The impact of co-existing immune-mediated diseases on phenotype and outcomes in inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel diseases lead to progressive bowel damage and need for surgery. While the increase in prevalence of other immune-mediated diseases in IBD is well recognised, the impact of this on the natural history of IBD is unknown. AIM: To determine the impact of concomitant immune-mediated diseases on phenotypes and outcomes in IBD. METHODS: Patients with IBD enrolled in a prospective registry were queried about the presence of other immune-mediated diseases, defined as those where immune dysregulation plays a role in pathogenesis. Demographics and disease-related information were obtained. Subjects also completed measures of quality of life. Multivariable regression models compared disease phenotype and outcomes of IBD patients with and without other immune-mediated diseases. RESULTS: The cohort included 2145 IBD patients among whom 458 (21%) had another immune-mediated disease. There was no difference in CD phenotype between the two groups. UC patients were more likely to have pancolitis in the presence of another immune-mediated disease (62%) compared to those without (52%, P = 0.02). IBD patients with another immune-mediated disease had higher rates of needing anti-TNF biologics [Odds ratio (OR) 1.31, 95% CI 1.05-1.63] and surgery (OR 1.26, 95% CI 0.99-1.61). The presence of another immune-mediated disease was also associated with lower disease-specific and general physical quality of life. CONCLUSIONS: The presence of another immune-mediated disease in IBD patients was associated with higher likelihood of pancolonic involvement in UC, and a modest increase in need for IBD-related surgery and anti-TNF biological therapy. Such patients also experienced worse quality of life.

Spironolactone interference in the immunoassay of androstenedione.

BACKGROUND: In an evaluation of androstenedione results from patient serum samples using the Siemens Immulite 2500 analyser and manual Coat-A-Count (CAC) methods, three outliers were evident with grossly elevated results in the CAC assay. METHODS: The clinic notes of three patients with apparently high serum androstenedione concentrations by the CAC assay were checked for medications. The samples were all from patients with polycystic ovary syndrome taking 100-200 mg/d of a steroidal antiandrogen (spironolactone). Two other patients on 50 mg spironolactone per day had less markedly higher androstendione results with the CAC assay. In a further five patients who were selected since they were on spironolactone and had high androstenedione results by the CAC method, spironolactone was temporarily withdrawn and fresh blood samples obtained for analysis. RESULTS: Spironolactone treatment was associated with higher androstenedione concentrations measured by the CAC assay that reverted to normal on treatment withdrawal. Based on a single test with spironolactone at 1000 ng/mL, the manufacturer reported only 0.109% interference in the CAC assay. CONCLUSIONS: Spironolactone (and/or its metabolites) may interfere in the Siemens CAC assay for androstenedione but not in the Immulite 2500 assay. This experience highlights the need for information from clinicians on drug treatment when laboratory investigations are requested. Drug interferences in immunoassay are common and need evaluation beyond tests performed to certify laboratory reagents.

Service users' experiences of obtaining and giving information about disorders of sex development.

OBJECTIVE: To quantify participants' experiences of obtaining and giving information about disorders of sex development (DSD). DESIGN: Cross-sectional survey study that asked people about their current and past experiences relating to DSD disclosure. SETTING: A large tertiary referral centre for DSD management in the UK. POPULATION: One hundred of 126 people with a confirmed diagnosis of DSD who were invited to participate in the study formed the usable sample. METHODS: All people who attended clinic for follow-up during the study period and members of a patient support group whose annual meeting fell within the study period were asked to complete the Middlesex Communication Survey. MAIN OUTCOME MEASURES: The Middlesex Communication Survey. RESULTS: Younger participants were more likely to report having been appropriately informed about their diagnosis than older people. Nearly half of the former had been fully informed about their diagnosis by age 15 years, compared with 0% of the older age group. In terms of information sharing, mothers were most likely to be the person with whom the participant had shared (almost/all) DSD information (74%), followed by current partners (71%). Information relating to genital surgery, presence of testes and clitoral anomalies were the least likely aspects to have been unambiguously shared with even the most informed person. CONCLUSIONS: Our results suggest that difficulties in obtaining DSD information from care providers were common, and that communication has improved for younger participants. The study also confirmed that many people with DSD continue to struggle with confiding, even in those closest to them, about aspects of their diagnosis. Care protocol needs to centralise psychological adaptation, which should also be a primary focus for future research.

Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome.

AIMS/HYPOTHESIS: Variants in the fat-mass and obesity-associated gene (FTO) influence susceptibility to type 2 diabetes via an effect on adiposity/obesity. Given the important role of obesity in the aetiology of both polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus, our aim was to establish whether FTO variants are also implicated in PCOS susceptibility. METHODS: We performed a genetic association study of FTO variant rs9939609 using case-control analyses, conducted in 463 PCOS patients (geometric mean BMI 27.5 kg/m(2)) and 1,336 female controls (geometric mean BMI 25.3 kg/m(2)) of UK British/Irish origin. We also sought evidence for associations between FTO variation and circulating testosterone levels in 324 UK PCOS patients and 1,000 women from the Northern Finland Birth Cohort of 1966. Outcome measures included FTO rs9939609 genotype frequencies by participant group and androgen measures (testosterone, free androgen index) by genotype. RESULTS: There was a significant association between FTO genotype and PCOS status in the UK case-control analysis, which was attenuated by adjustment for BMI (Cochran-Armitage test, odds ratio [per minor allele copy] 1.30 [95% CI 1.12, 1.51], p = 7.2 x 10(-4) [unadjusted], p = 2.9 x 10(-3) [adjusted]). This association was most evident in obese PCOS patients (PCOS patients below median BMI vs UK controls, p = 0.11; above median BMI vs controls, p = 2.9 x 10(-4)). No relationship between FTO genotype and androgen levels was seen. CONCLUSIONS/INTERPRETATION: We provide the first evidence that variants that predispose to common obesity also result in altered susceptibility to PCOS, confirming the mechanistic link between these conditions. The predominant effect of FTO variants on PCOS susceptibility is probably mediated through adiposity.

Comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis.

OBJECTIVES: To compare bone mineral density (BMD) and body proportions between women with complete androgen insensitivity syndrome (CAIS) and with gonadal dysgenesis (GD). SETTING: Adult Disorders of Sexual Development and Ovarian Failure Clinics at University College London Hospitals. DESIGN: Retrospective cross-sectional study of three groups of women aged 17-58 years with varying degrees of exposure to sex hormones and different combinations of sex chromosomes. Forty-six subjects had CAIS, 18 had GD and 46,XY (GD(XY)), and 25 had GD and 46,XX (GD(XX)). In addition, body proportions of subgroups of these women were analysed. OUTCOME MEASURES: Oestrogen therapy, karyotype, anthropometry and BMD. RESULTS: Height differed between groups (F ratio 5.2, P=0.007)), with GD(XX) women being the shortest (mean+/-s.d.: 1.66+/-0.10 m), GD(XY) women the tallest (1.74+/-0.09 m) and CAIS women were in-between (1.70+/-0.07 m). Delayed gonadectomy resulted in taller stature in CAIS women (P=0.011). The ratio of lower to upper body length in GD(XY) women was significantly (P=0.001) greater than that of CAIS women. Multivariate logistic regression analysis (adjusted for age and height) showed that among women with XY karyotype, GD(XY) women were 5.2 times (95% confidence interval (CI): 1.3-20.1, P=0.018) more likely than CAIS women to have a low hip BMD. This difference was not evident among women with GD of different karyotypes (P=0.938). Spinal BMD did not differ between subject groups. Further adjustment for oestrogen replacement did not alter these relationships. CONCLUSIONS: Taller stature in late gonadectomised CAIS women suggests an oestrogen deficiency in these women prior to gonadectomy. Increased lower to upper body ratio in GD(XY) women compared with the other groups implies that these subjects have the greatest degree of oestrogen deficiency in puberty. Androgen rather than sex chromosomes may play an important role in cortical bone mineralisation in CAIS women, probably via estrogen receptor-alpha either directly or via aromatisation during critical periods of growth prior to gonadectomy.

Swyer syndrome: presentation and outcomes.

OBJECTIVE: To establish the spectrum of presentation, natural history and gynaecological outcomes in women with Swyer syndrome. DESIGN: Retrospective notes review. SETTING: Tertiary referral centre for disorders of sex development. POPULATION: A total of 29 adult women with Swyer syndrome. METHODS: Information was collected on age at diagnosis, biometric characteristics, timing of gonadectomy, histology of gonad, bone mineral density, uterine size and fertility. MAIN OUTCOME MEASURES: Age at diagnosis, risk of gonadal malignancy, bone mineral density, uterine size. RESULTS: With regard to presentation, 26/29 (90%) women in this series presented with delayed puberty, and the median age at diagnosis was 17.2 years (range 0-55 years). The median age at gonadectomy was 18 years (range 9-33 years). Histology of the gonad was available in 22 women and demonstrated streak gonads with no evidence of malignancy in 12, dysgerminoma in 7 and gonadoblastoma in 3. The youngest patient diagnosed with dysgerminoma was 10 years old. The median height of the women was 1.73 m (range 1.54-1.95 m). Twelve out of the 20 (60%) women had evidence of osteopenia on dual energy X-ray absorptiometry scan. The uterine size and shape was assessed in eight women after completion of induction of puberty, and the uterine cross-section was found to be significantly lower than that in normal controls. Fertility was achieved with ovum donation in three women, all of whom had live births and one subsequently had a second successful pregnancy. CONCLUSION: Early diagnosis of Swyer syndrome is necessary in view of the risk of dysgerminoma that can develop at an early age. Adequate hormone replacement is required to maintain bone mineral density and may improve the uterine size and shape.

Thrombo-embolic and bleeding complications in patients with mechanical valve replacements--a prospective observational study.

BACKGROUND AND OBJECTIVES: Long-term anticoagulation therapy is essential to prevent thrombo-embolic events in patients with mechanical valve replacements. In order to offer indigent patients mechanical heart valve replacement surgery, dedicated anticoagulation clinics are necessary for follow-up. This study assessed the safety and efficacy of lifelong oral anticoagulation therapy in Johannesburg General Hospital mechanical heart valve replacement recipients. The incidence of bleeding and thrombo-embolic complications was documented in three groups of patients with mechanical valve replacements. The groups included patients with aortic valve replacements (AVRs), mitral valve replacements (MVRs) and double (aortic and mitral) valve replacements (DVRs). MATERIALS AND METHODS: A prospective observational study was conducted over a 4-month period. Data on 306 patients attending the Johannesburg General Hospital anticoagulation clinic between 2000 and 2005 were analysed. Of the total patients selected, 205 were assigned to the mechanical valve replacement group (which included 63 patients with AVRs, 93 with MVRs and 49 with DVRs); a control group of 101 nonmechanical valve replacement patients were also included. At each visit the level of anticoagulation was assessed from the international normalised ratio (INR) values, and the presence of bleeding and/or thrombo-embolic complications was documented. RESULTS: There were a total of 51 bleeding and thrombo-embolic complications in the study population. Patients with DVRs had a higher proportion of combined complications (30.61%) than patients with single valve replacements (14.29% in the AVR group and 18.05% in the MVR group) and patients in the control group (12.87%). There were 38 bleeding complications, 30 minor and 8 major. Twelve thrombo-embolic events were documented. Individually, there was no significant difference in thrombo-embolic and bleeding complications between the subgroups. Eighty-two per cent of patients in the mechanical valve replacement group were within the therapeutic range for anticoagulant control (INR 2.5-3.5) v. 54% in the control group (INR 2.0-3.0). Anticoagulant control was of a high quality and was not a contributing factor to the incidence of bleeding and/ or thrombo-embolic complications. CONCLUSION: The finding of a low incidence of bleeding and thrombo-embolic complications in patients with mechanical valve replacements supports the continued placement of mechanical valves in our setting and use of oral anticoagulation therapy at an INR of 2.5-3.5. However the increased risk of both bleeding and thrombo-embolic complications in the DVR group is cause for great concern and warrants further investigation.

Fertility outcomes in women with hypopituitarism.

BACKGROUND: Women with hypopituitarism are known to have a poor outcome once pregnancy has been achieved by ovulation induction. There are no data, however, recording the efficacy of ovulation induction and pregnancy rates in this group of subfertile women. METHODS: The outcome of fertility treatments in all 19 women with hypopituitarism attending the fertility clinics of University College London Hospitals over the past 20 years was audited. RESULTS: Ovulation was achieved in almost all women (95%) but occurred in only 60% of treatment cycles. Pregnancy was achieved in 47% of women or 11% of cycles resulting in a live birth rate of 6.7% per cycle. Seven of the 18 pregnancies (39%) miscarried. Only 42% of women treated achieved a live birth. CONCLUSION: Ovulation induction in women with hypopituitarism yields relatively low pregnancy rates in comparison to other causes of anovulation and a high miscarriage rate. Pituitary hormone deficiency beyond gonadotrophins has a major adverse effect on achieving pregnancy.

Radiofrequency ablation of neuroendocrine liver metastases: the Middlesex experience.

BACKGROUND: Current treatment options for neuroendocrine liver metastases are not widely applicable or not that effective. Image-guided thermal ablation offers the possibility of a minimally invasive, albeit palliative, treatment that decreases tumor volume, preserves most of the normal liver, and can be repeated several times. We report our experience with image-guided thermal ablation in 25 patients with unresectable liver metastases. METHODS: Since 1990 we have treated 189 tumors at 66 treatment sessions in 25 patients (12 female, 13 male; median age, 56 years; age range, 26--78 years). Thirty treatments were performed with a solid-state laser, and 36 treatments were performed with radiofrequency ablation. All but one treatment was performed percutaneously under image guidance. Sixteen patients had metastases from carcinoid primaries, three from gastrinoma, two from insulinoma, and four from miscellaneous causes. Fourteen of 25 had symptoms from hormone secretion. RESULTS: Imaging follow-up was available in 19 patients at a median of 21 months (range, 4--75 months). There was a complete response in six patients, a partial response in seven, and stable disease in one; hence, tumor load was controlled in 14 of 19 patients (74%). Relief of hormone-related symptoms was achieved in nine of 14 patients (69%). The median survival period from the diagnosis of liver metastases was 53 months. One patient with end-stage cardiac disease died after a carcinoid crisis. There were eight (12%) complications: five local and three distant, four major and four minor. CONCLUSIONS: As a minimally invasive, readily repeatable procedure that can be used to ablate small tumors, preferably before patients become severely symptomatic, radiofrequency ablation can provide effective control of liver tumor volume in most patients over many years.

Prevalence of polycystic ovaries and polycystic ovary syndrome in lesbian women compared with heterosexual women.

OBJECTIVE: To determine the prevalence of polycystic ovaries (PCO) and polycystic ovarian syndrome (PCOS) in lesbian women compared with heterosexual women undergoing fertility treatment. DESIGN: A prospective observational study. SETTING: The London Women's clinic and The Hallam Medical Center. Tertiary referral fertility setup. PATIENT(S): Six hundred eighteen women undergoing ovarian stimulation with or without IUI treatment between November 2001 and January 2003. Of these, 254 were self-identified as lesbians and 364 were heterosexual women. INTERVENTION(S): Baseline pelvic ultrasound examination and blood tests conducted to measure biochemical parameters such as FSH, LH, E(2), PRL, T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS were performed between day 2 and 3 of each woman's menstrual cycle. Tubal patency tests were performed by hysterosalpingography or laparoscopy. MAIN OUTCOME MEASURE(S): Biochemical parameters. RESULT(S): Eighty percent of lesbian women, compared with 32% of the heterosexual women, had PCO on pelvic ultrasound examination. Thirty-eight percent of lesbian women, compared with 14% of heterosexual women, had PCOS. There were no significant differences in the androgen concentrations between lesbian and heterosexual women with normal ovaries. However, lesbian women with PCO and PCOS had significantly higher androgen concentrations compared with heterosexual women with PCO and PCOS. Tubal disease was as common in lesbian women as in heterosexual women. CONCLUSION(S): There is a significantly higher prevalence of PCO and PCOS in lesbian compared with heterosexual women. Lesbian women with either PCO or PCOS had more pronounced hyperandrogenism than did heterosexual women with either PCO or PCOS.

Misdiagnosis of seizures: insulinoma presenting as adult-onset seizure disorder.

Once diagnosed with a refractory seizure disorder, patients often receive aggressive and escalating pharmacotherapy. However, a significant proportion of patients referred to neurologists do not have epilepsy. Toxic and metabolic causes of seizures should always be considered as they are potentially curable, and may be fatal if untreated. The following case report highlights the need for careful reassessment of all seizures that are atypical and refractory to medication.

Induction of puberty in the hypogonadal girl--practices and attitudes of pediatric endocrinologists in Europe.

The management of children and adolescents with hypogonadism and in particular the induction of puberty in the hypogonadal girl is subject to controversy. Therefore, under the auspices and through organization of the Drugs and Therapeutics Committee of the European Society of Paediatric Endocrinology (ESPE), an interactive voting session and workshop was held at the 39th ESPE Annual Meeting in Brussels to discuss these topics. Common practice in Europe and attitudes of pediatric endocrinologists in Europe were questioned and recorded in the 1.5-hour program. We now report on some of the results of the questionnaires and discussions of that session to further the discussion on and knowledge of current concepts of induction of puberty in the hypogonadal girl in Europe. It became clear from the data accumulated here that the start of treatment, the aims of therapy and the modalities of how to treat the hypogonadal girl vary amongst pediatric endocrinologists in Europe. For example, a chronological age > or =11 years was considered appropriate for the start of estrogen therapy by 40.4% (out of 188 answers), while 47.8 and 7.5% felt that a chronological age > or =13 and > or =15 years respectively was appropriate. In respect to the form and route of estrogen administration, the audience was asked for their common estrogen replacement practice: 31.9% used oral 17beta-estradiol treatment, while 10% would prescribe 17beta-estradiol transdermal patches. Another 12.2% would recommend conjugated estrogens (e.g. Premarin) orally, 4.8% use oral estradiol valerate and 39.3% ethinylestradiol orally. Only 1.8% out of 229 physicians answering were undecided. In addition, counseling of patients and their families is quite variable and perceptions for example regarding potential pregnancies in affected women are also not uniform. In this report the authors do not want to provide their own personal views but rather reflect current practice in Europe. It is hoped that a more uniform picture will emerge once European and international guidelines on how to treat the girl with hypogonadism will be available and even more discussions amongst doctors from different countries have been led.

Turner's syndrome in adulthood.

Turner's syndrome is the most common chromosomal abnormality in females, affecting 1:2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. However, it is becoming increasingly evident that adults with Turner's syndrome are also susceptible to a range of disorders, including osteoporosis, hypothyroidism, and renal and gastrointestinal disease. Women with Turner's syndrome have a reduced life expectancy, and recent evidence suggests that this is due to an increased risk of aortic dissection and ischemic heart disease. Up until recently, women with Turner's syndrome did not have access to focused health care, and thus quality of life was reduced in a significant number of women. All adults with Turner's syndrome should therefore be followed up by a multidisciplinary team to improve life expectancy and reduce morbidity.

Idiopathic gonadotrophin deficiency: genetic questions addressed through phenotypic characterization.

OBJECTIVE: The association of idiopathic hypogonadotrophic hypogonadism (IHH) with congenital olfactory deficit defines Kallmann's syndrome (KS). Although a small proportion of IHH patients have been found to harbour defined genetic lesions, the genetic basis of most IHH cases remains to be elucidated. Genes currently recognized to be involved comprise KAL (associated with X-linked-KS), the GnRH receptor (associated with resistance to GnRH therapy), DAX 1 (associated with adrenohypoplasia congenita) and three loci also associated with obesity, leptin (OB), leptin receptor (DB) and prohormone convertase (PC1). Because of the rarity of the condition and the observation that patients are almost universally infertile without assistance, familial transmission of IHH is encountered infrequently and pedigrees tend to be small. This has constrained the ability of conventional linkage studies to identify other candidate loci for genetic IHH. We hypothesized that a systematic clinical evaluation of a large patient sample might provide new insights into the genetics of this rare disorder. Specifically, we wished to examine the following propositions. First, whether normosmic (nIHH) and anosmic (KS) forms of IHH were likely to be genetically discrete entities, on the basis of quantitative olfactory testing, analysis of autosomal pedigrees and the prevalence of developmental defects such as cryptorchidism and cleft palate. Second, whether mirror movements and/or unilateral renal agenesis were specific phenotypic markers for X-linked-KS. DESIGN AND PATIENTS: We conducted a clinical study of 170 male and 45 female IHH patients attending the endocrinology departments of three London University teaching hospitals. Approximately 80% of data were obtained from case records and 20% collected prospectively. Parameters assessed included olfaction, testicular volume, family history of hypogonadism, anosmia or pubertal delay, and history or presence of testicular maldescent, neurological, renal or craniofacial anomalies. Where possible, the clinical information was correlated with published data on genetic analysis of the KAL locus. RESULTS: Olfactory acuity was bimodally distributed with no evidence for a spectrum of olfactory deficit. Testicular volume, a marker of integrated gonadotrophin secretion, did not differ significantly between anosmic and normosmic patients, at 2.0 ml and 2.2 ml, respectively. Nevertheless, the prevalence of cryptorchidism was nearly three times greater in anosmic (70.3%, of which 75.0% bilateral) than in normosmic (23.2%, of which 43.8% bilateral) patients. Individuals with nIHH, eugonadal isolated anosmia and/or KS were observed to coexist within 6/13 autosomal IHH pedigrees. On three occasions, fertility treatment given to an IHH patient had resulted in the condition being transmitted to the resulting offspring. Mirror movements and unilateral renal agenesis were observed in 24/98 and 9/87 IHH patients, respectively, all of whom were identifiable as X-KS males on the basis of pedigree analysis and/or defective KAL coding sequence. Abnormalities of eye movement and unilateral sensorineural deafness were observed in 10/21 and 6/111 KS patients, respectively, but not in nIHH patients. DISCUSSION: Patients with IHH are almost invariably either anosmic (KS) or normosmic (nIHH), rather than exhibiting intermediate degrees of olfactory deficit. Moreover, the prevalence of cryptorchidism is nearly three times greater in KS than in nIHH despite comparable testicular volumes, suggesting a primary defect of testicular descent in KS independent of gonadotrophin deficiency. Disorders of eye movement and hearing appear only to occur in association with KS. Taken together, these findings indicate a clear phenotypic separation between KS and nIHH. However, pedigree studies suggest that autosomal KS is an heterogeneous condition, with incomplete phenotypic penetrance within pedigrees, and that some cases of autosomal KS, nIHH and even isolated anosmia are likely to have a common genetic basis. The prevalences of anosmia, mirror movements and unilateral renal agenesis among X-KS men are estimated to be 100, 85 and 31%, respectively. In sporadic IHH, mirror movements and unilateral renal agenesis are 100% specific phenotypic markers of de novo X-KS. By comparison, only 7/10 X-KS families harboured KAL coding defects. Clinical ascertainment, using mirror movements, renal agenesis and ichthyosis as X-KS-specific phenotypic markers, suggested that de novo X-KS was unlikely to comprise more than 11% of sporadic cases. The majority of sporadic KS cases are therefore presumed to have an autosomal basis and, hence, the preponderance of affected KS males over females remains unexplained, though reduced penetrance in women would be a possibility.

Autoimmune thyroid syndrome in women with Turner's syndrome--the association with karyotype.

OBJECTIVE: Females with Turner's syndrome (TS) are at an increased risk of developing autoimmune thyroid disease. Studies assessing the influence of karyotype on thyroid autoimmunity in adults with TS have yielded conflicting results but have been limited by small numbers. The aim of this study was to determine the frequency of thyroid autoimmunity in a large cohort of women with TS and to assess the influence of karyotype on the development of thyroid disease. DESIGN, PATIENTS AND MEASUREMENTS: Data were available for 145 women with TS attending a dedicated adult Turner clinic. The mean age was 26 years (range 16-52 years). Information regarding the presence of thyroid disease, karyotype, thyroid autoantibodies and thyroid function was recorded in all. The chi-squared test with Yates' correction was used to assess the association between karyotype and thyroid autoimmunity. RESULTS: Forty-one per cent of women with TS had positive thyroid autoantibodies and 16% of women were hypothyroid on replacement therapy with thyroxine. However, 83% of women with an X-isochromosome had positive thyroid autoantibodies compared with 33% of women with other karyotypes (P < 0.0001). Women with an isochromosome-X karyotype were also significantly more likely to become frankly hypothyroid and require thyroxine compared with other karyotypes (37.5% isochromosome-X vs. 14% 45, X vs. 6% other karyotypes P = 0.0034). CONCLUSIONS: In this large cohort of women with TS we have shown that the risk of developing autoimmune thyroid disease is particularly high in women with an X-isochromosome, suggesting that a gene on the long arm of the X chromosome (Xq) may play an important pathogenetic role in the development of autoimmune thyroid disease.

Hormone replacement therapy may improve hepatic function in women with Turner's syndrome.

OBJECTIVE: Women with Turner's syndrome (TS) have recently been shown to be at an increased risk of developing chronic liver disease. There has been some concern that oestrogen replacement therapy may exacerbate hepatic dysfunction. The aim of this study was to assess hepatic function in women with TS and to determine the effect of oral oestradiol valerate on liver enzymes. DESIGN AND PATIENTS: A retrospective review of liver enzymes of 80 women with TS, followed by a prospective study looking at serum liver enzyme concentrations in 20 women with TS following 3 months on and off hormone replacement therapy (HRT) (oestradiol valerate, 2 mg/levonorgestril 75 microg). MEASUREMENTS: Liver enzymes (gamma glutamyl transferase, aspartate transaminase and alkaline phosphatase), albumin and bilirubin were measured on and off HRT. Viral hepatitis serology and liver autoantibodies were tested in patients with abnormal liver function. RESULTS: Thirty-five out of 80 women (44%) had elevated serum liver enzyme concentrations. Two women (2.5%) had a mildly raised serum bilirubin, but protein synthesis was normal in all subjects. HRT resulted in a significant fall in all liver enzymes (P < 0.05) but did not affect serum protein concentrations CONCLUSIONS: Women with Turner's syndrome often have elevated liver enzymes. Oestrogen/progestagen therapy using oestradiol valerate improves liver function in this group of patients. The mechanisms behind this are unclear.