Real-World Clinical Experience of Oral Semaglutide in a Secondary Diabetes Clinic in the UK: A Retrospective Observational Study.

INTRODUCTION: Oral semaglutide improves cardiovascular risk factors in people with type 2 diabetes (T2D) in clinical trials, though real-world evidence is limited. We aimed to determine the real-world impact of oral semaglutide on routinely collected clinical data in our practice. METHODS: People with T2D initiated on oral semaglutide in secondary care diabetes clinics at two hospital sites in Wales (United Kingdom) were included. Data were collected on reasons for oral semaglutide initiation and changes in bodyweight, blood pressure, glycemic control, and lipid profiles over follow-up at 3-6 months, and at 6-12 months. Data were collected to determine the safety of oral semaglutide. RESULTS: Seventy-six patients were included, with a median age 59.3 [51.4-67.6] years, and 38 (50.0%) patients were female. The most common reasons for oral semaglutide were need for weight loss and improved glycemia (69.8%), and improved glycemia alone (25.0%). Oral semaglutide associated with significantly reduced bodyweight (- 3.3 kg), body mass index (BMI) (- 0.9 kg/m2), glycated hemoglobin (HbA1c) (- 11 mmol/mol), and total cholesterol (- 0.4 mmol/l) by 3-6 months follow-up. At 6-12 months, there was a significant reduction in systolic blood pressure (- 7.0 mmHg), in addition to sustained reductions in other metabolic parameters. By 12 months, 18 (23.6%) patients had discontinued the drug, largely resulting from gastrointestinal disturbance, but there were no serious events in this cohort. CONCLUSIONS: Oral semaglutide was effective in improving cardiovascular risk factors in this real-world population living with T2D, and no serious events were identified related to oral semaglutide in this patient group.

Isolated central hypothyroidism: Underlying pathophysiology and relation to antidepressant and antipsychotic medications-A multi-centre South Wales study.

OBJECTIVE: Isolated biochemical central hypothyroidism is a presentation we are experiencing more frequently as endocrinologists, with variation in levels of investigation between physicians. We therefore conducted research to investigate the final diagnosis and clinical outcome of patients across multiple hospitals in South Wales with biochemical isolated central hypothyroidism; namely to establish whether this isolated biochemical picture was clinically significant. We also analysed whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications, and how common this is. DESIGN: We performed a retrospective observational study of patients across nine different hospitals in South Wales. We analysed patients referred to endocrinology at each site over a 6-year period with unexplained isolated biochemical central hypothyroidism. MATERIALS AND METHODOLOGY: 1022 individual patients' thyroid function test results were identified from our biochemical database using our inclusion criteria. After exclusion criteria were applied, 71 patients' results were analysed as to the final pathophysiology of their central hypothyroidism. RESULT: Of the 71 patients included in the study, none were found to have any clinically significant pathology on pituitary imaging. On reviewing their medications, 46/71 (65%) were found to be taking psychotropic medications. CONCLUSIONS: Our study strongly suggests isolated central hypothyroidism, in the absence of other pituitary hormone dysfunction or visual field defect, does not require further investigation, saving resources as well as sparing patients unnecessary anxiety. It also strongly supports a relationship between patients taking psychotropic medications and biochemical isolated central hypothyroidism, an association only described in a very limited amount of literature before this, and further supporting our previous single-centre study findings. The mechanism behind this is likely to be the suppression of thyrotropin secretion via antagonism of the dopamine-serotoninergic pathway. In our opinion, patients found to have isolated biochemical central hypothyroidism who are taking psychotropic medications can therefore be regarded to have a recognised cause for this biochemical finding and do not require further radiological investigation.

Central hypothyroidism related to antipsychotic and antidepressant medications: an observational study and literature review.

Objective: To investigate the final diagnosis and clinical outcome of patients referred to endocrinology in our district general hospital with biochemical isolated central hypothyroidism (CeH), and whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications. Methods: We performed a retrospective observational study of patients referred to endocrinology with unexplained biochemical isolated CeH over a 5-year period. Results: Of the 29 patients included in the study, 4 were found to have a partially empty or empty sella and 1 to have a bulky pituitary gland which was deemed to be an incidental radiological finding. No patients had any clinically significant pathology. On reviewing their medications, 18/29 (62%) were found to be on psychotropic medications. Conclusions: Our study suggests a relationship between patients on psychotropic medications and biochemical isolated CeH, an association only described in a very limited amount of literature prior to this. The mechanism behind this may be suppression of TSH secretion via antagonism of the dopamine-serotoninergic pathway. Determining a correlation between psychotropic medications and isolated CeH could lead to the avoidance of further radiological investigations and unnecessary anxiety for patients. However, a larger observational study is needed to provide further evidence to support/refute our finding.

Management of late-onset hypogonadism: person-centred thresholds, targets, techniques and tools.

Late-onset hypogonadism (LOH) is a complex and highly debatable syndrome in ageing men, which is characterised by reduced testosterone levels associated with classical symptoms of androgen deficiency. This article discusses the complex issues surrounding its management related to patient-centric thresholds and therapeutic targets. It specifically highlights the need to consider symptoms as the starting point, the key milestones in the management and the target of treatment, while ensuring safety at all times. The diagnosis of LOH requires a high index of suspicion and early identification of symptoms followed by appropriate investigations. The threshold for initiation of treatment has to be person centric and requires individualised decisions. The dose, preparation, route and follow up after testosterone initiation also may vary among different people. A person-centred approach is key to the successful management of this complex, nebulous yet debilitating disease.

The Impact of Vitamin D Deficiency on the Severity of Symptoms and Mortality Rate among Adult Patients with Covid-19: A Systematic Review and Meta-Analysis.

INTRODUCTION: We aimed to study the prevalence of vitamin D deficiency (VDD) in patients with COVID-19 infection and evaluate the impact of vitamin D levels on the severity of symptoms and the case fatality rate. EVIDENCE ACQUISITION: A comprehensive literature search was performed up to December 20, 2020, using the following databases: MEDLINE, PubMed, EMBASE, SCOPUS, Web of Science, and preprint databases (BioRxiv and MedRxiv). Any individual observational study related to the prevalence and impact of vitamin D deficiency/insufficiency (VDD/VDI) on the severity of COVID-19 symptoms and mortality rates was included. No language restrictions were applied, and both published and non-published studies were included. EVIDENCE SYNTHESIS: Two of the authors independently performed the literature search and assessed the eligibility of studies. The quality of studies included was assessed using the Newcastle-Ottawa Scale. Data were analyzed using the Review Manager Software (version 5) and Comprehensive Meta-analysis Software (version 3). A total of 43 studies were included with a sample size of 254,963 patients with COVID-19. Pooled analysis showed a higher prevalence of VDD and VDI in patients with COVID-19 (59.0% and 40.1%, respectively). Moreover, a significant association was noticed between vitamin D levels and severity of symptoms (odds ratio [OR] = 3.38, 95% confidence interval [CI]: 1.94-5.87, P < 0.0001), as well as the case fatality rate (OR = 2.30, 95% CI: 1.47-3.59, P < 0.00001). CONCLUSIONS: VDD is highly prevalent in patients with COVID-19 infection. Lower vitamin D levels correlate with disease severity and poor prognosis although most of the data have been derived from moderate-quality observational studies.

An Occult Leydig Cell Tumour in a Postmenopausal Woman Presenting with Alopecia and Hirsutism: A Case Report.

Progressive hirsutism and moderate to severe male-pattern balding in women requires exclusion of an adrenal or ovarian tumour, especially in the presence of significantly elevated androgen levels. We present the case of a 68-year-old woman who was referred to an endocrinology clinic with insidious onset excessive facial hair growth and loss of scalp hair. Her testosterone levels were significantly elevated at 13 nmol/L (normal range: 0.1-1.4 nmol/L), although dehydroepiandrosterone sulphate and 17-hydroxyprogesterone levels were normal, suggestive of an ovarian source of androgens. Repeated radiologic investigations, including pelvic ultrasound, and abdominal and pelvic computed tomography, could not identify the obvious source of androgens. Based on strong clinical suspicion of an ovarian tumour, she underwent an elective salpingo-oophorectomy, which detected an occult Leydig cell tumour on histopathological analysis. Post-operatively, her hyperandrogenic features significantly improved and testosterone levels normalized.

Testosterone in COVID-19 - Foe, Friend or Fatal Victim?

The evidence derived from observational studies suggests male gender, diabetes and central obesity to be risk factors associated with an increased COVID-19-related case fatality. The precise pathophysiology behind this gender difference in mortality outcomes remains unclear at this stage, although it is worth exploring a possible role of testosterone as one of the contributory factors. The observed role of androgens in transcription of transmembrane protease serine-2, which facilitates COVID-19 anchoring to angiotensin-converting enzyme 2 cell surface receptors, seems to suggest that higher testosterone levels might be detrimental for outcomes. On the other hand, men with type 2 diabetes mellitus and central obesity have an increased prevalence of hypogonadotropic hypogonadism, with inhibition of gonadotropin-releasing hormone secretion induced by inflammatory cytokines being one of the postulated mechanisms. The increased COVID-19 case fatality in this cohort might perhaps reflect an underlying pro-inflammatory state, with low testosterone levels being either a surrogate marker of a poor metabolic state or playing a more active role in propagation of inflammation and thrombosis.

Long term complications and rehabilitation of COVID-19 patients.

With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.

New testosterone 2% gel using Ferring Advanced Skin Technology (FAST), for the treatment of testosterone deficiency in men, with a novel applicator.

INTRODUCTION: Testosterone deficiency (TD) is an increasing problem that can affect a man's physical and psychological health, and quality of life. Testosterone replacement therapy (TRT), combined with weight reduction, lifestyle advice, and the treatment of co-morbidities, is the treatment of choice in men who are not concerned about fertility. However, there remains an unmet need in this therapeutic area, relating to factors such as inconvenient or painful administration, fluctuations in testosterone levels, supra-physiologic testosterone levels, poor tolerability, and secondary safety issues, which may be associated with the current TRT options. Advances in transdermal delivery systems have resulted in the development of a new 2% transdermal testosterone gel, that may offer some additional features over the other currently available TRTs. AREAS COVERED: We performed a comprehensive review of the published and gray literature to identify randomized studies and non-randomized studies (NRS) involving adult men receiving treatment for low testosterone levels. EXPERT OPINION: Topical gels are often the most convenient first-line treatment for testosterone deficiency, but options are important as patient preference is more important than virtually any other clinical area of medicine. The chosen therapy must be convenient to use and reach reliable therapeutic levels to effectively and consistently relieve symptoms. Testavan, a new 2% testosterone gel, goes some way to achieving these goals.

Vitamin D and obesity in adults: a pathophysiological and clinical update.

Vitamin D deficiency has become an increasing focus of clinical interest, especially in understanding its associations with obesity in adults. The pathological associations linking the two appear to demonstrate complex cellular inflammatory, hormonal and genetic pathways. Enhanced understanding at both microcellular and clinical levels will help clarify the role of obesity in the development of vitamin D deficiency.

Rare case of Hashimoto's encephalitis mimicking grief reaction.

A 46-year-old woman was admitted with tonic-clonic seizures. She was noticed to be withdrawn and low in mood for few months. She had reduced level of consciousness with hyper-reflexia and myoclonus. Metabolic, vasculitic, autoimmune, paraneoplastic and septic screen were normal. Lumbar puncture showed raised protein in the cerebrospinal fluid but the cytology, bacterial and viral screens were negative. A CT of the head revealed global brain swelling consistent with encephalitis which was empirically treated with antibiotics and antiviral therapy. Despite this she continued to have altered sensorium. She had moderately raised titres of antithyroid peroxidise antibodies suggestive of an underlying diagnosis of Hashimoto's encephalitis. She displayed a significant improvement in her cognitive functions with high-dose steroids which was further in keeping with this rare diagnosis.

Polyglandular endocrine emergency: lessons from a patient, which a book cannot teach.

A 30-year-old woman with polyglandular autoimmune type 2 syndrome was found collapsed at home with a cardiac arrest, which required direct current cardioversion. On admission, she was hypothermic, hypotensive and bradycardic. Initial biochemical investigations were consistent with a pre-renal acute kidney injury, metabolic acidosis and a possible sepsis. She had significantly elevated thyroid-stimulating hormone levels on admission with the clinical profile consistent with dual Addisonian and myxoedema crisis. She received intravenous liothyronine and hydrocortisone along with supportive therapy. Echo showed severe left ventricular impairment with apical ballooning although coronary angiogram disclosed nothing abnormal. She made a gradual recovery and was discharged home after 2 weeks. She was diagnosed to have primary autoimmune hypothyroidism, Addison's diseaseand type 1 diabetes and coeliac disease in October 2006, July 2007, May 2010 and September 2016, respectively. Her inability to stick to gluten-free diet at her workplace was considered a significant contributory factor for out-of-hospital cardiac arrest.

Livedo reticularis: a cutaneous clue to an underlying endocrine crisis.

A 54-year-old woman was admitted to hospital with a presumed allergic reaction to a single dose of amoxicillin given for a suspected upper respiratory tract infection. She complained of chest tightness although there was no wheeze or stridor. On examination, she was pyrexial, tachycardic, hypertensive and had a diffuse mottled rash on her lower limbs. Her initial investigations showed raised inflammatory markers. She was treated in the intensive care for a presumed anaphylactic reaction with an underlying sepsis. Further investigations including CT head and CSF examination were unremarkable; however, a CT abdomen showed a 10 cm heterogeneous right adrenal mass. Based on review by the endocrine team, a diagnosis of pheochromocytoma crisis was made, which was subsequently confirmed on 24-h urinary metanephrine measurement. An emergency adrenalectomy was considered although she was deemed unfit for surgery. Despite intensive medical management, her conditioned deteriorated and she died secondary to multi-organ failure induced by pheochromocytoma crisis. LEARNING POINTS: Pheochromocytoma have relatively higher prevalence in autopsy series (0.05-1%) suggestive of a diagnosis, which is often missed.Pheochromocytoma crisis is an endocrine emergency characterized by hemodynamic instability induced by surge of catecholamines often precipitated by trauma and medications (ß blockers, general anesthetic agents, ephedrine and steroids).Pheochromocytoma crisis can mimic acute coronary syndrome, cardiogenic or septic shock.Livedo reticularis can be a rare although significant cutaneous marker of underlying pheochromocytoma crisis.

Delayed dyskinesia and prolonged psychosis in a patient presenting with profound hyponatraemia.

SUMMARY: A 65-year-old woman was admitted to the emergency unit with a 48 h history of generalised weakness and confusion. On examination, she had mild slurring of speech although there was no other focal neurological deficit. She had profound hyponatraemia (serum sodium level of 100 mmol/L) on admission with the rest of her metabolic parameters being within normal range. Subsequent investigations confirmed the diagnosis of small-cell lung cancer with paraneoplastic syndrome of inappropriate antidiuresis (SIAD). She was monitored closely in high-dependency unit with an attempt to cautiously correct her hyponatraemia to prevent sequelae associated with rapid correction. The patient developed prolonged psychosis (lasting over 2 weeks) and displayed delayed dyskinetic movements, even after a gradual increase in serum sodium levels close to 130 mmol/L. To our knowledge, delayed neurological recovery from profound hyponatraemia (without long-term neurological sequelae) has previously not been reported. This case should alert a clinician regarding the possibility of prolonged although reversible psychosis and dyskinetic movements in a patient presenting with profound symptomatic hyponatraemia. LEARNING POINTS: Patients with profound hyponatraemia may develop altered sensorium, dyskinesia and psychotic behaviour.Full recovery from psychotic symptoms and dyskinesia may be delayed despite cautious correction of serum sodium levels.Careful and close monitoring of such patients can help avoid long-term neurological sequelae.

An Ectopic ACTH Secreting Metastatic Parotid Tumour.

A 60-year old woman presented with features of Cushing's syndrome (CS) secondary to an ectopic adrenocorticotropic hormone (ACTH) secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5-10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC) and neuroendocrine tumours (NET) account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH.

Dense calcification in a GH-secreting pituitary macroadenoma.

UNLABELLED: A 30-year-old female presented with a history of secondary amenorrhoea, acromegalic features and progressive visual deterioration. She had elevated serum IGF1 levels and unsuppressed GH levels after an oral glucose tolerance test. Magnetic resonance imaging revealed a heterogeneously enhancing space-occupying lesion with atypical extensive calcification within the sellar and suprasellar areas. Owing to the extent of calcification, the tumour was a surgical challenge. Postoperatively, there was clinical, radiological and biochemical evidence of residual disease, which required treatment with a somatostatin analogue and radiotherapy. Mutational analysis of the aryl hydrocarbon receptor-interacting protein (AIP) gene was negative. This case confirms the relatively rare occurrence of calcification within a pituitary macroadenoma and its associated management problems. The presentation, biochemical, radiological and pathological findings are discussed in the context of the relevant literature. LEARNING POINTS: Calcification of pituitary tumours is relatively rare.Recognising calcification in pituitary adenomas on preoperative imaging is important in surgical decision-making.Gross total resection can be difficult to achieve in the presence of extensive calcification and dictates further management and follow-up to achieve disease control.