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Background/Objectives : Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental hormones and angiogenic factors in pregnant women with TAI were evaluated. Methods : Fifty-eight hypothyroid women positive for TPOAb/TgAb, thirty-three hypothyroid women negative for TPOAb/TgAb, and thirty-nine healthy controls were enrolled in this study. Maternal thyroid function tests were established every month throughout pregnancy, and angiogenic placental factors, pro-angiogenic placental growth factor (PlGF); two anti-angiogenic factors, soluble vascular endothelial growth factor receptor 1 (sFlt-1) and soluble endoglin (sEng); and placental hormones, estradiol, progesterone, and hCG, were determined during each trimester. Results : Obstetrical and neonatal outcomes did not differ between the groups. However, several detrimental effects of thyroid antibodies were observed. These included a positive correlation between TgAb and the sEng/PlGF ratio in the first trimester and positive correlations between TPOAb and sFlt-1 and between TgAb and the sFlt-1/PlGF ratio in the third trimester. TgAbs in the first trimester was a risk factor for gestational hypertension and preeclampsia. Conclusions : Our study indicates that TPOAbs and TgAbs can exert a direct harmful effect on placentation, leading to disturbances in the production of placental angiogenic factors and, consequently, to an increased risk of gestational hypertension and preeclampsia.

Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that frequently produce and release catecholamines. Catecholamine excess can manifest in several cardiovascular syndromes, including cardiomyopathy. PPGL-induced cardiomyopathies occur in up to 11% of cases and are most often associated with an adrenal pheochromocytoma (90%) and rarely with a paraganglioma derived from the sympathetic ganglia (10%). PPGL-associated cardiomyopathies can be chronic or acute, with takotsubo cardiomyopathy being the most often reported. These two types of PPGL-induced cardiomyopathy seem to have different pathophysiological backgrounds. Acute catecholaminergic stress inundates myocardial β-adrenoceptors and leads to left ventricle stunning and slight histological apoptosis. In chronic cardiomyopathy, prolonged catecholamine exposure leads to extended myocardial fibrosis, inflammation, and necrosis, and ultimately it causes dilated cardiomyopathy with a low ejection fraction. Sometimes, especially in cases associated with hypertension, hypertrophic cardiomyopathy can develop. The prognosis appears to be worse in chronic cases with a higher hospital mortality rate, higher cardiogenic shock rate at initial presentation, and lower left ventricular recovery rate after surgery. Therefore, establishing the correct diagnosis at an early stage of a PPGL is essential. This mini-review summarizes current data on pathophysiological pathways of cardiac damage caused by catecholamines, the clinical presentation of PPGL-induced cardiomyopathies, and discusses treatment options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Szatko, Glinicki and Gietka-Czernel.)

Thyroid autoimmunity (TAI) is commonly defined as the presence of thyroperoxidase antibodies (TPOAbs) and/or thyroglobulin antibodies (TgAbs), which predisposes an individual to hypothyroidism. TAI affects nearly 10% of women of reproductive age and evokes great interest from clinicians because of its potentially negative impact on female fertility and pregnancy course. In this mini-review, we review the current literature concerning the influence of TPOAb or TPOAb/TgAb positivity without thyroid dysfunction on reproduction. TAI may negatively affect female fertility; several studies have found an increased prevalence of TAI in infertile women, especially in those with unexplained infertility and polycystic ovary syndrome. According to some observations, TAI might also be connected with premature ovarian insufficiency and endometriosis. The relationship between TAI and an increased risk of pregnancy loss is well documented. The pathophysiological background of these observations remains unclear, and researchers hypothesize on the direct infiltration of reproductive organs by thyroid antibodies, co-existence of TAI with other autoimmune diseases (either organ specific or systemic), immunological dysfunction leading to inhibition of immune tolerance, and relative thyroid hormone deficiency. Interestingly, in the current literature, better outcomes of assisted reproductive technology in women with TAI have been reported compared with those reported in earlier publications. One plausible explanation is the more widespread use of the intracytoplasmic sperm injection method. The results of randomized clinical trials have shown that levothyroxine supplementation is ineffective in preventing adverse pregnancy outcomes in women with TAI, and future research should probably be directed toward immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tańska, Gietka-Czernel, Glinicki and Kozakowski.)

Background: FGF21 pharmacological treatment reverses fatty liver and lowers serum triglyceride concentration but FGF21 serum level is increased in hepatic steatosis. FGF21 secretion is induced by thyroid hormones in vitro ., Purpose: To determine the influence of thyroid hormones and metabolic changes secondary to thyroid dysfunction on FGF21 secretion in humans., Materials and Methods: This was a case-control study. 82 hyperthyroid and 15 hypothyroid patients were recruited together with 25 healthy controls. Of those with hyperthyroidism, 56 received radioiodine treatment and 42 of them achieved hypothyroidism and then euthyroidism within one year following therapy. Radioiodine-induced hypothyroidism developed abruptly within a six week interval between clinic visits. FGF21 serum levels were determined with an ELISA method., Results: Serum FGF21 levels did not differ in hyper- and hypothyroid patients in comparison to controls [median 103.25 (interquartile range, 60.90-189.48) and 86.10 (54.05-251.02) vs 85.20 (58.00-116.80) pg/mL P=0.200 and 0.503, respectively]. In hyperthyroid patients treated with radioiodine, serum FGF21 levels increased significantly in rapid-onset hypothyroidism in comparison to the hyperthyroid and euthyroid phase [median 160.55 (interquartile range, 92.48 - 259.35) vs 119.55 (67.78-192.32) and 104.43 (55.93-231.93) pg/mL, P=0.034 and 0.033, respectively]. The rising serum FGF21 level correlated positively with serum triglycerides (Spearman coefficient rs=0.36, P=0.017) and inversely with serum SHBG (rs=-0.41, P=0.007), but did not correlate with thyroid hormone levels., Conclusions: There was a transient increase in FGF21 serum level during rapid-onset hypothyroidism following radioiodine treatment. There was no association between FGF21 serum level and thyroid hormones. In radioiodine-induced hypothyroidism, the rising serum FGF21 concentration correlated positively with rising serum triglycerides and negatively with falling SHBG, reflecting increased hepatic lipogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Szczepańska, Glinicki, Zgliczyński, Słowińska-Srzednicka, Jastrzębska and Gietka-Czernel.)

Fibroblast growth factor (FGF) 21 is a recently recognized metabolic regulator that evokes interest due to its beneficial action of maintaining whole-body energy balance and protecting the liver from excessive triglyceride production and storage. Together with FGF19 and FGF23, FGF21 belongs to the FGF family with hormone-like activity. Serum FGF21 is generated primarily in the liver under nutritional stress stimuli like prolonged fasting or the lipotoxic diet, but also during increased mitochondrial and endoplasmic reticulum stress. FGF21 exerts its endocrine action in the central nervous system and adipose tissue. Acting in the ventromedial hypothalamus, FGF21 diminishes simple sugar intake. In adipose tissue, FGF21 promotes glucose utilization and increases energy expenditure by enhancing adipose tissue insulin sensitivity and brown adipose tissue thermogenesis. Therefore, FGF21 favors glucose consumption for heat production instead of energy storage. Furthermore, FGF21 specifically acts in the liver, where it protects hepatocytes from metabolic stress caused by lipid overload. FGF21 stimulates hepatic fatty acid oxidation and reduces lipid flux into the liver by increasing peripheral lipoprotein catabolism and reducing adipocyte lipolysis. Paradoxically, and despite its beneficial action, FGF21 is elevated in insulin resistance states, that is, fatty liver, obesity, and type 2 diabetes., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

It is estimated that hypothyroidism treatment may be either suboptimal or excessive in about 32-45% patients treated with L-thyroxine (LT4). There are multiple possible causes of poor control of hypothyroidism, including narrow LT4 therapeutic index, food and drug interactions, comorbidities, and patient non-adherence. Some of these obstacles could possibly be overcome with the novel liquid LT4 formulation. Liquid LT4 reaches maximum blood concentration about 30 minutes faster than the tablet form. Faster pharmacokinetics might lead to more efficient LT4 absorption, as suggested by a recent real-world study in patients with primary and central hypothyroidism. Liquid LT4 treatment led to increased free thyroxine (FT4) and sex hormone binding globulin (SHBG) with decreased low-density lipoprotein (LDL) cholesterol concentration and substantially improved quality of life for the patients. Herein we present a series of 31 patients with hypothyroidism of different aetiologies treated with the novel liquid LT4 formulation in standard clinical care in light of the latest scientific publications on liquid LT4 formula. We observed normalization of thyroid function tests shortly after introduction of liquid LT4, irrespective of concurrent diseases or concomitant medications that could diminish LT4 absorption. In more detail, the treatment with liquid LT4 managed to normalize thyroid-stimulating hormone (TSH) concentrations in patients without any known causes of LT4 absorption disturbances, as well as in those with malabsorption: with gastric bypass, partial small and large intestine resection, scleroderma, gluten intolerance, celiac disease, atrophic gastritis, and polytherapy. In conclusion, considering many factors disturbing LT4 absorption, hypothyroidism therapy with liquid LT4 seems to be a particularly effective option.

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.

Levothyroxine (LT4) is a standard therapy in hypothyroidism; however, its bioavailability and therapeutic effects might be affected by many factors. Data shows that therapy with liquid LT4 characterized by quicker pharmacokinetics provides better thyroid hormones control than tablet LT4. We addressed the quality of life (QoL) and efficacy of the new ethanol-free formula of liquid LT4 (Tirosint ® SOL) treatment in 76 euthyroid patients with primary (PH, n = 46) and central hypothyroidism (CH, n = 30), and compared the results to retrospective data on equivalent doses of tablet L-T4 therapy. After 8 weeks of liquid LT4 therapy, we found a significant improvement in QoL in both PH and CH patients. TSH levels were unaltered in PH patients. Free hormone levels (fT4 and fT3) increased in all the patients, with the exception of fT3 in the CH group. SHBG and low-density lipoprotein (LDL) also improved. Liquid LT4 therapy provided a better thyroid hormone profile and improvement in patients' QoL than the tablet form, which was possibly due to the more favorable pharmacokinetics profile resulting in better absorption, as suggested by the increased free thyroid hormone levels. In summary, this is the first study addressing the QoL in hypothyroid patients, including primary and central hypothyroidism, treated with liquid LT4 formula in everyday practice.

The negative impact of even subtle maternal thyroid hormone deficiency on the pregnancy outcome and intellectual development of the progeny has been known for many years, but unfortunately the diagnosis and treatment of subclinical hypothyroidism in pregnant women still evokes controversies. Due to physiological changes in thyroid function and thyroid hormones metabolism during pregnancy, the trimester‑specific reference ranges for thyroid‑stimulating hormone (TSH) and free thyroid hormones should be established. However, because of interassay variability and other confounders including ethnicity and iodine intake, such norms are reliable only for local populations and a specific laboratory method. In turn, the fixed reference ranges suggested by endocrine societies may carry a risk of misclassificating some healthy pregnant women to be hypothyroid. The effect of levothyroxine treatment on pregnancy and children's cognitive outcomes remains unclear. Therapeutic benefits in decreasing miscarriage and preterm delivery rates were observed when intervention was held in the first trimester in women with a TSH level between 2.5 to 10 mU/l, mainly higher than or equal to 4 mU/l. The possible harmful effect of treatment includes preterm delivery, gestational diabetes, hypertension, and pre‑eclampsia. The only 3 prospective, randomized, placebo‑controlled trials evaluating the efficacy of levothyroxine therapy on children's intelligence quotient were started in the second trimester, which may be too late to demonstrate differences between treatment and placebo groups. Awaiting the results of future trials, clinicians should be aware of the fact that low‑dose levothyroxine at a daily dose of 25 to 50 µg is probably not harmful and may be beneficial, but the routine implementation of the therapy in each pregnant women with a TSH level exceeding 2.5 mU/l seems too premature.

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.

Hypothyroidism is a common endocrine disorder affecting 3-15% of the adult population in subclinical form and 0.3-0.8% as overt disease. The mainstay of treatment is replacement monotherapy with levothyroxine (LT4). Currently several oral LT4 formulations including tablets, softgel capsules, and liquid formulations are available. Liquid LT4 is manufactured as LT4 solution in 85% glycerol and 96% ethanol and as LT4 solution in purified water and glycerol. The latest formulation, Tirosint SOL, gained FDA approval in 2017. To evaluate the clinical utility of liquid LT4 we reviewed the literature using three databases: PubMed/MEDLINE, Scopus, and Embase and found 405 articles among which 23 prospective and two retrospective studies were further evaluated. Finally, several case reports on rare clinical conditions were discussed. Our review demonstrated that liquid LT4 was more effective than tablet formulation in patients with malabsorption caused by interfering diseases, drugs, and bariatric surgery. The better pharmacokinetics of liquid LT4 was also confirmed in subjects without malabsorption: patients on replacement or suppressive therapy, who switched from tablet to liquid formulation in equivalent dose, gained better hormonal control, and required less frequent TSH measurements. The drug also appeared effective and easy to handle in patients fed by enteric tube. Liquid LT4 appeared equally effective whenever taken before or during breakfast. The analysis of the drug utility in particular populations including newborns, pregnant women, and the elderly confirmed the high value and safety of liquid LT4. However, in neonates the higher incidence of TSH suppression on liquid in comparison to tablet LT4 therapy was noted, and particular attention to avoid over-treatment must be paid. Concluding: the literature review revealed that liquid LT4 is especially advantageous in patients with malabsorption and the critically ill, but it seems also very promising in common therapy. The lack of alcohol content in the new formulation makes Tirosint SOL especially attractive.

Introduction: Foetal hypothyroidism negatively impacts somatic and neurological child development and can be the cause of serious obstetric and perinatal complications. We present a rare case of a large foetal dyshormonogenetic goitre, causing foetal neck hyperexten-sion, oesophageal compression, and cardiac high-output failure., Material and Methods: A foetal goitre complicated by cardiomegaly and polyhydramnios was diagnosed at 23 weeks of gestation (WG) on a routine ultrasonographic (US) assessment in a healthy nullipara. Foetal blood sampling was performed and a severe foetal hypothyroid-ism was diagnosed. Treatment was undertaken with an intra-amniotic followed by combined intra-amniotic and intravenous injections of L-thyroxine (L-T4). A total of 11 doses of L-T4 were administered between 24-37 WG to the foetus., Results: A complete regression of foetal goitre, cardiomegaly, and polyhydramnios was observed. At 38 WG the patient delivered vagi-nally a male infant with mild hypothyroidism and no signs of goitre or cardiomegaly on postnatal US. Neurological development of the one year old baby is normal., Conclusions: The effective diminishing of serum TSH concentration and goitre size was reached after combined intra-amniotic and in-travenous L-T4 injections were given. L-T4 requirement in the foetus is equal to or above 15 μg/kg daily and should be given in weekly intervals due to its rapid metabolism by the foetus and by placental type 3 deiodinase. Intra-amniotic L-T4 administration may be inef-fective when a large goitre indisposes amniotic fluid swallowing by the foetus, so then the combined L-T4 injections into the umbilical vein and intra-amniotically in experienced hands seems to be a reasonable and effective option.

Numerous concerns about menopause exist among women, and fear of an increase in body weight is one of the most important of them. This paper presents an overview of current knowledge concerning the etiology of obesity related to menopause and about the mechanisms of its development, with particular regard to the hormonal changes that occur during this period of life. The role of estrogens in the regulation of energy balance and the effect of sex hormones on metabolism of adipose tissue and other organs are presented. The consequence of the sharp decline in the secretion of estrogens with subsequent relative hyperandrogenemia is briefly discussed. The main intention of this review is to clarify what is inevitable and what perhaps results from negligence and unhealthy lifestyles. In the last part of the paper the possibilities of counteracting the progress of adverse changes in body composition, by promoting beneficial lifestyle modifications and the use of hormonal substitution treatment, in cases where it is reasonable and possible, are described.

The incidence of most thyroid diseases: hypothyroidism, nodular goitre, and cancer is highest among postmenopausal and elderly women. The diagnosis of thyroid dysfunction in this group of patients is difficult because the symptoms can be nonspecific or common with menopausal and ageing complaints. In the interpretation of thyroid function tests the physiological changes in secretion and metabolism of thyrotropin (TSH) and thyroid hormones must be considered, as well as the influence of comorbidities. Unrecognised thyroid dysfunction leads to increased: cardiovascular risk, bone fractures, cognitive impairment, depression, and mortality. Therapy of thyroid dysfunction is different in postmenopausal and elderly women than in young people; hypothyroidism should be treated with caution, because high doses of L-thyroxine can lead to cardiac arrhythmias and increased bone turnover, and hyperthyroidism should be preferentially treated with radioiodine. Thyroid status beneficially influencing longevity relates to low thyroid function. Thyroid nodules and cancer often affect women over 50 years old; the diagnostic and therapeutic approach is the same as in the general population, but the surgical risk and cancer prognosis is worse than in young patients.

Primary aldosteronism (PA) is estimated to occur in 5-12% of patients with hypertension. Assessment of aldosterone / plasma renin activity (PRA) ratio (ARR) has been used as a screening test in patients suspected of PA. Direct determination of renin (DRC) and calculation of aldosterone / direct renin concentration ratio (ADRR) could be similarly useful for screening patients suspected of PA. The study included 62 patients with indication for evaluation of the renin-angiotensin-aldosterone system and 35 healthy volunteers. In all participants we measured concentrations of serum aldosterone, plasma direct renin, and PRA after a night's rest and again after walking for two hours. The concentrations of aldosterone, direct renin, and PRA were measured by isotopic methods (radioimmunoassay (RIA) / immunoradiometric assay (IRMA)). Correlations of ARR with ADRR in the supine position were r = 0.9162, r(2) = 0.8165 (p < 0.01); and in the up-right position were r = 0.7765, r(2) = 0.9153 (p < 0.01). The cut-off values of ARR and ADRR ≥ 100 presented highest specificity (99%) for the diagnosis of PA; however, quite acceptable specificity and sensitivity (> 80% and 100%, respectively) appeared for the ratios ≥ 30. We suggest that for practical and economic reasons ARR can be replaced by ADRR., (© The Author(s) 2014.)

Introduction: Performing measurements of plasma renin activity (PRA) or direct renin concentration (DRC) and aldosterone concentration, we should be well informed about requirements concerning blood sample processing., Material and Methods: Forty-seven patients had blood collected in the supine and upright positions. Blood was withdrawn into two EDTA2K tubes and one with clot activator. One EDTA2K tube was cooled at +4 °C and centrifuged at +4 °C whereas the other was prepared at room temperature. PRA and DRC were measured by radioimmunoassay (RIA) and radioimmunometry (IRMA), respectively, in both cooled and not cooled plasma samples, and aldosterone was measured by RIA in not cooled plasma and in serum., Results: In all the groups, with low, medium, and high values of PRA and direct renin, the temperature of sample processing within 30 minutes had no marked influence on the final result (correlation coefficient for renin was 0.9994, and for PRA, 0.8297). The measured concentrations of aldosterone also showed high correlation (r = 0.9790) but were markedly higher in plasma., Conclusion: The measurements of DRC, and to a lesser extent PRA, were similar regardless of temperature condition during the 20-30 minutes necessary for blood sample processing. Aldosterone concentrations in plasma vs serum samples appeared to be markedly higher., (© The Author(s) 2013.)

Foetal ultrasonography monitoring is a valuable tool in assessing foetal thyroid function when pregnancy is complicated by maternal Graves' disease with accompanying high levels of TSH receptor antibodies, or when antithyroid drug therapy is instituted. Among several ultrasonographic signs of foetal thyroid disorder such as abnormalities in bone maturation and heart rhythm, cardiac failure, hydrops, intrauterine growth restriction and polyhydramnios, goitre is the most sensitive one. Here we report three cases of pregnant women with Graves' disease accompanied by very high serum levels of TSH receptor antibodies. In all three cases, as documented by foetal or neonatal serum TSH and thyroid hormones measurements, foetal thyroid dysfunction occurred. The only ultrasonographic sign of foetal involvement was a goitre with decreased echogenicity and increased vascularisation, central or peripheral. This is the first report demonstrating that a foetal thyroid gland when affected by transplacental passage of maternal TSH receptor stimulating antibodies can present exactly the same characteristic ultrasound pattern of Graves' disease as in adults.

Introduction: To evaluate the usefulness of measuring maternal anti-TSH receptor antibodies (TRAbs) and foetal ultrasound (US) monitoring in cases of current or past maternal hyperthyroidism., Material and Methods: 77 pregnant women suffering from hyperthyroidism or with a history of Graves' hyperthyroidism were observed prospectively. Maternal serum TSH, fT4, fT3, TRAbs, and foetal US were performed at baseline and repeated every 2-4 weeks when needed. Neonatal thyroid status was assessed based on serum TSH, fT4 and fT3 obtained in the first days of life., Results: 35 women were diagnosed with gestational hyperthyroidism and 42 with Graves' disease; among them 26 had current and 16 past hyperthyroidism. Foetal and neonatal thyroid dysfunction occurred only in cases of maternal Graves' disease: nine (21%) and three (7%), respectively. Active maternal Graves' hyperthyroidism and TRAbs elevated at least five times above the upper normal limit predisposed to foetal hyperthyroidism. Maternal anti-thyroid drug therapy (ATD) and low TRAbs and fT4 were the risk factors of foetal hypothyroidism. Abnormal foetal thyroid sonogram was the only sign of foetal thyroid dysfunction. Four patients (9.5%) had high TRAbs in the 3rd trimester (10.8-29.9 IU/mL), but neither foetal nor neonatal thyroid dysfunctions were noted., Conclusions: In the cases of maternal Graves' disease, foetal thyroid dysfunction occurs more often than commonly assumed. Foetal thyroid US is a valuable tool in early diagnosis and monitoring of the foetal thyroid status in pregnancy complicated by maternal Graves' disease. The evaluation of biological activity of maternal TRAbs may be helpful in prenatal diagnosis in some cases.

Introduction: Adrenal tumours can produce specific hormones and cause characteristic symptoms. The majority of adrenal incidentalomas are clinically silent, but some may be malignant or pose other potential threats to life. Chromogranin A (CgA) is the main, nonspecific marker of neuroendocrine tumours (NET). In the adrenals, CgA is produced by chromaffin cells localised in the adrenal medulla. Therefore its measurement in blood might be used as a screening test for pheochromocytoma after the exclusion of other various causes of an increased CgA level. The aim of our study was to investigate plasma CgA concentration in various adrenal tumours., Material and Methods: EDTA2K plasma samples were obtained from 195 patients with adrenal tumours and from 50 blood donors. CgA was measured in plasma-EDTA2K by immunoradiometric (IRMA) method., Results: In the majority of patients with adrenal tumours not derived from neuroendocrine cells (chromaffin cells), except those with significant hypercortisolaemia and some patients with adrenal carcinoma, the plasma CgA concentrations were below the cut-off value. In adrenal tumours derived from chromaffin cells (pheochromocytoma), CgA levels were markedly elevated., Conclusion: In differential diagnosis of adrenal tumours, non-increased CgA level might be useful initial screening evidence for the exclusion of pheochromocytoma.

Thyroid cancer has had an increasing prevalence over recent years and poses an extraordinary challenge when diagnosed during pregnancy. Although in the majority of cases in pregnant patients there occurs a well differentiated papillary carcinoma which has an excellent prognosis and for which surgery can be delayed until the postpartum period, in rare cases of advanced or rapidly growing tumour, and in a case of medullary or anaplastic cancer, surgery should be undertaken during pregnancy. Here, we present the case of a 30 year-old woman with Hürthle cell neoplasm recognised on cytology during the second trimester. Because of the neck lymph nodes metastases diagnosed on ultrasonography and cytology, which also could be seen as calcified foci on a chest X-ray examination performed three years earlier, she underwent surgery before the 22(nd) week of gestation. The course of surgery was successful and uneventful and she delivered a healthy child on term. An approach to pregnant patients with differentiated thyroid carcinoma is discussed.

Objective: To establish fetal thyroid nomograms based on gestational age and biparietal diameter and to compare obtained results with previously published data., Study Design: A cross-sectional study of 241 healthy pregnant women at 14-38 week of gestation was undertaken. Exclusion criteria were: known maternal thyroid or systemic disease, unknown date of last menstrual period, multiple pregnancy and fetal malformations. Fetal thyroid diameter (FTD), circumference (FTC) and area (FTA) were measured by two-dimensional ultrasonography and plotted against gestational age (GA) and biparietal diameter (BPD)., Results: FTD, FTC and FTA increased logarithmically to GA and BPD. Fetal thyroid measurements as a function of GA were expressed by logarithmic formulas: ln(FTD)=3.6025-23.0315/GA, ln(FTC)=4.6227-22.8003/GA, ln(FTA)=6.6303-45.0831/GA. The following logarithmic formulas were obtained for fetal thyroid measurements according to BPD: ln(FTD)=3.4068-45.4271/BPD, ln(FTC)=4.4271-44.8359/BPD, ln(FTA)=6.2390-88.4408/BPD. There were highly significant correlations between thyroid measurements and GA or BPD: r=0.87-0.90, p<0.00001., Conclusions: We have established age-dependent and age-independent nomograms of fetal thyroid. These nomograms will enable prenatal diagnosis in fetuses at risk of thyroid disorders., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The management of thyroid disorders during pregnancy is one of the most frequently disputed problems in modern endocrinology. It is widely known that thyroid dysfunction may result in subfertility, and, if inadequately treated during pregnancy, may cause obstetrical complications and influence fetal development. The 2007 Endocrine Society Practice Guideline endorsed with the participation of the Latino America Thyroid Association, the American Thyroid Association, the Asia and Oceania Thyroid Association and the European Thyroid Association, greatly contributed towards uniformity of the management of thyroid disorders during pregnancy and postpartum. Despite the tremendous progress in knowledge on the mutual influence of pregnancy and thyroid in health and disease, there are still important areas of uncertainty. There have been at least a few important studies published in the last 3 years, which influenced the thyroidal care of the expecting mother. It should also be remembered that guidelines may not always be universally applied in all populations with different ethnical, socio-economical, nutritional (including iodine intake) background or exposed to different iodine prophylaxis models. The Task Force for development of guidelines for thyroid dysfunction management in pregnant women was established in 2008. The expert group has recognized the following tasks: development of the coherent model of the management of thyroid dysfunction in pregnant women, identification of the group of women at risk of thyroid dysfunction, who may require endocrine care in the preconception period, during pregnancy and postpartum - that is in other words, the development of Polish recommendations for targeted thyroid disorder case finding during pregnancy, and the development of Polish trimester-specific reference values of thyroid hormones. Comprehensive Polish guidelines developed by the Task Force are to systematize the management of the thyroid disorders in pregnant women in Poland.

Introduction: Real-time elastography (RTE) is a non-invasive ultrasound method of estimation of tissue stiffness by measuring the degree of local tissue displacements after a small compression. Recent data has shown its ability to differentiate benign from malignant tumours. The aim of this study was to evaluate the accuracy of RTE in the diagnosis of malignant and benign thyroid nodules., Material and Methods: 71 thyroid nodules in 52 patients: 42 females and 10 males aged 28-77 were examined using conventional ultrasonography (US), fine-flow CD imaging and RTE. All nodules previously underwent fine-needle aspiration biopsy (FNAB), and patients with malignant and suspicious cytological results were referred for surgery. The final diagnosis was based on FNAB results in patients with benign cytology and on the histopathology reading in those who underwent surgery. An elasticity score (ES) from 1 to 5 was determined for each nodule according to the Ueno classification., Results: An elasticity score (ES) of 4 or 5 was found in 19 out of 22 (86.5%) thyroid cancers and in only 1 out of 31 (3%) benign nodules. This was strongly indicative for malignancy (p 〈 0.0001) with sensitivity 86%, specificity 97%, positive predictive value (PPV) 95% and negative predictive value (NPV) 91%., Conclusions: RTE is a highly sensitive and specific method of diagnosing thyroid nodules. This technique can be employed in selecting thyroid nodules for fine-needle aspiration biopsy.

Introduction: Until 1997, Poland was one of the European countries suffering from mild/moderate iodine deficiency. In 1997, a national iodine prophylaxis programme was implemented based on mandatory iodisation of household salt with 30 ± 10 mg KI/kg salt, obligatory iodisation of neonatal formula with 10 μg KI/100 mL and voluntary supplementation of pregnant and breast-feeding women with additional 100-150 μg of iodine. Our aim in this study was to evaluate the iodine status of pregnant women ten years after iodine prophylaxis was introduced., Material and Methods: A cross-sectional study was undertaken in 100 healthy pregnant women between the fifth and the 38th week of gestation with normal thyroid function, singleton pregnancy, normal course of gestation, without drugs known to influence thyroid function except iodine. Serum TSH, fT(4), fT(3), thyroglobulin (TG), anti-peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (TGAb) and urinary iodine concentration (UIC) were determined. Thyroid volume and structure were evaluated by ultrasonography., Results: Fifty nine per cent of studied pregnant women had a diet rich with iodine carriers and 35% obtained iodine supplements. Twenty eight per cent appeared to have a goitre: 11 diffuse and 17 a nodular one, median goitre volume was 18.7 mL (range 6.8-29.0 mL). Median UIC was 112.6 μg/L (range 36.3-290.3 μg/L), only 28% of women had UIC ≥ 150 μg/L. Median UIC was significantly higher in the group receiving iodine supplements than in the group without iodine supplements: 146.9 μg/L v. 97.3 μg/L respectively, p 〈 0.001. Serum TSH, fT(3) and fT(3)/fT(4) molar ratio increased significantly during pregnancy while fT(4) declined. Median serum TG was normal: 18.3 ng/mL (range 0.4-300.0 ng/mL) and did not differ between trimesters. Neonatal TSH performed on the third day of life as a neonatal screening test for hypothyroidism was normal in each case: median value was 1.49 mIU/L (range 0.01-7.2 mIU/L). Less than 3% (2 out of 68) of results were 〉 5 mIU/L., Conclusion: Iodine supplements with 150 μg of iodine should be prescribed for each healthy pregnant woman according to the assumptions of Polish iodine prophylaxis programme to obtain adequate iodine supply. (Pol J Endocrinol 2010; 61 (6): 646-651).

Current thyrotropin (TSH) reference range established by sensitive assays is from 0.2-0.4 mj.m./l to 4.0-4.5 mj.m./l. Serum TSH reference range was performed using specimens from healthy volunteers without history of thyroid disease but the values distribution is not concordant with Gaussian curve and is skewed toward upper values. It is claimed that upper reference limit for TSH should be declined because of possible incorporation of individuals with unrecognized chronic lymphocytic thyroiditis into initial study. American National Academy of Clinical Biochemistry recommends to examine only euthyroid healthy volunteers without personal or family history of thyroid dysfunction, visible or palpable goiter, with no detectable thyroid antibodies measured by sensitive immunoassays and without any medication except estrogen. Many authors observed that even in such rigorously selected population the upper limit of TSH does not decrease significantly. The other possible factors which may influence TSH values are ethnic features, age, iodine intake, time of phlebotomy or assay sensitivity and specificity. Furthermore there are no epidemiological data showing adverse consequences of serum TSH between 3.0 mj.m./l and 5.0 mj.m./l. And because of it current upper limit for TSH should remain unchanged. However one must realize that many people with TSH values between 3.0 mj.m./l and 5.0 mj.m./l have unrecognized chronic lymphocytic thyroiditis and should be followed because of possible future hypothyroidism. The special care is needed for pregnant women or those planning to be pregnant.

The case of 54-year old woman with severe Graves thyrotoxicosis and antithyroid drugs intolerance is presented. She was admitted to Endocrinology Department and therapy with propranolol, lithium, glucocorticoids, iodine contrast media was instituted. Then ablative dose of radioiodine was given; all these appeared to be ineffective. To avoid thyrotoxic storm thyroidectomy was undertaken. Surgical procedure was uneventful and successful. Surgical intervention should be considered in severe life-threatening cases of thyrotoxicosis.

The role of glycan moieties in thyrotropin receptor molecule in binding of antibodies is a subject of intense debate. To approach the function of sugars in recognition by antibody of the extracellular part of the receptor (ETSHR) we studied the reaction of the HPLC purified ETSHR from insect cells in the reaction with autoantibodies and antibodies of animal origin. None of the autoantibodies from Graves' patients sera bound to ETSHR. In contrast, each of the animal antibodies: three monoclonal, five polyclonal antireceptor and two polyclonal anti peptide corresponding to the amino acid sequence present in the receptor, became bound to the native receptor from insect cells as well as to its deglycosylated form. The shape of the dilution curves of particular antibodies in the reaction with either form of the receptor was almost the same. The coefficients of correlation was about 0.9. It seems that the correct receptor glycosylation is not crucial for binding of animal origin antibodies.

In a study designed to detect the presence of soluble, secreted A subunit of thyrotropin hormone receptor (TSHR) in serum, using anti-TSHR murine antibodies (mAbs) and peptide specific antiserum for Western blotting of human serum proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) it was consistently observed that only one mAb, termed A10, reacted strongly with the 53 kd serum protein. The reaction was specific with the mAb A10 only, but not with another mAb or polyclonal antiserum. Furthermore, A10 immunoreactivity was documented in a variety of sera from healthy donors and patients, including patients whose thyroid gland was ablated during treatment for thyroid cancer. This suggests that the A10 cross-reactive protein was not derived from thyroid cells. The A10 cross-reactive protein was purified from normal serum and subjected to N-terminal sequence analysis, which identified the protein as alpha(1)-antitrypsin. Further experiments by enzyme-linked immunosorbent assay (ELISA) and the binding of antibody with deglycosylated or elastase-treated purified serum protein confirmed the cross-reactivity of mAb A10 with alpha(1)-antitrypsin. Alignment of the TSHR amino acid sequence with that of alpha(1)-antitrypsin identified five identical amino acids in a short stretch of residues 34-39 (EEDFRV) in TSHR and residues 205-210 (EEDFHV) in alpha(1)-antitrypsin. Analysis of the structural model of alpha(1)-antitrypsin revealed that these residues were exposed on the surface of alpha(1)-antitrypsin and were accessible for antibodies. Autoantibodies in patients with Graves' disease do not appear to recognize this region of the receptor and hence do not react with serum alpha(1)-antitrypsin.

Total thyroidectomy followed by 131I ablation and thyroxine suppressive therapy is recommended for the treatment of differentiated thyroid carcinomas. Thyroxine should be given at a dose sufficient to suppress TSH to low or undetectable levels. These patients are categorized as subclinical hyperthyroidism subjects. Some cardiovascular effects of subclinical hyperthyroidism, such as an increase in left ventricular mass and accelerated bone loss, should be taken into consideration. Estrogens reduce the loss of bone mass in thyrotoxic postmenopausal patients and have cardioprotective effects. The relatively high incidence of thyroid carcinoma in women suggests that estrogen and/or progesterone may be important for the development of these neoplasms. Immunohistochemical study has established that steroid receptors are present in thyroid tissue. Many authors suggest that estrogens by itself do not appear to affect the natural history of thyroid cancer. Besides the thyroid, active iodide transports catalysed by the sodium/iodide symporter occurs in the lactating mammary gland. An increased risk of breast carcinoma in women with thyroid carcinoma due to carcinogenicity of radioiodine has been reported by some but not all investigators. Hormone replacement therapy in the thyroxine treated postmenopausal women consists in conventional oral or transdermal estrogen combined with progesterone. In some cases the daily dose of thyroxine should be increased to achieve TSH suppression.

Unlabelled: The aim of the study was to estimate the dose of thyroxine required by pregnant women who had undergone total thyreoidectomy and radioiodine treatment for thyroid cancer. Material consisted of 4 pregnant women, aged mean 30.8 years. One of patients was studied during 2 consecutive pregnancies. The daily mean dose of thyroxine was 175 micrograms. The control group consisted of 7 women with primary hypothyroidism aged mean 33.5 years, who were treated with replacement doses of thyroxine. One of them was pregnant twice. The mean daily dose of thyroxine was 106.3 micrograms. The estimation of TSH, fT4 were repeated every 4 weeks., Results: In all cases natural deliveries took place. All infants were alive and had no congenital malformations and no clinical or biochemical thyroid dysfunction was found. Pregnant women treated for thyroid cancer needed to have optimized their suppressive therapy by increasing the dose of thyroxine by 26% at the first trimester, 27% at the second and 38% at the last one. Statistically significant increase was found at the 1st trimester of pregnancy and it remained at the same level till the delivery. Pregnant hypothyroid women needed to have optimized their replacement thyroxine therapy by increasing of the dose by 53% at the first trimester, by 49% at the second and by 53% at the last one. Similarly to the 1st group of patients, we noticed statistically significant increase at the 1st trimester of pregnancy., Conclusion: In pregnant women who have been previously treated for thyroid cancer the suppressive dose of thyroxine needs to be increased by 26-38% which is slightly less than the increase of the replacement dose in hypothyroid pregnant women.