Antonia Brooke

Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves’ disease: a retrospective observational study

Two widely used antithyroid drug (ATD) regimes for Graves’ disease (GD) include the ‘block & replace’ (B&R) regime (a fixed high‐dose of ATD combined with levothyroxine) and the ‘titration’ regime (a titrating dose of ATD). Anecdotally, it is believed that B&R is less prone to fluctuating thyroid function.

Safety and Convenience of Once-Weekly Somapacitan in Adult GH Deficiency: A 26-Week Randomized, Controlled Trial

Objective Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed. Design 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Methods Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P = 0.0171). Conclusions In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin.

Mosaic Turner syndrome shows reduced penetrance in an adult population study.

PurposeMany women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, ascertainment of cases in the clinic may mean that the penetrance has been overestimated.MethodsWe characterized the prevalence and phenotypic consequences of X chromosome aneuploidy in a population of 244,848 women over 40 years of age from UK Biobank, using single-nucleotide polymorphism (SNP) array data.ResultsWe detected 30 women with 45,X; 186 with mosaic 45,X/46,XX; and 110 with 47,XXX. The prevalence of nonmosaic 45,X (12/100,000) and 47,XXX (45/100,000) was lower than expected, but was higher for mosaic 45,X/46,XX (76/100,000). The characteristics of women with 45,X were consistent with the characteristics of a clinically recognized Turner syndrome phenotype, including short stature and primary amenorrhea. In contrast, women with mosaic 45,X/46,XX were less short, had a normal reproductive lifespan and birth rate, and no reported cardiovascular complications. The phenotype of women with 47,XXX included taller stature (5.3 cm; SD = 5.52 cm; P = 5.8 × 10−20) and earlier menopause age (5.12 years; SD = 5.1 years; P = 1.2 × 10−14).ConclusionOur results suggest that the clinical management of women with 45,X/46,XX mosaicism should be minimal, particularly those identified incidentally.

Pregnancy on vandetanib in metastatic medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2B

Vandetanib is a tyrosine kinase inhibitor (TKI) used in the treatment of medullary thyroid carcinoma occurring in >95% of patients with multiple endocrine neoplasia type 2b (MEN 2b). Pregnancy in women with MEN 2b on vandetanib is previously unreported and has multiple potential implications for both the mother and developing fetus [1]. We describe the case of a 22 year old woman with a background of MEN 2b who was first diagnosed aged 6 presenting with marfanoid habitus, and oral mucosal neuromas. This article is protected by copyright. All rights reserved.

Phenotypes associated with female X chromosome aneuploidy in UK Biobank: an unselected, adult, population-based cohort

Women with X chromosome aneuploidy such as 45,X (Turner syndrome) or 47,XXX (Triple X syndrome) present with characteristics including differences in stature, increased cardiovascular disease risk and primary ovarian insufficiency. Many women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, ascertainment of cases in the clinic may mean that the phenotypic penetrance is overestimated. Studies of prenatally ascertained X chromosome aneuploidy cases have limited follow-up data and so the long-term consequences into adulthood are often not reported. We aimed to characterise the prevalence and phenotypic consequences of X chromosome aneuploidy in a large population of women over 40 years of age. We detected 30 women with 45,X, 186 with mosaic 45,X/46,XX and 110 with 47,XXX among 244,848 UK Biobank women, using SNP array data. The prevalence of non-mosaic 45,X (1/8,162) and 47,XXX (1/2,226) was lower than expected, but was higher for mosaic 45,X/46,XX (1/1,316). The characteristics of women with 45,X were consistent with the characteristics of a clinically recognised Turner syndrome phenotype, including a 17.2cm shorter stature (SD = 5.72cm; P = 1.5 × 10−53) and 16/30 did not report an age at menarche. The phenotype of women with 47,XXX included taller stature (5.3cm; SD = 5.52cm; P = 5.8 × 10−20), earlier menopause age (5.12 years; SD = 5.1 years; P = 1.2 x 10−14) and a lower fluid intelligence score (24%; SD = 29.7%; P = 3.7 × 10−8). In contrast, the characteristics of women with mosaic 45,X/46,XX were much less pronounced than expected. Women with mosaic 45,X/46,XX were less short, had a normal reproductive lifespan and birth rate, and no reported cardiovascular complications. In conclusion, the availability of data from 244,848 women allowed us to assess the phenotypic penetrance of traits associated with X chromosome aneuploidy in an adult population setting. Our results suggest that the clinical management of women with 45,X/46,XX mosaicism should be minimal, particularly those identified incidentally. Funding NoneWomen with X chromosome aneuploidy such as 45,X (Turner syndrome) or 47,XXX (Triple X syndrome) present with a range of characteristics including differences in stature, an increased risk of cardiovascular disease and premature ovarian insufficiency. Many women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, biased ascertainment of cases may mean that the penetrance of phenotypes is overestimated. We aimed to characterise the prevalence and phenotypic consequences of X chromosome aneuploidy in a large population of older adults. We detected 30 women with 45,X, 186 with mosaic 45,X/46,XX and 110 with 47,XXX in 245,203 women from UK Biobank, using SNP array data. The phenotypic features of women with full aneuploidy (whether 45,X or 47,XXX) were similar to those previously reported. Consistent with the recognised Turner syndrome phenotype, those with 45,X were 17.2cm shorter than controls and 53% did not go through menarche. Similarly, the phenotype of women with 47,XXX included increased height (on average 5.3cm taller than controls, P = 1 x 10-18), earlier menopause age (on average 5.12 years earlier than controls, P = 1.2 x 10-14) and a lower fluid intelligence (on average 24% lower than controls, P = 3.7 x 10-8). In contrast, women with 45,X/46,XX mosaicism had a very mild phenotype; were not as short, had a normal reproductive lifespan and birth rate, with no reported cardiovascular complications. This study characterises X chromosome aneuploidy phenotypes in an adult population-based sample of older individuals and suggests that clinical management of women with a 45,X/46,XX mosaic karyotype should be minimal, particularly those identified incidentally.

Interpretation of thyroid scintigraphy is inconsistent among endocrinologists

This study was supported by the Small Grants Scheme of the Research & Development Department, Royal Devon and Exeter Hospital NHS Foundation Trust. KAP is funded by the Wellcome Trust (110082/Z/15/Z).

Acromegaly and Cushing's syndrome caused by a neuroendocrine tumor arising within a sacrococcygeal teratoma

A 60‐year‐old man with a pre‐existing stable sacrococcygeal teratoma developed acromegaly, ectopic Cushings syndrome, and 5HIAA secretion. To our knowledge, this represents the first reported case of ACTH and serotonin secretion, and likely GHRH or GH cosecretion, from a sacrococcygeal teratoma in an adult.

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI

OBJECTIVE To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).

Recurrent phaeochromocytoma along the laparoscopic portal sites.

discontinued after complete molecular remission for 2 years, and most relapses occurred within 6 months. We would expect the outcome for imatinib cessation in lesser degrees of remission to be worse. Imatinib therapy has been associated with congenital malformations and its use is not recommended in pregnancy. Interferon has, however, been shown in several observational studies to be safe in pregnancy with minimal risk of teratogenicity. Interferon maintenance has also been shown to maintain remission in the majority of patients who ceased imatinib in a series where many patients were not in MR. We consider this approach of transition from TKI to (pegylated) interferon alpha is a safe and reasonable option in women wanting to become pregnant who are yet to achieve MR.

Adrenocortical carcinoma, where's the delay?

Introduction • Adrenocortical carcinomas are rare (incidence 1-2 per million), present late and have a poor prognosis (1). • Appropriate management of adrenal carcinomas involves collaboration within a multidisciplinary team (MDT) involving endocrinologist, surgeon, oncologist, pathologists, nurse specialists and radiologists (2) • Rarity of the condition often necessitates multi-centre collaboration