The role of intraoperative frozen section of central neck lymph nodes in the management of patients preoperatively diagnosed with low- risk differentiated cancer.

INTRODUCTION: Histological examination during surgery (FS) has a place in the surgical management of differentiated thyroid carcinoma (DTC). Extending the indication for limited surgery to 4 cm tumor size (ATA guidelines 2015) cytologically verified DTCs, increases the emphasis on accurate patient selection. In our work, we reflected on the effectiveness of FS and its relationship to optimal patient management. METHODS: In a single-center retrospective study, we evaluated the documentation of patients indicated for primary surgery for DTC from January 1, 2016 to December 31, 2020 - there was 489 patients collectively, 121 were men, median age was 50 years (1681), 73 patients (female, age 1845 years) with preoperatively identified low-risk DTC (size 1140mm) were indicated for lobectomy. RESULTS: 34 patients (46.6%) did not meet the criteria for limited surgery 15 patients were identified from FS of the lymph nodes of the central compartment (LNCK) (15 of 25 patients) - 1 patient with false negative result and 6 patients with FS of the thyroid gland (SH) (6 / 41) - 11 patients with false negative findings. Two-step OP surgery was performed on 13 patients (17.8%). FS of LNCK identified high-risk cancer and reduced the risk of two-step surgery compared to the group of patients in whom FS was not performed or was performed from thyroid gland. The difference was statistically significant (OR 1.93, p=0.026). CONCLUSION: Approximately ½ of the patients from preoperatively identified low-risk cancers in our cohort met the criteria for limited surgery. About 30% of them eventually needed a two-step operation. Perioperative examination of LNCK helps to perform radical surgery at one time.

Recombinant human thyrotropin in follow-up of patients with differentiated thyroid cancer.

BACKGROUND: Despite very good prognosis patients with previously treated well-differentiated thyroid cancer (DTC) require lifelong monitoring for recurrent disease. Apart from neck ultrasonography (USG) two diagnostic tests play a central role in follow-up of these patients: radioiodine whole body scanning and serum thyroglobulin (Tg) measurement. The diagnostic value of both tests is most accurate during thyroid stimulating hormone (TSH) stimulation. Temporary discontinuation of thyroid hormone therapy was previously the sole effective approach for TSH-stimulated testing. However, hormone withdrawal was associated with the morbidity of severe hypothyroidism. The introduction of recombinant human TSH (rhTSH)-stimulated testing offers an alternative way. Recent clinical trials have shown that measurement of the rhTSH-stimulated serum Tg concentration (rhTSH-Tg) alone is the most sensitive way to detect residual or recurrent thyroid cancer. OBJECTIVES: The aim of the study was to investigate rhTSH-Tg in patients considered to be cured with already finished radioiodine treatment 1-3 years ago (routine follow-up) and in patients more years after radioiodine therapy with a new indefinite (mild) suspicion for DTC recurrence and to report the first experience with this diagnostic procedure in Slovakia. PATIENTS AND METHODS: RhTSH-Tg was examined in 84 patients (72 women and 12 men) clinically free of disease, 1-3 years after finishing radioiodine therapy. Second group consisted of 4 patients (2 women and 2 men) 5, 9, 12 and 38 years after 1311 treatment with a mild suspicion of DTC recurrence. RESULTS: RhTSH testing was well tolerated. No adverse events were detected. In the first group clinically free of disease undetectable rhTSH-Tg (< 0.2 ng/ml) was found in 77 patients (91.7%), Tg above diagnostic cutoff (> 2 ng/ml) in 4 patients (4.8%) and Tg in the range 0.6-2 ng/ml in 3 cases (3.6%). In all patients of second group previous indefinite suspicion of DTC recurrence was confirmed by the rhTSH-Tg rise (2.9-7.3 ng/ml). CONCLUSION: In accordance with the literature rhTSH-Tg concentration in combination with neck USG has the highests sensitivity and negative predictive value in detecting residual or recurrent DTC (Tab. 1, Fig. 1, Ref. 14). Full Text (Free, PDF) www.bmj.sk.

Current status of iodine deficiency-related disorders prophylaxis in Slovakia - the life's work of Julian Podoba remained unfinished.

OBJECTIVE: Prophylaxis of iodine deficiency-related disorders with iodized salt in Slovakia was introduced in 1951. This prophylactic measure yielded remarkably good results. Endemic goiter and endemic cretinism disappeared. Sufficient iodine intake, mainly in children and adolescents, was confirmed in several local and international studies carried out in the period 1991-95. Unfortunately, since seventies, there has been no institution which would have dealt with iodine prophylaxis in such an extent as this important measure of Slovak preventive medicine would require. Neither systematic monitoring of iodine intake nor systematic population epidemiological studies have been carried out. We do not have any data on the iodine intake in pregnant women, the most vulnerable population group in relation to the iodine deficiency. During the period June 2014 - October 2015, we examined iodine excretion in 426 probands from three regions of Slovakia with an emphasis on the pregnant women. RESULTS: Iodine intake was found to be sufficient, even more than adequate, in all age groups of Slovak population. The only population group with iodine intake borderline or very mild iodine deficiency are pregnant women. CONCLUSIONS: 1/ Iodine nutrition in Slovakia is generally sufficient, even oversteps the requirement, with the exception of pregnant women. Iodine intake in pregnant women should be fortified by iodine containing multivitamin preparations. 2/ We recommend to include the examination of urinary iodine into the screening of thyropathies in early pregnancy. 3/ It is not enough to implement the iodine deficiency-related disorders prevention programs, it is also necessary to stabilize such programs over time and balance the benefits with possible side effects of this program.

Thyroid volumes and urinary iodine in Swiss school children, 17 years after improved prophylaxis of iodine deficiency.

Salt iodine content in Switzerland was raised from 7.5 to 15 mg per kg in 1980, and since then dietary iodine intake has been considered to be sufficient, even though a slight decrease due to imported food has recently been reported. The aim of this study was to establish normal values for thyroid volumes of school children who can be assumed to have had a sufficient iodine intake all their lifetime. Moreover. the present investigation was undertaken to verify that iodine sufficiency had been achieved equally in two regions each served by one of the two Swiss salt producers. Mean iodine concentration in urine spot samples from school children was 16.1 microg/dl, and it was identical in both the city of Lausanne (n=215) and the city of Solothurn (n=208). Thus it can be stated that in both cities (served by two different salt producers) iodine intake is equal and sufficient. Accordingly, thyroid volumes measured by ultrasound in school children aged 6 to 16 years were the same in both Lausanne (n=202) and Solothurn (n=207). Moreover, the age-adjusted median volumes at the 97th percentiles closely agree with and validate provisional international reference values recently proposed by the World Health Organisation and by the International Council for Control of Iodine Deficiency Disease.

Toward a consensus on reference values for thyroid volume in iodine-replete schoolchildren: results of a workshop on inter-observer and inter-equipment variation in sonographic measurement of thyroid volume.

OBJECTIVE: Interpretation of thyroid ultrasonography for assessing goiter prevalence requires valid reference criteria from iodine-sufficient populations. Reports have suggested the current reference criteria for thyroid volume (T(vol)) of WHO/ICCIDD (International Council for the Control of Iodine Deficiency Disorders) may be too high. Our objective was to determine if inter-observer and/or inter-equipment variability contributes to the disagreement in sonographic T(vol) in children reported from iodine-sufficient areas. DESIGN: A 2-day workshop in which four experienced ultrasound examiners from around Europe measured T(vol) in 45 6--12-year-old Swiss schoolchildren using four different portable ultrasound machines. One of the participating examiners (observer A) had generated the T(vol) data in European children that are the basis for the WHO/ICCIDD reference criteria. METHODS: Sonographic T(vol) was measured in each child by all four examiners on all four machines. Six hundred and eighty-four examinations were completed, with examiners having no knowledge of one another's results. Inter-observer and inter-equipment variation was calculated. RESULTS: Mean inter-equipment variation in T(vol) was 15.2% (95% CI: 14.1, 16.3%). There were no significant differences in T(vol) between equipment (P=0.51). For all observers, the mean inter-observer variation in T(vol) was 25.6% (95% CI: 23.9, 27.2%). At all ages and all body surface areas, there was a large systematic measurement bias (+30% volume) between the mean T(vol) of observer A and the mean Tvol of observers B, C and D. Reanalysis using data from observers B, C and D reduced the mean inter-observer variation in T(vol) to 13.3% (95% CI: 11.9, 14.7%). A correction factor for the systematic difference of operator A for the P50 and P97 of T(vol) was estimated using analysis of covariance. When applied to the WHO/ICCIDD reference data, it sharply reduced the discrepancy between the WHO/ICCIDD criteria and those from other iodine-sufficient children around the world. CONCLUSIONS: Inter-equipment error contributes minimally to reported differences in sonographic T(vol). Even among experienced examiners, inter-observer variation in sonographic T(vol) in children can be high, and probably contributes to the current disagreement on normative values in iodine-sufficient children. A systematic bias at least partially explains why the WHO/ICCIDD reference data differ from those reported from other iodine-sufficient children around the world. The findings argue strongly for the standardization of methods used for sonographic measurement of T(vol) in children.

A survey of iodine intake and thyroid volume in Dutch schoolchildren: reference values in an iodine-sufficient area and the effect of puberty.

BACKGROUND: Iodine deficiency and endemic goiter have been reported in the past in The Netherlands, especially in the southeast. OBJECTIVE: To evaluate iodine intake and thyroid size in Dutch schoolchildren, contrasting those living in a formerly iodine-deficient region in the east (Doetinchem) with those living in an iodine-sufficient region in the west (Amsterdam area). DESIGN: Cross-sectional survey of 937 Dutch schoolchildren aged 6--18 years, of whom 390 lived in the eastern and 547 in the western part of the country. METHODS: Thyroid size was assessed by inspection and palpation as well as by ultrasound. Iodine intake was evaluated by questionnaires on dietary habits and by measurement of urinary iodine concentration. RESULTS: Eastern and western regions were similar with respect to median urinary iodine concentration (15.7 and 15.3 microg/dl, NS, Mann-Whitney U test), goiter prevalence by inspection and palpation (0.8 and 2.6%, P=0.08, chi-squared test), and thyroid volumes. The P97.5 values of thyroid volumes per age and body surface area group were all lower than the corresponding sex-specific normative WHO reference values. Iodized salt was not used by 45.7% of households. Daily bread consumption was five slices by boys and four slices by girls. Weekly milk consumption was 3 liters by boys and 2 liters by girls. Seafish was consumed once monthly. From these figures we calculated a mean daily iodine intake of 171 microg in boys and 143 microg in girls, in good agreement with the measured median urinary concentration of 16.7 microg/dl in boys and 14.5 microg/dl in girls. The sex difference in iodine excretion is fully accounted for by an extra daily consumption of one slice of bread (20 microg I) and one-seventh of a liter of milk (8.3 microg I) by boys. Thyroid volume increases with age, but a steep increase by 41% was observed in girls between 11 and 12 years, and by 55% in boys between 13 and 14 years, coinciding with peak height velocity. Girls have a larger thyroid volume at the ages of 12 and 13 years, but thyroid volume is larger in boys as of the age of 14 years. CONCLUSIONS: (1) Iodine deficiency disorders no longer exist in The Netherlands. (2) Bread consumption remains the main source of dietary iodine in The Netherlands; the contribution of iodized table salt and seafish is limited. (3) The earlier onset of puberty in girls renders their thyroid volume larger than in boys at the age of 12--13 years, but boys have a larger thyroid volume as of the age of 14 years.

Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency.

Up to 1992, most European countries used to be moderately to severely iodine deficient. The present study aimed at evaluating possible changes in the status of iodine nutrition in 12 European countries during the past few years. Thyroid volume was measured by ultrasonography in 7599 schoolchildren aged 7-15 years in one to fifteen sites in The Netherlands. Belgium, Luxemburg, France, Germany, Austria, Italy, Poland, the Czech and Slovak Republics, Hungary and Romania. The concentrations of urinary iodine were measured in 5709 of them. A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites in the 12 countries. All ultrasounds and all urinary iodine assays were performed by the same investigators. The status of iodine nutrition in schoolchildren has markedly improved in many European countries and is presently normal in The Netherlands, France and Slovakia. It remains unchanged in other countries such as Belgium. There is an inverse relationship between urinary iodine and thyroid volume in schoolchildren in Europe. Goiter occurs as soon as the urinary iodine is below a critical threshold of 10 micrograms/dl. Its prevalence is up to 10 to 40% in some remote European areas. This work produced updated recommendations for the normal volume of the thyroid measured by ultrasonography as a function of age, sex and body surface area in iodine-replete schoolchildren in Europe. This study proposes a method for a standardized evaluation of iodine nutrition on a continental basis, which could be used in other continents.

A programme of iodine supplementation using only iodised household salt is efficient--the case of Poland.

BACKGROUND: Iodine prophylaxis in Poland started in 1935 and has been interrupted twice: by World War II and in 1980 for economic reasons. Epidemiological surveys carried out after the Chernobyl accident in 1989 as well as in 1992/1993 and in 1994 as a 'ThyroMobil' study, revealed increased prevalence of goitre in children and adults. Ninety per cent of Poland was classified as an area of moderate iodine deficiency, and 10%, in the seaside area, as mild iodine deficiency territory. Iodine prophylaxis based on iodisation of household salt was introduced again in 1986 as a voluntary model and in 1997 as a mandatory model with 30+/-10 mg KI/kg salt. OBJECTIVE: The evaluation of the obligatory model of iodine prophylaxis in schoolchildren from the same schools in 1994 and 1999. METHODS: Thyroid volume was determined by ultrasonography. Ioduria in casual morning urine samples was measured using Sandell-Kolthoff's method, within the framework of the ThyroMobil study. RESULTS: Goitre prevalence decreased from 38.4 to 7% and urinary iodine concentration increased from 60.4 to 96.2 microg/l mean values between 1994 and 1999. In four schools the prevalence of goitre diminished below 5%. In 1999, 70% of children excreted over 60 microg I/l, and 36% over 100 microg I/l, whereas in 1994 the values were 44 and 13% respectively. CONCLUSION: The present findings indicate that iodine prophylaxis based only on iodised household salt is highly effective.

Environmental risk factors for delirium in hospitalized older people.

OBJECTIVES: To evaluate the relationship of environmental risk factors in hospitals to changes over time in delirium symptom severity scores. DESIGN: Observational prospective clinical study with repeated measurements, several times during the first week of hospitalization and then weekly during hospitalization. SETTING: University-affiliated general community hospital. PARTICIPANTS: Four hundred forty-four patients age 65 and older admitted to the medical wards: 326 with delirium and 118 without delirium. Patients with prior cognitive impairment were oversampled. MEASUREMENTS: The severity of delirium symptoms was measured with the Delirium Index, a scale developed and validated by our group, based on the Confusion Assessment Method. Potential environmental risk factors assessed included isolation, hospital unit, room changes, levels of sensory stimulation, aids to orientation, and presence of medical (e.g., intravenous) or physical restraints. RESULTS: Controlling for initial severity of delirium and patient characteristics, variables significantly related to an increase in delirium severity scores included hospital unit (intensive care or long-term care unit), number of room changes, absence of a clock or watch, absence of reading glasses, presence of a family member, and presence of medical or physical restraints. CONCLUSION: The associations of intensive care and medical and physical restraints with severity of delirium symptoms may be due to uncontrolled confounding by indication. However, the other factors identified suggest potentially modifiable risk factors for symptoms of delirium in hospitalized older people.

Thyroid hormone receptors and type I iodothyronine 5'-deiodinase activity of human thyroid toxic adenomas and benign cold nodules.

The majority of thyroid adenomas are of clonal origin. In a subset of toxic adenomas (TAs) and cold nodules (CNs) activating mutations in the thyrotropin (TSH) receptor or G s -alpha gene may explain the altered functions in these benign tumours. The present study was undertaken to investigate the status of functional thyroid hormone receptors, major thyroid hormone signal mediators, in both the human TAs and CNs in comparison with a normal thyroid tissue from the same patient. Electrophoretic mobility shift assays using a DR4 ("direct repeats" 4), a thyroid hormone responsive element (TRE) of human type I iodothyronine 5'-deiodinase demonstrated the DNA-binding of thyroid hormone receptors (TRs) in thyroid tissue nuclear extracts. A significant increase (p < 0.05) in the functional binding properties of TRs to the DR4 thyroid hormone responsive element was found in TAs when compared to normal thyroid tissue. Contrary, a marked diminution in the TR-TRE complex formation was found in CNs in comparison with normal thyroid tissue. In addition, functional activity of the iodothyronine 5'-deiodinase (5'DI) was analyzed in benign tumours, thyroid TAs and CNs in comparison with that of normal thyroid tissue. A significantly increased (p < 0.01) activity of 5'DI was demonstrated in TAs, and in contrast, decreased values of the enzyme activity were found in CNs when compared to a normal tissue. From the data it is suggested that both the status of TR-TRE complex formation and the activity of the 5'DI may be altered in benign tumours of human thyroid gland.

[Thin-needle aspiration biopsy in the preoperative diagnosis of non-toxic nodular goiter]. / Aspiracná tenkoihlová biopsia v predoperacnej diagnostike netoxickej uzlovej strumy.

The ascertainment of diagnostic reliability of fine needle aspiration biopsy in preoperative examination of non-toxic goitres is performed by comparing its results with the findings of the definitive histologic examination. The set of patients did not include those with the cytological finding of Hürtle tumour for the impossibility to distinguish between adenomas and carcinomas from oxyphilic cells by means of cytologic examination. Aspirates were stained by May, Grunwald and Giemsa method. Histologic results were gained from 185 patients. Cytologic findings were considered as benign in 95 cases (however 3 cases of cancer were revealed by the histologist--false negativity). In 90 cases, atypia, findings of suspectivity, or diagnosis of malignity were described, however the histologist evaluated 49 cases of goitres as being benign (false positivity). Totally 44 cases of malignant tumours were histologically diagnosed. Diagnostic sensitivity in our set of patients was 0.97 and diagnostic specificity was 0.46. In accordance with the available literature, fine needle cytodiagnosis is considered to represent an appropriate screening method in the process of decision as to whether conservative or surgical therapy with histologic verification in patients with non-toxic nodular goitres is to be indicated. (Tab. 1, Ref. 6.).

[The effectiveness of iodine prophylaxis of endemic goiter in Slovakia from the viewpoint of physical and ultrasonographic examinations of the thyroid gland]. / Ucinnost jódovej profylaxie endemickej strumy na Slovensku z hl'adiska fyzikálneho a ultrasonografického vysetrenia stítnej zl'azy.

Being aimed at the effectivity of iodine prophylaxis of endemic goitre the authors examined 2946 children and adolescents at the age of 6-18 years during the period from 1989 to 1995 in 6 regions of Slovakia. The thyroid glands were examined physically and ultrasonographically. The authors have found out that the occurrence rate of diffuse goitre is acceptable and it is not meeting the criteria of endemic goitre. No case of nodular goitre was revealed. Similarly to the relative frequency of diffuse goitre, neither the ultrasonographically measured volumes of thyroid glands differed among various areas. They are comparable with the volumes detected in countries with a sufficient iodine supply. The use of criteria for iodine deficiency evaluation recommended by WHO (goitre occurrence, thyroid gland volume, ioduria) leads the authors to consider the current prophylaxis of endemic goitre as being effective and successful. (Tab. 5, Ref. 20.).

[Thyrotropin-secreting adenomas of the hypophysis]. / Tyreotropín secernujúce adenómy hypofýzy.

Thyrotropin secreting pituitary adenomas are scarce. They may cause an extremely rare form of hyperthyroidism. The diagnosis is often delayed because the clinical symptoms are attributed to common types of hyperthyroidism. The diagnosis involves detection of elevated or normal (unsuppressed) thyrotropin levels in hyperthyroid patients and evidence of a pituitary adenoma by computed tomography or magnetic resonance imaging. The thyrotropin response in the thyrotropin-releasing hormone test is either absent or insufficient. When the pituitary microadenoma appears to be undetectable, the familiar syndrome of selective pituitary resistance to thyroid hormones has to be excluded. Treatment involves extirpation of the tumour. If the macroadenoma is not removed completely, external radiotherapy of the pituitary follows. If this conventional treatment does not produce an adequate effect, treatment with long-acting somatostatin analogues is recommended.

[Fibrillary glomerulopathy]. / Fibrilárne glomerulopatie.

The authors present an account on contemporary knowledge of the diagnosis and differential diagnosis of fibrillar glomerulopathies. The latter are characterized by extracellular localized microfibrils and microtubules resp. in the glomeruli of the kidneys, their diameter being 8-60 nm. They are divided into amyloid and non-amyloid types. The others are classified according to the immunofluorescent finding into immunoglobulin positive and negative ones. The differential diagnosis is important in particular in immunoglobulin positive ones as they are present in serious diseases such as cryoglobulinaemia, monoclonal gammapathy, systemic lupus erythematosus and immunotactoid glomerulopathy.

[Octreotide in the treatment of thyrotropin-secreting pituitary adenomas]. / Oktreotid v liecbe tyreotropín secernujúcich adenómov hypofýzy.

The authors detected in a 30-year-old patient a very rare type of hyperthyroidism caused by a thyrotropin secreting pituitary adenoma. Scintigraphic examination of the pituitary by means of 111In radiolabelled octreotide revealed an increased accumulation of the radiopharmaceutical preparation in the tumour, which confirmed the high density of somatostatin receptors. After onset of octreotide treatment (Sandostatin, Sandoz, Switzerland) 3 x 100 ug/day by the s.c. route a brisk decline and normalization of thyrotropin already after the first dose was recorded. The thyroxine concentration declined slowly to the upper range of normal values. After 5 months treatment despite the positive response to receptor scintigraphy diminution of the adenoma was not recorded. Again an increase of thyrotropin above the upper limit of the reference range and a marked rise of thyroxinaemia were observed. Six months after radical selective trans-sphenoidal adenomectomy normal pituitary function was confirmed.

[Surgical treatment of hyperparathyroidism]. / Chirurgická liecba hyperparatyreoidizmu.

The authors present their experience with the diagnosis and treatment of hyperparathyroidism in a group of eight patients operated between June 1993 and November 1993 at the Surgical Clinic of Dérer's Hospital in Bratislava-Kramáre. They summarize the findings on the disease from the literature and compare them with their own clinical observations, which confirm the indication of surgical revision as a useful localizing method, and the necessity of perioperative histological diagnosis to determine the extent of surgery.

Effect of growth hormone replacement therapy on plasma brain natriuretic peptide concentration, cardiac morphology and function in adults with growth hormone deficiency.

OBJECTIVE: The impact of growth hormone (GH) replacement on plasma brain natriuretic peptide (BNP) in association with cardiac morphology and function in adults with growth hormone deficiency (GHD) was evaluated. SUBJECTS AND METHODS: Fifty nine adult patients with GHD (29 men, age 19-59 years) received a starting dose of 0.1-0.2 mg/day recombinant GH, which was subsequently adjusted to the 50th percentile of normal serum insulin-like growth factor (IGF-1) over a 6 month period. Plasma BNP and IGF-I levels before, 3 and 6 months after treatment were determined, as were the echocardiographic data, such as ejection fraction (EF), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular mass (LVM), E/A wave and deceleration time (DT). RESULTS: Mean plasma BNP levels (53.1+/-8 pg/ml) and echocardiographic parameters were within the normal range at baseline, although men had higher LVM, IVST, PWT, LVEDV and LVEDD, respectively. A significant decrease in plasma BNP was observed after 6 months (27+/-5.6 pg/ml, P<0.05). No significant changes in echocardiographic parameters were observed except for a mild tendency to increase in LVM, and a borderline decrease in DT (181+/-8.1 vs. 155+/-9 ms, P<0.01). CONCLUSIONS: Six months GH replacement therapy induced a significant decrease in plasma BNP levels despite the majority of patients having plasma BNP within the normal range at baseline. A borderline decrease in diastolic deceleration time was observed, the clinical significance of which is unclear.