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T R Einarson

Publications and source records attributed to T R Einarson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pharmacoeconomic analysis of venlafaxine in the treatment of major depressive disorder.

We conducted a cost-effectiveness analysis of acute major depressive disorder (MDD) using serotonin-norepinephrine reuptake inhibitors (SNRIs; venlafaxine), selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, sertraline, paroxetine), or tricyclic antidepressants (TCAs; amitriptyline, imipramine, desipramine, nortriptyline). A decision-tree model over 6 months was constructed using an expert panel. The analytic perspective was that of the Ontario Ministry of Health as payor for all direct costs, which were derived from standard lists and included the cost of the drug as well as those for medical care, laboratory services, hospitalisation and managing adverse events. Success and dropout rates were determined from a meta-analysis of published randomised controlled trials. Medline, Embase, and International Pharmaceutical Abstracts were searched from 1984 to 1996, as were references from retrieved articles and reviews. Inpatients and outpatients were analysed separately. SSRIs were used as backup therapy for patients receiving venlafaxine and TCAs, and SNRIs were used as backup therapy for patients receiving SSRIs. Pharmacoeconomic outcomes were expected cost per success, expected cost per symptom free day (SFD), and incremental cost per success and per SFD. The meta-analysis identified 56 treatment arms from 36 randomised controlled trials involving 2953 patients (2380 outpatients and 573 inpatients). SNRIs had the highest success rates. The respective costs (in 1996 $Can; $Can1 = $US0.74) for outpatients and inpatients are given below. The expected costs per success were $6044 and $17,234 for venlafaxine, $6634 and $20,874 for SSRIs, and $9035 and $20,459 for TCAs in outpatients and inpatients, respectively. The respective expected costs per SFD were $45.92 and $127.31 for venlafaxine, $51.64 and $157.04 for SSRIs, and $70.71 and $152.43 for TCAs. Venlafaxine was dominant for all incremental pharmacoeconomic analyses. Sensitivity analyses indicated that the results were robust for outpatients but somewhat sensitive for inpatients. In conclusion, venlafaxine is a cost-effective drug for the treatment of MDD in adult outpatients and inpatients.

Antidepressive Agents, Second-Generation↗
PubMed1997

Quality assessment of economic evaluations published in PharmacoEconomics. The first four years (1992 to 1995).

Our objective was to assess the quality of reporting of original economic research articles in PharmacoEconomics from inception to the end of 1995, in order to identify areas of strength and weakness, and analyse trends over time. Each regular issue of the journal was examined for original economic evaluations. Accepted articles were categorised by study type and by year of publication. A previously developed 13-item quality-scoring checklist was applied. The maximum possible score that an article could be assigned was 4.0. Quality scores were analysed over time and by study type. 54 articles were identified for analysis. Mean overall score (OS) ranged from a minimum of 1.80 to a maximum of 3.75, with a mean OS of 3.01 [standard deviation (SD) = 0.47]. The item with the highest mean score was the 'definition of study aim' (mean OS = 3.46, SD = 0.69). The item with the lowest score was 'ethical problems discussed and identified' (mean OS = 1.44, SD = 0.92). Only 4 items on the checklist had mean scores lower than 3.0. No significant time trend was apparent for OS (R2 = 0.002). Cost-benefit (mean OS = 3.25, SD = 0.85, n = 5), cost-effectiveness (mean OS = 3.11, SD = 0.97, n = 27), and cost-utility (mean OS = 3.29, SD = 0.93, n = 6) analyses had mean scores significantly higher than cost-analysis/cost-of-illness studies (mean OS = 2.51, SD = 1.14, n = 8). The mean OS for cost-minimisation studies was 2.74 (SD = 0.49, n = 8). Despite some weaknesses in particular aspects of economic evaluations published in PharmacoEconomics, we conclude that the journal has offered publications with acceptable overall quality and adequate methodology.

Economics, Pharmaceutical↗
PubMed1996

A survey of population-based drug databases in Canada.

OBJECTIVE: To identify the population-based drug databases in Canada and to determine their comprehensiveness and accessibility for performing pharmacoepidemiologic and outcomes research. DESIGN: Survey (four-part mailed questionnaire). SETTING: Public and private third-party drug plans across Canada. PARTICIPANTS: All provincial and territorial drug plan or pharmacare managers as well as selected private plan managers including health benefit consultants, group insurers and claims adjudicators/pharmacy benefit managers (CA/PBMs). OUTCOME MEASURES: Patient, drug and pharmacy information; potential for electronic linkages to other provincial databases (e.g., physician, hospital, vital statistics); accessibility of information; population profile. RESULTS: Of the 32 recipients of the questionnaire 29 (91%) responded and 18 (56%) completed the survey. Most databases were reported to contain patient information (e.g., patient identification number, age, sex and medication history) and prescription drug information (e.g., drug identification number, strength, quantity and cost). Six provinces and one territory reported the capability to link to other databases (e.g., hospital and physician databases). One CA/PBM reported some links to selected long-term disability data. All of the government databases except those in British Columbia and the Yukon Territory allowed use of the data for research purposes. Manitoba and Saskatchewan included all residents of the province in their database; the others included selected groups (e.g., residents 65 years of age or older, people on social assistance or people covered by private group insurance). CONCLUSION: A number of public and private population-based databases are available for use in pharmacoepidemiologic and outcomes research.

Canada↗
PubMed1996

Clinical and economic factors in the treatment of onychomycosis.

Onychomycosis is a fungal infection of fingernails and toenails, most cases of which are caused by dermatophytes. The disease accounts for 15% of all nail disease, and affects approximately 2 to 3% of people of all ages and both sexes. Topical treatment with tioconazole, amorolfine or ciclopirox has limited effectiveness. Oral griseofulvin 500 to 1000mg daily has been the mainstay of treatment, but prolonged therapy is required and success rates are low. Therapy with itraconazole 200mg daily for 3 to 6 months is more effective (70 to 85% success), although so-called 'pulse' therapy has shown similar success with potentially fewer adverse effects. Terbinafine 250mg daily produces clinical and mycological cure in approximately 80% of patients treated for 6 and 12 weeks for fingernail and toenail infections, respectively. The overall costs of treating onychomycosis are substantial, and it has been estimated that direct costs for Medicare patients with the disease were $US43 million in 1 year. In addition, the disease has a negative impact on quality of life, in the domains of mental functioning, health concern, social functioning, and physical appearance. Few pharmacoeconomic analyses have been published, but all have indicated an advantage of oral terbinafine over griseofulvin and other oral agents. To date, no economic studies have been performed on topical agents, pulse therapy or combination treatments.

Animals↗
PubMed1995

Safety of metronidazole in pregnancy: a meta-analysis.

OBJECTIVE: Our purpose was to determine from published experience in humans whether metronidazole exposure during the first trimester of pregnancy is associated with an increased teratogenic risk. STUDY DESIGN: All published articles reporting on metronidazole use during pregnancy were screened by two independent reviewers to select those including pregnant patients exposed during the first trimester and comparing the outcomes of their pregnancies with that of patients either not exposed to metronidazole or exposed only during the third trimester. The outcome under consideration was the occurrence of birth defects in live-born infants. The overall odds ratios of first-trimester exposure versus no first-trimester exposure was calculated by combining the selected studies in a meta-analysis according to the procedure of Mantel and Haenszel. RESULTS: From 32 identified studies, 7 met the inclusion criteria for meta-analysis. Six were prospective and included 253 women exposed to the drug in the first trimester of pregnancy; one was retrospective and reported on 1083 exposed women. The overall weighted odds ratio of exposure versus no exposure during the first trimester calculated by meta-analysis of the 7 studies was 0.93 (95% confidence interval 0.73 to 1.18). The odds ratio calculated from the 6 prospective studies was 1.02 (95% confidence interval 0.48 to 2.18). CONCLUSION: Metronidazole does not appear to be associated with an increased teratogenic risk.

Abnormalities, Drug-Induced↗
PubMed1995

Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis.

OBJECTIVE: To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations. DATA SOURCES: MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English-language articles on first-trimester sex-hormone exposure and fetal genital changes. METHODS OF STUDY SELECTION: One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure. DATA EXTRACTION AND SYNTHESIS: The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24-3.94). CONCLUSION: There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation.

Case-Control Studies↗
PubMed1995

Spectrophotometry of amniotic fluid: a simple and rapid method for distinguishing between gestational sacs in second-trimester amniocentesis of twin pregnancies.

OBJECTIVE: To evaluate the use of an alternative and simple spectrophotometric method that could replace the intraamniotic injection of dye in the second-trimester amniocentesis of twins. METHODS: Optical densities (OD) of amniotic fluid (AF) obtained at second-trimester genetic amniocentesis were measured at 360 nm. Comparison was made between 36 twin pregnancies and 60 singleton controls. RESULTS: The mean difference in OD between two samples taken from the same sac of singleton pregnancies was very small (mean 0.004, standard deviation [SD] 0.003). However, samples drawn from each of the twin pairs' amniotic sacs varied widely (raw mean 0.176, SD 0.223; median 0.096, range 0.011-0.943). The difference between the groups was highly significant statistically (P < .001). CONCLUSION: Our preliminary experience with spectrophotometry of AF in twin amniocentesis suggests that this simple test may be useful in ascertaining that the AF samples were obtained from each of the two gestational sacs.

Amniocentesis↗
PubMed1995

Meta-analysis of parenteral clindamycin dosing regimens.

OBJECTIVE: We used meta-analysis to compare clinical cure and success rates for parenteral clindamycin 600 mg q8h or 900 mg q8h therapy to treat adult intraabdominal or female pelvic infections. DATA SOURCES: We located English-language articles describing clindamycin use in humans using MEDLINE, International Pharmaceutical Abstracts, and Embase and from personal and drug information center files, plus all article references. STUDY SELECTION: Eligible studies used parenteral clindamycin 600 mg q8h or 900 mg q8h to treat intraabdominal or pelvic infection in at least 1 arm of a study and provided a definition of clinical outcome. Accepted were comparative trials in adults who were not critically ill or expected to die. DATA SYNTHESIS: The DerSimonian and Laird method was used to calculate weighted overall success rates for cure and success (cure plus improved) rates along with 95% confidence intervals for each dosage in intraabdominal and pelvic infections. Regimens were compared with respect to both cure and success rates using the Mann-Whitney U test. MAIN RESULTS: Twenty-three articles were eligible for inclusion. Abdominal cure rates were 75.6% and 90.5% for clindamycin 600 mg q8h and 900 mg q8h, respectively (p = 0.03): success rates were 89.8% and 92.5%, respectively (p = 0.29). Pelvic cure rates were 82.8% and 89.4%, respectively (p = 0.51): success rates were 87.2% and 89.9%, respectively (p = 0.51). CONCLUSIONS: In pelvic infections, a dosage of clindamycin 600 mg q8h appears to be clinically acceptable for all patients. Although clinical outcomes for intraabdominal infections are generally similar for both regimens, the significantly higher cure rate with a dosage of clindamycin 900 mg q8h suggests that dosage recommendations should be patient specific.

Abdomen↗
PubMed1995

Pharmacoeconomic analysis of topical treatments for tinea infections.

The purpose of this study was to perform a government-perspective economic analysis of the most widely used topical creams [namely, ciclopirox (CIC), clotrimazole (CLO), ketoconazole (KET), miconazole (MIC), and terbinafine (TER)], for the treatment of 2 types of dermatophyte skin infections: dermatophytosis major (excluding onychomycosis) and dermatophytosis minor. A 3-phase approach was used. In phase I, experts were assembled to identify the standard approach for management of fungal infections and a decision tree was constructed to model the process; in phase II, meta-analysis was used to determine success, failure, and relapse rates; and in phase III, economic analyses were performed including cost of regimen, total expected cost and cost-effectiveness analysis. Sensitivity analyses (robustness analyses) were also performed in phase III. It was found that while TER was successful following 1 week of administration for minor infections and after 2 weeks for major infections, duration of drug treatment was usually twice that time. Other comparators (CIC, CLO, KET and MIC) took 4 weeks to achieve a successful outcome. In addition, an extra 2 weeks were often needed to clear both types of infections because the comparators are fungistatic, whereas TER is fungicidal. In the total expected cost analysis, TER had the lowest overall cost of treating patients for both infection categories. It was also responsible for the highest number of disease-free days and, consequently, the lowest cost per disease-free day. Sensitivity analyses confirmed that TER was the most cost-effective topical agent for treating dermatophytosis major (excluding onychomycosis) and dermatophytosis minor.

Administration, Topical↗
PubMed1994

Quality of nonstructured and structured abstracts of original research articles in the British Medical Journal, the Canadian Medical Association Journal and the Journal of the American Medical Association.

OBJECTIVE: To assess and compare the quality of nonstructured and structured abstracts of original research articles in three medical journals. DESIGN: Blind, criterion-based observational study. SAMPLE: Random sample of 300 abstracts (25 abstracts per journal each year) of articles published in the British Medical Journal (BMJ), the Canadian Medical Association Journal and the Journal of the American Medical Association (JAMA) in 1988 and 1989 (nonstructured abstracts) and in 1991 and 1992 (structured abstracts). MAIN OUTCOME MEASURES: The quality of abstracts was measured against 33 objective criteria, which were divided into eight categories (purpose, research design, setting, subjects, intervention, measurement of variables, results and conclusions). The quality score was determined by dividing the number of criteria present by the number applicable; the score varied from 0 to 1. RESULTS: The overall mean quality scores for nonstructured and structured abstracts were 0.57 and 0.74 respectively (p < 0.001). The frequency in meeting the specific criteria was generally higher for the structured abstracts than for the nonstructured ones. The mean quality score was higher for nonstructured abstracts in JAMA than for those in BMJ (0.60 v. 0.54, p < 0.05). The scores for structured abstracts did not differ significantly between the three journals. CONCLUSIONS: The findings support recommendations that promote the use of structured abstracts. Further studies should be performed to assess the effect of time on the quality of abstracts and the extent to which abstracts reflect the content of the articles.

Abstracting and Indexing↗
PubMed1994

Challenges in comparing treatment outcome from a prospective with that of a retrospective study: assessing the merit of gentamicin therapeutic drug monitoring in pediatric oncology.

The objectives of this study were: (a) to assess whether treatment outcome with gentamicin in pediatric oncology patients could be improved by a pharmacy based therapeutic drug monitoring (TDM) service that included pharmacokinetic interpretation; and (b) to describe the challenges in comparing treatment outcome from a prospective to a retrospective study when the merit of gentamicin therapeutic drug monitoring (TDM) was assessed in pediatric oncology patients. Two groups of pediatric oncology patients, aged 1-18 years, received empiric gentamicin therapy for fever and for confirmed or suspected infection, with the same inclusion and exclusion criteria. Group 1 consisted of patients from a prospective gentamicin pharmacokinetic study with a formalized pharmacy-based TDM service (n = 52). Group 2 consisted of patients admitted to the oncology units who had gentamicin levels analyzed in the TDM Laboratory without the formalized TDM Service (n = 25). Gentamicin dosage adjustments were recommended based on three blood samples (one pre- and two postdose concentrations) collected between the third and sixth doses from each patient in the TDM group, utilizing pharmacokinetic principles and the Sawchuk-Zaske method. In the non-TDM group, dosage adjustments based on two routine blood samples (one pre- and post-gentamicin dose) were performed by physicians without the help of the formalized TDM Service. Multiple regression analysis showed that time periods (TDM, non-TDM), duration of neutropenia, intravenous methotrexate, and types of cancer, e.g., hematologic malignancy vs. solid tumor, had significant effects on duration of fever. Initial absolute neutrophil count, insertion of central venous line, intravenous cloxacillin administration, bacteriologic cultures, and initial post gentamicin levels > or = 5 mg/ml had no significant effects on the duration of fever. Mean duration of fever in the TDM group (2.8 +/- 2.4 days) was significantly shorter than that in the non-TDM group (9.0 +/- 8.8 days) (p < 0.001). Therapeutic serum concentrations were achieved more promptly in the TDM group, with significantly fewer patients requiring dose changes and fewer sets of serum concentrations required. One patient from each group had a > 100% increase in serum creatinine on day 5 compared to baseline. No apparent nephrotoxicity was observed in other patients. Although there was an association of shorter duration of fever with prompt achievement of therapeutic gentamicin serum concentrations with the TDM Service, there were several unresolved factors that affected duration of fever. A randomized prospective and controlled study would be required to substantiate the merit of TDM in shortening the duration of fever in pediatric oncology patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Cost-effectiveness analysis for onychomycosis therapy in Canada from a government perspective.

An economic analysis of the oral antifungal drugs griseofulvin (GRI), ketoconazole (KET), and terbinafine (TER), currently registered and used in treating onychomycosis of fingernails and toenails, was performed using a model that incorporates elements of both meta-analysis and pharmacoeconomics. The meta-analysis of published studies determined rates of success, relapse and side-effects. The perspective taken for the analysis was that of the government payer, with expected total cost and cost-effectiveness being calculated. A multiphase approach was used. The studies of onychomycosis of the fingernails showed that TER had a 95.0% success rate, KET 80.9%, and GRI 59.6%. GRI had the lowest acquisition costs. The success rates for onychomycosis of the toenails were: TER 78.3%, KET 40.8%, and GRI 17.5%. GRI had the lowest acquisition costs. However, expected cost comparison showed TER had the lowest cost because of shorter treatment duration. The expected cost of therapy with a 100% government payer perspective for fingernail onychomycosis was the lowest for TER ($439.83), followed by GRI ($480.80), then KET ($755.46). Toenail onychomycosis showed the same order for the comparators, with TER $1049.77, GRI $1388.54 and KET $1936.48. When compared with TER, fingernail cost-effectiveness ratios for GRI and KET were 1.51 and 2.00. Toenail cost-effectiveness ratios were 2.49 and 2.48, respectively. For both fingernail and toenail onychomycosis, TER had the greatest number of disease-free days (973 for fingernails; 1073 for toenails), followed by KET (837; 798), then GRI (702; 569).(ABSTRACT TRUNCATED AT 250 WORDS)

Antifungal Agents↗
PubMed1994

A multinational pharmacoeconomic analysis of oral therapies for onychomycosis. The Onychomycosis Study Group.

Due to increased interest in economic evaluation and the rapid international spread of new healthcare technologies across borders, there is a need to interpret economic evaluations on a worldwide basis. We conducted a multinational cost-effectiveness analysis, from a government payer perspective, comparing four primary oral treatment regimens for onychomycosis of the fingernails and toenails: griseofulvin, itraconazole, ketoconazole and terbinafine. We used a four-step pharmacoeconomic research model which includes all relevant factors affecting costs in 13 countries: Austria, Belgium, Canada, Finland, France, Germany, Greece, Italy, The Netherlands, Portugal, Spain, Switzerland and the U.K. A worldwide meta-analysis of published clinical data served as the statistical input for the pharmacoeconomic model, and demonstrated that terbinafine had the highest success rates (95.0% and 78.3%) of the clinical comparators for fingernails and toenails, respectively. We found that terbinafine was the most effective therapy in relation to cost (therefore giving it the lowest cost-effectiveness ratio) for both infections in all health-care systems analysed.

Antifungal Agents↗
PubMed1993

Maternal noncompliance with antibiotics during breastfeeding.

OBJECTIVE: To determine the incidence of antibiotic prescription failure in breastfeeding women, and to characterize breastfeeding patterns during antibiotic therapy. DESIGN: Prospective cohort study by telephone follow-up of 203 breastfeeding women who were prescribed antibiotics as monotherapy. SETTING: A teratogen/drug information service (the Motherisk Program) in a tertiary care, pediatric hospital in Toronto, Canada. MAIN OUTCOME MEASURES: Number of breastfeeding women who did not initiate the antimicrobial therapy, and breastfeeding patterns during therapy in women who started it. RESULTS: Of 203 breastfeeding women who consulted the Motherisk Program for information about the safety of antimicrobials during breastfeeding, 125 (62 percent) were followed within 32 weeks (median 11). Nineteen of the 125 (15 percent) did not initiate the antimicrobial therapy. Of the remaining 106 women, 7 (7 percent) stopped breastfeeding during therapy. Despite reassuring advice, 1 in 5 women either did not initiate therapy or did not continue breastfeeding. CONCLUSIONS: Physicians should be aware of the substantial rate of noncompliance with drug regimens among nursing women and the potential negative impact of drug therapy on breastfeeding.

Anti-Bacterial Agents↗
PubMed1992

The effects of impaired liver function on the elimination of antineoplastic agents.

OBJECTIVE: To critically review available data on the disposition of cancer chemotherapy in patients with hepatic dysfunction, and to derive at dose recommendation. DATA SOURCES: All published studies in English. STUDY SELECTION: Both human and animal studies. DATA SYNTHESIS: The available studies were sequentially qualitatively described and critically discussed. CONCLUSIONS: The liver is responsible for the metabolism and elimination of many anticancer agents. Their accumulation during hepatic insufficiency may expose the patient to increased risk of drug toxicity. A variety of clinical methods have been described to estimate the need to decrease doxorubicin dose according to degree of hepatic failure to avoid serious toxicity. In some studies prospective ascertainment of clinical indices such as hepatic enzymes and bilirubin was successful in preventing doxorubicin-induced hepatotoxicity. Liver dysfunction has a major impact on cyclophosphamide pharmacokinetics. However, because such impairment leads to less production of the active aldophosphamide, fewer adverse effects were observed in hepatically impaired patients. Vinca alkaloids are extensively metabolized by the liver and excreted in the bile. Systemic exposure to these drugs is inversely correlated to the degree of hepatic failure measured by serum alkaline phosphatase. Although hepatic metabolism is a major route of elimination of fluorouracil, the kidney also plays an important role in its elimination. It has been suggested to reduce its dose in cirrhotic patients. Available pharmacokinetic data and their clinical implications are also discussed for azathioprine, mercaptopurine, etoposide, epirubicin, amsacrine, cytarabine, and other less-studied drugs. Recommendations for dose adjustments are presented and discussed.

Animals↗
PubMed1991

Quality of abstracts of original research articles in CMAJ in 1989.

PURPOSE: To evaluate the quality of abstracts of original research articles. DESIGN: Blind, criterion-based survey. SAMPLE: Systematic sample of 33 abstracts of original research articles published in CMAJ in 1989. MEASUREMENT: The quality of abstracts was measured against a checklist of evaluation criteria, which were divided into eight categories. A score for each abstract was obtained by dividing the number of criteria present by the number applicable. The overall mean score was also determined. RESULTS: The overall mean score of abstract quality was 0.63 (standard deviation 0.13) out of 1. Of the abstracts reporting study design 56% did not include specific technical descriptors. About 52% did not explicitly describe the study variables. In describing subject selection 79% failed to use specific technical terms. Of the abstracts reporting results 66% did not provide appropriate supporting data. Of those that gave conclusions 86% did not address study limitations and 93% made no recommendations for future study. CONCLUSION: Most of the abstracts provided some information pertaining to each evaluation criterion but did not provide detail sufficient to enhance the reader's understanding of the article. On the basis of the study sample the abstracts need improvement in description of research design, reporting of subject selection and results, and statements of limitations and recommendations. The small sample from one journal and the absence of comparison between the contents of the abstracts and the contents of the articles were limitations. Future studies should address these issues and compare the quality of traditional and structured abstracts.

Abstracting and Indexing↗
PubMed1991

Age-related patterns of thyroid-stimulating hormone response to thyrotropin-releasing hormone stimulation in Down syndrome.

Thyroid function in subjects with Down syndrome was studied using the thyrotropin-releasing hormone test. Forty-seven infants and children with Down syndrome were investigated. Ages ranged from 1 month to 7 years; there were 26 boys and 21 girls. Fourteen of the subjects with Down syndrome who had an exaggerated thyroid-stimulating hormone response to thyrotropin-releasing hormone stimulation had two or more annual follow-up tests. The remaining 33 subjects who only underwent one thyrotropin-releasing hormone test were compared with 22 age-matched controls (11 boys and 11 girls). Mean basal thyroxine 4 and triiodothyronine 3 values were in the normal ranges. All thyroid antibody titers were negative. Mean basal thyroid-stimulating hormone levels of subjects with Down syndrome were significantly higher than those of controls for all ages, even though there was a decline in thyroid-stimulating hormone levels in both groups. Peak thyroid-stimulating hormone response levels were significantly greater in the subjects with Down syndrome than in the controls. Longitudinal study of the 14 children with Down syndrome with an exaggerated thyroid-stimulating hormone response showed that the response remained exaggerated until the third year of life, when it declined to normal levels. Thyroid dysfunction during the growth spurt of infancy or delayed maturation of the hypothalamic pituitary thyroid axis are proposed mechanisms.

Analysis of Variance↗