Changes in Serum Thyroid Function Predict Cognitive Decline in the Very Old: Longitudinal Findings from the Newcastle 85+ Study.

Low serum thyrotropin (TSH) has been associated with an increased risk of cognitive impairment in observational studies of older individuals, but the mechanism underlying this is unclear. We investigated the association between changes in thyroid status and cognitive impairment in very old adults, using prospective data from the Newcastle 85+ study. A cohort of 85-year-old individuals was assessed for health status and thyroid function.

MANAGEMENT OF ENDOCRINE DISEASE: Residual adrenal function in Addison's disease.

Over the last 10 years, evidence has accumulated that autoimmune Addison's disease (AAD) is a heterogeneous disease. Residual adrenal function, characterised by persistent secretion of cortisol, other glucocorticoids and mineralocorticoids is present in around 30% of patients with established AAD, and appears commoner in men. This persistent steroidogenesis is present in some patients with AAD for more than 20 years, but it is commoner in people with shorter disease duration.

Natural History of Adrenal Steroidogenesis in Autoimmune Addison's Disease Following Diagnosis and Treatment.

Context: The natural history of adrenal function in autoimmune Addison disease once diagnosed and treated has not been systematically studied, but several case reports of recovery from established adrenal failure suggest it may not be uniform.

Objective: To ascertain steroidogenic function in autoimmune Addison disease immediately following diagnosis and during prolonged treatment.

Design: We studied peak serum cortisol in response to ACTH1-24 in 20 newly diagnosed autoimmune Addison disease patients at first presentation and then again within a month.

Residual Adrenal Function in Autoimmune Addison's Disease-Effect of Dual Therapy With Rituximab and Depot Tetracosactide.

Context: In autoimmune Addison's disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion. Patients on long-term steroid replacement have increased morbidity, reduced life expectancy, and poorer quality of life.

Objective: The objective of this article is to restore adrenocortical steroidogenic function in recent-onset AAD.

An unusual cause of adrenal insufficiency and bilateral adrenal masses.

Unlabelled: Primary adrenal insufficiency secondary to syphilis is extremely rare, with only five cases being reported in the literature. We report a case of adrenal insufficiency as a manifestation of infection (tertiary syphilis). A 69-year-old, previously fit and well Caucasian male was found to have adrenal insufficiency after being admitted with weight loss, anorexia and postural dizziness resulting in a fall.

Isolation of a multipotent mesenchymal stem cell-like population from human adrenal cortex.

Background: The highly plastic nature of adrenal cortex suggests the presence of adrenocortical stem cells (ACSC), but the exact identity of ACSC remains elusive. A few studies have demonstrated the differentiation of adipose or bone marrow-derived mesenchymal stem cells (MSC) into steroid-producing cells. We therefore investigated the isolation of multipotent MSC from human adrenal cortex.

Tremelimumab-Induced Graves Hyperthyroidism.

Tremelimumab and ipilimumab are monoclonal antibodies directed against the extracellular domain of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and have been used as immunotherapies against immune checkpoints that suppress T-cell activation. Anti-CTLA-4 antibody-based therapies have been shown to be effective in treating various cancers including metastatic melanoma. However, a few immune-related adverse events including hypophysitis and thyroid disorder have been reported, mostly developed within the first year of receiving treatment.

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison's disease.

The treatment for autoimmune Addison's disease (AAD) has remained virtually unchanged in the last 60 years. Most patients have symptoms that are relatively well controlled with exogenous steroid replacement, but there may be persistent symptoms, recurrent adrenal crisis and poor quality of life, despite good compliance with optimal current treatments. Treatment with conventional exogenous steroid therapy is also associated with premature mortality, increased cardiovascular risk and complications related to excessive steroid replacement.

Loperamide-induced hypopituitarism.

Loperamide is the most commonly used antidiarrhoeal medication in the UK. We report a serious and hitherto undocumented adverse effect of chronic use in a 45-year-old man with inflammatory bowel disease. He presented to the endocrine clinic with fatigue and low libido; biochemical assessment revealed hypogonadism and adrenal insufficiency without any elevated adrenocorticotropic hormone.

Expression of melanocortin receptors in human endometrium.

Study Question: Are melanocortin receptors (MCR1-5) expressed in the endometrium?

Summary Answer: MCR1-5 are expressed in endometrium to varying degrees, with MC2R, MC3R and MC5R being the most abundant and the majority of expression being observed in glandular epithelium.

What Is Known Already: Women with Addison's disease who were being administered synthetic ACTH reported menstrual complications as a side effect. There is no previous literature on expression of the melanocortin receptors within the endometrium, and therefore whether ACTH may directly affect the endometrial vasculature.

Spontaneous and tetracosactide-induced anti-ACTH antibodies in man.

Context: During a clinical trial of regular tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antitetracosactide (ACTH1-24 ) antibodies.

Design: Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves' disease (GD), 15 patients with isolated ACTH deficiency and 102 controls.

High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients.

The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease.

Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts.

Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.

Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.

Residual adrenal function in autoimmune Addison's disease: improvement after tetracosactide (ACTH1-24) treatment.

Context: Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility.

Objective: We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease.

A UK epidemic of testosterone prescribing, 2001-2010.

Context: Testosterone replacement therapy is the standard treatment for male hypogonadism. There has lately been increased marketing in the medical media promoting testosterone replacement for men with erectile dysfunction or for older men with low serum testosterone, despite the lack of long-term safety and efficacy data. Therefore, we aimed to examine trends in testosterone prescribing in UK primary care over the last 10 years.

The effect of B cell depletion therapy on anti-TSH receptor antibodies and clinical outcome in glucocorticoid-refractory Graves' orbitopathy.

Objective: This case series documents the response of nine individuals with glucocorticoid-refractory Graves' orbitopathy (GO) to B cell depletion therapy with rituximab (RTX).

Context: Graves' disease (GD) is one of the commonest autoimmune conditions and is frequently associated with inflammatory changes around the eyes (GO). GO frequently results in significant functional visual impairment, and in the most severe cases, it can result in permanent loss of sight.

The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease.

Background: Autoimmune Addison's disease (AAD) is a rare condition with a complex genetic basis. A panel of rare and functionally defective genetic variants in the sialic acid acetylesterase (SIAE) gene has recently been implicated in several common autoimmune conditions. We performed a case-control study to determine whether these rare variants are associated with a rarer condition, AAD.

Clinical review: The thyroid in mind: cognitive function and low thyrotropin in older people.

Context: Several studies have reported an association between low serum TSH, or subclinical hyperthyroidism (SH), and dementia, but little emphasis has been placed on this field because not all studies have demonstrated the same association. We performed a detailed systematic review to assess the evidence available to support the association between these two conditions.

Methods: We performed a systematic search through the PubMed, Embase (1996 to 2012 wk 4), Cochrane Library, and Medline (1996 to January wk 4, 2012) electronic databases using key search terms encompassing subclinical hyperthyroidism, TSH, dementia, and cognitive impairment.

The role of a nonsynonymous CD226 (DNAX-accessory molecule-1) variant (Gly 307Ser) in isolated Addison's disease and autoimmune polyendocrinopathy type 2 pathogenesis.

Context: Genome-wide association studies have discovered various susceptibility alleles that are shared among different autoimmune conditions, implicating several biochemical pathways in the pathogenesis of autoimmunity. A nonsynonymous polymorphism in exon 7 of the gene encoding the lymphocyte cell-surface CD226 (DNAM1) receptor, Gly307Ser (rs763361), has recently been identified as conferring risk to many autoimmune disorders. We performed a case-control study to determine if the CD226 307Ser variant is also associated with autoimmune Addison's disease (AAD).