Thyrotoxic periodic paralysis after allogeneic haematopoietic stem cell transplantation.
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Adult↗
Biomedical subjects
A W Kung
Publications and source records attributed to A W Kung.
Body fat determination by dual energy X-ray absorptiometry and its relation to body mass index and waist circumference in Hong Kong Chinese.
OBJECTIVE: To determine the relationship between percent body fat and body mass index (BMI) in the Chinese population of Hong Kong and to investigate whether the newly proposed lower BMI cut-offs for obesity in the Asia-Pacific Region recommended jointly by the International Association for the Study of Obesity, the International Obesity Task Force and the WHO are appropriate for Hong Kong Chinese. METHODS: A total of 190 female and 140 male healthy subjects were recruited from the community. BMI was calculated as weight/height(2). Body fat content (%BF) was measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Comparing %BF measured by DEXA with predicted %BF derived from BMI using a prediction formula developed in Caucasian population showed that the formula significantly under-predicted %BF by 1.1% in males and 3.4% in females. A predicted BMI of 25 and 30 kg/m(2) using a Caucasian-based formula corresponds to an actual BMI of 23 and 25 kg/m(2), respectively. On linear regression analysis, 25% BF corresponds to a BMI of 24.6 kg/m(2) in males and a waist circumference of 86 cm; 35% BF corresponds to a BMI of 22.6 kg/m(2) and a waist circumference of 73.5 cm in females. CONCLUSION: Hong Kong Chinese population have a higher %BF for a given BMI which would partly explain why the health risks associated with obesity occur at a lower BMI. Our results would support the recommendations of using lower BMI cut-offs to define obesity in the Asia Region.
Absorptiometry, Photon↗
Association of the HLA A2-B46-DR9 haplotype with autoimmune thyroid dysfunction after bone marrow transplantation in Chinese patients.
Autoimmune thyroid disease (AITD) may occur in patients after bone marrow transplantation (BMT). At a median follow-up of 4 years, among 194 allografts and 28 autografts, four patients (three allografts, one autograft) developed AITD. All carried the human leucocyte antigen (HLA) A2-B46-DR9 haplotype, strongly associated with AITD in the Chinese population. No significant thyroid disorder was detected in 190 patients without this haplotype. The frequency of AITD in BMT patients with the HLA A2-B46-DR9 haplotype was 12.5%, with a relative risk of 7.8 times that of non-carriers (P < 0.001). The risk of AITD should be recognized in recipients with high-risk HLA haplotypes, and regular screening might be warranted.
Adult↗
High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women.
Animal studies demonstrated that phytoestrogen had a protective effect against bone loss after ovariectomy. However, data on dietary phytoestrogen intake as well as its relationship with bone mineral density (BMD) in human are not available. Six hundred fifty southern Chinese women, aged 19 to 86 yr, were recruited to determine their dietary phytoestrogen intake by a food frequency questionnaire. BMDs at the lumbar spine and hip region were measured using dual energy x-ray absorptiometry. The subjects were analyzed according to various tertiles of phytoestrogen intake. Among the postmenopausal women (n = 357), significant differences in the lumbar spine (L2-4) BMD (0.820 +/- 0.145 vs. 0.771 +/- 0.131 g/cm2, P < 0.05) and Ward's triangle BMD (0.450 +/- 0.151 vs. 0.415 +/- 0.142 g/cm2; P < 0.05) were found between the highest and lowest intake of isoflavone after adjusting for age, height, weight, years since menopause, smoking, alcohol consumption, HRT usage, and daily calcium intake. Women with the highest intake of isoflavone had significantly lower levels of serum PTH (19.38 +/- 14.61 vs. 26.56 +/- 11.19 pg/ml; P < 0.05), osteocalcin (4.95 +/- 3.61 vs. 6.69 +/- 5.05 mg/liter; P = 0.05), and urinary N-telopeptide (34.18 +/- 25.31 vs. 49.66 +/- 41.00 nmol bone collagen equivalents/mmol creatinine; P < 0.05) when compared with those with the lowest intake of isoflavone. No association between dietary phytoestrogen intake and BMDs was seen in the premenopausal women with high endogenous E (n = 293). In conclusion, postmenopausal women with habitually high intake of dietary isoflavone are associated with higher BMD values at both the spine and hip region. Customarily high isoflavone intake may help to reverse the state of secondary hyperparathyroidism associated with E withdrawal and hence lower the rate of bone turnover in postmenopausal women.
Adult↗
Epitope mapping of tsh receptor-blocking antibodies in Graves' disease that appear during pregnancy.
Spontaneous remission of Graves' disease during pregnancy is thought to be due to a reduction of thyroid-stimulating antibody activity. We suspected, however, that a broader change in TSH receptor antibody characteristics might play an important role in modulating disease activity during pregnancy. We measured TSH binding inhibitory Ig, thyroid-stimulating antibody, and thyroid stimulating-blocking antibody activities in 13 pregnant Graves' disease patients at first, second, and third trimesters and 4 months postpartum. To measure and epitope-map thyroid-stimulating antibody and thyroid stimulating-blocking antibody activities, we used CHO cells transfected with wild-type human TSH receptor or with several TSH receptor-LH/hCG receptor chimeras: Mc1+2, Mc2, and Mc4. These chimeric cells have their respective TSH receptor residues 9-165, 90-165, and 261-370 substituted with equivalent residues of the LH/hCG receptor. Overall thyroid-stimulating antibody decreased, whereas thyroid stimulating-blocking antibody increased progressively during pregnancy. TSH binding inhibitory Ig fluctuated in individual patients, but overall the activities remained statistically unchanged. Thyroid stimulating-blocking antibody appeared in subjects who were either negative for thyroid-stimulating antibody or whose thyroid-stimulating antibody activity increased or decreased during pregnancy. Epitope mapping showed that the thyroid-stimulating antibodies were mainly directed against residues 9-165 of the N-terminus of the TSH receptor extracellular domain. All thyroid stimulating-blocking antibodies had blocking activities against residues 261-370 of the C-terminus of the ectodomain. However, the majority of the thyroid stimulating-blocking antibodies had a hybrid conformational epitope directed against N-terminal residues 9-89 or 90-165 as well. Despite a change in the activity level, we did not observe any change in the epitope of either the stimulatory or blocking Abs as pregnancy advanced. In conclusion, a change in the specificity of TSH receptor antibody from stimulatory to blocking activity was observed during pregnancy, and the appearance of thyroid stimulating-blocking antibody may contribute to the remission of Graves' disease during pregnancy.
Adult↗
Mild iodine deficiency and thyroid disorders in Hong Kong.
OBJECTIVES: To review evidence of iodine deficiency and clinical thyroid disorders in Hong Kong. DATA SOURCES: Publications on local dietary iodine intake, the iodine content of local food items, and clinical thyroid problems in the Hong Kong population. DATA EXTRACTION: Data was extracted and evaluated independently by the authors. DATA SYNTHESIS: Iodine is an essential nutrient. Iodine deficiency can lead to goitre, hypothyroidism, mental deficiency, and impaired growth. It is now appreciated that determination of goitre incidence in children alone may grossly underestimate the problem of iodine deficiency in a population. In total, the evidence indicates that iodine deficiency exists in Hong Kong, leading to clinical problems of transient neonatal hypothyroidism, goitrogenesis, and thyroid disorders in pregnant women and neonates, as well as thyroid dysfunction in the elderly. CONCLUSION: A supplementation programme aimed at a relatively uniform iodine intake is recommended to avoid deficient or excessive iodine intake in subpopulations.
Adult↗
PvuII polymorphisms of the estrogen receptor alpha and bone mineral density in healthy southern Chinese women.
The association between PvuII polymorphisms of the estrogen receptor alpha (ERalpha) gene and total as well as regional bone mineral density (BMD) in healthy Chinese women (n = 182) was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), where P indicated the absence and p the presence of PvuII restriction sites. Subjects with PP genotype had significantly higher BMD at the thoracic spine and ribs (both P < 0.05) when compared with those with Pp and pp genotypes. Although PP genotype had slightly higher BMD values at the lumbar spine L2-L4 region and hip by 8% and 7%, respectively, the results failed to reach statistical significance. After adjusting for age, height, weight, and years since menopause, PP genotype had higher BMD at the left (P < 0.02) and right (P < 0.05) rib region but not at the thoracic spine (P = 0.056). Analyzing the premenopausal subjects alone (n = 64) revealed that subjects with PP genotype had higher adjusted BMD at the right rib region (P < 0.05). When only the postmenopausal women (n = 118) were analyzed, the adjusted BMD of the PP genotype at the thoracic spine was significantly higher (P < 0.05) than the other two groups. In conclusion, estrogen receptor gene has a role in determining bone mass but the clinical impact on its own is probably small.
Asian People↗
The efficacy and tolerability of alendronate in postmenopausal osteoporotic Chinese women: a randomized placebo-controlled study.
Osteoporosis is a growing health problem in Asian women and it is expected that half of the world's hip fractures will occur in Asia in 50 years' time. As the use of hormonal replacement therapy (HRT) is extremely low in postmenopausal Asian women, nonhormonal agents will be more acceptable for the treatment and prevention of osteoporosis. The efficacy, tolerability, and acceptability of alendronate, an amino-bisphosphonate, for Asian women was evaluated in 70 osteoporotic southern Chinese women in a prospective, randomized, double-blind study. The subjects were randomized to receive either alendronate 10 mg daily or placebo, plus calcium supplementation 500 mg daily. The baseline L 1-4 and hip bone mineral density (BMD) were similar between both groups. At the end of 1 year, there was an increase of 5.8% in the lumbar spine BMD and 3.4% at the total hip with alendronate treatment when compared with baseline values (P < 0.001). Alendronate treatment for 1 year resulted in significant improvement in BMD at all sites measured when compared with placebo. There was also marked reduction in serum alkaline phosphatase (ALP) and urinary n-telopeptide (NTx) in the alendronate group when compared with the placebo group (ALP 25% versus 2%, NTx 75% versus 14%, both P < 0.005). The changes in ALP and NTx at 6 and 12 months correlated with the change in BMD at all sites measured at 1 year (P all <0.05). Alendronate was well tolerated and accepted, although two cases of gastric ulcer were reported. We conclude that alendronate is an effective and well-accepted agent for the treatment of osteoporosis in Asian women.
Absorptiometry, Photon↗
Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area.
OBJECTIVE: Severe iodine deficiency disorders (IDDs) may have been eradicated in many parts of the world, but milder forms still exist and may escape detection. We evaluated the impact of pregnancy on the maternal and fetal thyroid axis in Hong Kong, a coastal city in southern China with borderline iodine intake. DESIGN: A prospective study performed in a maternity hospital. PATIENTS: Two hundred and thirty pregnant women were prospectively studied and their neonates assessed at birth. MEASUREMENTS: Urine iodine concentration, thyroid function tests and thyroid volume (TV) by ultrasound were determined in the mothers during pregnancy and up to 3 months postpartum and in the neonates. RESULTS: Increased urinary iodine concentration was seen from first trimester onwards and the proportion of women having urine iodine concentration of < 0.4 micromol/l decreased from 11.3% in the first trimester to 4.7% in the third trimester. There was progressive reduction in circulating fT4 and fT3 concentrations and free thyroxine index (FTI) with increasing gestation and the percentage of women having subnormal levels at term were 53.2%, 61.1% and 4.8%, respectively. The serum TSH concentration during pregnancy doubled towards term. In the first trimester, multiparous women had significantly larger TV than the nulliparous women (P < 0.001). By the third trimester, TV had increased by 30% (range 3-230%) so that the goitre incidence was 14.1%, 21.8%, 25.9% during the three trimesters of pregnancy, and 24.3% and 21.9% at 6 weeks and 3 months postpartum (ANOVA, P < 0.05). The change in thyroid volume during pregnancy correlated positively with the change in thyroglobulin (r = 0.225, P < 0.002) and negatively with urinary iodine concentration (r = - 0.149, P < 0.02). Fourteen women with excessive thyroidal stimulation in the second trimester (defined as those with thyroglobulin (Tg) concentrations in the highest tertile and FTI in the lowest tertile) were found to have lower urine iodine concentrations and larger TV (both P < 0.005) throughout pregnancy, and their neonates had higher cord TSH (P < 0.05), Tg (P < 0.05) and slightly larger TV (P = 0.06) as compared to the findings in 216 pregnant women without evidence of thyroid stimulation. Seven neonates (50%) born to these women had subnormal fT4 levels at birth. CONCLUSION: In a borderline iodine sufficient area, pregnancy posed an important stress resulting in higher rates of maternal goitrogenesis as well as neonatal hypothyroxinaemia and hyperthyro- trophinaemia. An adequate iodization program is necessary to eliminate iodine deficiency disorders during pregnancy.
Analysis of Variance↗
Changes in cytokine production during pregnancy in patients with Graves' disease.
In order to investigate the role of type 1 and type 2 cytokines in the remission of Graves' disease (GD) during pregnancy, spontaneous and mitogen-stimulated production of interleukin (IL)-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunospot assay of peripheral blood mononuclear cells from 10 pregnant women with GD, 8 healthy pregnant women, and 10 healthy nonpregnant women. Tests were performed in the first, second, and third trimesters of pregnancy and 10-17 weeks after delivery. IL-4 production was not affected greatly by normal or GD pregnancy, whereas IFN-gamma production was suppressed throughout pregnancy but returned to normal levels after delivery in both controls and patients. IL-6 and TNF-alpha tended to be higher in GD pregnancy than normal pregnancy, especially in the second and third trimesters. Controls had raised IL-10 in the first trimester with a return to normal levels by the third trimester, whereas patients had raised levels throughout pregnancy. IL-12 levels were suppressed to a greater extent in control than Graves' pregnancy, especially during the second and third trimesters. Ratios of IL10:IL12 in phytohemaglutinin (PHA)-stimulated cultures were much lower in GD than normal pregnancy and cross-regulation of IL-10 and IL-12 may be deficient in GD.
Adult↗
Characterization of thyroid-stimulating blocking antibodies that appeared during transient hypothyroidism after radioactive iodine therapy.
Hypothyroidism after radioactive iodine (RAI) therapy for Graves' disease can be transient or permanent. The cause for early transient hypothyroidism is unknown. We evaluated 11 patients who developed transient hypothyroidism within 6 months of RAI and 12 who remained euthyroid after RAI. Approximately equal numbers of patients in each group had thyroid-stimulating antibody (TSAb) that increased cyclic adenosine monophosphate (cAMP) levels in Chinese hamster ovary (CHO) cells transfected with the recombinant human thyrotropin receptor (TSHR) (WT cells). Approximately equal numbers of patients from both groups had an increase in TSAb activity post-RAI. All TSAbs had their dominant functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity because they, but not TSH, completely lost stimulating activity in a receptor chimera, wherein TSHR residues 90-165 were substituted by equivalent residues of the lutropin/choriogonadotropin receptor (LH/CGR). Although equal numbers of patients in both groups had thyrotropin-binding inhibiting immunoglobulin activity (TBII), as measured by radioreceptor assay before RAI, patients with transient hypothyroidism had a surge in TBII activity and all except one became positive for thyroid-stimulating blocking antibodies (TSBAb), as measured by inhibition of TSH-stimulated cAMP from WT cells. When immunoglobulin G (IgGs) were epitope-mapped using TSHR/LH-CGR chimeras with different substitutions, 8 hypothyroid subjects had TSBAbs directed against residues 90-165 of the TSHR, as well as TSHR residues 261-370. Two had functional epitopes directed at residues 9-89 as well as TSHR residues 261-370. None of the euthyroid control patients developed TSBAbs and their TBII activity decreased post-RAI. When patients with transient hypothyroidism reverted to a euthyroid state, TSAb was still detectable in 5; however, TBII was present in all and TSBAb, although decreased, was still positive in 9. In summary, RAI therapy was associated with a change in thyroid antibody characteristics in most patients. Additionally, patients with a surge in TBII and the appearance of TSBAb developed transient hypothyroidism after RAI.
Adult↗
An adolescence girl with an anterior mediastinal mass.
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Adolescent↗
Effect of calcitriol on bone mineral density in premenopausal Chinese women taking chronic steroid therapy. A randomized, double blind, placebo controlled study.
OBJECTIVE: To study the effect of chronic steroid therapy on bone mineral density (BMD) in premenopausal women with normal menstrual cycles and its treatment. METHODS: A double blind placebo controlled study to evaluate 81 premenopausal women with systemic lupus erythematosus (SLE), aged 31.1 +/- 6 years, taking chronic steroid therapy, with a mean cumulative prednisone dose of 28 +/- 16.2 g. They were randomly allocated to 3 groups: Group 1: 0.5 microg calcitriol and 1200 mg calcium daily; Group 2: 1,200 mg calcium and placebo calcitriol; and Group 3: both placebo calcitriol and placebo calcium. RESULTS: Baseline T score at the lumbar spine was > -1 in 56.8% and < -2.5 in 3.7% of the patients. At the end of 2 years, patients in the calcitriol group exhibited a significant increase of 2.1 +/- 2.4% in BMD at the lumbar spine compared to baseline value (p < 0.05). This change was not significantly different from the respective change in either calcium or placebo group (0.4 +/- 2.9% and 0.3 +/- 3.5%, respectively). No significant changes were observed in any treatment group in BMD at the hip or radius. Alkaline phosphatase increased both in the placebo (baseline: 57.5 +/- 17.5 IU/I; year 2: 60.9 +/- 15.3 IU/A) and the calcium group (baseline: 53.6 +/- 16.6 IU/I; year 2: 59.0 +/- 22.8 IU/1), but this increase reached statistical significance only in the calcium group, while the same variable remained stable in the calcitriol group (baseline: 53.9 +/- 14.1 IU/I; year 2: 54.6 +/- 12.3 IU/I). CONCLUSION: Premenopausal women with SLE taking prolonged steroid therapy had lower BMD but showed no significant bone loss over the 2 year study period. The beneficial effect of calcitriol treatment in these premenopausal women was small, at least when it was instituted late in the course of steroid therapy.
Adrenal Cortex Hormones↗
Management of steroid-induced osteoporosis.
PURPOSE: To review the pathogenesis, clinical presentation, diagnostic assessment and treatment regimens of steroid-induced bone loss. DATA SOURCES: An English-language literature search (MEDLINE 1966-1999) and bibliographic reviews of textbooks and review articles. STUDY SELECTION: Cross-sectional and prospective studies with BMD measurements or fracture rate. RESULTS: The greatest rate of bone loss occur during the first 6 to 12 months of steroid therapy, affecting trabecular more than cortical bone. High steroid dosage for a prolonged period, prevalent fracture, hypogonadism, older age, low calcium intake and family history of osteoporosis are risk factors for steroid-induced bone loss. Based on bone density results, patients with osteoporosis or osteopenia with a T-score below -1.5 should receive antiresorptive treatment during steroid therapy. Among the various antiresorptive agents, bisphosphonates have the strongest evidence of preventing steroid-induced bone loss. CONCLUSION: The most important step in the management of steroid-induced osteoporosis is the proper assessment of the individual patient's risk of bone loss, and the selection of appropriate anti-resorptive agent for each patient.
Algorithms↗
Evaluation of a new calcaneal quantitative ultrasound system and determination of normative ultrasound values in southern Chinese women.
Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. The present study aimed at evaluating the precision of the Sahara bone ultrasound densitometer and to determine the normative QUS data in healthy southern Chinese women. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and qualitative ultrasound index (QUI) were determined. The long-term in vitro precision of the Sahara machine over 6 months was 4.6% for BUA and 0.39% for SOS. The short-term in vivo precision was 3.2 +/- 1.3% for BUA, 0.3 +/- 0.2% for SOS and 1.8 +/- 1.0% for QUI. The standardized precision for BUA, SOS and QUI was 4.4, 3.8 and 2.2 respectively. The normative data were determined in 1086 healthy subjects. Postmenopausal women had significantly lower BUA, SOS and QUI levels than the premenopausal women. Significant negative correlations were observed between QUS indices and age. Bone mineral density (BMD) assessments was performed on 349 of these subjects. BUA correlated significantly with lumbar spine BMD (r = 0.326) and femoral neck BMD (r = 0.395). Similar correlations were observed between SOS, QUI and BMD, with r values ranging between 0.446 to 0.522. Despite the fact that Chinese women have significantly lower BMD values than Caucasian women, the mean BUA values for pre- and postmenopausal Chinese women (73 +/- 18 and 59 +/- 18 dB/MHz respectively) were almost the same as those reported for Caucasian women. These normative data will be useful in the assessment of southern Chinese women with fracture risk.
Absorptiometry, Photon↗
Quantitative ultrasound and symptomatic vertebral fracture risk in Chinese women.
Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n = 53), normal postmenopausal women (group II, n = 198), and osteoporotic women without (group III, n = 141) and with vertebral fractures (group IV, n = 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <-2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was -2.87 +/- 1.02 for BUA, -2.54 +/- 0.79 for SOS, -3.17 +/- 0.70 for QUI, -2.65 +/- 0.86 for L2-4 BMD and -2.53 +/- 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2-2.6) for each 1 SD reduction in BUA, 2.72 (1.3-5.3) for SOS, 2.58 (1.4-4.6) for QUI, 2.33 (1.6-3.3) for L2-4 BMD, 2.09 (1. 37-3.20) for femoral neck BMD and 1.88 (1.34-2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0. 92, for SOS, QUI, L2-4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91.
Absorptiometry, Photon↗
Dual-energy X-ray absorptiometry for body composition estimation in Chinese women.
OBJECTIVE: To determine whether dual-energy X-ray absorptiometry (DXA) is a valid method for body composition assessment of obese and non-obese subjects. DESIGN: Cross-sectional study. SUBJECTS: Chinese women living in Hong Kong; 66 of 91 subjects had body mass index (BMI) of >25 kg/m2. MEASUREMENTS: Anthropometrics, including body weight, body height, waist and hip girth. Percentage body fat (%BF) and fat-free mass (FFM) from DXA (Hologic 2000 plus, Enhanced Array Whole Body Version 5.63) were compared with that based on a tracer dose of deuterium oxide for the determination of total body water (TBW). RESULTS: In both obese and non-obese subjects, FFMDXA was similar to FFMTBW. The Bland and Altman-type analysis indicated that comparable between-methods differences (mean bias) and limits of agreement were obtained in obese and non-obese subjects for FFM (0.4, between -4.4 and 5.2 kg vs 0.5, between -3.1 and 4.1 kg) and %BF (-0.6, between -7.6 and 6.4% vs -1.2, between -8.6 and 6.2%). The %BF bias was independent of age, BMI, hip circumference, and waist-to-hip ratio, but correlated with waist girth (r=0.24, P=0. 021). CONCLUSION: The sources of bias are methodological and anthropometric in nature. The between-methods differences, however, are small and clinically insignificant. DXA is a valid method for assessing the body composition of obese patients. SPONSORSHIP: This study was supported by a HKU-CRCG grant.
Absorptiometry, Photon↗
Alterations in hepatic lipase and lipoprotein subfractions with transdermal testosterone replacement therapy.
OBJECTIVES: The effect of sex hormone replacement therapy on lipoprotein metabolism is thought to be less marked with the transdermal route because of the lack of hepatic first-pass effect. The aim of this study was to evaluate the effects of testosterone replacement therapy given transdermally via a permeation-enhanced system on plasma lipolytic enzymes (hepatic and lipoprotein lipase), LDL and HDL subfraction concentrations. MEASUREMENTS: Ten patients with primary testicular failure were started on transdermal testosterone (Testoderm(R)). Plasma lipids, lipoproteins and post-heparin plasma lipolytic enzymes were evaluated before and after 3 months of treatment. LDL and HDL subfractions were measured by density gradient ultracentrifugation and hepatic and lipoprotein lipase activities by radio-enzymatic method. RESULTS: Serum testosterone level increased to within the normal range in all subjects whereas serum dihydrotestosterone (DHT) increased to supra-normal values. Plasma hepatic lipase (HL) activity increased after testosterone replacement (24.7 +/- 7.5 vs. 29.2 +/- 8.3 micromol free fatty acid released per hour, P < 0.05) and the increase in HL correlated with the increase in DHT (r = 0.64, P < 0. 05). Small changes were observed in LDL subfraction pattern with an increase in the concentration of small dense LDL-III (80.1 +/- 30.3 vs. 93.0 +/- 27.8 mg/l, P < 0.05). No significant change was seen in the HDL2 subfraction but HDL3 decreased after treatment (0.93 +/- 0. 17 vs. 0.79 +/- 0.14 mmol/l, P < 0.01). CONCLUSIONS: Testosterone replacement, given via a permeation-enhanced transdermal system, is associated with changes in hepatic lipase activity and in LDL and HDL subfractions. Whether these changes adversely influence the cardiovascular risk in the longterm remains to be determined.
Administration, Cutaneous↗