The effect of short-term treatment with lithium carbonate on the outcome of radioiodine therapy in patients with long-lasting Graves' hyperthyroidism.

OBJECTIVE: The outcome of radioiodine therapy (RIT) in Graves' hyperthyroidism (GH) mainly depends on radioiodine (131I) uptake and the effective half-life of 131I in the gland. Studies have shown that lithium carbonate (LiCO3) enhances the 131I half-life and increases the applied thyroid radiation dose without affecting the thyroid 131I uptake. We investigated the effect of short-term treatment with LiCO3 on the outcome of RIT in patients with long-lasting GH, its influence on the thyroid hormones levels 7 days after RIT, and possible side effects. METHODS: Study prospectively included 30 patients treated with LiCO3 and 131I (RI-Li group) and 30 patients only with 131I (RI group). Treatment with LiCO3 (900 mg/day) started 1 day before RIT and continued 6 days after. Anti-thyroid drugs withdrawal was 7 days before RIT. Patients were followed up for 12 months. We defined a success of RIT as euthyroidism or hypothyroidism, and a failure as persistent hyperthyroidism. RESULTS: In RI-Li group, a serum level of Li was 0.571 ± 0.156 mmol/l before RIT. Serum levels of TT4 and FT4 increased while TSH decreased only in RI group 7 days after RIT. No toxic effects were noticed during LiCO3 treatment. After 12 months, a success of RIT was 73.3% in RI and 90.0% in RI-Li group (P < 0.01). Hypothyroidism was achieved faster in RI-Li (1st month) than in RI group (3rd month). Euthyroidism slowly decreased in RI-Li group, and not all patients became hypothyroid for 12 months. In contrast, euthyroidism rapidly declined in RI group, and all cured patients became hypothyroid after 6 months. CONCLUSION: The short-term treatment with LiCO3 as an adjunct to 131I improves efficacy of RIT in patients with long-lasting GH. A success of RIT achieves faster in lithium-treated than in RI group. Treatment with LiCO3 for 7 days prevents transient worsening of hyperthyroidism after RIT. Short-term use of LiCO3 shows no toxic side effects.

Short term treatment with lithium carbonate as adjunct to radioiodine treatment for long-lasting Graves' hyperthyroidism.

OBJECTIVE: Lithium carbonate is primarily used for the treatment of patients with bipolar affective disorders. Initial treatment of Graves' hyperthyroidism (GHT) with antithyroid drugs (ATD) has limitations at over 50% of treated patients because of significant side effects and relatively high relapses of the disease after drugs withdrawal. Till now, the influence of LiCO3on RIT outcome was mainly studied in patients with recent onset of GHT, and results were contradicted. Meta-analysis of case-control studies showed higher rated hypothyroidism in patients with mood disorders treated with LiCO3(121/869) than in controls (10/578). Although in a small number of patients (n=28) with long-lasting GHT, preliminary results of ours showed that ¹³¹I treatment with LiCO3for 7 days significantly improved the efficacy of RIT versus the non-LiCO3treated patients (P<0.001). Lithium treated patients were cured faster (12 of 13 patients were cured after one month) than those treated only with ¹³¹I (8 patients were cured after one and 11/15 patients after 12 months). Fewer patients treated with ¹³¹I and LiCO3had persistent hyperthyroidism than those treated with ¹³¹I alone. There were no toxic effects of LiCO3during 7 days treatment. CONCLUSION: These observations indicate of that short-term treatment with LiCO3in GHT patients as adjunct to ¹³¹I-NaI improves the efficacy of RIT, prevents transient exacerbation of hyperthyroidism, early induction of hypothyroidism and does not worsen ophthalmopathy.

Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy, a worldwide disease.

BACKGROUND: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease occurring in people living in along the tributaries of the Danube River. The aim of the study was to determine serum level and urinary excretion of placental growth factor (PlGF) and placental protein 13 (PP13) in patients with BEN. METHODS: Thirty patients with BEN from the South Morava River region of Serbia and 18 controls were studied. Age of patients was 74 yr (53-87) and 73 yr (66-83) in controls. RESULTS: In patients with BEN, serum creatinine was significantly higher than in controls (129.7 vs. 83.2 µmol/L, respectively), but GFR was lower in patients than in controls (40.7 vs. 54.6 mL/min). Serum PlGF was significantly higher in BEN patients than in controls (9.90 vs. 6.80 pg/mL), urinary excretion being significantly lower in patients (0.20 vs. 0.90 pg/mmol creat.). Serum PP13 was significantly lower in BEN patients (208.2 vs. 291.0 pg/mL). Urinary excretion of PP13 was also significantly lower in BEN patients than in controls (32.5 vs. 182.5 pg/mmol creat). In multivariate regression analysis BEN, sex and age were significant determinants of the observed changes in PlGF and PP13. CONCLUSION: Important changes of PlGF and PP13 in patients with BEN were demonstrated, where kidney disease, female sex, and the age have been significant determinants.

Urinary protein patterns in patients with Balkan endemic nephropathy.

PURPOSE: Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls. METHODS: The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN. RESULTS: In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m(2) isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m(2), beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m(2) 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m(2) only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent. CONCLUSION: Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m(2). IgG was increasingly found as eGFR decreased.

Tubular marker excretion in children from families with Balkan nephropathy.

Balkan nephropathy (BN) has not been described in children; however, some previous studies in children from families with BN have revealed abnormalities of the urinary tract. In this study, urinary excretion of beta2-microglobulin, N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (GGT) was studied three times a year: spring, autumn, and winter, during a 3-year period, in 703 healthy children, initial age 9-13, from endemic and nonendemic settlements around the South Morava River. Beta-2-microglobulin excretion in urine, in all three seasons, was highest in children from families with BN compared with the excretion in children from the city, nonendemic villages, and those from nonendemic families. Increased urinary GGT excretion in children from endemic villages in October was higher than in children from the city and control villages, being the same in both endemic and nonendemic families. However, in February, it was similar in children from the city, endemic, and control villages. In conclusion, children from families with BN excreted significantly more beta2-microglobulin in all three seasons (spring, autumn, winter) of the study, in multivariate analysis significant for family status, gender, and the season (p < 0.001). NAG emerged as a potentially useful marker for seasonal exposure to an environmental nephrotoxin.

Upper urothelial carcinoma in Balkan endemic nephropathy and non-endemic regions: a comparative study of pathological features.

Upper urothelial carcinoma (UUC), a rare neoplasm, occurs more frequently in some regions of Balkan countries than in other areas in the world. The aim of this study is to compare phenotypic morphological characteristics of UUC in Balkan endemic nephropathy (BEN) region and control rural and city populations free of BEN, and to determine the characteristic(s) that could discriminate tumors in endemic and non-endemic regions. The authors analyzed biopsies from 88 patients with UUC, 40 patients who live in Balkan endemic (BEN) settlements and 48 control subjects. The histological sections were used to assess morphological variables: histologic grade, pathologic stage (pT), growth pattern, pattern of invasion, lympho-vascular invasion (LVI), presence of necrosis and metaplastic changes (squamous or glandular) within the tumor. Statistically significant differences between the groups were found concerning tumor grade, pattern of invasion, growth pattern and metaplastic changes. High-grade tumors and trabecular/infiltrative patterns of invasion were more frequent in the group of BEN tumors (chi(2)=4.583, p<0.05; chi(2)=8.064, p<0.05). Moreover, solid growth and metaplastic changes are significant in BEN tumor, chi(2)=9.696, p<0.01; chi(2)=9.35, p<0.01, respectively. Discriminant analysis of morphological variables had indicated that BEN and control tumors are significantly different (Wilks' lambda=0.833, chi(2)=15.044 and p<0.05). The best characteristic that differentiated them was growth pattern; i.e., solid growth for BEN tumors and papillary for control tumors.

Diagnostic value of the aminopeptidase N, N-acetyl-beta-D-glucosaminidase and dipeptidylpeptidase IV in evaluating tubular dysfunction in patients with glomerulopathies.

AIM: The aim of the present study was to investigate the value of the urine cell glycoprotein 1 (PC-1), aminopeptidase N (APN), N-acetyl-beta-D-glucosaminidase (NAGA), and dipeptidylpeptidase IV (DPP IV) in the evaluation of tubular damage in patients with primary glomerulonephritis, diabetic nephropathy, and lupus nephritis. SUBJECTS AND METHODS: PC-1, APN, NAGA, and DPP IV activities were determined in serum, urine, and lymphocytes of 178 subjects, including 10 patients with membranous nephropathy, 38 with IgA nephropathy, 29 with lupus nephritis, 51 with diabetic nephropathy, and 50 control subjects. RESULTS: Urinary PC-1 excretion in IgA nephropathy group was significantly higher (p < 0.05) than in controls. Urinary NAGA excretion was markedly (p < 0.01) higher in membranous nephropathy group, and APN excretion in diabetic nephropathy group was significantly higher (p < 0.01) than in healthy controls. Urinary APN activity was significantly (p < 0.01) higher in both type 1 and type 2 diabetic patients with microalbuminuria, as well as urinary NAGA and DPP IV activities in type 2 diabetics with microalbuminuria (p < 0.01 and p < 0.05, respectively) compared to controls. Serum PC-1 and APN activities were significantly higher than the control level in membranous nephropathy group, as well as serum PC-1 and DPP IV activities in IgA nephropathy patients (p < 0.05). However, significantly lower serum DPP IV and APN activity was observed in type 2 diabetics with microalbuminuria compared to controls (p < 0.05). CONCLUSION: Damage of tubules in primary glomerulonephritis, lupus nephritis, and diabetic nephropathy is accompanied by a release of several tubular enzymes, with possible diagnostic and prognostic significance. Increased serum PC-1, APN, and DPP IV activities could be also of diagnostic significance.

Radionuclide staging of renal function in type 1 diabetes mellitus.

AIM: The aim of this study was to assess renal function in different stages of type 1 diabetes mellitus by radionuclide methods. Additionally, glomerular and tubular functions were correlated with urinary albumin (UAER) and N-acetyl-beta-D-glucosaminidase (NAGA) excretion rates. PATIENTS AND METHODS: Fifty-three patients with diabetes mellitus were classified into four groups: normoalbuminuric (NA, 18 patients), microalbuminuric (MiA, 12 patients), macroalbuminuric (MaA, 13 patients), and chronic renal failure group (CRF, 10 patients). Glomerular filtration rate (GFR) was estimated by diethylenetriamine pentaacetic acid-technetium 99m ((99m)Tc-DTPA) clearance rate while tubular function was calculated as a percentage of net injected activity fixed in both kidneys, 4 h after intravenous injection of dimercaptosuccinate acid-technetium 99m ((99m)Tc-DMSA). Additionally, (99m)Tc-DTPA clearance was correlated with estimated GFR (eGFR) by using modified Modification of Diet in Renal Disease (MDRD) Study Group formula. RESULTS: (99m)Tc-DTPA clearance and (99m)Tc-DMSA fixation were found significantly higher in normoalbuminuric group (p < 0.05 and p < 0.02, respectively), unchanged in microalbuminuric group (p > 0.05, p > 0.05), and decreased in both macroalbuminuric (p < 0.0001, p < 0.00001) and chronic renal failure group (p < 0.0001, p < 0.00001). Renal function was denoted as normal, increased (hyperfunction), or decreased (hypofunction). It was found normal in a high percentage of patients with normalbuminuria (filtration 44.4%, fixation 72.2% pts) and microalbuminuria (66.7% and 66.7%). Renal hyperfunction was not only found frequent in normalbuminuric group (55.6% and 27.8%), but was also recorded in microalbuminuric group (8.3% and 8.3%). Renal hypofunction was present in all macroalbuminuric patients and in one-quarter of those with microalbuminuria as well. Such distribution of renal function conditions indicated normalbuminuric and microalbuminiric groups functionally heterogeneous. Regression analysis showed a significant correlation between (99m)Tc-DTPA clearance and eGFR in MaA and CRF groups only. Although urinary NAGA excretion rate was shown as a less sensitive staging parameter, being significantly increased when compared to control group only in MaA and CRF groups (p < 0.05), it significantly correlated with (99m)Tc-DTPA clearance rate (r = -0.485, p = 0.0004) and (99m)Tc-DMSA tubular fixation (r = -0.526, p = 0.0002). CONCLUSIONS: The results of this study favor the performance of radionuclide studies together with the determination of urinary albumin excretion rate in patients with type 1 diabetes mellitus in order to achieve more reliable staging of diabetic kidney disease. The demonstration of glomerular hyperfiltration and tubular hyperfunction by radiopharmaceuticals contributes to the early detection of diabetic kidney disease, while the quantification of renal function enables the follow-up of the progressive function loss in the later course of the disease.

Thyroid blood flow and uptake of technetium-99m pertechnetate in Graves' disease.

The aim of this study was to assess the relation of early thyroid blood flow (EBF) and technetium-99m pertechnetate ((99m)TcO(-)(4)) uptake, as an early diagnostic index in patients with Graves' disease (GD) by dynamic thyroid scintigraphy (40 frames, 3 sec/frame). Thirty patients with GD with mean age 50.0 +/- 9.0 y, range: 35.0-69.0 y, were studied. The results obtained were compared with those of 30 euthyroid individuals (EI) of mean age 46.9 +/- 12.5 y, range: 22.0-68.0 y. The parameters of (99m)TcO(-)(4) EBF and early uptake studied, derived from the background subtracted time activity curves, were as follows: a) The duration of the EBF in sec; b) The perfusion index (PI) - the ratio of counts at the beginning and at the end of the EBF; c) The uptake index 1 (UI1)- the counts ratio between the counts at the end of the EBF and at the 2nd min d) The uptake index 2 (UI2) - the counts ratio between the 1st min and the 2nd min of the uptake curve and e) Delayed (99m)TcO(-)(4) thyroid uptake (TcTU) at 20 min was also calculated as a percentage of net counts activity accumulated in the thyroid gland at 20 min. Results were as follows: a) The mean values of the duration of the EBF were shorter in GD patients (9.90 +/- 2.94 sec) than in EI (15.70 +/- 4.01 sec; P<0.0001); b) PI did not differ significantly (P>0.05); c) The mean UI1 and UI2 values of thyroid uptake of 99m TcO4- were significantly lower in GD (UI1=0.621, UI2=0.772) as compared to EI (UI1=1.106, UI2=0.947; P<0.0001 for both) and d) TcTU values were significantly higher in GD (13.6%) than in the group of EI (1.29%; P<0.0001). A good correlation was found in patients with GD between early (UI1 and UI2) and delayed TcTU (r = -0.562; P=0.010 and r = -0.459; P=0.042 respectively). Also, in patients with GD the EBF correlated poorly with UI1, UI2 and TcTU (P>0.05 for all these parameters). In conclusion, the results of this study indicate that the duration of EBF did not relate significantly to the height of TcTU values in patients with GD. On the contrary, the early uptake, indices UI1 and especially UI2 were shown to be faster in the majority of GD patients and correlated well with the TcTU. These parameters may be used as diagnostic indices for GD. Further investigation is required to support the above findings.

Diuresis renal scintigraphy "F-0" in diagnosing of upper urinary tract obstruction in children: the clinical significance.

BACKGROUND: The aim of this study was to assess the clinical relevance of diuresis renal scintigraphy after simultaneously administered radiopharmaceutical and diuretic (DRS "F-0") in diagnosing obstruction of upper urinary tract in children with previously documented hydronephrosis and ureterohydronephrosis, analyzing the value of qualitative and quantitative scintigraphy parameters. MATERIAL AND METHODS: This retrospective study enrolled 82 children (30 girls and 52 boys aged between 2 months and 16 years; mean 5.8 +/- 4.5 years) with previously documented hydronephrosis or ureterohydronephrosis (42 left-sided, 28 right-sided and 12 bilateral). DRS "F-0" was started after intravenous administration of diethylene-triamine- pentaacetic acid (DTPA) mixed with furosemide. Results of DRS "F-0" were analyzed qualitatively (visual analysis of scintigrams and renography curves) and quantitatively (time to reach maximum of the kidney curve-T max, washout of the tracer-WO, the furosemide clearance half-time (F/2) and individual kidney function - IKF) and compared with the final diagnoses obtained in 37 children (42 nephroureteric units - NU) after surgery, in 41 children (48 NU) during the medical follow-up lasting at least 6 months, and in 4 children (4 NU) using invasive diagnostic procedures. Diagnostic criteria for obstructed NU (kidney with corresponding ureter) considered presence of pathological at least two of five scintigraphy variables characterized as a sign of obstruction. RESULTS: Forty true positive and 37 true negative results were detected using diagnostic criteria for obstructed and normal NU by means of DRS "F-0". DRS "F-0" failed to detect obstruction in 5 children with a total of 6 obstructed NU, while the results were marked as false positive in 9 children (11 NU). Qualitative scintigraphy analysis was found to be the most sensitive (91%) and accurate predictor (85%) in differentiating obstruction from non-obstructive renal unit. High sensitivity in predicting obstruction was also found for both washout of the radiopharmaceutical (87%) and for furosemide clearance half time (85%). Overall sensitivity of DRS "F-0" using proposed diagnostic criteria in differentiating obstruction was 87%, specificity 77% and accuracy 82%. However, DRS "F-0" has been shown to be more sensitive (90%) in children with UPJ and UVJ obstruction concerning children in whom obstruction was caused by other urinary tract diseases. CONCLUSION: This study showed DRS "F-0" as a sensitive and reliable method in diagnosing children with obstructions of the upper urinary tract. The great advantage of the protocol DRS "F-0" over other diuresis renography protocol modalities is due to the shorter time of the acquisition by half, and the avoidance of additional diuretic application. However, conventional quantitation of diuresis renogram did not improve the sensitivity and specificity with respect to the qualitative analysis of scintigrams and renography curves.

Radionuclide voiding patterns in children with vesicoureteral reflux.

The purpose of this study was to evaluate bladder function in children with vesicoureteral reflux (VUR) by means of indirect radionuclide cystography (IRNC), and to investigate whether IRNC can identify those children with voiding dysfunction. The study enrolled 74 neurologically intact children, 14 boys and 60 girls aged 2-14 years, with VUR documented using contrast micturating cystourethrography as the initial method. In all patients, IRNC was performed using technetium-99m diethylene triamine penta-acetate (DTPA). Based on the urodynamic findings, three groups were distinguished: a group with VUR and normal urodynamic findings ( n=27), a group with VUR and detrusor hyper-reflexia ( n=43) and a group with VUR and detrusor-sphincter dyssynergia ( n=4). A control group comprised 64 healthy children, aged 2-13 years, without any symptoms of lower urinary tract dysfunction. The dynamics of bladder emptying were studied in the posterior view after intravenous injection of 37 MBq/10 kg b.w. DTPA, with acquisition of 90 2-s frames during voiding. The parameters evaluated were: voided urine volume (VV), bladder capacity, functional bladder capacity (FBC), residual urine, voiding time, average flow rate, peak flow rate (PFR) and ejection fraction (EF). With regard to the final urodynamic diagnosis, FBC, PFR and EF were found to be significant IRNC predictor variables using the logistic regression method. If abnormality on at least two of the three significant predictor variables was taken as the criterion of voiding dysfunction, the overall sensitivity, specificity and accuracy of IRNC in the detection of voiding dysfunction were 81%, 78% and 80%, respectively. Three radionuclide voiding patterns were detected in children with VUR: (1) a normal voiding pattern characterised by normal FBC with near-normal PFR and EF values, (2) a markedly reduced FBC with significantly reduced VV, PFR and EF values (in children with bladder instability), and (3) a higher bladder volume with a near-normal value for PFR and a slightly reduced or near-normal EF (in children with detrusor-sphincter dyssynergia). This study confirmed the association between lower urinary tract dysfunction and congenital VUR. IRNC was found to be a simple, non-invasive method which allows reliable differentiation of voiding patterns in patients with VUR. IRNC can be used as a first-line method for screening in children with VUR to identify those with abnormal voiding patterns.

Alteration of 99mTc-DMSA biodistribution in glomerulonephritis.

BACKGROUND: The aim of this study was to assess the relation between (99m)Tc-DMSA biodistribution and its reliability as a marker of renal function in patients with glomerular kidney diseases. MATERIAL AND METHODS: Sixty-seven patients involved in this study were classified into two groups according to (99m)Tc-DTPA clearance and serum creatinine values: the 1st group consisted of 42 patients without renal failure while the 2nd group included 25 patients with renal failure. (99m)Tc-DMSA biodistribution was determined by measuring kidney, blood and urine activity at 2 h and 4 h. RESULTS: The results, compared with those of 23 healthy volunteers, indicated the quantitative alteration of (99m)Tc-DMSA distribution in both glomerulonephritis patient groups. In reference to the control mean values of 2 h and 4 h, in patients without renal failure, kidney activity was found decreased to 52% and 57%, while the blood activity increase of 37% and 44% was recorded together with the urine activity increase of 38% and 23%. In patients with renal failure the alterations of renal and blood activity were more remarkable, but the urine loss was found to be unchanged. CONCLUSIONS: It is suggested that these biodistribution changes originate mainly from tubular impairment. However, in glomerulonephritis patients, altered glomerular filtration might considerably affect biodistribution of this radiopharmaceutical and limits its suitability for precise quantitative estimation of renal function.