Assessment of different markers of ovarian reserve in women with papillary thyroid cancer treated with radioactive iodine.

Treatment with radioactive iodine (RAI) in women with differentiated thyroid cancer is associated with decreased serum concentrations of anti-Müllerian hormone (AMH); however, other markers have not been investigated. Therefore, this study aimed to evaluate the effect of RAI treatment on antral follicle count (AFC) and the serum concentration of inhibin B, follicle-stimulating hormone (FSH), and AMH in women with papillary thyroid cancer (PTC) treated with RAI. We examined 25 women at a median age of 33 years treated with a single dose of RAI. We divided the participants into women over (n = 11) and under 35 years of age (n = 14). Serum concentrations of inhibin B, FSH, AMH, and AFC were assessed at baseline and 1 year after RAI treatment. We found decreased AFC (P = 0.03), serum levels of AMH (P < 0.01), inhibin B (P = 0.03), but not FSH (P = 0.23), 1 year after RAI treatment in comparison to baseline in the whole group. When we compared serum levels of AMH in younger vs older women separately, we observed a significant reduction of this hormone's serum level after RAI treatment in both groups (P < 0.01; P = 0.04, respectively). We concluded that RAI treatment significantly impacts the functional ovarian reserve in premenopausal women with PTC.

Assessment of Clinical Utility of Assaying FGF-23, Klotho Protein, Osteocalcin, NTX, and Sclerostin in Patients with Primary Hyperparathyroidism.

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium-phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed.

Dosimetry during adjuvant 131I therapy in patients with differentiated thyroid cancer-clinical implications.

The activity of radioiodine (131I) used in adjuvant therapy for thyroid cancer ranges between 30 mCi (1.1 GBq) and 150 mCi (5.5 GBq). Dosimetry based on Marinelli's formula, taking into consideration the absorbed dose in the postoperative tumour bed (D) should systematise the determination of 131I activity. Retrospective analysis of 57 patients with differentiated thyroid cancer (DTC) after thyreidectomy and adjuvant 131I therapy with the fixed activity of 3.7 GBq. In order to calculate D from Marinelli's formula, the authors took into account, among other things, repeated dosimetry measurements (after 6, 24, and 72 h) made during scintigraphy and after administration of the therapeutic activity or radioiodine. In 75% of the patients, the values of D were > 300 Gy (i.e. above the value recommended by current guidelines). In just 16% of the patients, the obtained values fell between 250 and 300 Gy, whereas in 9% of the patients, the value of D was < 250 Gy. The therapy was successful for all the patients (stimulated Tg < 1 ng/ml and 131I uptake < 0.1% in the thyroid bed in follow-up examination). Dosimetry during adjuvant 131I therapy makes it possible to diversify the therapeutic activities of 131I in order to obtain a uniform value of D.

Pre-Processing Method for Contouring the Uptake Levels of [18F] FDG for Enhanced Specificity of PET Imaging of Solitary Hypermetabolic Pulmonary Nodules.

BACKGROUND: The paper presents a pre-processing method which, based on positron-emission tomography (PET) images of 18F-fluorodeoxyglucose ([18F] FDG) hypermetabolic pulmonary nodules, makes it possible to obtain additional visual characteristics and use them to enhance the specificity of imaging. MATERIAL AND METHODS: A retrospective analysis of 69 FDG-PET/CT scans of solitary hypermetabolic pulmonary nodules (40 cases of lung cancer and 29 benign tumours), where in each case, the standardised uptake value of the hottest voxel within the defined volume of interest was greater than 2.5 (SUVmax > 2.5). No diagnosis could be made based on these SUVmax values. All of the PET DICOM images were transformed by means of the pre-processing method for contouring the uptake levels of [18F] FDG (PCUL-FDG). Next, a multidimensional comparative analysis was conducted using a synthetic variable obtained by calculating the similarities based on the generalised distance measure for non-metric scaling (GDM2) from the pattern object. The calculations were performed with the use of the R language. RESULTS: The PCUL-FDG method revealed 73.9% hypermetabolic nodules definitively diagnosed as either benign or malignant lesions. As for the other 26.1% of the nodules, there was uncertainty regarding their classification (some had features suggesting malignancy, while the characteristics of others made it impossible to confirm malignancy with a high degree of certainty). CONCLUSIONS: Application of the PCUL-FDG method enhances the specificity of PET in imaging solitary hypermetabolic pulmonary nodules. Images obtained using the PCUL-FDG method can serve as point of departure for automatic analysis of PET data based on convolutional neural networks.

The Role of the CYP11B2 Promoter Polymorphism in the Diagnosis of Primary Aldosteronism.

BACKGROUND: nowadays, primary aldosteronism (PA) is suggested to be the most frequent cause of secondary hypertension and it reaches 10% of whole hypertensive population. The CYP11B2 promoter polymorphism might cause aldosterone overproduction. The aim of this study was to establish whether the polymorphism CYP11B2 promoter has a significant impact on diagnostic of PA. MATERIAL AND METHODS: study group consisted of 239 hypertensive patients previously diagnosed with adrenal incidentaloma. For diagnose of PA were performed: screening test-aldosterone-renin ratio (ARR) and saline suppression test (SIT) as a confirmatory test. Genotyping was carried out by the real time PCR method. The significance of differences between the groups was evaluated through Student's t-test. RESULTS: our study revealed that genotype TT had plasma aldosterone concentration (PAC), ARR and SIT significantly higher in comparison with CC patients. The mean PAC in CC was 12.71 ng/dL vs. 20.55 ng/dL in TT patients (p = 0.037), which consequently gave a higher ARR in TT patients (119 vs. 44, p = 0.034). Mean aldosterone concentration in SIT was 2.40 ng/dL in CC patients and 9.99 ng/dL in TT patients (p = 0.046). Patients with CC genotype required less hypotensive drugs in comparison with TT genotype (p = 0.044). PA was recognized in 16 patients. Nine patients had TC genotype, six TT, and one with CC genotype. CONCLUSION: our study revealed predisposing TT genotype to PA. Additionally, patients with TT genotype, regardless of the PA presence, had more severe hypertension. The determination of the CYP11B2 promoter polymorphism seems to be useful in the diagnosis of PA, especially in cases where it is difficult to properly prepare patients for hormonal tests or even results of the hormonal test are incoherent.

Enhancing the efficacy of 131I therapy in non-toxic multinodular goitre with appropriate use of methimazole: an analysis of randomized controlled study.

PURPOSE: It is possible to raise the rate of the uptake of 131I in the thyroid gland (RAIU) by increasing the endogenous TSH level through appropriate use of methimazole (MMI) prior to 131I therapy. The purpose of this paper is to assess the impact of pre treatment with MMI on the efficacy of 131I therapy in non-toxic multinodular goitre (NMG). METHODS: Thirty-one patients with NMG received 131I treatment in order to reduce the volume of the thyroid (TVR). Those in group 1 (n = 16) were administered 10 mg of methimazole for 6 weeks. Four days after its discontinuation, they received 131I. Patients in group 2 (n = 15) were given a placebo instead of MMI. The therapeutic activity of 131I was constant (800 MBq) and was repeated every 6 months. Treatment was discontinued when TVR reached <40 ml. RESULTS: In group 1, RAIU increased approximately twofold. Ten patients from group 2 and four patients from group 1 received further doses of 131I. The median of time until TVR decreased below 40 ml was 9 months [6-12 months] and 18 months [14-22 months] in group 2. At 2 years after the 131I therapy, the occurrence of hypothyroidism did not differ significantly (36% in group 1 and 33% in group2, p = 0.074). CONCLUSIONS: Radioiodine treatment of NMG preceded with appropriate application of MMI is efficient thanks to increased RAIU, shorter period of treatment, and lower frequency of 131I administration, without an increase in the incidence of post-treatment hypothyroidism.

Efficacy of 99mTc-DTPA SPECT/CT in diagnosing Orbitopathy in graves' disease.

BACKGROUND: The most frequently used methods of assessing Graves' orbithopathy (GO) include: Clinical Activity Score (CAS), ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI). There exists another, slightly forgotten, imaging method: single-photon emission computed tomography (SPECT) with the use of diethylenetriaminepentaacetic acid tagged with 99mTc (99mTc-DTPA). These days it is possible to conduct a SPECT examination fused with a CT scan (SPECT/CT), which increases the diagnostic value of the investigation. The aim of this paper is to evaluate the usefulness of 99mTc-DTPA SPECT/CT in diagnosing Graves orbitopathy, as compared with other methods. METHODS: Twenty-three patients with suspected active (infiltrative-edematous) Graves' orbithopathy were included in the study. Each patient underwent a CAS, an MRI, and a SPECT/CT. The obtained results were analysed statistically, with the assumed statistical significance of p < 0.05. RESULTS: The SPECT/CT and MRI were found to have the highest sensitivity: 0.93 each. The SPECT/CT had the highest specificity: 0.89. MRI and CAS had lower values: 0.78 and 0.56, respectively. The occurrence of an active form of GO had no impact on the exacerbation of exophthalmos or the thickness of the oculomotor muscles. CONCLUSIONS: The 99mTc-DTPA SPECT/CT method provides a very good tool for assessing the active form of GO and can, alongside the MRI scan, be used as a referential diagnostic procedure in GO.

Diagnostics of hypercortisolism - comparison between the clinical usefulness of salivary and serum cortisol measurements.

INTRODUCTION: The aim of this study was the comparison of 24h urine free cortisol (UFC), serum cortisol at 11pm (SCM) and late-nightsalivary cortisol (LSC) in patients suspected for hypercortisolism, and an assessment of the usefulness of these measurements in diagnosingovert Cushing's (OCS) syndrome, pseudo Cushing's state (PCS) and subclinical Cushing's syndrome (SCS). MATERIAL AND METHODS: The study group consisted of 82 patients, of whom four patients had SCS, three OCS and eight PCS. For measurementsof LSC, the ELISA method was used, and for UFC and SCM determination, chemiluminescent microparticle immunoassay was used. RESULTS: The highest correlation coefficient characterised LSC and SCM (r = 0.72). Area under curve (AUC) for SCM and LSC in receiveroperating characteristic (ROC) for OCS was: 0.86 v. 0.74; for PCS: 0.83 v. 0.70; and for SCS: 0.74 v. 0.79. CONCLUSIONS: Our findings suggest that LSC is more useful compared to SCM in diagnosing subclinical Cushing's syndrome. Moreover,LSC seems to be a valuable diagnostic criterion to distinguish pseudo Cushing's state. However, to obtain reliable cut-offs for LSC values,a larger group of hypercortisolic patients is needed.

Pheochromocytoma--analysis of 15 consecutive cases from one centre.

INTRODUCTION: Pheochromocytoma is a rare tumour, but one of great clinical importance as a risk factor of malignancy, cardiovascular diseases and sudden death. MATERIAL AND METHODS: 15 consecutive patients (eight women and seven men) were hospitalised and submitted for adrenalectomy with pheochromocytoma confirmed by histopathologic examination. Adrenalectomies were performed laparoscopically in 14 cases (93.3%): in nine by the retroperitoneal posterior mode and in five by the transperitoneal lateral approach. RESULTS: Molecular-genetic examination of VHL, RET, SDHB, SDHC and SDHD genes revealed inherited predisposition for PHEO in three of 15 patients (20%): RET mutations typical for MEN 2a in two patients and VHL mutation in one patient. Disturbances of the carbohydrate metabolism occurred in nine patients (60%). Ten patients (66%) reported paroxysmal symptoms. In all cases, with the exception of a von Hippel-Lindau patient, density of tumours exceeded 20 HU. In all studied patients, urine concentration of normetanephrines exceeded their normal range and greatly prevailed over metanephrines values, which were increased in six of them (40%). CONCLUSIONS: Urine metoxycatecholamines and increased tissue density are sufficient in pheochromocytoma detection. However, taking into account clinical and supplemental biochemical data may be helpful in the diagnostic process. Laparoscopic adrenalectomy is a fully sufficient and safe method of pheochromocytoma excision.

Diagnostics of primary aldosteronism: is obligatory use of confirmatory tests justified?

INTRODUCTION: Assessment of the renin-angiotensin-aldosterone system has been recently granted a much greater role in the evaluation of patients with arterial hypertension. There is no single test efficient in selection of patients for second-step etiological investigation. METHODS: Altogether, 198 consecutive patients--119 women (60%) and 79 men (40%)--hospitalized in years 2009-2011 at the Clinical Department of Endocrinology Medical University of Bialystok were diagnosed with primary aldosteronism. In each patient, plasma renin activity and plasma aldosterone concentration (basic and after 2 l NaCl infusion) were evaluated. RESULTS: The percentage of patients with plasma aldosterone concentration ≥ 15 ng/ml was 53 and the percentage of patients with plasma renin activity ≤ 0.1 ng/ml/h was 20. The percentage of patients screened for primary aldosteronism in which the aldosterone:renin ratio exceeded consecutive cut-offs of 20, 30, 40 and 50 were respectively 57, 45, 34 and 29. Among 15 patients in which plasma aldosterone concentration after infusion of 2 l of saline was ≥ 6.5 ng/dl (8.6%), 13 (6.6%) were diagnosed with primary aldosteronism. CONCLUSION: The obligatory use of tests confirming autonomy of aldosterone secretion in patients screened for primary aldosteronism seems cost-effective in limiting the number of patients for further diagnosis.

Modelling, solubility and pK(a) of five sparingly soluble drugs.

Drug solubility is an important aspect of drug development. The objective of this investigation was to measure solubilities of five drugs (cimetidine, phenylbutazone, fenbufen, nitrofurantoin, triamterene) at constant pH in range of temperature from 270 to 340K in three solvents: water, ethanol and 1-octanol with the dynamic-visual method and the saturation shake-flask method using spectrophotometric analysis. The Barton group contribution method was used for the calculations of molar volumes of solutes. The thermodynamic description of the solubility curves was made using the thermophysical properties obtained with the differential scanning microcalorimetry technique (DSC). The DSC measurements have shown different than existing in the literature enthalpies of melting for phenylbutazone and fenbufen. The experimental solubility data also differ from the literature data, normally measured at one, or two temperatures only. The solubility data have been correlated by means of three commonly known excess Gibbs energy, G(E) equations. The activity coefficients of drugs at saturated solutions were calculated from the experimental data. Reexamination of the pK(a) values using diluted solutions was made with the Bates-Schwarzenbach method for the pK(a) measurements. The association constants and corresponding pK(a) values of drugs were close to the most of the literature data. We hope that our new solubility data, thermophysical data, and pK(a) values will improve all prediction-methods and their precision.

Problems in diagnostics of primary aldosteronism - analysis of the own data.

INTRODUCTION: During the last few years, increasing evidence suggests that primary aldosteronism is the cause of over 10% of arterial hypertension (AH). There are no "gold standard" methods for PA screening. The aim of study was plasma renin activity (PRA), plasma aldosterone concentration (PAC), and ARR assessment as criteria for diagnosis of PA and their usefulness in clinical practice. MATERIAL AND METHODS: Eighty-one consecutive patients were admitted for diagnosis of primary aldosteronism: 51 women and 30 men, aged 31-69 years. In each patient, PAC and PRA were evaluated by radioimmunoassay. In 65 patients, urine concentration of catecholamine metabolites was assayed, and in 51 patients, diagnostics for hypercortisolaemia was carried out. In patients with adrenal incidentaloma, 16-row computer tomography was performed. RESULTS: The proportion of patients with PAC over 150 pg/ml was 35% (n = 28). The number of patients with PRA under 0.07 ng/ml/h was 19 (n = 15). The ratio of patients whose values of ARR exceeded over 20, 30, 40, 50, and 180 were 55, 47, 37, 28, and 15%, respectively. CONCLUSIONS: The most common indication for primary screening was the presence of incidentally found adrenal mass. The quotient of plasma aldosterone concentration/plasma renin activity at whichever cut-off point is not effective enough for the selection of patients for further diagnostics or its cessation. (Pol J Endocrinol 2010; 61 (1): 2-5).