Gilad Karavani

Increases in Thyrotropin Within the Near-Normal Range Are Associated With Increased Triiodothyronine But Not Increased Thyroxine in the Pediatric Age Group

CONTEXTnTSH has been shown in vitro to increase conversion of T4 to T3 and to preferentially increase thyroidal T3 secretion. Whether or not these effects are significant in vivo, other than in obesity, is unclear.nnnOBJECTIVEnTo test whether the incremental relationships between free T4 (FT4), free T3 (FT3), and TSH are compatible with TSH enhancement of a preferential increase in serum FT3.nnnDESIGN AND SETTINGnA large database of pediatric and adolescent thyroid test results drawn in community clinics from children and adolescents without known thyroid disease was analyzed.nnnPATIENTS AND METHODSnRESULTS of FT3, FT4, and TSH were studied anonymously. They were crossed with electronic charts to exclude a history of positive thyroid autoantibodies and use of thyroid hormone preparations, antithyroid medication, or drugs known to affect thyroid function. All samples from patients appearing more than once in the database were removed. After exclusions, 3276 samples remained. FT4, FT3, and the FT3/FT4 ratios were correlated with TSH for the entire group, and the same parameters were segregated by TSH quartile. RESULTS were stratified for body mass index and studied separately in a normal-weight subgroup.nnnMAIN OUTCOME MEASURESnStepwise correlations of FT4, FT3, and FT3/FT4 ratios with TSH.nnnRESULTSnThere was a significant positive linear correlation of TSH with FT3 and FT3/FT4 ratios (R = 0.12; P < .0001 in both), but not with FT4.nnnCONCLUSIONnWithin the near-euthyroid range, increasing TSH levels are associated with increasing FT3 levels, without an increase in FT4. This provides in vivo support for TSH enhancing preferentially T3 production and/or secretion.

Time to menarche and final height after histrelin implant treatment for central precocious puberty

OBJECTIVEnTo compare final height, change in body mass index (BMI), and time from end of treatment until menarche in girls with central precocious puberty treated with the histrelin implant versus depot gonadotropin releasing hormone agonist injections.nnnSTUDY DESIGNnChart review, interview, and final height measurements of 2 groups of girls with central precocious puberty; triptorelin depot (TD) group: 23 girls were treated from age 8.4 ± 0.3 with monthly injections of TD, for 26.7 ± 2.5 months; histrelin implant group: 11 girls were treated from age 8.7 ± 0.3 years for 28.4 ± 3.7 months, of whom 9 initially received monthly TD injections for 1.5-39 months. Final height, BMI (pretreatment vs recent), and time between either implant removal or last injection to menarche were compared.nnnRESULTSnTime between removal of implant or last injection and menarche was 9.3 ± 1.5 (histrelin implant group) versus 16.1 ± 1.7 (TD group) months (P = .02). Predicted height at implant insertion was 156.8 ± 2.6 cm, and final height was 161.1 ± 2.0 cm (not significant [NS]). Predicted height for TD was 155.2 ± 1.9 cm and final height was 157.9 ± 1.7 cm (NS). Change from onset of treatment to final BMI-SDS for histrelin implant was -0.41 ± 0.3, and for TD was -0.03 ± 0.2 (NS).nnnCONCLUSIONSnMenarche occurred sooner after implant removal. There was no difference in final height or BMI outcomes between the 2 treatment modalities.

Comparison of Pediatric Appendectomy Outcomes Between Pediatric Surgeons and General Surgery Residents

BACKGROUNDnAppendectomy is the most common urgent procedure in children, and surgical outcomes may be affected by the surgeons experience. This studys aim is to compare appendectomy outcomes performed by pediatric surgeons (PSs) and general surgery residents (GSRs).nnnMATERIALS AND METHODSnA retrospective review of all patients younger than 16y treated for appendicitis at two different campuses of the same institution during the years 2008-2009 was performed. Appendectomies were performed by PS in one campus and GSR in the other. Primary end points included postoperative morbidity and hospital length of stay.nnnRESULTSnDuring the study period, 246 (61%) patients were operated by senior GSR (postgraduate year 5-7) versus 157 (39%) patients by PS. There was no significant difference in patients characteristics at presentation to the emergency room and the rate of appendeceal perforation (11% versus 15%, P=0.32), and noninfectious appendicitis (5% versus 5% P=0.78) also was similar. Laparoscopic surgery was performed more commonly by GSR (16% versus 9%, P=0.02) with shorter operating time (54±1.5 versus 60±2.1, P=0.01). Interestingly, the emergency room to operating room time was shorter for GSR group (419±14 versus 529±24min, P<0.001). The hospital length of stay was shorter for the GSR group (4.0±0.2 versus 4.5±0.2, P=0.03), and broad-spectrum antibiotics were used less commonly (20% versus 53%, P<0.0001) and so was home antibiotics continuation (13% versus 30%, P<0.0001). Nevertheless, postoperative complication rate was similar (5% versus 7%, P=0.29) and so was the rate of readmissions (2% versus 5%, P=0.52).nnnCONCLUSIONSnThe results of this study suggest that the presence of a PS does not affect the outcomes of appendectomies.

TSH enhancement of FT4 to FT3 conversion is age dependent

OBJECTIVEnWe previously reported increasing free T3 (FT3) to free T4 (FT4) ratios as thyroid-stimulating hormone (TSH) increases within the normal range in children. It is not known if this phenomenon is age-related among humans, as previously reported in rats. This study examines the relationships between TSH and FT3/FT4 ratios in different ages.nnnDESIGNnRetrospective examination of thyroid tests from patients without thyroid disease from community clinics.nnnMETHODSnFree T3, free T4, and TSH levels from 527 564 sera collected from patients aged 1 year or greater were studied. Exclusion criteria were the following: missing data, TSH greater than 7.5mIU/L, and medications that may interfere with thyroid hormone activity. A total of 27 940 samples remaining after exclusion were stratified by age. Samples with available anthropometric data were additionally stratified for body mass index (BMI). Correlations of TSH to FT4, FT3, and FT3/FT4 ratios by age group were examined.nnnRESULTSnUp to age 40, for each increasing TSH quartile, FT3 and the FT3/FT4 ratio increased and FT4 decreased significantly (for both FT3, FT4 and FT3/FT4 ratio, P<0.05 for every TSH quartile when compared with the 1st quartile, except FT3 in the 30-40 age group). In older age groups, increasing TSH was not associated with increased FT3/FT4 ratio.nnnCONCLUSIONnAs TSH levels increase, FT3/FT4 ratios increase until age 40, but this differential increase does not occur in older age groups. This may reflect a decrease in thyroxine (T4) to triiodothyronine (T3) conversion with age, which may be part of the aging process.

Normal limits for serum thyrotropin vary greatly depending on method

Thyroid‐stimulating hormone (TSH) levels within populations do not follow Gaussian distribution, and normal limits are derived after mathematical normalization. The clinical relevance of these limits is unknown. The objective of this study was to compare upper and lower TSH limits by four data normalization methods with non‐normalized data and assess their clinical relevance.

Does cryopreservation of sperm affect fertilization in nonobstructive azoospermia or cryptozoospermia

OBJECTIVEnTo compare intracytoplasmic sperm injection (ICSI) outcomes with the use of fresh or frozen-thawed ejaculated or testicular sperm in patients with cryptozoospermia or nonobstructive azoospermia.nnnDESIGNnRetrospective cohort study.nnnSETTINGnTertiary medical center IVF unit.nnnPATIENT(S)nA total of 274 patients evaluated from 1999 toxa02011.nnnINTERVENTION(S)nA total of 103 patients underwent testicular sperm extraction (TESE) because of nonobstructive azoospermia, and 171 patients were diagnosed with cryptozoospermia.nnnMAIN OUTCOME MEASURE(S)nICSI outcomes during the first cycle in each technique performed according to the sperm origin (testicular vs. ejaculated) and processing (frozen vs. fresh).nnnRESULT(S)nForty-eight cycles with the use of frozen testicular sperm, 22 cycles with fresh testicular sperm, 66 cycles with frozen ejaculated sperm, and 138 cycles with fresh ejaculated sperm were examined. Significantly more motile sperm were found in the fresh ejaculate group compared with the frozen-thawed ejaculate group (96% vs. 88%, respectively). Furthermore, fresh ejaculated sperm were found to have better fertilization rates than frozen ejaculated sperm (64% vs. 56%, respectively). No significant difference was found between fresh and frozen-thawed testicular sperm, either in motile sperm available for ICSI or in fertilization rate (64% vs. 62% and 52% vs. 49%, respectively).nnnCONCLUSION(S)nIn cases of cryptozoospermia, frozen-thawed ejaculated sperm is inferior to fresh ejaculated sperm in fertilization rates. However, in nonobstructive azoospermia, no major differences were found between fresh and frozen-thawed testicular sperm. Therefore, uncoupled TESE/oocyte pick-up (OPU) should be considered in NOA cases to prevent possible unnecessary ovarian stimulation and OPU when no sperm cells are detected.

Transvaginal ultrasound to guide embryo transfer: a randomized controlled trial

OBJECTIVEnTo compare sonographic visualization and patient pain in conventional transabdominal ultrasound (TAUS) with transvaginal ultrasound (TVUS) sonographic-guided embryo transfer (ET).nnnDESIGNnProspective, randomized, controlled study.nnnSETTINGnTertiary medical center, inxa0vitro fertilization (IVF) unit.nnnPATIENT(S)nOne hundred and twenty patients younger than 40xa0years old scheduled for ET.nnnINTERVENTION(S)nPatients (32.9 ± 4.5xa0years old) undergoing fresh cleavage-stage ET were randomly assigned to the study group (TVUS; n = 60) or control group (TAUS; n = 60). After ET each patient filled out a questionnaire based on a visual analogue scale (VAS) to evaluate pain and discomfort before, during, and after the procedure. The physician assessed the quality of sonographic visualization. The follow-up observation lasted 12xa0months and included pregnancy rates.nnnMAIN OUTCOME MEASURE(S)nVisualization of the uterus and ET location and pain before, during, and after the ET procedure.nnnRESULT(S)nVisualization of the uterus and the ET location by the physician was statistically significantly better in the TVUS than in the TAUS group (9.57 vs. 8.42 and 9.58 vs. 8.82, respectively). Pain sensation assessed by a visual analogue scale (VAS) before, during, and after the procedure was statistically significantly lower in the study group compared with the control group (5.45 vs. 1.48, 5.03 vs. 2.42 and 2.97 vs. 1.52). The implantation and live-birth rates did not differ between the two groups (32.9% vs. 23.4%, OR 1.61; 95% CI, 0.85-3.07; 31.6% vs. 25.0%, OR 1.39; 95% CI, 0.63-3.09, respectively).nnnCONCLUSION(S)nTVUS guidance to facilitate ET is superior to TAUS in visualization of ET location and in lessening the pain and discomfort of the patients.nnnCLINICAL TRIAL REGISTRATION NUMBERnNCT008263312.

FT3 IS HIGHER IN MALES THAN IN FEMALES AND DECREASES OVER THE LIFESPAN

OBJECTIVEnNormal changes in free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels over the lifespan and differences between sexes are not well documented, mainly because even the largest-scale studies available include relatively small cohorts. The aim of this study was to define age-related trends including sex differences based on reliable data.nnnMETHODSnA large database including serum thyroid tests drawn in community clinics was studied. FT3, FT4, and TSH levels from 527,564 sera samples taken from patients age 1 year or greater were included. After highly extensive exclusion criteria applied to remove all samples that may have been taken from unhealthy people, 27,940 samples remained. These were stratified by decades of age and by sex.nnnRESULTSnFT3 decreases throughout life, significantly more so among females, with equalization between sexes with greater age. FT4 declines to a lesser extent, also more among females than among males. Among the very old, females have higher levels of FT4. In contrast, TSH declines until age 50 and then increases slightly in both sexes.nnnCONCLUSIONnThis study provides reliable data regarding trends in hormonal levels by age and sex, with the major finding being higher FT3 in males throughout life except in the very young and very old. These results have important implications for diagnosing and treating thyroid conditions.nnnABBREVIATIONSnANOVA = analysis of variance; BMI = body mass index; FT3 = free triiodothyronine; FT4 = free thyroxine.

Reducing Fluid-Related Complications During Operative Hysteroscopy: Use of a New Mandatory Fluid-Balance Form

STUDY OBJECTIVEnTo examine whether our new reporting system and mandatory fluid-balance form could improve the communication and awareness within the surgical team and therefore the safety of hysteroscopic operations.nnnDESIGNnA case-control study (Canadian Task Force classification II-2).nnnSETTINGnAn endoscopic gynecology unit at a tertiary-care university hospital.nnnPATIENTSnWomen aged 17 to 88xa0years (median, 43.9) who underwent operative hysteroscopy to treat uterine pathology.nnnINTERVENTIONSnOperative hysteroscopy was performed using bipolar technology and normal saline as an irrigation media with the new fluid-balance form and a mandatory reporting system. The control group was composed of women who underwent the procedure using the same technology, with a previous protocol.nnnMEASUREMENTS AND MAIN RESULTSnData regarding intraoperative and postoperative short-term complications were prospectively collected during surgery and at the 2-week follow-up visit. About 2000 procedures were investigated (601 in the study group and 1396 in the control group). In the control group there were 20 incidents of fluid deficit over 2xa0L. In 4 of these cases the procedure was terminated, but in the other 16 cases the procedure was continued, with or without awareness of the surgeons to the deficit. Of these cases, 2 suffered from media-related complications, and in 3 others complications were avoided by diuretics. In contrast, in the study group there were 10 incidents of fluid deficit over 2xa0L, of which 5 cases were terminated on time and the other 5 continued under the informed decision of the surgeon. In this group, none of the women experienced a media-related complication. The difference between the number of procedures that were terminated on time between the control and study groups was not statistically significant (pxa0=xa0.115). There was a statistically significant reduction in the total complication rate between the study group (1.8%) and the control group (3.9%; pxa0=xa0.019).nnnCONCLUSIONSnThe fluid-balance form and mandatory reporting system have been shown to reduce the rate of total complications in hysteroscopic surgeries, in particular media-related complications. This result is achieved by an improvement of the awareness and communication among the operating team, leading to an improvement in procedure safety.

A “See and Treat” Office Procedure for Retained Products of Conception Removal After Normal Vaginal Delivery Using Manual Vacuum Aspiration: Preliminary Efficacy and Reproductive Outcomes

STUDY OBJECTIVEnTo compare the efficacy and reproductive outcomes of an ultrasound-guided manual vacuum aspiration (MVA) procedure with the widely accepted operative hysteroscopic (OH) procedure in the removal of retained products of conception (RPOCs) after normal vaginal delivery.nnnDESIGNnA retrospective cohort study (Canadian Task Force classification II-2).nnnSETTINGnA university-affiliated tertiary medical center.nnnPATIENTSnEighty-six patients after normal vaginal delivery diagnosed with RPOCs from 2005 through 2015. This study was approved by the local institutional review board.nnnINTERVENTIONSnTreatment with either MVA or OH for patients diagnosed with RPOCs.nnnMEASUREMENTS AND MAIN RESULTSnOf 86 patients, 23 underwent remnant removal by ultrasound-guided MVA using a 6- to 7-mm catheter in a see and treat office procedure. Sixty-three patients underwent remnant removal using the OH procedure. Follow-up included sonographic examination 3 to 5xa0weeks after the procedure and long-term follow-up on complications and reproductive outcomes. Successful remnant evacuation and the overall complications rates were similar when comparing the MVA group and the OH group (95.7% vs 96.8% and 4.3% vs 4.7%, respectively). Conception rates and miscarriage rates were comparable in the MVA and OH groups (78.6% vs 72.2% and 9.1% vs 14.8%, respectively).nnnCONCLUSIONnPreliminary results from 23 patients suggest that MVA is an efficient procedure with low complication rates and satisfactory reproductive outcomes. It does not require anesthesia or operating room facilities, allowing an immediate and inexpensive see and treat option for RPOCs. Further larger controlled trials are required.