Determination of glucose cut-off points for optimal performance of glucagon stimulation test.

Introduction: The glucagon stimulation test (GST) is widely used to assess growth hormone (GH) and cortisol secretion, nevertheless the precise mechanisms underpinning these hormonal responses remain unclear. We have endeavoured to explore the relationship between glucose and insulin fluctuations during GST and their impact on GH and cortisol secretion. Subjects and methods: We retrospectively studied 139 subjects (mean age 35.5 ± 15.1 years, BMI 26.6 ± 6.61 kg/m²), including 62 individuals with a history of pituitary disease (27 with an intact adrenal axis) and 77 healthy controls. Standard dose intramuscular GST was performed in all subjects. Results: Once BMI and age were excluded from multivariate model, the nadir of glucose concentration during GST was the sole variable associated with maximal GH secretion (ΔGH, p<0.0003), while neither glucose/insulin peak, nor Δglucose/Δinsulin concentrations contributed to ΔGH. 100% pass rate for GH secretion above 3 ng/ml or 1.07 ng/ml cut-offs was observed for glucose concentrations at, or below 60 mg/dl (3.33 mmol/l) (for Controls), or 62 mg/dl (3.44 mmol/l) (for Controls and patients with an intact adrenocortical axis). Such low glucose concentrations were obtained, however, only in about 30% of studied individuals. Conversely, cortisol secretion did not correlate with glucose or insulin fluctuations, suggesting alternative regulatory mechanisms. Conclusions: This study reveals that glucose nadir below 3.33 mmol/l is the only biochemical biovariable linked with optimal GH secretion during GST, whereas mechanisms responsible for cortisol secretion remain unclear. We emphasize the importance of glucose monitoring during GST to validate GH stimulation and support clinical decisions in GH deficiency management.

The Increased FCRL mRNA Expression in Patients with Graves' Disease Is Associated with Hyperthyroidism (But Not with Positive Thyroid Antibodies).

Background: Fc receptor-like (FCRL) genes play a role in the immune system by encoding proteins that function as receptors on the surface of immune cells. The clinical significance of FCRL gene expression in Graves' Disease (GD) and Graves' Orbitopathy (GO) remains unclear. We evaluated the expression of FCRL 2, 3, 4 mRNA in patients with GD and GO and its role in the development and activity of these diseases. Methods: Peripheral blood samples from patients with GD (n = 24) or GO (n = 49) hospitalized in the Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, were collected. Expressions of FCRL2, FCRL3 and FCRL4 were measured by real-time PCR. Results: FCRL3 expression was higher in patients with GD compared to GO (1.375 vs. 0.673, p = 0.004) and, specifically, active GO (1.375 vs. 0.639, p = 0.005). Regarding FCRL4, mRNA expression was higher in GD compared to Control (3.078 vs. 0.916, p = 0.003), GO (3.078 vs. 1.178, p < 0.001), active GO (3.078 vs. 1.186, p = 0.002) and inactive GO (3.078 vs. 1.171, p = 0.008). In turn, FCRL4 mRNA expression was higher in patients with hyperthyroidism (subclinical + overt) than in euthyroid patients (2.509 vs. 0.995, p = 0.001 when the whole group of individuals was considered; 2.509 vs. 1.073, p = 0.004 when GO + GD was considered). Conclusions: The increased FCRL mRNA expression in patients with GD is associated with hyperthyroidism (but not with positive TSHRAbs), and our study is the first one to confirm this relationship.

Polish diagnostic and therapeutic recommendations for adrenocortical carcinoma.

Advances in the diagnosis and treatment of adrenocortical carcinoma (ACC), along with the development of new therapeutic and diagnostic methods, have prompted a team of experts to formulate the first Polish guidelines for managing ACC. This article presents the diagnostic and therapeutic recommendations resulting from the discussion of specialists from various medical specialities, who participated in a series of online meetings aimed at developing consistent and effective recommendations under the National Oncology Strategy. These guidelines aim to optimise ACC treatment in Poland through coordinated efforts of multidisciplinary specialist teams, ensuring an effective and modern approach.

Indole-3-Butyric Acid, a Natural Auxin, Protects against Fenton Reaction-Induced Oxidative Damage in Porcine Thyroid.

We present results on the potential protective antioxidant properties of indole-3-butyric acid. Indole-3-butyric acid is an indole derivative defined as an auxin and widely known as a plant growth regulator. It naturally occurs in Arabidopsis thaliana, which is applied as a model plant in genetic studies. Oxidative damage to membrane lipids (lipid peroxidation; LPO) in porcine thyroid homogenates was induced by Fenton reaction substrates (Fe2+ + H2O2). Iron (Fe2+) was used in very high concentrations of 1200, 600, 300, 150, 75, 37.5, 18.75, 9.375, 4.687, and 2.343 µM. Indole-3-butyric acid (10.0, 5.0, 2.5, 1.25, and 0.625 mM) was applied to check whether it prevents the above process. The LPO level, expressed as malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration, was measured spectrophotometrically. Expectedly, Fenton reaction substrates, in a Fe2+ concentration-dependent manner, increased LPO level, with the lowest effective concentration of iron being 9.375 µM. In the case of almost all concentrations of indole-3-butyric acid, this auxin has exhibited very promising antioxidant protection, with the most effective concentrations being 10.0 and 5.0 mM; however, as low concentrations of indole-3-butyric acid at 1.25 mM was still effective. Indole-3-butyric acid used alone did not change the basal level of LPO, which is a favourable effect. To summarise, indole-3-butyric acid has protective antioxidant properties against experimentally induced oxidative damage to membrane lipids in the thyroid, and this is for the first time documented in the literature. This compound can be considered a natural protective agent present in plants, which can serve as a dietary nutrient.

Protective Effects of Melatonin against Carcinogen-Induced Oxidative Damage in the Thyroid.

Melatonin, primarily synthesized in the pineal gland, plays a crucial role in regulating circadian rhythms and possesses significant antioxidative properties. By neutralizing free radicals and reducing oxidative stress, melatonin emerges as a promising agent for the prevention and therapy of many different disorders, including cancer. This paper reviews the relationship between the thyroid gland and melatonin, presenting experimental evidence on the protective effects of this indoleamine against oxidative damage to macromolecules in thyroid tissue caused by documented carcinogens (as classified by the International Agency for Research on Cancer, IARC) or caused by potential carcinogens. Furthermore, the possible influence on cancer therapy in humans and the overall well-being of cancer patients are discussed. The article highlights melatonin's essential role in maintaining thyroid health and its contribution to management strategies in patients with thyroid cancer and other thyroid diseases.

Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice.

Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging - the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1df gene mutation, these mice exhibit a deficiency in growth hormone (GH), prolactin, and TSH, alongside extremely low circulating IGF-1 levels. Intriguingly, while surgical removal of visceral fat (VFR) enhances insulin sensitivity in normal mice, it paradoxically increases insulin resistance in Ames dwarfs. This suggests an altered profile of factors produced in visceral fat in the absence of GH, indicating a unique interplay between adipose tissue function and hormonal influences in these models. Our aim was to analyze the gene expression related to lipid and glucose metabolism, insulin pathways, inflammation, thermoregulation, mitochondrial biogenesis, and epigenetic regulation in the visceral (perirenal and epididymal) adipose tissue of Ames dwarf and normal mice. Our findings reveal an upregulation in the expression of key genes such as Lpl, Adrß3, Rstn, Foxo1, Foxo3a, Irs1, Cfd, Aldh2, Il6, Tnfα, Pgc1α, Ucp2, and Ezh2 in perirenal and Akt1, Foxo3a, PI3k, Ir, Acly, Il6, Ring1a, and Ring 1b in epididymal fat in df/df mice. These results suggest that the longevity phenotype in Ames dwarfs, which is determined by peripubertal GH/IGF-1 levels, may also involve epigenetic reprogramming of adipose tissue influenced by hormonal changes. The increased expression of genes involved in metabolic regulation, tumor suppression, mitochondrial biogenesis, and insulin pathways in Ames dwarf mice highlights potentially beneficial aspects of this model, opening new avenues for understanding the molecular underpinnings of longevity and aging.

Exogenous Melatonin Protects against Oxidative Damage to Membrane Lipids Caused by Some Sodium/Iodide Symporter Inhibitors in the Thyroid.

The thyroid gland is the primary site of sodium/iodide symporter (NIS), an intrinsic plasma membrane protein responsible for the active uptake of iodine, which is indispensable for thyroid hormone synthesis. Since exposure of the thyroid to NIS inhibitors can potentially have harmful effects on the entire organism, it is important to investigate the potential protective effects of known antioxidants, such as melatonin and indole-3-propionic acid (IPA), against pro-oxidative action of classic NIS inhibitors. The study aimed to check if and to what extent melatonin and IPA interact with some confirmed NIS inhibitors regarding their effects on oxidative damage to membrane lipids in the thyroid. For comparison with the thyroid gland, in which NIS is typically present, the liver tissue-not possessing NIS-was applied in the present study. Thyroid and liver homogenates were incubated in the presence of tested NIS inhibitors (i.e., NaClO3, NH4SCN, KSeCN, KNO3, NaF, KClO4, and BPA) in different ranges of concentrations with/without melatonin (5 mM) or IPA (5 mM). The malondialdehyde+4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. NaClO3 increased LPO in the thyroid and in the liver, but these pro-oxidative effects were not prevented by either melatonin or IPA. Instead, pro-oxidative effects of NH4SCN observed in both tissues were prevented by both indole substances. KSeCN and NaF increased LPO only in the thyroid, and these pro-oxidative effects were prevented by melatonin and IPA. KNO3, KClO4, and BPA did not increase LPO, which can be due to their low concentrations resulting from restricted solubility. In conclusion, as melatonin prevented oxidative damage to membrane lipids in the thyroid caused by some sodium/iodide symporter inhibitors, this indoleamine shoud be considered as a potential protective agent when produced appropriately in living organisms but also as an exogenous substance recommended to individuals overexposed to NIS inhibitors.

The Protective Effect of Exogenous 17ß-Estradiol against Experimentally Induced Oxidative Damage to Membrane Lipids Is Stronger in Male vs. Female Porcine Thyroids: Preliminary Results.

It is well-known that thyroid diseases are more prevalent in women than in men. The contribution of sex hormones may explain such disparity. The aim of this study was to check if there are any differences between sexes concerning the effects of 17ß-estradiol on oxidative damage to membrane lipids (lipid peroxidation) in porcine thyroid homogenates under basal conditions and in the presence of Fenton reaction (Fe2+ + H2O2→Fe3+ + •OH + OH-) substrates. We observed that 17ß-estradiol did not change the basal level of lipid peroxidation (measured spectrophotometrically as concentrations of malondialdehyde + 4-hydroxyalkenals) in thyroid homogenates, and no differences were found between sexes. The lipid peroxidation level in response to Fe2+ + H2O2 plus 17ß-estradiol was lower in male thyroids. In turn, in male thyroids, 17ß-estradiol reduced experimentally induced lipid peroxidation in as low of a concentration as 0.1 µM, whereas in female thyroids the lowest effective concentration of 17ß-estradiol was 10 µM, i.e., 100 times higher than in males. In conclusion, the protective effects of exogenous 17ß-estradiol against experimentally induced oxidative damage to membrane lipids is stronger in male than in female thyroids. Our observation suggests that female tissue is less sensitive to the protective effects of exogenous 17ß-estradiol. This sexual dimorphism of oxidative processes in the thyroid may constitute one of the mechanisms of the different prevalence of thyroid diseases in women and in men.

Decreased mannan-binding lectin level in adults with hypopituitarism; dependence on appropriate hormone replacement therapies.

Background: Mannan-binding lectin (MBL) is a main component of the lectin pathway of the complement system. Although there are some studies showing links between endocrine and immune systems, the ones concerning hypopituitarism are limited. The aim of this study was to check whether there is any association between blood MBL level and pituitary hormone deficiencies and whether this relationship is affected by appropriate hormone replacement therapies. Methods: One hundred and twenty (120) inpatients, aged 18-92, were divided into two main groups, i.e. control individuals (21/120) and patients with pituitary diseases (99/120). The latter were diagnosed either with hypopituitarism (n=42) or with other pituitary diseases (not causing hypopituitarism) (n=57). Additionally, hypopituitary patients on appropriate replacement therapies (compensated hypopituitarism) were compared to patients on inappropriate replacement therapies (non-compensated hypopituitarism). Several parameters in blood serum were measured, including MBL level, pituitary and peripheral hormones and different biochemical parameters. Results: Serum MBL level was significantly lower in patients with hypopituitarism comparing to controls (1358.97 ± 244.68 vs. 3199.30 ± 508.46, p<0.001) and comparing to other pituitary diseases (1358.97 ± 244.68 vs. 2388.12 ± 294.99, p=0.015) and this association was confirmed by univariate regression analysis. We evaluated the distribution of patients with relation to MBL level; there was a clear difference in this distribution between control individuals (among whom no subjects had MBL level <500 ng/mL) and patients with hypopituitarism (among whom 43% of patients had MBL level <500 ng/mL). Moreover, patients with non-compensated hypopituitarism had lower mean and median MBL levels comparing to patients with compensated hypopituitarism (1055.38 ± 245.73 vs. 2300.09 ± 579.93, p=0.027; 488.51 vs. 1951.89, p=0.009, respectively) and this association was confirmed in univariate regression analysis. However, mean and median MBL levels in patients with compensated hypopituitarism vs. controls did not differ significantly (2300.09 ± 579.93 vs. 3199.30 ± 508.46, p=0.294; 1951.90 vs. 2329.16; p=0.301, respectively). Conclusion: Hypopituitarism in adults is associated with a decreased blood concentration of mannan-binding lectin, a phenomenon which does not exist in hypopituitary patients on the appropriate hormone replacement therapies. Therefore measurement of mannan-binding lectin level in patients with hypopituitarism may be considered as a parameter contributing to adjust optimal doses of hormone replacement therapies.

Sorafenib versus Lenvatinib Causes Stronger Oxidative Damage to Membrane Lipids in Noncancerous Tissues of the Thyroid, Liver, and Kidney: Effective Protection by Melatonin and Indole-3-Propionic Acid.

Sorafenib and lenvatinib are multi-targeted tyrosine kinase inhibitors which are currently approved to treat advanced hepatocellular carcinoma, renal cell carcinoma and radioiodine-refractory differentiated thyroid carcinoma. However this treatment is often limited due to common adverse events which may occur via oxidative stress. The study aims to compare sorafenib- and lenvatinib-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) in homogenates of porcine noncancerous tissues of the thyroid, the liver, and the kidney and to check if it can be prevented by antioxidants melatonin and indole-3-propionic acid (IPA). Homogenates of individual tissues were incubated in the presence of sorafenib or lenvatinib (1 mM, 100 µM, 10 µM, 1 µM, 100 nM, 10 nM, 1 nM, 100 pM) together with/without melatonin (5.0 mM) or IPA (5.0 mM). The concentration of malondialdehyde + 4-hydroxyalkenals, as the LPO index, was measured spectrophotometrically. The incubation of tissue homogenates with sorafenib resulted in a concentration-dependent increase in LPO (statistically significant for concentrations of 1mM and 100 µM in the thyroid and the liver, and of 1 mM, 100 µM, and 10 µM in the kidney). The incubation of thyroid homogenates with lenvatinib did not change LPO level. In case of the liver and the kidney, lenvatinib increased LPO but only in its highest concentration of 1 mM. Melatonin and IPA reduced completely (to the level of control) sorafenib- and lenvatinib-induced LPO in all examined tissues regardless of the drug concentration. In conclusion, sorafenib comparing to lenvatinib is a stronger damaging agent of membrane lipids in noncancerous tissues of the thyroid, the liver, and the kidney. The antioxidants melatonin and IPA can be considered to be used in co-treatment with sorafenib and lenvatinib to prevent their undesirable toxicity occurring via oxidative stress.

Thyroid diseases and fertility disorders - Guidelines of the Polish Society of Endocrinology [Choroby tarczycy a zaburzenia plodnosci - rekomendacje Polskiego Towarzystwa Endokrynologicznego].

Thyroid hormones influence female fertility, directly stimulating oocyte maturation and regulating prolactin and sex hormone binding globulin (SHBG) concentrations. Hyperthyroidism affects 1-2%, overt hypothyroidism 0.3%, and subclinical hypothyroidism up to 15% of women of childbearing age. Approximately 10% of euthyroid women have elevated concentrations of anti-thyroid peroxidase antibodies (aTPO) and/or anti-thyroglobulin (aTg) antibodies. Hypothyroidism can cause menstrual and ovulation disorders, and impact fertility. Studies carried out to date have not conclusively demonstrated that subclinical hypothyroidism or elevated aTPO/aTg concentrations make it harder to conceive, but they do increase the risk of pregnancy loss. Subclinical hypothyroidism and elevated aTPO/aTg concentrations without thyroid disorders are more common in polycystic ovary syndrome, premature ovarian insufficiency, and idiopathic infertility. Fertility problems are therefore an indication for screening for thyroid diseases (in females as well as in some males). A thyroid disorder diagnosed in subfertile couples should be treated appropriately, especially before attempting assisted reproductive techniques. These recommendations are intended as a guide for the management of thyroid diseases associated with infertility.

Correction: Iwan et al. Pro-Oxidative Effect of KIO3 and Protective Effect of Melatonin in the Thyroid-Comparison to Other Tissues. Life 2021, 11, 592.

In the original article [...].

Membrane Lipids in the Thyroid Comparing to Those in Non-Endocrine Tissues Are Less Sensitive to Pro-Oxidative Effects of Fenton Reaction Substrates.

Iron is an essential microelement for the proper functioning of many organs, among others it is required for thyroid hormone synthesis. However, its overload contributes to the increased formation of reactive oxygen species via Fenton chemistry (Fe2++H2O2→Fe3++˙OH + OH-), and it is potentially toxic. Individual organs/tissues are affected differently by excess iron. The excessive absorption of iron with subsequent deposition in various organs is associated with diseases such as hemochromatosis. Such an iron deposition also occurs in the thyroid gland where it can disturb thyroid hormone synthesis. In turn, melatonin is an effective antioxidant, which protects against oxidative damage. This study aims to check if lipid peroxidation resulting from oxidative damage to membrane lipids, is caused by Fenton reaction substrates, and if protective effects of melatonin differ between the thyroid and various non-endocrine porcine tissues (liver, kidney, brain cortex, spleen, and small intestine). To mimic the conditions of iron overload, Fe2+ was used in extremely high concentrations. Homogenates of individual tissues were incubated together with Fenton reaction substrates, i.e., FeSO4 (9.375, 18.75, 37.5, 75, 150, 300, 600, 1,200, 1,800, 2,100, 2,400, 3,000, 3,600, 4,200, and 4,800 µM)+H2O2 (5 mM), either without or with melatonin (5 mM). The concentration of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as the LPO index, was evaluated by a spectrophotometrical method. Fenton reaction substrates increased concentrations of LPO products in all chosen tissues. However, in the thyroid, compared to non-endocrine tissues, the damaging effect was generally weaker, it was not observed for the two lowest concentrations of iron, and the LPO peak occurred with higher concentrations of iron. Melatonin reduced experimentally induced LPO in all examined tissues (without differences between them), and these protective effects did not depend on iron concentration. In conclusion, membrane lipids in the thyroid compared to those in non-endocrine tissues are less sensitive to pro-oxidative effects of Fenton reaction substrates, without differences regarding protective effects of melatonin.

Iodine as a potential endocrine disruptor-a role of oxidative stress.

PURPOSE: Iodine is an essential micronutrient required for thyroid hormone biosynthesis. However, overtreatment with iodine can unfavorably affect thyroid physiology. The aim of this review is to present the evidence that iodine-when in excess-can interfere with thyroid hormone synthesis and, therefore, can act as a potential endocrine-disrupting chemical (EDC), and that this action, as well as other abnormalities in the thyroid, occurs-at least partially-via oxidative stress. METHODS: We reviewed published studies on iodine as a potential EDC, with particular emphasis on the phenomenon of oxidative stress. RESULTS: This paper summarizes current knowledge on iodine excess in the context of its properties as an EDC and its effects on oxidative processes. CONCLUSION: Iodine does fulfill the criteria of an EDC because it is an exogenous chemical that interferes-when in excess-with thyroid hormone synthesis. However, this statement cannot change general rules regarding iodine supply, which means that iodine deficiency should be still eliminated worldwide and, at the same time, iodine excess should be avoided. Universal awareness that iodine is a potential EDC would make consumers more careful regarding their diet and what they supplement in tablets, and-what is of great importance-it would make caregivers choose iodine-containing medications (or other chemicals) more prudently. It should be stressed that compared to iodine deficiency, iodine in excess (acting either as a potential EDC or via other mechanisms) is much less harmful in such a sense that it affects only a small percentage of sensitive individuals, whereas the former affects whole populations; therefore, it causes endemic consequences.

Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych doroslych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022].

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. Update of the 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych doroslych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022 - uzupelnienie].

N/A.

Thyroid diseases in pregnancy: guidelines of the Polish Society of Endocrinology [Choroby tarczycy w ciazy: zalecenia postepowania Polskiego Towarzystwa Endokrynologicznego].

Appropriate care of pregnant women with coexisting thyroid dysfunction is still a subject of much controversy. In recent years, there has been a dynamic increase in the number of scientific reports on the diagnosis and treatment of thyroid diseases in women planning pregnancy, pregnant women, and women in the postpartum period. These mainly concern the management of hypothyroidism, autoimmune thyroid diseases, and fertility disorders. Therefore, the Polish Society of Endocrinology deemed it necessary to update the guidelines on principles of diagnostic and therapeutic management in this group of patients, previously published in 2011. The recommendations were prepared by Polish experts according to evidence based medicine principles, if such data were available.

Potential Risk Factors for Isolated Hypothyroxinemia in Women of Childbearing Age-Results from Retrospective Analysis.

Isolated hypothyroxinemia (IH) unfavorably affects reproduction. This study aimed to evaluate retrospectively if any routinely measured clinical/laboratory parameters are associated with IH among women of childbearing age hospitalized in the endocrine department. A group of 466 female non-pregnant inpatients (age range 13-57 years) was considered. IH (decreased free thyroxine (FT4) with normal TSH) was found in 8/466 patients (1.72%). Vitamin D deficiency (<30 ng/mL) was found in all patients with IH, whereas severe Vitamin D deficiency (<20 ng/mL) was found in 5/6. Vitamin D concentration was lower in IH females. FT4 concentration was lower in patients with severe vitamin D deficiency and correlated positively with vitamin D concentration. Insulin resistance index (IRI) was increased (>1.25) in 5/6 patients with IH. IRI was higher in IH patients and it was the only independent linear factor for IH in the univariate regression. FT4 concentration was lower in patients with increased IRI and correlated negatively with IRI. FT4 concentration correlated negatively with body mass index (BMI) and LDL cholesterol or triglycerides, and positively with HDL cholesterol or HDLC/cholesterol ratio. Vitamin D deficiency, insulin resistance and increased BMI (as potential causative factors), and abnormal lipid profile (as a possible consequence), are associated with IH in women of childbearing age. Eliminating risk factors for hypothyroxinemia may improve reproductive health.

Melatonin and Indole-3-Propionic Acid Reduce Oxidative Damage to Membrane Lipids Induced by High Iron Concentrations in Porcine Skin.

Iron excess in tissues results in increased oxidative damage. Among different tissues, the skin can particularly be severely damaged by oxidative stress, as it is exposed not only to endogenous but also directly to exogenous pro-oxidants. The skin is especially vulnerable to harmful oxidative stress. Melatonin and indole-3-propionic acid (IPA), two indole substances, are efficient antioxidants. This study aims to evaluate the potential protective effects of melatonin and IPA against oxidative damage to membrane lipids (lipid peroxidation (LPO)), induced in porcine skin homogenates by the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH-) when iron is used in extremely high concentrations. Skin homogenates were incubated in the presence of FeSO4 (2400, 1200, 600, 300, 150 and 75 µM) + H2O2 (5 mM) with/without melatonin or IPA. LPO level (MDA + 4-HDA/mg protein) was measured spectrophotometrically. Melatonin, in its highest used concentration (5.0 mM), prevented FeSO4 (1200 mM)-induced LPO, whereas it was effective in concentrations as low as 2.5 mM against all lower iron concentrations. IPA was protective in concentrations as low as 2.5 mM independently of FeSO4 concentration. In conclusion, melatonin and IPA effectively protect against oxidative damage to membrane lipids induced by high concentrations of iron in porcine skin; therefore, both can be considered pharmacological agents in the case of disorders associated with excessive iron accumulation in the skin.

Contribution of Ghrelin to the Pathogenesis of Growth Hormone Deficiency.

In this review we described the interactions between ghrelin and the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis in children and adults with growth hormone deficiency (GHD). A possible involvement of these interactions in the pathogenesis of unexplained cases of GHD was suggested. Current research provides more and more details to the knowledge on the circadian rhythm of ghrelin. We gathered reports on the decreasing effect of Helicobacter pylori-related chronic gastritis on the number of ghrelin immunopositive cells and the consequent decrease in ghrelin serum concentration. The gastrointestinal tract microflora modification of the ghrelin action, by the mechanism of molecular mimicry, was also stressed. Moreover, the mutual relationships between ghrelin and the TSH-FT4/FT3 axis in growth and metabolic processes are described. It is to be recalled that FT4 and FT3 exert a permissive impact on IGF-1 action and, in turn, GH, in reaction mediated by IGF-1, enhances the monodeiodination of FT4 to FT3. Finally, we discussed the latest attempts to use the GH secretagogue receptor (GHS-R) analogues for possible diagnostic and therapeutic purposes.