secretion after falling asleep is too low with respect to the requirements for screening test. The ROC curve analysis showed 95% sensitivity for the screening test on the level of 19.0 ng/ml; however, with a very low specificity – below 25%, thus making this test completely useless as a screening procedure. [b]conclusions.[/b] The obtained results strongly contradict the opinion that the assessment of GH secretion after falling asleep should be a screening test in diagnosing GHD in children with short stature

Effects of one-year low-dose growth hormone (GH) therapy on body composition, lipid profile and carbohydrate metabolism in young adults with childhood-onset severe GH deficiency confirmed after completion of growth promotion

Wstęp: Niedobór hormonu wzrostu (GHD) u dorosłych charakteryzuje się między innymi: nieprawidłowym składem ciała, zaburzeniami profilu lipidowego, wczesną miażdżycą oraz pogorszeniem jakości życia. Celem badania było wyodrębnienie pacjentów z ciężkim przetrwałym GHD, spośród grupy pacjentów z rozpoznanym w dzieciństwie, leczonym GHD, oraz ocena korzystnego wpływu kontynuacji terapii GH w życiu dorosłym, a także ustalenie optymalnej dawki GH u młodych dorosłych osób z ciężkim GHD. Materiał i metody: Badaniem objęto 54 osoby (38 mężczyzn), w wieku 17,6 &#177; 1,5 roku z rozpoznanym w dzieciństwie GHD, które uzyskały wzrost ostateczny. U wszystkich pacjentów po okresie - co najmniej - 1 miesiąca od zaprzestania leczenia promującego wzrastanie, przeprowadzono kolejną ocenę wydzielania GH. Ciężką przetrwałą postać GHD stwierdzono u 13 (24%) pacjentów, ale do ponownego leczenia GH włączono tylko 9 osób (4 mężczyzn). Wyniki: Obserwowano korzystny wpływ ponownego włączenia terapii GH na skład ciała (znamienny wzrost beztłuszczowej masy ciała i zmniejszenie tłuszczowej masy ciała), profil lipidowy (znamienne obniżenie stężenia cholesterolu frakcji LDL, jednakże z towarzyszącym nieznamiennym obniżeniem stężenia cholesterolu frakcji HDL) oraz poprawę wyników testów oceniających jakość życia (QoL). Podczas terapii obserwowano nieznamienny wzrost stężenia insuliny na czczo, bez zmian dotyczących stężenia glukozy na czczo oraz z jedynie nieznacznym wzrostem odsetka HbA1c. Obserwowano również zmniejszenie insulinowrażliwości, chociaż stężenie insuliny na czczo i wskaźniki insulinooporności pozostawały w zakresie wartości referencyjnych. Wniosek: Korzystne zmiany dotyczące składu ciała i profilu lipidów oraz QoL przy braku powikłań wskazują na potrzebę leczenia hormonem wzrostu młodych osób dorosłych z ciężkim GHD.Introduction: The symptoms of GH deficiency (GHD) in adults include: abnormalities in body composition, unfavourable lipid profile, early atherosclerosis and impaired quality of life. The aim of the study was the selection of patients with confirmed severe GHD from among all the children treated due to GHD, who could benefit from GH therapy continuation in adulthood and the optimization of GH dosage in young adults with severe GHD. Material and methods: The study group consisted of 54 young adults (38 male), age 17.6 &#177; 1.5 years, with childhood-onset GHD, who had reached final height. At least 1 month after the GH therapy withdrawal, the second evaluation of GH secretion was performed in all the patients. In 24% of patients, permanent severe GHD (PSGHD) was confirmed, but a group of 9 patients (4 male) was involved in renewed GH therapy. Results: The renewed GH therapy gave positive effects, including a significant increase in fat-free mass and a decrease in fat mass, and a significant decrease in LDL-cholesterol, but connected with an insignificant decrease of HDL-cholesterol serum concentration and improved results of quality of life (QoL) assessment. During the therapy, an insignificant increase of fasting insulin was observed, with no change in fasting glucose and only a slight increase in HbA1c percentage. A decrease of insulin sensitivity was also observed, but both insulin secretion and the values of insulin resistance indices still remained within the reference range. Conclusions: The observed positive effects on body composition, lipid metabolism and QoL, together with the absence of adverse events, confirm the indications for GH therapy in young adults with severe GHD

Incidence and predictors of persistent growth hormone deficiency (GHD) in patients with isolated, childhood-onset GHD

Wstęp: U znacznej części pacjentów z rozpoznaną w dzieciństwie somatotropinową niedoczynnością przysadki (SNP) stwierdza się normalizację wydzielania hormonu wzrostu (GH) po osiągnięciu wzrostu końcowego (FH). Celem pracy była ocena częstości i czynników prognostycznych trwałego i przemijającego niedoboru GH u dzieci z rozpoznaną w dzieciństwie izolowaną, nienabytą SNP.Materiał i metody: Analizą objęto 150 dzieci (117 chłopców) z niedoborem wzrostu, z rozpoznaną w dzieciństwie izolowaną, nienabytą SNP, którzy zakończyli terapię GH i uzyskali FH. Przed leczeniem i po osiągnięciu FH oceniono wybrane wskaźniki auksologiczne oraz wydzielanie GH i IGF-I; przed leczeniem zmierzono ponadto wysokość przysadki (PHt).Wyniki: Częstość trwałego niedoboru GH wynosiła 12,0%. Pacjenci z trwałym niedoborem GH mieli przed leczeniem znamiennie niższe wydzielanie GH i niższe stężenia IGF-I, a także uzyskali większy przyrost SDS wysokości ciała (DHSDS) podczas terapii GH niż pacjenci z przemijającym niedoborem GH. Stwierdzono ujemną korelację pomiędzy DHSDS i wydzielaniem IGF-I, przy braku korelacji między DHSDS a wydzielaniem GH. Częstość występowania hipoplazji przysadki u pacjentów z trwałym i przejściowym niedoborem GH nie różniła się znamiennie.Wnioski: Częstość trwałego niedoboru GH u pacjentów z rozpoznaną w dzieciństwie izolowaną, nienabytą SNP jest względnie niska. Pomimo istnienia czynników warunkujących trwały niedobór GH w tej grupie pacjentów, możliwych do zidentyfikowania w momencie rozpoznania SNP w dzieciństwie, u wszystkich pacjentów z tej grupy rozpoznanie niedoboru GH wymaga weryfikacji podczas ponownej diagnostyki przeprowadzonej po uzyskaniu FH. (Endokrynol Pol 2014; 65 (5): 334–341)Introduction: In a considerable proportion of patients with childhood-onset growth hormone (GH) deficiency (GHD), a normalisation of GH secretion at the attainment of final height (FH) is observed. The aim of the present study was to assess the incidence of, and to find out the predictors of, persistent and transient GHD, available in the pre-treatment period, in patients with childhood-onset isolated, non-acquired GHD.Material and methods: The analysis comprised 150 short children (117 boys), with childhood-onset isolated, non-acquired GHD who completed GH therapy and attained FH. Before treatment and at FH (in retesting), auxological parameters were measured, GH peak in stimulation tests and IGF-I concentration were assessed, and pituitary height (PHt) was measured before treatment.Results: The incidence of persistent GHD was 12.0%. The patients with persistent GHD had before treatment significantly lower GH and IGF-I secretion, as well as significantly better increase of height SDS (DHSDS) during GH therapy than those with transient GHD. A negative correlation was observed between DHSDS and IGF-I concentration, but not between DHSDS and GH peak. There was no significant difference in the incidence of pituitary hypoplasia between the patients with persistent and transient GHD.Conclusions: The incidence of persistent GHD in patients with childhood-onset, isolated, non-acquired GHD is relatively low. Despite the fact that the predictors of persistent and transient GHD may be identified in childhood, a diagnosis of GHD should be verified in retesting after the attainment of FH in each case. (Endokrynol Pol 2014; 65 (5): 334–341