National Health and Nutrition Examination Survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction.

CONTEXT: The setting of the TSH upper reference limit impacts the diagnosis of mild hypothyroidism and is currently controversial. OBJECTIVE: Our objective was to evaluate factors influencing the TSH reference range. DESIGN: Nonpregnant subjects aged 12 yr and older from National Health and Nutrition Examination Survey III were used to study the relationships between TSH, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies in different ethnic groups. RESULTS: TPOAb prevalence was lowest (<3%) when TSH was between 0.1 and 1.5 mIU/liter in women and between 0.1 and 2.0 mIU/liter in men and progressively increased to above 50% when TSH exceeded 20 mIU/liter. TSH reference range parameters (2.5th, 50th, and 97.5th percentiles) were analyzed according to thyroid antibody status, race/ethnicity, and age for the 14,202 subjects made up of non-Hispanic Blacks (B), non-Hispanic whites (W), and Mexican-Americans (M) who did not report thyroid disease or taking thyroid-altering medications and whose total T(4) was within the reference range. For each age group of each ethnicity, the inclusion of antibody-positive subjects increased TSH medians and upper limits (97.5th percentiles). The TSH upper limit was lower for the entire B cohort vs. W or M. However, this difference was lost when age cohorts with a similar prevalence of TPOAb (B age 40-49 yr vs. W and M age 20-29 yr) were compared. CONCLUSIONS: Ethnic differences in TSH were not present when populations with the same relative frequency of thyroid antibodies were compared. TSH upper reference limits may be skewed by TPOAb-negative individuals with occult autoimmune thyroid dysfunction.

Reliability of stimulated and spontaneous growth hormone (GH) levels for identifying the child with low GH secretion.

The reliability of stimulated and spontaneous GH levels for identifying the child with low GH secretion has been the subject of debate. We compared the ability of GH concentrations after pharmacological stimulation with levodopa and clonidine and of spontaneous peak and 12-h pooled GH concentrations during sleep on a single night to estimate the maximum spontaneous GH secretion from 2 nights in 55 children, aged 5-16 yr, with heights below the 3rd percentile and/or height velocities below the 25th percentile for age, who had two consecutive overnight GH secretory profiles. Maximum stimulated GH concentrations correctly categorized 80% of children who had maximum spontaneous GH concentrations above and below 4 micrograms/L using a double monoclonal immunoradiometric assay for GH (Tandem-R HGH, Hybritech). The remaining 20% of children had stimulated GH concentrations below but spontaneous GH concentrations above 4 micrograms/L. Using this cut-off, the maximum GH concentrations from the first and second nights correctly categorized 98% and 95% of the children, respectively. Night to night variation in GH secretion was low in children who had low spontaneous GH secretion (maximum spontaneous peak and pool GH concentrations, less than 4 and less than or equal to 0.7 micrograms/L, respectively), and pooled GH concentrations from the 2 nights were concordant in 98% of the cases. We conclude that it is not uncommon for stimulated GH concentrations to underestimate spontaneous GH secretion. Even without acclimatization to the hospital setting, measurement of spontaneous GH secretion on a single night was more reliable for identifying the child with low endogenous GH secretion than was GH stimulation testing alone.

Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994)

Iodine deficiency in a population causes increased prevalence of goiter and, more importantly, may increase the risk for intellectual deficiency in that population. The National Health and Nutrition Examination Surveys [NHANES I (1971-1974) and (NHANES III (1988-1994)] measured urinary iodine (UI) concentrations. UI concentrations are an indicator of the adequacy of iodine intake for a population. The median UI concentrations in iodine-sufficient populations should be greater than 10 microg/dL, and no more than 20% of the population should have UI concentrations less than 5 microg/dL. Median UI concentrations from both NHANES I and NHANES III indicate adequate iodine intake for the overall U.S. population, but the median concentration decreased more than 50% between 1971-1974 (32.0+/-0.6 microg/dL) and 1988-1994 (14.5+/-0.3 microg/dL). Low UI concentrations (<5 microg/dL) were found in 11.7% of the 1988-1994 population, a 4.5-fold increase over the proportion in the 1971-1974 population. The percentage of people excreting low concentrations of iodine (UI, <5 microg/dL) increased in all age groups. In pregnant women, 6.7%, and in women of child-bearing age, 14.9% had UI concentrations below 5 microg/dL. The findings in 1988-1994, although not indicative of iodine deficiency in the overall U.S. population, define a trend that must be monitored.

Growth hormone therapy in achondroplasia.

A pilot study was carried out to examine the safety and efficacy of recombinant human growth hormone for growth-promoting therapy of achondroplasia. The data suggest that the agent in doses used to treat non-GH-deficient forms of short stature (0.3 mg/kg/wk) modestly increases overall height velocity in some children with achondroplasia. The effect was seen mainly in children with the lowest growth velocities prior to treatment. No untoward effects were noted. Several questions were raised that require further study.

Radiologic technique to mark ureteral calculi for extracorporeal shock-wave lithotripsy.

A technique is described to bypass ureteral calculi with a catheter and radiologically mark the exact position of the calculus on the horizontal and vertical planes to perform extracorporeal shock-wave lithotripsy.

Trimester-specific changes in maternal thyroid hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations across trimesters in iodine sufficiency.

OBJECTIVES: To describe the interrelationships of thyroid functions based on trimester-specific concentrations in healthy, iodine-sufficient pregnant women across trimesters, and postpartum. METHODS: Circulating total 3,5,3'- triidothyronine (T(3)) and thyroxine (T(4)) concentrations were determined simultaneously using liquid chromatography tandem mass-spectrometry (LC/MS/MS). Free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and thyroglobulin (Tg) were measured using immunoassay techniques. Linear mixed effects models and correlations were calculated to determine trends and associations, respectively, in concentrations. RESULTS AND CONCLUSIONS: Trimester-specific T(3), FT(4), TSH, and Tg concentrations were significantly different between the first and third trimesters (all p < 0.05); second and third trimester values were not significantly different for FT(4), TSH, and Tg (all p > 0.25) although T3 was significantly higher in the third, relative to the second trimester. T(4) was not significantly different at any trimester (all p > 0.80). With two exceptions, analyte concentrations tended not to be correlated at each trimester and at 1-year postpartum. One exception was that T(3) and T(4) tended to be associated (all p < 0.05) at all time points except the third trimester (rho = 0.239, p > 0.05). T(4) and FT(4) concentrations tended to correlate positively during pregnancy (rho 0.361-0.382, all p < 0.05) but not postpartum (rho = 0.179, p > 0.05). Trends suggest that trimester-specific measurements of T(3), FT(4), Tg, and possibly TSH are warranted.

Lung cancer excess in an abandoned lead-zinc mining and smelting area.

Analysis of cancer mortality in whites has revealed a significant excess in both males and females in an old lead/zinc mining and smelting area. This area consists of three rural contiguous counties: Cherokee County, Kansas, Jasper County, Missouri, and Ottawa County, Oklahoma. The lung cancer excess has persisted for at least 28 years for males and 5 years for females. A pilot case/control study is underway in Cherokee County to assess the influence of cigarette smoking, occupation, and residence on the lung cancer excess. Analysis will incorporate the histologic findings. From an environmental perspective, there are numerous mine tailings containing lead, zinc, cadmium, sulfur, germanium, and other chemicals. Considerable dust is airborne. Numerous openings (sink holes and bore holes) connect the old mines with the surface. Radium 226 has been detected in the untreated groundwater.

Management of undescended testis may be improved with educational updates for referring providers.

OBJECTIVE: A large proportion of boys referred for undescended testis (UDT) is not managed optimally prior to the referral, with the majority seen at >1 year of age and many having unnecessary ultrasound (US). Our objective was to assess the magnitude of these problems in our area and to determine if unnecessary US decreased following interventions to educate referring providers (RPs). MATERIALS AND METHODS: A chart review was done on new patients referred for UDT from January 2010 to June 2012. Data collection included age on date of pediatric urology office visit, whether or not RPs obtained an US, and whether the pediatric urology examination revealed an UDT or retractile testis. Several educational updates for RPs were provided and the proportion having US was tracked during the study period. RESULTS: Of 363 boys referred for UDT, only 17% (62) were seen at <1 year of age, and 62% (227) had retractile testis. US had been obtained in 24% (87/363). There was a statistically significant decrease in the proportion of patients having had an unnecessary US following the last update (p < 0.01). CONCLUSIONS: Delayed urology consultation and unnecessary US for UDT are common in our area. A brief focused educational update was effective in decreasing US in our area.

Community-based projects for the prevention of developmental disabilities.

Community projects are a central feature of the Centers for Disease Control's (CDC's) Disabilities Prevention Program. Twenty-eight states now have such programs, and they use community projects to stimulate local involvement in disability prevention and as a setting to evaluate prevention needs and preventive interventions.

Surgical management of incontinence in bladder exstrophy.

Between 1978 and 1990, 86 patients with previously closed classical bladder exstrophy and 10 patients seeking undiversion have presented for continence management and have undergone selective reconstruction designed for voiding and/or intermittent urethral catheterisation. The reconstruction in these 96 patients has been reviewed. Eight of the 10 patients undergoing undiversion achieved a satisfactory state of continence but 4 required Mitrofanoff procedures to enable catheterisation. Of the other 86 patients, 2 reached a satisfactory state of continence without further surgery; 79 underwent bladder neck surgery for continence either without augmentation (n = 32) or with augmentation (n = 47). Twenty of the 32 patients who were treated by bladder neck reconstruction alone were later found to require augmentation. Five patients had very early augmentation either to facilitate neonatal closure or on account of severe upper tract dilatation. Of these, 1 became continent without further surgery and 4 demonstrated the need for bladder neck reconstruction. Thus 12 children achieved successful continence (n = 6) or are evolving satisfactorily with potential success (n = 6) as a result of bladder neck reconstruction. Of the 71 patients requiring bladder neck reconstruction and augmentation, 68 have completed their surgery. The current status of these patients is: satisfactory in 57 (80%) (42 void/urethral clean intermittent catheterisation (CIC), 7 waiting to learn CIC, 5 Mitrofanoff, 3 artificial urinary sphincter (AUS]. Of the remaining 11 patients (20%), 8 are unsatisfactory to varying degrees and the status of the other 3 is unknown.

X-linked congenital panhypopituitarism.

Two half brothers with panhypopituitary dwarfism are reported who have the same mother and different, unrelated fathers. The subject of hereditary panhypopituitarism is reviewed briefly. It is concluded that there are at least two forms of hereditary panhypopituitary dwarfism, one of which may be X-linked.

Multimodality treatment of complex renal calculi.

More than 2,500 patients were treated for urolithiasis from 1984 to 1987. In an effort to define the relative role of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy with respect to size, location and composition of the calculus 912 of these patients (224 of whom underwent percutaneous nephrolithotomy and 688 of whom underwent extracorporeal shock wave lithotripsy) were reviewed. Size proved to be the only significant factor in the success and complication rates of extracorporeal shock wave lithotripsy but it did not affect the outcome of percutaneous nephrolithotomy. The roles of these 2 modalities were then examined with respect to the treatment of complex renal calculi. We reviewed 376 patients with complex renal calculi, including 40 percutaneous nephrolithotomy patients from the initial 912 patients studied. The initial therapy in 100 of these patients, treated consecutively, was extracorporeal shock wave lithotripsy. The remaining 276 patients were treated by percutaneous nephrolithotomy. The success rate of extracorporeal shock wave lithotripsy monotherapy in the treatment of complex renal calculi was 36%. The success rate of primary percutaneous nephrolithotomy was 83%. We conclude that percutaneous nephrolithotomy should be the primary therapy for patients with complex renal calculi. Extracorporeal shock wave lithotripsy is the preferred treatment for patients with smaller calculi and as an adjunct to percutaneous nephrolithotomy.

Nephroblastoma and end-stage renal failure with bilateral cystic kidneys.

A child of 10 years 5 months presenting with chronic renal failure had bilateral cystic kidneys. Biopsy of a right lower-pole solid mass revealed nephroblastoma. At bilateral nephrectomy, both kidneys were both replaced by variable-sized cysts with a unifocal nephroblastoma on the right. Renal failure with nephroblastoma is uncommon and is usually either a manifestation of the Drash syndrome or a complication of chemotherapy. The need to assess both kidneys in a child with any other renal abnormality in addition to a renal mass should always be considered.

Evaluation and treatment of incontinence after bladder neck reconstruction in exstrophy and epispadias.

Twenty-five children with exstrophy/epispadias who had had at least one bladder neck operation (but no augmentation) for incontinence underwent cystometrography (CMG) and urethral pressure profile (UPP) studies. The purpose of this study was to examine all components of lower urinary tract function and to determine how the properties of the bladder and the properties of the bladder neck/urethra interacted to achieve continence or to result in incontinence in the individual child. Examination of detrusor function during filling revealed involuntary contractions in 12 children and an end-fill pressure > 10 cm H2O in 8. Of the 21 children in whom voiding could be evaluated only 6 could initiate a detrusor contraction. In the 18 incontinent children leak pressure could be measured and was > or = 15 cm H2O in 12. Five of the 7 continent children also demonstrated at least one abnormality in lower tract function. The maximum pressure of the UPP did not agree with the leak pressure and may not be a valid measure of the closing pressure of the bladder neck/urethra in this patient population. Detailed urodynamic investigation is necessary in these children to guide the next step of management and to evaluate objectively each form of treatment.

Long-term treatment with growth hormone of children with short stature and normal growth hormone secretion.

Children with short stature but normal growth rate and/or normal growth hormone response to sleep and secretagogues were treated with recombinant methionyl human growth hormone, 0.3 mg/kg per week. In each year of treatment, about 80% of the subjects maintained an increase in growth rate greater than the defined limit (greater than 1 cm/yr above pretreatment growth rate) for continuation of human growth hormone treatment. Comparison of the group that continued to respond to human growth hormone with the group that did not maintain an accelerated growth rate did not reveal differences in bone age delay, sleep or secretagogue-stimulated human growth hormone secretion, degree of short stature either absolute or relative to target height, and somatomedin C concentration before or after initiation of therapy. The group that failed to respond to the human growth hormone treatment in the first year of treatment was younger and had a higher pretreatment growth rate. Review of the longitudinal growth curves revealed five patterns of response to human growth hormone treatment: (1) failure to increase growth rate in two subjects with height SD scores within 1 SD of target height, (2) failure to increase growth rate in five subjects with height SD scores greater than 1 SD less than the target height, (3) acceleration in growth rate in three subjects that was not maintained until achievement of a height within 1 SD of the target height, (4) acceleration of growth rate in five subjects that was maintained until achievement of a height within 1 SD of the target height, and (5) acceleration in growth rate that was maintained during the 3 years of treatment in 15 subjects who had not attained a height within 1 SD of the target height. We conclude that human growth hormone treatment of some but not all short children with "normal" growth hormone secretion will result in sustained acceleration of growth rate and attainment of prepubertal heights that are closer to but do not exceed their genetic height potential. A clinical trial of human growth hormone may be necessary to determine which subjects will benefit from the treatment.

Lower urinary tract function after exstrophy closure.

Twenty-eight children with bladder exstrophy, prior to surgery for continence, underwent a urodynamic evaluation, cystogram, ultrasound and dimercaptosuccinic acid scan, to define parameters of lower urinary tract function that are a risk for upper tract damage and/or impair development of bladder capacity. The bladders in 7 of 28 demonstrated no storage function [leak pressure)LP) = 0]; but storage parameters could be measured in the other 21. Their LP was 10-35 cm H2O; 17 of 21 revealed involuntary contractions and 7 of 21 had an end-fill pressure greater than 10 cm H2O. Bladder capacity was better in those with a higher LP and those with no involuntary contractions. The 4 patients with bilateral hydronephrosis (3 of whom also had bilateral multiple scars) were among the 6 with LP greater than 30 cm H2O. Of the 7 with an end-fill pressure greater than 10 cm H2O, 5 had upper tract damage. Involuntary contractions may impair development of capacity. A LP of greater than 30 cm H2O is a risk factor for upper tract damage and an end-fill pressure greater than 10 cm H2O may also be a factor.

Coexisting ureteropelvic junction obstruction and vesicoureteral reflux: diagnostic and therapeutic implications.

The coexistence of ureteropelvic junction obstruction and vesicoureteral reflux was seen in 17 (14 per cent) of 147 consecutive patients undergoing pyeloplasty. These patients were analyzed to determine the therapeutic implications of this association. They fell into 3 clinical groups: group 1--primary ureteropelvic junction obstruction, group 2--ureteropelvic junction obstruction secondary to high grade reflux and group 3--pseudo-ureteropelvic junction obstruction. There were 11 patients in group 1. These patients had incidental low grade reflux. Pyeloplasty should be the initial procedure with use of a nephrostomy tube or Foley catheter postoperatively. Vesicoureteral reflux resolved spontaneously with linear growth in approximately half of the cases. There were 4 patients in group 2. The obstructive uropathy should be treated initially, since primary ureteral reimplantation may provoke acute ureteropelvic junction decompensation. There were 2 patients in group 3. Pseudo-ureteropelvic junction obstruction is suggested when pelvic dilatation on the voiding cystourethrogram suggests obstruction but drainage films or antegrade studies document good drainage. The recognition of pseudo-ureteropelvic junction obstruction is important to avoid surgery on a ureteropelvic junction that is not obstructed. Primary correction of the reflux is appropriate. However, it must be recalled that a fixed kink may rarely develop later leading to true secondary ureteropelvic junction obstruction, which will require surgical correction. We recommend that a voiding cystourethrogram be part of the routine evaluation of children with suspected ureteropelvic junction obstruction.

Embryologic considerations of diphallus and associated anomalies.

Two patients, 1 adult and 1 infant, with complete duplication of the penis are described. The adult had a single bladder, a bifid scrotum, a low abdominal wall hernia, separation of the symphysis pubis, bilateral inguinal hernias, rectal prolapse, bilateral vesicoureteral reflux and bilateral staghorn calculi. The infant had duplication of the bladder, hypoplasia of the left kidney, lumbosacral anomalies, a hypoplastic left lower extremity, an imperforate anus, a infraumbilical wall hernia and separation of the symphysis pubis. A survey of the anomalies accompanying the 2 main types of diphallus (shaft and glans, and glans alone)showed that there was a preponderance of anomalies of posterior structures such as colon, bladder and spine in the shaft and glans diphallus, and a higher incidence of isolated exstrophy of the bladder in diphallus of the glans alone. The embryogenic implications of these findings are discussed.