Depot Pure GnRH Antagonist for Long-term Treatment of Ovarian Hyperthecosis Monitored by Multisteroid LCMS Profiling.

Ovarian hyperthecosis (OHT), severe hyperandrogenism after menopause in the absence of ovarian or adrenal tumors, is usually treated by surgical excision. We report a 58-year-old woman presenting with severe hyperandrogenism (serum testosterone 15.7-31.0 nmol/L, normal female <1.8 nmol/L) with menopausal gonadotropins and virilization but no adrenal or ovarian lesions. Multisteroid profiling by liquid chromatography mass spectrometry (LCMS) of adrenal and ovarian vein samples identified strong gradients in the left ovarian vein (10- to 30-fold vs peripheral blood in 17OHP4, 17 hydroxyprogesterone, 17 hydroxypregnenolone, androstenedione, testosterone, dehydroepiandrosterone) but the right ovarian vein could not be cannulated with the same findings in a second ovarian vein cannulation. OHT diagnosis was confirmed by an injection of a depot pure gonadotropin-releasing hormone (GnRH) antagonist (80 mg Degarelix, Ferring) producing a rapid (<24 hour) and complete suppression of ovarian steroidogenesis as well as serum luteinizing hormone and follicle-stimulating hormone lasting at least 8 weeks, with reduction in virilization but injection site reaction and flushing and vaginal spotting ameliorated by an estradiol patch. Serum testosterone remained suppressed at 313 days after the first dose despite recovery of menopausal gonadotropins by day 278 days. This illustrates use of multisteroid LCMS profiling for confirmation of the OHT diagnosis by ovarian and adrenal vein sampling and monitoring of treatment by peripheral blood sampling. Injection of a depot pure GnRH antagonist produced rapid and long-term complete suppression of ovarian steroidogenesis maintained over 10 months. Hence a depot pure GnRH antagonist can not only rapidly confirm the OHT diagnosis but also induce long-term remission of severe hyperandrogenism without surgery.

Managing type 1 diabetes during the COVID-19 pandemic is a team effort: a qualitative study of the experiences of young people and their parents.

Objective: To explore the experiences of young people with type 1 diabetes mellitus (T1DM) and their parents in accessing integrated family-centred care in the Australian Capital Territory during the COVID-19 pandemic. Methods and analysis: This is a pragmatic, qualitative descriptive study for which we conducted semistructured interviews with 11 young people with T1DM aged 12-16 years and 10 of their parents who attended an outpatient diabetes service in Canberra, Australia. Thematic analysis was conducted in accordance with the methods outlined by Braun and Clarke. Results: Three themes were identified: feeling vulnerable, new ways of accessing care and trust in the interdisciplinary diabetes healthcare team. Participants believed having T1DM made them more vulnerable to poor outcomes if they contracted COVID-19, resulting in avoidance of face-to-face care. Telephone consultations offered a convenient and contact-free way to undertake 3-monthly reviews. The greatest difference between telephone and face-to-face consultations was not having access to the whole interdisciplinary diabetes support team at one appointment, physical examination and haemoglobin A1c testing during telehealth consultations. Participants trusted that clinicians would arrange face-to-face meetings if required. Some felt a video option might be better than telephone, reflecting in part the need for more training in communication skills for remote consultations. Conclusion: Young people with T1DM and their parents require collaborative care and contact with multiple healthcare professionals to facilitate self-management and glycaemic control. While telephone consultations offered convenient, safe, contact-free access to healthcare professionals during the COVID-19 pandemic, the added value of video consultations and facilitating access to the whole interdisciplinary diabetes support team need to be considered in future clinical implementation of telehealth.

Exophthalmos and multinodular goitre, an unusual combination.

Multinodular goitre is not associated with eye disease, unless in a rare case of Marine-Lenhart syndrome where it coexists with Grave's disease. Therefore, other causes of exophthalmos need to be ruled out when the eye disease is seen in a patient with multinodular goitre. Confusion can arise in patients with features suggestive of Graves' ophthalmopathy in the absence of thyroid-stimulating hormone receptor autoantibodies and no evidence of other causes of exophthalmos. We present a case of multinodular goitre in a patient with exophthalmos which flared up after iodine contrast-based study. A 61-year-old Australian presented with a pre-syncopal attack and was diagnosed with toxic multinodular goitre. At the same time of investigations, to diagnose the possible cause of the pre-syncopal attack, computerised tomographic (CT) coronary artery angiogram was requested by a cardiologist. A few days after the iodine contrast-based imaging test was performed, he developed severe eye symptoms, with signs suggestive of Graves' orbitopathy. MRI of the orbit revealed features of the disease. Although he had pre-existing eye symptoms, they were not classical of thyroid eye disease. He eventually had orbital decompressive surgery. This case poses a diagnostic dilemma of a possible Graves' orbitopathy in a patient with multinodular goitre. Learning points: Graves' orbitopathy can occur in a patient with normal autothyroid antibodies. The absence of the thyroid antibodies does not rule out the disease in all cases. Graves' orbitopathy can coexist with multinodular goitre. Iodine-based compounds, in any form, can trigger severe symptoms, on the background of Graves' eye disease.

Development of autoantibodies to islet antigens during childhood: implications for preclinical type 1 diabetes screening.

OBJECTIVE: Serum islet antibodies signify increased risk for type 1 diabetes (T1D). Knowledge of the relationship between age and seroconversion would guide screening for at-risk individuals. We aimed to determine the effectiveness of islet antibody screening in early childhood, in particular the proportion of negative children who subsequently seroconverted. METHODS: We identified 554 children with a first-degree relative with T1D who had tested negative for islet cell antibodies (ICA) and insulin autoantibodies (IAA) when first screened at a mean age of 7.2 yr. Of 423 who were eligible, 350 consented to re-testing for ICA and IAA and antibodies to glutamic acid decarboxylase (GADAb) and tyrosine phosphatase-like insulinoma antigen IA-2 (IA2Ab) at a mean age of 11.1 yr. GADAb and IA2Ab were measured in 239 of the initial stored samples. RESULTS: Of the 350 children who tested negative at first screening, 12 (3.4%) subsequently seroconverted, becoming positive for ICA (n = 4), IAA (n = 7), GADAb (n = 6) or IA2Ab (n = 2). Of 239 initially negative for ICA and IAA, 8/239 (3.3%) now tested positive for GADAb (n = 7) or IA2Ab (n = 1). Four of these children were positive for GADAb in both tests; the one child initially positive for IA2Ab only was positive for all four antibodies 4.6 yr later and developed diabetes. CONCLUSION: Screening for ICA and IAA failed to identify 2-3% of genetically at-risk children who subsequently developed islet antibodies. Testing for GADAb and IA2Ab would not have avoided this. Maximizing the sensitivity of detecting risk for T1D requires repeat screening for islet antibodies throughout childhood.