Increased Admissions Due to Cardiac Complications of Thyrotoxicosis in Maori.

BACKGROUND: As thyrotoxicosis is a risk factor for atrial fibrillation, current guidelines recommend measuring a thyroid-stimulating hormone level in patients with this disorder. Hyperthyroidism may also be associated with other heart diseases including cardiac ischaemia and cardiac failure. Currently, the prevalence of thyrotoxicosis in cardiac admissions in the absence of a rhythm disorder is unknown. AIMS: The aims of this study were: 1) to calculate the prevalence of admissions for thyrotoxicosis-associated cardiac disease, 2) determine the type of cardiac disease i.e. dysrhythmic, ischaemic or cardiac failure, and 3) to assess whether Maori are over-represented amongst patients admitted to hospital with cardiac complications of thyrotoxicosis. METHODS: A retrospective review of admissions with both thyrotoxicosis and cardiac disease from 1 January 2005 to 31 December 2012 inclusive. RESULTS: Seventy-two patients were identified as being admitted for a cardiac complication of thyrotoxicosis, giving a mean of nine admissions per year. Dysrhythmia was the cause for admission in 32 patients, ischaemia in 12, cardiac failure in 11 and mixed cardiac disease in 17. Graves' disease and amiodarone-induced were the most common causes of the thyrotoxicosis (25 and 19 cases, respectively). Of the cohort 26 (36.1%) were Maori (compared to 16.8% of all cardiac admissions over the same period). Maori were more likely to present with cardiac failure than non-Maori (57.7% vs. 26.1%, p=0.008 respectively). CONCLUSIONS: Maori are over-represented amongst patients admitted with cardiac complications of thyrotoxicosis and more often present with cardiac failure than non-Maori. Measurement of thyroid function should be considered in patients presenting not only with atrial fibrillation but also in patients presenting with cardiac failure, particularly if they are Maori.

Treatment choice, satisfaction and quality of life in patients with Graves' disease.

BACKGROUND: Thyrotoxicosis, most often caused by Graves' disease (GD), when treated inadequately may result in premature mortality. There is little consensus as to which of the 3 treatment options available - antithyroid drugs (ATD), radioactive iodine (RAI) and surgery, is better. AIMS: (i) To assess factors involved in treatment choice and treatment satisfaction in patients treated for Graves' disease; (ii) To assess quality of life (QoL) following treatment of Graves' disease. METHOD: Participants were selected from a prospective study cohort assessing thyrotoxicosis incidence and severity. Of the 172 eligible patients with Graves' disease, 123 treated patients participated (64% had received ATD only, 11% RAI and 25% total thyroidectomy, the latter 2 usually after a period of ATD), along with 18 untreated patients with newly diagnosed Graves' disease (overall participation rate, 73%). Consented patients completed a questionnaire detailing factors involved in treatment choice, QoL and satisfaction with treatment. RESULTS: Participants reported that the most important factors in choosing a treatment were the following: the effects on activities of daily living, concern about use of radioiodine, possibility of depression or anxiety, and doctor's recommendations. Satisfaction levels were high across all 3 treatment types. QoL 1-year following treatment was higher than in untreated patients, and comparable with other international studies. CONCLUSIONS: Patient satisfaction with therapy and QoL does not differ by treatment type. Therefore, clinical and social factors, in combination with patient choice and resource availability, should determine which treatment modality patients with Graves' disease should receive.

Absence of Myostatin Improves Cardiac Function Following Myocardial Infarction.

BACKGROUND: Myostatin inhibits the development of skeletal muscle and regulates the proliferation of skeletal muscle fibroblasts. However, the role of myostatin in regulating cardiac muscle or myofibroblasts, specifically in acute myocardial infarction (MI), is less clear. This study sought to determine whether absence of myostatin altered left ventricular function post-MI. METHODS: Myostatin-null mice (Mstn-/-) and wild-type (WT) mice underwent ligation of the left anterior descending artery to induce MI. Left ventricular function was measured at baseline, days 1 and 28 post-MI. Immunohistochemistry and immunofluorescence were obtained at day 28 for cellular proliferation, collagen deposition, and myofibroblastic activity. RESULTS: Whilst left ventricular function at baseline and size of infarct were similar, significant differences in favour of Mstn-/- compared to WT mice post-MI include a greater recovery of ejection fraction (61.8±1.1% vs 57.1±2.3%, p<0.01), less collagen deposition (41.9±2.8% vs 54.7±3.4%, p<0.05), and lower mortality (0 vs. 20%, p<0.05). There was no difference in the number of BrdU positive cells, percentage of apoptotic cardiomyocytes, or size of cardiomyocytes post-MI between WT and Mstn-/- mice. CONCLUSIONS: Absence of myostatin potentially protects the function of the heart post-MI with improved survival, possibly by limiting extent of fibrosis.

Quality of Life and Sexual Distress in Women With Erosive Vulvovaginal Lichen Planus.

OBJECTIVES: Erosive vulvovaginal lichen planus (EVLP) is a chronic and painful genital dermatosis. Little is published about its impact on quality of life. This study aimed to evaluate quality of life and sexual function in women with EVLP. MATERIALS AND METHODS: Women with genital dermatoses were surveyed using the Dermatology Life Quality Index (DLQI) and Hospital Depression and Anxiety Scales. A subgroup completed the Female Sexual Distress Scale and Female Sexual Function Index subscales. Patient characteristics including age, diagnosis, and current treatment were recorded. Results from women with EVLP were compared with other diagnoses. RESULTS: Data from 77 women who participated between March 2013 and March 2014 were analyzed. Of these, 17 had EVLP. Comparator groups included women with vulval lichen sclerosus (n = 48) and vulval dermatitis (n = 12). In women with EVLP, 59% reported at least moderate impact on quality of life; mean DLQI scores: EVLP, 7.18; lichen sclerosus, 3.79; dermatitis, 8.67; p = .008. Overall, scores suggested depression in 14% and anxiety in 16% of participants. Sexual distress scores 11 or higher were recorded by 69% of women with EVLP, 63% of women with lichen sclerosus, and 56% of women with dermatitis. In those completing all sections of the survey (n = 40), DLQI was significantly correlated with depression (p = .004), sexual distress (p = .001), and sexual satisfaction (p = .01). CONCLUSIONS: Sixty-nine percent of women with EVLP reported sexual distress. Women with EVLP reported lesser quality of life than those with lichen sclerosus. Quality of life, anxiety and depression, sexual distress, and sexual function were all related in these participants.

A low incidence of iodine-induced hyperthyroidism following administration of iodinated contrast in an iodine-deficient region.

OBJECTIVE: There are limited data on the incidence of iodinated contrast-induced thyrotoxicosis, particularly in iodine-deficient regions. The aim of this study was to determine the incidence of iodinated contrast-induced thyrotoxicosis and to determine whether thyrotoxicosis was more common in patients ≥70 years compared to those <70 years of age. DESIGN: A prospective study of adult patients undergoing an outpatient CT with iodinated contrast was performed. MEASUREMENTS: Thyroid function tests (TFTs) and urine iodine measurements were performed prior to the scan. TFTs were repeated at 4- and 8-weeks postscan. Changes in TFTs from baseline were analysed. RESULTS: A total of 102 patients were included in the final analysis. Overall, TSH levels dropped (P = 0·0002), and free T3 (FT3 ) levels increased (P = 0·04) between baseline and week 4 with normalization by week 8; however, these changes were not considered clinically significant. No significant differences in free T4 (FT4 ) occurred in the overall group (P = 0·82). There were no differences in TFTs between baseline and 4 or 8 weeks for those patients aged <70 compared to ≥70 years. Two patients developed new subnormal TSH values. Of these, one had a 90-mm follicular variant papillary thyroid carcinoma diagnosed while the other had a normal thyroid assessment and TSH spontaneously normalized by 12 weeks. CONCLUSIONS: Only 2% of patients developed subclinical hyperthyroidism following a standard dose of iodinated contrast for CT investigations. Given the low incidence of iodine-induced thyrotoxicosis, there is no indication for routine pre- and post-CT thyroid function testing in our region.

Retrospective investigation of testosterone undecanoate depot for the long-term treatment of male hypogonadism in clinical practice.

INTRODUCTION: Testosterone undecanoate depot (TUD) administered intramuscularly is an effective form of testosterone replacement therapy (TRT) for male hypogonadism. Because of the ease of administration, TUD therapy may be preferable to subcutaneously implanted extended release T pellet implants (TI). AIM: The primary objective was to retrospectively assess the efficacy and safety of long-term (≥ 2 years therapy) TUD therapy in the clinical setting. The secondary objective was to retrospectively compare TUD with TI therapy. METHODS: Retrospective data were collected from the Waikato Hospital Endocrine Database for 179 hypogonadal men treated with TUD for ≥ 2 years from 1998-2011, with 124 of these men receiving previous TI therapy. MAIN OUTCOME MEASURES: The main outcome measure for efficacy was serum trough total testosterone (TT), and for safety an increase in hemoglobin (Hb) and/or hematocrit (Hct), rise in prostate-specific antigen (PSA) and/or prostatic biopsy and alteration in body mass index and lipid profile. Additional outcome measures were changes in the dosing and/or interval regimens for TUD therapy. RESULTS: Overall, 72% of trough TT levels were in the normal range for TUD therapy compared with 53% of trough TT levels during TI therapy. TUD therapy was well tolerated with 162 men (90.5%) completing 2 years of treatment, and only seven men (3.9%) stopping TUD because of adverse effects. A rise in Hb and/or Hct occurred in 25 men (14%), and a significant rise in PSA in 20 men (13%) at some stage during TUD therapy. At 2 years, 91% of men received the standard 1,000 mg TUD dose with 66% at the standard dosing interval of 10-14 weekly. CONCLUSIONS: TUD is an efficacious, safe, and well tolerated form of TRT, and individual optimisation of the dose and/or interval is only required in the minority of men. Particularly given the ease of administration, TUD was the preferred TRT for both patients and clinicians.

Pregnancy after definitive treatment for Graves' disease--does treatment choice influence outcome?

BACKGROUND: Women requiring thyroid hormone replacement after definitive therapy (surgery or radioiodine) for Graves' disease who later conceive require an early increase in levothyroxine dose and monitoring of thyroid hormone levels throughout pregnancy. In addition, as TSH receptor antibodies (TRAb) can cross the placenta and affect the fetus, measurement of these antibodies during pregnancy is recommended. AIM: To review the management of pregnancies following definitive treatment for Graves' disease in order to assess the rates of maternal hypothyroidism and TRAb measurement. MATERIALS AND METHODS: Retrospective chart review of women who had undergone definitive treatment for Graves' disease at a tertiary hospital and subsequently had one or more pregnancies. RESULTS: A total of 29 women were identified, each of whom had at least one pregnancy since receiving definitive treatment for Graves' disease: there were a total of 49 pregnancies (22 in the surgical group and 27 in the radioiodine group). Both groups had high rates of hypothyroidism documented during pregnancy (47 and 50%, respectively). The surgical group was more likely to be euthyroid around the time of conception. Less than half of the women were referred to an endocrinologist or had TRAb measured during pregnancy. Neonatal thyroid function was measured in one-third of live births. One case of neonatal thyrotoxicosis was identified. CONCLUSIONS: Adherence to the current American Thyroid Association guidelines is poor. Further education of both patients and clinicians is important to ensure that treatment of women during pregnancy after definitive treatment follows the currently available guidelines.

Couples' reasons for adherence to, or discontinuation of, PDE type 5 inhibitors for men with erectile dysfunction at 12 to 24-month follow-up after a 6-month free trial.

INTRODUCTION: The history of treatments for erectile dysfunction (ED) has involved a repeated pattern of uptake, followed by abandonment of the various therapies in the medium term. Even effective and simple to use medications are not necessarily continued; discontinuation rates range between 15% and 60%. Despite the association between partner sexual function and men's use of PDE5, no previous studies have reported any contact with partners of men taking PDE5 for their ED. This study involved both partners in couples followed up at least 1 year after treatment of ED. AIM: The study sought clarification of factors influencing adherence to, or discontinuation of, oral ED medications from couples. We hypothesized that many factors contribute to decision making about ED medication use at >12 months. MAIN OUTCOME MEASURES: The main outcome measures of this article were interviews and International Index of Erectile Function-erectile function domain. METHODS: A total of 155 interviews were conducted seeking details of frequency of usage and preference for the drugs available; reasons for that choice, or for discontinuation of use, were also sought. RESULTS: Of men interviewed, 71% were using PDE5 at 18 months. Most men interviewed were using the oral medications either 1-2x/week or 1-2x/month. Forty-four percent of men who had decreased their use of the medications reported less need for them. Thirty-four men said the main reason they were using less medication was cost. "Partner issues" from the men's perspective were seldom reported in this study. However, for a number of women, "partner issues" meant a range of problems from separation to alcohol abuse, lack of communication, and lack of confidence, or fear of failure. CONCLUSIONS: This is the first study to ask couples why they decided to continue or stop using PDE5 when followed up. Female partners provided a different perspective on "partner issues" often cited as reasons for discontinuing PDE5 use. It was also clear that discontinuation did not mean couples were no longer sexually active.

Hypercalcaemia due to parathyroid carcinoma presenting in the third trimester of pregnancy.

Primary hyperparathyroidism (pHPT) in pregnancy may be associated with significant maternal and fetal morbidity and mortality. Medical management of pHPT in pregnancy is limited, and surgery is the only definitive therapeutic option. The ideal timing for surgery is mid-second trimester, but surgery may also be safely performed in the third trimester. Delayed parathyroid surgery may result in a hypercalcaemic crisis postpartum owing to loss of active placental calcium transfer. We present a case of parathyroid carcinoma in pregnancy presenting with pre-eclampsia at 32 weeks' gestation.

Mortality and morbidity in Cushing's syndrome in New Zealand.

OBJECTIVE: Untreated Cushing's syndrome (CS) is associated with significant morbidity and mortality. However, recent operative series suggest low morbidity and mortality for CS, whereas population-based surveys report elevated mortality rates. We investigated the mortality and morbidity of CS in New Zealand. DESIGN: A nationwide retrospective survey of patients with CS between 1960 and 2005 managed at the four main endocrinology services. PATIENTS: A total of 253 patients with CS were identified, excluding adrenal carcinoma and malignant ectopic CS. MEASUREMENTS; The primary outcome was the standardized mortality ratio (SMR), comparing the observed number of deaths with the expected number for the population matched for age, sex and duration of follow-up. Secondary outcomes were the change in prevalence of co-morbidities at presentation and at final follow-up. RESULTS: The approximate prevalence and incidence of CS was 79/million and 1·8/million/y. The mean age at presentation was 39 year, and median duration of follow-up was 6·4 year (range 0-46). Overall, 89% achieved biochemical cure at last follow-up, with >90% achieving biochemical cure for CS from adrenal adenoma and pituitary causes. Thirty-six patients died during follow-up compared with 8·8 expected deaths (SMR 4·1, 95%CI 2·9-5·6). While hypertension, sexual dysfunction, myopathy and mild psychiatric illness were significantly reduced after treatment, hypertension, diabetes mellitus, moderate or major psychiatric illness, and osteoporosis were common at final follow-up. CONCLUSION: CS is associated with both high mortality and a high prevalence of co-morbidities, even when biochemical cure rates are between 80% and 90%.

The impact of oral ED medication on female partners' relationship satisfaction.

INTRODUCTION: Research has demonstrated that erectile dysfunction (ED) is a couple's problem, and that treatment for this condition is likely to impact on the man and his partner. AIM: The current study utilized a qualitative approach to evaluate the impact of treatment for ED on the female partner's perception of changes in the relationship. MAIN OUTCOME MEASURES: Analyses of the transcripts from the interviews. METHODS: In total, 96 men were treated for ED using tadalafil and then sildenafil (or vice versa) each for 3 months. Their female partners were interviewed 3 months after the commencement of treatment. RESULTS: The findings demonstrated an overall positive effect of the treatment. Female partners perceived improvements in emotional closeness, and communication, and reported that their relationship was more loving, less stressful, and more stable. CONCLUSIONS: This study demonstrates the positive effects of treatment for ED on the female partner; in particular, on her perception of the quality of her relationship.

Thyrotoxicosis in an Indigenous New Zealand Population - a Prospective Observational Study.

BACKGROUND: Reported international incidence rates of thyrotoxicosis vary markedly, ranging from 6 to 93 cases per 100 000 per annum. Along with population demographics, exposures, and study design factors, ethnicity is increasingly being recognized as a potential factor influencing incidence. This study aimed to document the epidemiology and clinical presentation of thyrotoxicosis for Maori, the indigenous population in New Zealand. METHODS: A prospective study of adult patients presenting with a first diagnosis of thyrotoxicosis between January 2013 and October 2014 to a single New Zealand center. Demographic data were collected, and detailed clinical assessment performed. RESULTS: With 375 patients, an incidence rate of thyrotoxicosis of 73.0 per 100 000 per annum was identified. Of these, 353 (94.1%) participated in the study. The median age of the cohort was 47 years, 81% were female, and 58% had Graves disease. The overall incidence of thyrotoxicosis for Maori, the indigenous people of New Zealand, was higher than non-Maori (123.9 vs 57.3 per 100 000 per annum). Rates of both Graves disease and toxic multinodular goiter were higher in Maori as compared to non-Maori (incidence rate ratios of 1.9 [1.4, 2.6] and 5.3 [3.4, 8.3], respectively), with this increase being maintained after controlling for age, deprivation, and smoking. CONCLUSIONS: Maori, the indigenous people of New Zealand, have an increased incidence of thyrotoxicosis compared to non-Maori and, in particular, toxic multinodular goiter. A greater understanding of the epidemiology of thyrotoxicosis in other indigenous and marginalized ethnic groups may help to optimize therapeutic pathways, equitable care and outcomes.

The decrease in mature myostatin protein in male skeletal muscle is developmentally regulated by growth hormone.

Myostatin inhibits myogenesis and there is reduced abundance of the mature protein in skeletal muscles of adult male compared with female mice. This reduction probably occurs after translation, which suggests that it is a regulated mechanism to reduce the availability of myostatin in males. Reduced myostatin may, thereby, contribute to the development of sexually dimorphic growth of skeletal muscle. Our first objective was to determine if the decrease in mature myostatin protein occurs before the linear growth phase to aid growth, or afterwards to maintain the mass of adult muscle. Mice were killed from 2 to 32 weeks and the gastrocnemius muscle was excised. Myostatin mRNA increased from 2 to 32 weeks and was higher in males than females (P < 0.001). In contrast, mature protein decreased in males after 6 weeks (P < 0.001). Our second objective was to determine if growth hormone (GH) induces the decrease in mature myostatin protein. GH increased myostatin mRNA and decreased the abundance of mature protein in hypophysectomised mice (P < 0.05). Our final objective was to determine if the decrease in mature protein occurs in skeletal muscles of male Stat5b(-/-) mice (Stat5b mediates the actions of GH). As expected, mature myostatin protein was not reduced in Stat5b(-/-) males compared with females. However, myostatin mRNA remained higher in males than females irrespective of genotype. These data suggest that: (1) the decrease in mature myostatin protein is developmentally regulated, (2) GH acting via Stat5b regulates the abundance of mature myostatin and (3) GH acts via a non-Stat5b pathway to regulate myostatin mRNA.

The effects of treating male hypogonadism on couples' sexual desire and function.

INTRODUCTION: Hypogonadism is a common endocrine condition characterized by low levels of testosterone (T) and marked by numerous symptoms, one of which is low sexual desire. Studies comparing T delivery systems have suggested that hypogonadal men's partners may be at risk from exposure to T gels. Little other mention is found of the impact of hypogonadism and its treatment on a man's partner and the couple's sexual function. AIM: To assess sexual desire and sexual function in hypogonadal men and their woman partners before and after treatment with T replacement therapy. METHODS: Twenty-one hypogonadal men and 18 partners were recruited from a tertiary endocrine clinic, and were compared with a control group of 20 eugonadal age-matched men and their partners. All men had baseline blood tests to confirm their status as hypogonadal or eugonadal, and hypogonadal men repeated tests at 3-month intervals. All participants completed the Sexual Desire Inventory (SDI) and sexual function questionnaires at baseline and at 3-month intervals until the hypogonadal men attained normal T levels. MAIN OUTCOME MEASURES: Pre- and post-treatment SDI and sexual function questionnaires were compared once T normalization was achieved. Between- and within-group comparisons were carried out. RESULTS: Pretreatment hypogonadal men recorded lower levels of sexual desire and function than controls, but significantly improved once hypogonadism was corrected. Eugonadal controls recorded no significant changes in either sexual desire or function during the study. Partners of the hypogonadal men reported no changes on the SDI, but significant improvements in sexual function as their partners recovered. CONCLUSION: SDI and sexual function measures reflect sexual changes that accompany rising serum T levels during correction of male hypogonadism. Women partners reported more satisfaction, less pain, and improved sexual function following the men's treatment. Treatments affecting one partner potentially have important effects on the other.

Lymphocytic hypophysitis with associated thyroiditis in a man with aseptic meningitis.

OBJECTIVE: Lymphocytic hypophysitis (LH) is a rare chronic inflammatory disorder characterized by lymphocytic infiltration of the pituitary gland commonly affecting women during pregnancy or post-partum period. The pathogenesis remains uncertain, however an autoimmune process is frequently implicated. There is limited data on the occurrence of LH outside the setting of autoimmunity. CASE: We describe a 37-year-old man presenting with diarrhoea, nausea, weight loss, low-grade fever, headache and cerebrospinal fluid analysis consistent with aseptic meningitis. Magnetic resonance imaging (MRI) demonstrated a homogenously enlarged pituitary gland with biochemical testing revealing partial hypopituitarism with adenocorticotrophic hormone and gonadotrophin deficiency. Notably, his free thyroid hormone levels were elevated with a suppressed thyroid-stimulating hormone and a suppressed thyroid technetium scan consistent with thyroiditis. Tissue antibodies including thyroid antibodies were negative. Following introduction of hydrocortisone, he developed transient diabetes insipidus which spontaneously resolved after 4 months. Thyrotoxicosis resolved after 5 weeks and thyroxine was commenced as he developed secondary hypothyroidism. Repeat MRI 3 months later showed a reduction in the size of the pituitary gland which by 6 months had returned to normal size. He remains well on hydrocortisone, thyroxine and testosterone replacement. CONCLUSIONS: Based on clinical and radiological grounds, the diagnosis was consistent with lymphocytic hypophysitis associated with subacute thyroiditis. This is only the second report of this combination in the absence of autoimmunity and the first report of LH and thyroiditis with associated aseptic meningitis in the absence of tissue autoantibodies. We propose a possible viral illness as the unifying aetiological cause.

GH replacement titrated to serum IGF-1 does not reduce concentrations of myostatin in blood or skeletal muscle.

OBJECTIVE: Traditional weight-based regimens of GH replacement are more effective at reversing the loss of skeletal muscle in GH-deficient adults than currently recommended regimens, where the dose of GH is increased to restore serum concentrations of IGF-1. While weight-based regimens increase concentrations of IGF-1 and decrease concentrations of myostatin, it is not known whether the reduced effectiveness of individually titrated GH regimens is due to ongoing hypersecretion of myostatin. Consequently, the aims of this study were to determine whether concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults, and whether these concentrations are decreased by GH replacement regimens titrated to restore serum IGF-1. DESIGN: Twenty-six GH deficient adults (18 men and 8 women) were treated with individualised regimens of recombinant human GH aiming to achieve serum concentrations of IGF-1 within one standard deviation of the age- and gender-adjusted mean. Plasma concentrations of myostatin were measured at baseline and after 6 months of treatment were compared to fifteen healthy controls (9 men and 6 women). Skeletal muscle biopsies were performed in 19 of these GH-deficient adults (15 men and 4 women) and 10 of the healthy controls (6 men and 4 women). Expression of IGF-1 and myostatin mRNA was determined by qPCR. RESULTS: Concentrations of IGF-1 in serum and mRNA in skeletal muscle were reduced, and concentrations of myostatin in plasma and mRNA in skeletal muscle were increased in GH-deficient adults at baseline (P < .05 versus healthy controls). Despite restoring concentrations of IGF-1, GH replacement did not reduce concentrations of myostatin in either blood or skeletal muscle. Concentrations of IGF-1 and myostatin in both blood and skeletal muscle were positively correlated in GH-deficient adults at baseline (P < .05), but not in GH-replete adults. CONCLUSIONS: Concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults. Despite normalising concentrations of IGF-1, individualised regimens of GH replacement do not reduce concentrations of myostatin in blood or skeletal muscle. Ongoing hypersecretion of myostatin may explain why individually titrated GH replacement regimens are less effective than higher weight-based regimens in increasing skeletal muscle mass.

Inequitable Long-Term Outcomes for an Indigenous Population After Definitive Treatment of Patients With Graves Disease.

BACKGROUND: Maori, the indigenous people of Aotearoa/New Zealand, have an increased incidence of Graves disease and often require more than one radioiodine (RAI) dose, raising the question as to whether surgery may be preferable in this population. However, there is a lack of outcome data after definitive therapy in an indigenous population. AIM: To assess ethnic differences in thyroid status after definitive therapy for Graves disease. METHODS: Single-center retrospective review of patients treated by RAI or thyroidectomy from 1 December 2001 to 31 March 2013. TSH levels at 1, 2, 5, and 10 years after treatment were recorded. RESULTS: A total of 798 patients were included: 589 received RAI, and 209 underwent surgery. Overall, 48% of patients were euthyroid at 1 year after definitive treatment, and 63.5% were euthyroid by 10 years. Maori were less likely to be euthyroid when compared with Europeans at all time points (e.g., 29.7% vs 57.3% at 1 year and 52.2% vs 70.9% at 10 years, P < 0.0005). Maori were more likely to receive more than one dose of RAI compared with Europeans (30.2% vs 14.2%, P < 0.0005). Persistent thyrotoxicosis at 1 year after RAI was seen in 25.8% of Maori compared with 8.3% of Europeans (P < 0.0005). CONCLUSIONS: Maori have lower rates of optimal thyroid levels than their European counterparts at all time points studied. Early disparity was associated with a higher RAI failure rate. Late differences were due to higher rates of untreated hypothyroidism. Overall, euthyroid rates were low, indicating the need for improvement in care, particularly for indigenous peoples.

Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific.

BACKGROUND: Sexually dimorphic growth has been attributed to the growth hormone (GH)/insulin-like growth factor 1 (IGF1) axis, particularly GH-induced activation of the intracellular signal transducer and activator of transcription 5B (STAT5B), because deletion of STAT5B reduces body mass and the mass of skeletal muscles in male mice to that in female mice. However, it remains unclear why these effects are sex- and species-specific, because the loss of STAT5B retards growth in girls, but not in male mice. Our objectives were to determine whether sexually dimorphic growth of skeletal muscle persisted in STAT5B-/- mice and investigate the mechanisms by which STAT5B regulates sexually dimorphic growth. METHODS: Blood and skeletal muscle were harvested from male and female STAT5B-/- mice and their wild-type littermates from the onset of puberty to adulthood. RESULTS: Growth of the skeleton and skeletal muscles was retarded in both sexes of STAT5B-/- mice, but more so in males. Although reduced, sexually dimorphic growth of skeletal muscle persisted in STAT5B-/- mice with an oxidative shift in the composition of myofibres in both sexes. Concentrations of IGF1 in blood and skeletal muscle were reduced in male STAT5B-/- mice at all ages, but only in female STAT5B-/- mice at the onset of puberty. Expression of androgen receptor (AR) and oestrogen receptor alpha (ERα) mRNA and protein was reduced in skeletal muscles of male and female STAT5B-/- mice, respectively. Loss of STAT5B abolished the sexually dimorphic expression of myostatin protein and Igf1, Ar, Erα, suppressor of cytokine signalling 2 (Socs2), and cytokine-inducible SH2-containing protein (Cis) mRNA in skeletal muscle. CONCLUSIONS: STAT5B appears to mediate GH signalling in skeletal muscles of male mice at all ages, but only until puberty in female mice. STAT5B also appears to mediate the actions of androgens and oestrogens in both male and female mice, but sexually dimorphic growth persists in STAT5B-/- mice.

Wnt pathway inhibitors are strongly down-regulated in pituitary tumors.

The etiology of sporadic pituitary tumors is currently unknown. The Wnt pathways have been implicated in the pathogenesis of a variety of human tumors, but the role of these pathways in pituitary tumors is unclear. Microarray analysis using the Affymetrix HG U133 plus 2.0 GeneChips identified four secreted frizzled-related protein (sFRP) family members of Wnt pathway inhibitors that were differentially expressed in both nonfunctioning and clinically functioning pituitary tumors (n = 20) compared with normal pituitary controls (n = 3). Reduced tumor expression of Wnt inhibitory factor-1 (WIF1), sFRP2, and sFRP4 mRNA was confirmed by real-time quantitative RT-PCR (P <0.001 and P = 0.002 and 0.013, respectively) in all pituitary subtypes. Hypermethylation of the WIF1 promoter was present in 88% of the pituitary tumors (n = 41). Seventy-six percent of pituitary tumors demonstrated absent or weak cytoplasmic WIF1 staining by immunohistochemistry (n = 41), although preserved staining was seen in some functioning tumors, with strong staining in 92% of normal pituitary controls (n = 13). The Wnt pathway target gene cyclin D1 was found to be up-regulated specifically in the nonfunctioning pituitary tumors compared with controls at both mRNA and protein level, supportive of activation of the Wnt-beta-catenin pathway. Nuclear accumulation of beta-catenin, however, was not observed in any pituitary tumors (n = 70). By transfecting GH3 cells with WIF1, decreased cell proliferation and colony formation was observed compared with empty vector controls. In conclusion, our data suggest that WIF1 may be a tumor suppressor, specifically in nonfunctioning pituitary tumors, and that the Wnt pathways are important in pituitary tumorigenesis.

Investigating women's preference for sildenafil or tadalafil use by their partners with erectile dysfunction: the partners' preference study.

INTRODUCTION: Several preference studies comparing a short-acting with a longer-acting phosphodiesterase type 5 inhibitor have been conducted in men. Most men in those studies preferred tadalafil rather than sildenafil, and recent post hoc analysis of one study described several factors associated with men's treatment preference. No prospective studies have investigated the woman partners' preferences. AIM: To investigate the treatment preference of women who were partners of men using oral medications for erectile dysfunction (ED) in a single-center open-label crossover study. METHODS: One hundred heterosexual couples in stable relationships, with male partners having ED based on the erectile function subscale of the International Index of Erectile Function, were randomly assigned to receive sildenafil or tadalafil for a 12-week phase, followed by another 12-week period using the alternate drug. Male and female participants completed sexual event diaries during both study phases, and the female participants were interviewed at baseline, midpoint, and end of study. MAIN OUTCOME MEASURES: Primary outcome data were the women's final interviews during which they were asked which drug they preferred and their reasons for that preference. RESULTS: A total of 79.2% of the women preferred their partners' use of tadalafil, while 15.6% preferred sildenafil. Preference was not affected by age or treatment order randomization. Women preferring tadalafil reported feeling more relaxed, experiencing less pressure, and enjoying a more natural or spontaneous sexual experience as reasons for their choice. Mean number of tablets used, events recorded, events per week, and days between events were not significantly different during each study phase. CONCLUSION: Women's preferences were similar to men when using these two drugs. While the women's reasons for preferring tadalafil emphasized relaxed, satisfying, longer-lasting sexual experiences, those preferring sildenafil focused on satisfaction and drug effectiveness for their partner.