The robustness of the Patlak-Rutland slope for the determination of split renal function.

The aim of this study was to evaluate the variability of the Patlak-Rutland slope as applied to the renal clearance method. We analysed the 99Tcm-mercaptoacetyltriglycine renograms of 17 non-selected patients (both children and adults, number of kidneys = 34) with a single kidney glomerular filtration rate of 6-73 ml min-1 1.73 m-2. the acquisition time for the renograms was 20 min with a frame duration of 20 s. First, correction for background activity was introduced using the perirenal area and the size ratio between the kidney and the perirenal area. The Patlak plot was then applied. The first two points were systematically rejected and a series of linear fits calculated from the experimental points, starting from the third point (i.e. 1 min). The final point of the fit never exceeded the time of the peak of the renogram minus one minute (Tmax - 1) and was always less than 5 min. Although simple visual inspection of the slopes would suggest that the experimental points were distributed accurately along a straight line, it appeared that the slope was strongly dependent on the number of points used for the determination of the fit. As a second step, we restricted the number of points for fitting to the time interval between 1 min and 2 min 40 s. This procedure appeared to show that the Patlak methodology is reliable, giving rise to only small variations in slope, depending on the number of points chosen. However, even in this narrow time interval, significant errors can be made, either because of the very early escape of the radionuclide or because of statistical noise (e.g. in renal failure the signal-to-noise ratio is unfavourable). Therefore, it is advisable, when using this methodology, to restrict the fitting procedure to the second minute of the study and to check visually that this fixed time interval gives rise to a slope that is well adapted to the Patlak plot.

Overall accuracy of technetium-99m-MAG3 clearance measurements obtained with a gamma camera heart curve.

UNLABELLED: The aim of the present study was to evaluate the accuracy of 99mTc-MAG3 clearance measurements using a precordial gamma camera curve calibrated by a single plasma sample. METHODS: Technetium-99m-MAG3 was administered to ten young normal volunteers. A 60-min gamma camera acquisition was performed. Five different segments of the gamma camera curve were determined: 3 min to 20 min, 3 min to 30 min, 3 min to 40 min, 3 min to 50 min and 3 min to 60 min. A biexponential function was fitted on each of these five different segments, which were thereafter calibrated using eight different blood samples. These blood samples were successively used for calibration at 5, 10, 15, 20, 30, 40, 50 and 60 min. The single injection, multiple plasma sample method was used as reference. RESULTS: Camera clearances varied markedly based on the length of the precordial curve and on the time of the calibration sample. Different regression equations were obtained for each duration of the camera curve, and for each blood sample timing. Correlation coefficients were > 0.95 in most cases recording period of at least 50 min, however, was necessary to obtain a s.e.e. better than those obtained using a single blood sample method without gamma camera curve. CONCLUSION: The 99mTc-MAG3 clearance determination using a gamma camera heart curve calibrated with a single blood sample does not necessarily improve the accuracy of the one blood sample method.

Reproducibility of technetium-99m mercaptoacetyltriglycine clearance.

The aim of this paper was to determine the reproducibility (precision) of technetium-99m mercaptoacetyltriglycine (MAG3) clearance and to compare it with that of chromium-51 ethylenediamine tetra-acetic acid (EDTA). Twelve young volunteers (aged between 21 and 34 years), without any history of medical problems, were enrolled in this study. The test was performed twice, at an interval of 8 days and under similar physiological conditions. After the intravenous injection of both tracers, 15 blood samples were taken between 3 and 240 min. A biexponential fit was adapted to the plasma disappearance curves (5- to 120-min samples for 99mTc-MAG3 and 10- to 240-min samples for 51Cr-EDTA); the clearances were calculated according to Sapirstein and corrected for body surface area. The mean clearance values were 110 (range 85-130) and 226 (range 109-319)ml/min/1.73 m2, respectively, for 51Cr-EDTA and 99mTc-MAG3. For 51Cr-EDTA clearance, the mean difference between the first and the second measurement was -2.1% of the mean of the two successive values (SD: 8.4%). In ten cases, the difference was less than 12%; in two cases, the differences were 15% and 18%, respectively. For 99mTc-MAG3 clearance, the mean difference between the first and the second measurement was -20% of the mean of the two successive values (SD: 25%). In six cases, the difference was less than 12%; in four cases, between 15% and 40%; and in two cases, more than 60%. Methodological factors (impurities contained in the commercial kit, variable protein binding) as well as physiological factors (pH of urine, sodium load, stress) may explain the lack of precision of the 99mTc-MAG3 clearance. It is concluded that changes in 99mTc-MAG3 plasma clearance should be interpreted with care in daily routine.

Precision and accuracy of in vivo bone mineral measurement in rats using dual-energy X-ray absorptiometry.

The aim of this study was to evaluate the precision and accuracy of dual-energy X-ray absorptiometry (DXA) for measuring bone mineral content at different sites of the skeleton in rats. In vitro the reproducibility error was very small (< 1%), but in vivo the intra-observer variability ranged from 0.9% to 6.0%. Several factors have been shown to affect in vivo reproducibility: the reproducibility was better when the results were expressed as bone mineral density (BMD) rather than bone mineral content (BMC), intra-observer variability was better than the inter-observer variability, and a higher error was observed for the tibia compared with that for vertebrae and femur. The accuracy of measurement at the femur and tibia was assessed by comparing the values with ash weight and with biochemically determined calcium content. The correlation coefficients (R) between the in vitro BMC and the dry weight or the calcium content were higher than 0.99 for both the femur and the tibia. SEE ranged between 0.0 g (ash weight) and 2.0 mg (Ca content). Using in vitro BMC, ash weight could be estimated with an accuracy error close to 0 and calcium content with an error ranging between 0.82% and 6.80%. The R values obtained between the in vivo and in vitro BMC were 0.98 and 0.97 respectively for femur and tibia, with SEE of 0.04 and 0.02 g respectively. In conclusion, the in vivo precision of the technique was found to be too low. To be of practical use it is important in the design of experimentation to try to reduce the measurement error.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects.

One hundred and eighty euthyroid pregnant women were selected at the end of the first trimester of gestation on the basis of biochemical criteria of excessive thyroid stimulation, defined as supranormal serum thyroglobulin (TG > 20 micrograms/L) associated with a low normal free T4 index (< 1.23) and/or an increased T3/T4 ratio (> 25 x 10(-3)). Women were randomized in a double blind protocol into three groups and treated until term with a placebo, 100 micrograms potassium iodide (KI)/day, or 100 micrograms iodide plus 100 micrograms L-T4/day. Parameters of thyroid function, urinary iodine excretion, and thyroid volume were monitored sequentially. Neonatal thyroid parameters, including thyroid volume by echography, were also assessed in the newborns from mothers of the three groups. In women receiving a placebo, the indices of excessive thyroid stimulation worsened as gestation progressed, with low free T4 levels, markedly increased serum TG and T3/T4 ratio. Serum TSH doubled, on the average, and was supranormal in 20% of the cases at term. Urinary iodine excretion levels were low, around 30 micrograms/L at term. The thyroid volume increased, on the average, by 30%, and 16% of the women developed a goiter, confirming the goitrogenic stimulus associated with pregnancy. Moreover, the newborns of these mothers had significantly larger thyroid volumes at birth as well as elevated serum TG levels. In both groups of women receiving an active treatment, the alterations in thyroid function associated with pregnancy were markedly improved. The increase in serum TSH was almost suppressed, serum TG decreased significantly, and changes in thyroid volume were minimized (group receiving KI) or almost suppressed (group receiving KI combined with L-T4). Moreover, in the newborns of the mothers in the two groups receiving an active treatment, serum TG was significantly lower, and thyroid volume at birth was normal. The effects of therapy were clearly more rapid and more marked in the group receiving a combination of T4 and KI than in the women receiving KI alone. The differences could be partly attributed to the slightly higher amount of iodine received by women in the combined treatment. However, the main benefits of the combined treatment were almost certainly attributable to the hormonal effects of the addition of L-T4. Furthermore, the study demonstrated that the administration of T4 did not hamper the beneficial effect of iodine supplementation. In conclusion, the present work emphasizes the potential risk of goitrogenic stimulation in both mother and newborn in the presence of mild iodine deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of hyperfiltration on long-term follow-up of glomerular filtration rate in male Wistar rats.

It has been suggested that a prolonged course of hyperfiltration could lead to progressive deterioration of renal function. In order to test this hypothesis, the following protocol was applied to 60 male Wistar rats. At 12 weeks of life, the rats were submitted to a surgical procedure: sham operation (25 rats), unilateral nephrectomy (25 rats) or 3/4 nephrectomy (10 rats). The three groups were again divided into two subgroups: one with high-protein intake (36%) and one with a low-protein intake (12%). In order to avoid any additional traumatic procedure which could shorten the animal's life, the glomerular filtration rate (GFR) was measured without blood sampling, using a previously validated technique based on an image recorded by a gamma camera between the 9th and the 10th min after intravenous injection of 99m technetium diethylenetriaminepentaacetate (DPTA). The sum of both kidneys and bladder activity was expressed as a percentage of the injected dose. The test was performed before surgery and every month thereafter. Six weeks after surgery, the highest filtration rate was found in the rats with "two kidneys/high-protein diet", followed by the "two kidneys/low-protein diet", the "one kidney/high-protein diet", the "one kidney/low-protein diet" and the "1/2 kidney". The overall GFR in the one kidney/high-protein diet rat and in the 1/2 kidney rat was respectively 80% and 55% of the pre-operative values. Until 109 weeks of age, the survival rate was comparable in the five groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders.

A prospective study was undertaken in 87 healthy pregnant women with thyroid antibodies and normal thyroid function at initial presentation [asymptomatic autoimmune thyroid disorders (AITD)]. The aims of the study were to assess whether women with AITD constitute a group at risk of developing subclinical hypothyroidism during pregnancy, and whether a mild thyroid function impairment may be associated with obstetrical repercussions. The women investigated were selected among a cohort of 1660 consecutive pregnancies on the basis of 1) no previous history of thyroid disease, 2) euthyroidism at initial presentation, and 3) positive thyroglobulin antibodies and/or thyroid peroxidase antibodies (TPO-Ab). Women with AITD had a basal TSH value significantly higher, albeit still normal, in the first trimester (1.6 vs. 0.9 mU/L; P < 0.001) than that in women with healthy pregnancies used as controls. Despite a 60% average reduction in TPO-Ab titers during gestation, serum TSH remained higher in women with AITD than in controls throughout gestation: at delivery, 40% of the cases had serum TSH levels above 3 mU/L, and 16% had serum TSH levels above 4 mU/L. A TRH test carried out in the days after parturition showed an exaggerated response in 50% of the cases. Furthermore, free T4 concentrations were in the range of hypothyroid values in 42% of the women. Obstetrical repercussions were observed, namely increased rates of spontaneous miscarriage and premature deliveries. In conclusion, women with asymptomatic AITD who are euthyroid in early pregnancy carry a significant risk of developing hypothyroidism progressively during gestation, despite a marked reduction in antibody titers. Hypothyroidism results from the reduced ability of the gland to adjust to the changes in thyroidal economy associated with pregnancy. At the individual level, progression to subclinical hypothyroidism was broadly predictable on the basis of serum TSH levels and TPO-Ab titers in the first trimester. Hence, these parameters provide useful markers to identify women who carry a higher risk, allowing for a close monitoring of thyroid function during pregnancy and the administration of L-T4 in specific cases. Taken together with the known incidences of postpartum thyroiditis and hypothyroidism in women with AITD, the present observations in our opinion justify systematic screening of thyroid autoimmunity during pregnancy.

Improving the accuracy of 99Tcm-mercaptoacetyltriglycine clearance by using two blood samples instead of one? Paediatric Task Group of the EANM.

From a database of 133 patients (98 children and 35 adults) who underwent multiple blood sampling for 99Tcm-mercaptoacetyltriglycine (MAG3) clearance, we determined simplified algorithms allowing the estimation of clearance. A one-compartment model with two blood samples was applied. The best choices for the adult population were the 12 and 90 min blood samples, giving a standard error of the estimate (S.E.E.) of less than 10 ml min-1 1.73 m-2; for the children, the 10 and 80 min blood samples gave a S.E.E. of 20 ml min-1 1.73 m-2; for both the adults and the children, the 10 and 70 min blood samples gave the best results with, however, a S.E.E. of 19 ml min-1 1.73 m-2. The use of such a combined algorithm will therefore result in a degradation of the results in adults, suggesting that a separate algorithm for each group is preferable. We compared the accuracy of the two blood sample method to the one blood sample method based on previously published algorithms for children and adults, respectively. The S.E.E. was significantly lower, in adults as well as in children, using the empirical two blood sample method. This two blood sample method seems potentially useful for routine practice in adult patients. The advantages of using such a method in children is balanced by the practical problems inherent in the need to take a second blood sample during the first 10 min, at a time when the plasma activity is rapidly decreasing.

Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy.

The main objective of the present study was to present additional evidence of the potentially important thyrotropic role of hCG to regulate the maternal thyroid gland during normal pregnancy. Sequential determinations (first and last trimesters) of intact hCG, free alpha and beta-hCG subunits concentrations (using monoclonal IRMAs), and assessment of parameters of thyroid function and thyroid volume were carried out in 62 pregnant women who exhibited during the first trimester of gestation low TSH levels (< or = 0.20 mU/L), and compared to 276 pregnant women with normal TSH levels. The prevalence of having low serum TSH represented 18% of all pregnancies, with almost one half of cases who transiently had undetectable TSH levels. Lowering of TSH was associated with high hCG levels, and occurred primarily during the first trimester. About 10% of women with low TSH presented transient gestational thyrotoxicosis, frequently associated with vomiting. In comparison to control subjects, women with a suppressed serum TSH had significantly and markedly higher intact hCG and free beta-hCG subunit concentrations. The results suggest that TSH reduction may result from a relative oversecretion of both intact hCG and free beta-hCG subunits, compatible with three hypotheses: a) transient overexpression of the beta-hCG gene, leading to enhanced production of hCG heterodimer; b) increased glycosylation of circulating hCG, with in turn a prolonged half life; c) larger syncytiotrophoblast mass with increased hCG production.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal and neonatal thyroid function at birth in an area of marginally low iodine intake.

Thyroid function was evaluated in cord serum of healthy full-term newborns and compared to that of mothers immediately after parturition. The study was carried out in an area without overt iodine deficiency, but with a marginal iodine supply (less than 100 micrograms/day in 80% of women). The aim of the study was to delineate the interrelationships between the thyroid statuses of mother and child at birth. Maternal thyroid function was characterized at delivery by relative hypothyroxinemia; increased T3/T4 ratios, indicating preferential T3 secretion; slightly increased TSH levels within the normal range in 97% of women; increased serum thyroglobulin (TG) values, which were above normal in 60% of women; and also goiter formation in almost 10% of women. The findings indicated glandular stimulation and confirmed our earlier reports that pregnancy constitutes a stress for the maternal thyroid economy, enhanced by the limited availability of iodine in the diet. By contrast, newborns showed a strikingly distinct pattern: there was no relative hypothyroxinemia and free T4 levels were significantly higher than in the respective mothers (19.4 vs. 14.7 pmol/L; P less than 0.001). In spite of these differences, however, mean neonatal TSH and TG levels were significantly higher than maternal values, respectively 6.0 vs. 1.9 mU/L for TSH (P less than 0.001) and 70 vs. 40 micrograms/L for TG (P less than 0.001). Furthermore, neonatal TG and TSH levels increased in parallel and were highly correlated with maternal data, suggesting a regulatory link between both thyroid economies. The results suggested that the common regulatory link is the limited availability of the iodine supply. In conclusion, the present study demonstrates that even in conditions with a marginally low iodine intake, pregnancy constitutes a stimulus for both the maternal and newborn thyroids. Changes in both groups are associated and the abnormalities in TSH and TG are amplified in the newborns. The TSH and TG alterations at birth in full-term healthy newborns, associated with similar alterations in maternal thyroid function, provide evidence for a common stimulatory factor, relative iodine deficiency. The data emphasize the hypersensitivity of neonatal thyroid function to marginal iodine deficiency and point to the need to increase the iodine supply in groups at risk, such as women during pregnancy, and also newborns in the perinatal period.

Partial reversibility during late postpartum of thyroid abnormalities associated with pregnancy.

The aim of the present work was to assess during late postpartum the reversibility of thyroidal alterations associated with pregnancy. Thyroid function was reinvestigated 6 months after delivery in 100 randomly selected healthy women and thyroid volume was reevaluated 12 months after delivery in 10 other selected women. The subjects had previously been carefully followed during gestation as they were included in a prospective cohort investigation of the regulation of the thyroid during pregnancy, in an area with a limited dietary iodine intake (less than 100 micrograms/day in 85% of the women). Six months after delivery, an overall normalization of thyroid function was observed. However, an increase in the T3/T4 ratio, which was present in half the cases at delivery, was still evident 6 months postpartum, suggesting the persistence of relative iodine deficiency, probably prolonged in some women through breast-feeding. Furthermore, serum thyroglobulin levels, which were increased in half the women at delivery, remained abnormally high in 40% of them 6 months later. Twelve months after delivery thyroid volume, which had increased in average by 54% during pregnancy, had not reverted to the values found during early gestation. Moreover a goiter was still evident in 2/4 cases in whom it had developed during pregnancy. In conclusion, the present study indicates that pregnancy may constitute a prolonged stimulus for the thyroid and shows for the first time that the alterations associated with gestation are not limited to the period of pregnancy, being only partially reversible during late postpartum. In conditions with a limited iodine intake, pregnancy constitutes a risk for the maternal thyroid: goitrogenesis does occur and may be maintained after delivery. The glandular stress of pregnancy may therefore provide a clue to understanding the high prevalence of thyroid disorders in women. The present study provides additional arguments to suggest that iodine supply be increased during pregnancy but also after parturition, in particular in breast-feeding mothers.

Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions.

A prospective study was undertaken during pregnancy in 120 euthyroid women presenting with mild thyroid abnormalities (TA): 11 with a past history of thyroid disorder, 44 with goiter, 20 with nodules, and 45 with thyroid autoantibodies. The aims of the study were to assess whether the pattern of thyroid alterations during gestation was different in women with TA compared to that in healthy control pregnant subjects and to evaluate possible obstetrical and neonatal repercussions. The overall prevalence of underlying subtle thyroid abnormalities in the cohort was 17%, probably as the result of the environmental moderately low iodine intake. Despite the intrinsic heterogeneity of the four groups of women with TA, the adaptation of the thyroid to the stress of pregnancy was different from that of the control subjects. Noteworthy were 1) the marked elevation of serum thyroglobulin in women with past history of thyroid disorder, goiter and thyroid nodules; 2) the increase in goiter size in a third of the goitrous women, associated with biochemical evidence of functional stimulation of the gland; 3) the indirect evidence of partial thyroidal autonomy in goitrous patients; and 4) the increase in the number and size of thyroid nodules during gestation. Taken together, the data indicated that pregnancy was associated with a greater thyroidal risk in patients with TA compared to healthy subjects. In relation to thyroid autoimmunity, most patients remained euthyroid during gestation, but in a few cases, TSH was elevated at delivery, suggesting diminished thyroidal reserve. Also, 40% of newborns from mothers with thyroid autoimmunity had elevated thyroid peroxidase antibody titers at birth, and there was a highly significant correlation between maternal and neonatal thyroid peroxidase antibody titers. Finally, thyroid autoimmunity was clearly associated with an increased risk of spontaneous abortion (13.3 vs. 3.3%; P less than 0.001). Thyroid function in newborns from mothers with TA was normal and not different from that in controls; similarly, obstetrical features were similar in patients with TA and control subjects. In conclusion, pregnancy is associated with a greater thyroidal risk in women with TA, thereby emphasizing a potential link between pregnancy and thyroid disorders. It is recommended that patients with known, even subtle, thyroid abnormalities be closely monitored during pregnancy, in particular those with a goiter, nodules, or thyroid autoimmunity, especially in areas with a moderately low iodine intake, where the prevalence of mild thyroid disturbances is high.

Regulation of maternal thyroid during pregnancy.

A prospective study was undertaken in 606 healthy women during pregnancy to evaluate the changes occurring in maternal thyroid economy as a result of 1) the increased thyroid hormone-binding capacity of serum, 2) the effects of increased levels of hCG on TSH and on the thyroid, and 3) a marginally low iodine intake in the population (50-75 micrograms/day). Four main features were observed. First, thyroidal activity adjusted to the marked increase in serum T4-binding globulin: pregnancy was accompanied by an overall reduction in the T4/T4-binding globulin ratio, with lower free T4 and T3 levels, although in most cases free hormone levels remained within the normal range. The adjustment of thyroidal output of T4 and T3 did not occur similarly in all subjects. In approximately one third of the women, there was relative hypothyroxinemia, higher T3/T4 ratios (presumably indicating preferential T3 secretion), and higher, although normal, serum TSH concentrations. Second, high hCG levels were associated with thyroid stimulation, both functionally (lower serum TSH) and anatomically (increased thyroid size). The data are consistent with a TSH-like effect of hCG on the thyroid. Hence, regulation of the maternal thyroid is complex, resulting from both elevated hCG (mainly in the first half of gestation) and increasing TSH (mainly in the second half of gestation). Third, a significant increase in serum thyroglobulin levels was observed throughout gestation, especially during the last trimester. Fourth, increased thyroid volume was common, and goiter formation not uncommon (goiter was found in 9% of women at delivery). In conclusion, the alterations in maternal thyroid function during gestation are intricate and far from fully understood. In areas of marginally low iodine intake, gestation is associated in a significant number of women with relative hypothyroxinemia, increased thyroglobulin, and enlarged thyroid.

Long-term follow-up of separate glomerular filtration rate in partially obstructed kidneys. Experimental study.

An often encountered assumption is that non-relieved renal obstruction will lead soon or late to progressive deterioration of the renal function. The effect of non-relieved partial ureteral obstruction on the separate glomerular filtration rate (SGFR) was studied throughout the whole life of a series of rats, who were submitted at the age of 3 months to partial obstruction of the left ureter. An initial and variable postoperative SGFR decrease was gradually observed, but after this period, SGFR remained stable until the natural death of the animal.

Technetium-99m DMSA imaging and the obstructed kidney.

Although several authors have claimed that the function of an obstructed kidney could be overestimated on Tc-99m DMSA imaging, the clinical importance of such an overestimation has not been well documented. Partial obstruction of one ureter was created in a rat, and a relative Tc-99m DMSA uptake was obtained 4 hours after intravenous injection. By puncture of the isolated obstructed kidney, it was shown that the function of that kidney was overestimated by at least 17%.

Sensitivity of cortical transit and furosemide response in the diagnosis of renal obstruction. An experimental model.

Several radionuclide parameters are routinely used for the diagnosis of renal obstruction. In order to evaluate the sensitivity of those parameters, an experimental model of partial ureteral obstruction in rats was used. Neither the cortical transit time, nor the response to furosemide could serve to discriminate between obstructive and nonobstructive kidneys. These parameters were, however, more or less related to the degree of impairment of the single kidney glomerular filtration rate and should probably be considered as functional parameters reflecting the grade of the obstructive phenomenon.