This corrects the article: “Boro H, Sharma H, Mittal D, et al. Parathyroid Carcinoma Presenting as Recurrent Primary Hyperparathyroidism and Neck Mass: A Case Report. touchREVIEWS in Endocrinology. 2023;19(2):80-85” The patient consent statement was added incorrectly due to an editorial error. The correct patient informed consent statement, provided by the authors, is included below.
Polycystic ovary syndrome (PCOS) is a very frequent disease that affects reproductive ability and menstrual regularity. Other than the criteria established at the Rotterdam consensus, in these last few years a new issue, insulin resistance, has been found frequently, and at a very high grade, in patients with PCOS. Insulin resistance occurs for several factors, such as overweight and obesity, but it is now clear that it occurs in patients with PCOS with normal weight, thus supporting the hypothesis that insulin resistance is independent of body weight. Evidence shows that a complex pathophysiological situation occurs that impairs post-receptor insulin signalling, especially in patients with PCOS and familial diabetes. In addition, patients with PCOS have a high incidence of non-alcoholic fatty liver disease related to the hyperinsulinaemia. This narrative review focuses on the recent new insights about insulin resistance in patients with PCOS, to better understand the metabolic impairment accounting for most of the clinical signs/symptoms of PCOS.
Diabetes is the ninth leading cause of death, directly accounting for 1.5 million deaths annually worldwide. Despite several breakthrough discoveries, little progress has been made in type 2 diabetes outcomes over the past 100 years. Younger age (below 60 years), a diet high in calories and processed food, and severe obesity (body mass index >35 kg/m2) may identify reversible beta cell dysfunction. Much of the clinical presentation pertains to flooding the body's adaptive limits with overnutrition. Recognizing this as a global societal trend brought about by lifestyle changes, sedentary work, mental stress and unlimited access to calorie-dense foods is crucial. Insulin resistance and genetic abnormalities cannot account for the dramatic increase in diabetes, from only 1% five decades ago to nearly 10% today. Obesity - and not insulin resistance - is at the core of the problem. As well as hyperglycaemia, end-organ damage can also be reversed with diet and weight loss in many affected individuals. We present the evolution of our understanding and compelling reasons to reframe diabetes in the severely obese to what it really is - overweight hyperglycaemia. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles. The objective of this review is to better understand global trends and the potential to improve outcomes by reframing the diabetes narrative towards remission. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles.
There has been an exponential increase in the global prevalence of fatty liver disease in recent years in association with the obesity pandemic worldwide. 'Metabolic dysfunction-associated fatty liver disease', the new terminology adopted by an international panel of experts in 2020 to largely replace the old term 'non-alcoholic fatty liver disease', has now been accepted by most hepatologists and diabetologists across the globe. The term metabolic dysfunction-associated fatty liver disease was created to better reflect the metabolicand liver-specific manifestations and complications of fatty liver disease. It is important to disseminate our current understanding of this enigmatic disease among the global scientific fraternity. Recent publications, including articles from the latest issue of Endocrinology & Metabolism Clinics of North America, are attempting to fill this knowledge gap.
Previous studies have suggested that corticotroph tumours are associated with the overexpression of cyclin E and that the inactivation of cyclin-dependent kinases, which activate cyclin E, may have antisecretory and antiproliferative effects. Seliciclib, also known as R-roscovitine, is a pituitary-targeting agent shown to inhibit the growth of corticotroph tumour cells via cyclin E and retinoblastoma protein-mediated pathways. A recent study investigated the role of seliciclib in regulating biochemical parameters in a small number of patients with Cushing’s disease, providing preliminary data on its possible therapeutic effectiveness in treating this disorder.
Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle. To improve acceptance and ultimately improve wellbeing of these individuals, two oral SRLs, oral octreotide capsules (OOC) and paltusotine, have been developed. The OOC combines an enteric coating to allow delivery to the small intestines and a transient permeability enhancer to enable oral bioavailability. Comparable octreotide levels are obtained with twice-daily OOC and subcutaneous octreotide 100 μg. Phase III studies show OOC to maintain equivalent biochemical control in at least 60% of patients previously receiving a stable dose of iSRL. In longer-term studies, the response to OOC was durable up to 3 years. Paltusotine is a novel potent orally available non-peptidyl somatostatin receptor subtype-2 ligand. Studies in healthy volunteers show dose-dependent suppression of growth hormone-releasing hormone-induced growth hormone secretion and suppression of insulin-like growth factor-I (IGF-I) with repeat doses. In the recent phase II study, patients with acromegaly who were partial responders (IGF-I 1.0 – 2.5 × upper limit of normal) to monotherapy with iSRL when switched to once-daily paltusotine maintained control of IGF-I within 20% of baseline or lower in 87% after 13 weeks. Adverse events with both OOC and paltusotine were reflective of those recognized with iSRL and occurred at a similar frequency. OOC and paltusotine are well-received additions to the therapeutic armamentarium in medical therapy for the management of acromegaly; however, further data on efficacy, tumour control and shrinkage are required to allow positioning of this medication within the management algorithm for acromegaly.
Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge due to the high rate of local recurrence of the tumour. We report the case of a middle-aged north Indian woman who presented with recurrent primary hyperparathyroidism due to parathyroid carcinoma. She presented with a recurrent palpable hard neck mass and underwent radical dissection of the neck six times. At the time of writing this report, she was referred for external beam radiotherapy to the neck. Parathyroid carcinoma is a rare malignancy with an indolent but tenacious course. Complete resection at the time of initial surgery determines the prognosis of the neoplasm. Chemotherapy and radiotherapy are usually ineffective. Hypercalcaemia needs to be aggressively managed. A multidisciplinary team is required to effectively manage parathyroid carcinoma.
Background: To determine the prevalence and risk of malignancy (ROM) in solid atypical mixed echogenicity thyroid nodules (SAMENs) with sonographic patterns not classifiable by the 2015 American Thyroid Association Ultrasound Risk Stratification System (NC ATA). Methods: We searched our prospectively collected endocrine surgery thyroid nodule (TN) database, with particular attention to those solid nodules that were NC ATA. An algorithm assigned each into one of the five ATA risk groups per the 2015 American Thyroid Association Ultrasound Risk Stratification System (ATA USRSS). TNs that the algorithm could not assign to a risk group were deemed NC ATA and were subsequently analyzed. Additionally, we categorized this group using an algorithm based on the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). We were specifically interested in the characteristics that resulted in non-classification by the 2015 ATA USRSS and the fine needle aspiration biopsy (FNAB) cytology and surgical pathology results from the group. Results: We evaluated data from 5,040 nodules, of which 1,772 had surgical pathology. There were 150 solid nodules not classified by 2015 ATA USRSS, all of which demonstrated atypical features along with iso-, hetero-, hyper- and mixed echogenicity (solid atypical mixed echogenicity nodules- SAMENs). Sixty of these nodules were excised and sent for surgical pathology, while 90 were followed without surgical excision. Out of the 90 that did not undergo surgery, 82 underwent FNAB with cytologic evaluation. Of our 150 SAMENs, 40 were malignant by surgical histology and six were likely malignant by cytology (total SAMEN ROM without noninvasive follicular thyroid neoplasm with papillary-like nuclear features 31%). The most common sonographic pattern present in our SAMEN group consisted of an isoechoic solid component with microcalcifications (28/40–70% of all excised malignant nodules). In our excised malignant SAMENs, 50% demonstrated follicular-patterned neoplastic architecture while 48% displayed papillary architecture. Conclusion: Our study demonstrates that SAMENs with at least one suspicious sonographic feature: including (1) microcalcifications; (2) irregular or other suspicious margins,;opulation, and a higher ROM (31%) than the intermediate-risk group of the 2015 ATA USRSS (10–20%).
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition characterized by the irreversible destruction of the β cells of the pancreas, which leads to a lifelong dependency on exogenous insulin. Despite the advancements in insulin delivery methods, the suboptimal outcomes of these methods have triggered the search for therapies that may prevent or reverse the disease. Given the autoimmune aetiology of T1DM, therapies counteracting the immune-mediated destruction of the β-cells are the obvious target. Although several treatment strategies have been attempted to target cellular, humoral and innate immunity, very few have had a clinically meaningful impact. Of all the available immunomodulatory agents, cluster of differentiation (CD) 3 antibodies have exhibited the most promising preclinical and clinical results. Muromonab-CD3, which also happened to be a murine CD3 antibody, was the first monoclonal antibody approved for clinical use and was primarily indicated for graft rejection. The adverse effects associated with muromonab-CD3 led to its withdrawal. Teplizumab, a newer CD3 antibody, has a better side-effect profile because of its humanized nature and non-Fc- receptor- binding domain. In November 2022, teplizumab became the first immunomodulatory agent to be licensed by the US Food and Drug Administration for delaying the onset of T1DM in high-risk adults and children over 8 years old. The mechanism seems to be enhancing regulatory T-cell activity and promoting immune tolerance. This article reviews the mechanism of action and the clinical trials of teplizumab in individuals with T1DM or at risk of developing the disease.
Glycated haemoglobin is currently used for diagnosis and follow-up of diabetes mellitus. However, it has important limitations; as it only reflects the average glycaemia over the last 3 months, it does not allow the identification of crucial events, such as episodes of hypoglycaemia and hyperglycaemia. Strict control of hyperglycaemia can result in severe hypoglycaemia that can be life threatening and can have important sequelae. Recently, the concept of glycaemic variability has been developed to provide information about the magnitude of glycaemic excursions and the duration of these fluctuations. This new approach has the potential to improve outcomes, decrease the risk of hypoglycaemia, and decrease cardiovascular risk. This review describes the most commonly prescribed non-insulin anti-diabetic drugs for diabetes management, their mechanism of action, and the existing evidence about their effectiveness in improving glycaemic variability and diabetes control.
Diabetes poses a significant threat to public health. In the last 30 years, the worldwide incidence of type 2 diabetes mellitus (T2DM) has increased drastically among adolescents. Since the number of young people with T2DM is rising, it is anticipated that early-onset T2DM will become a common characteristic of the diabetes population in developed and developing nations. Current evidence suggests that β-cell function declines more rapidly in early-onset T2DM than in older-onset T2DM. In addition, early-onset T2DM appears to be associated with a greater risk of complications, comorbidities and mortality than type 1 diabetes mellitus. A stressful lifestyle, a shifted dietary habit and a lack of physical activity are cited as causes of early-onset T2DM. Early-onset T2DM is, therefore, an urgent public health concern requiring early prevention, efficient screening and prompt intervention. This article discusses the recent literature on the incidence, mortality, morbidity and risk variables of early-onset T2DM, and the current priorities and prospective directions.
Alopecia is comorbid with several illnesses, including various autoimmune conditions such as thyroid disease. Leukocyte-mediated inflammation of hair follicles in alopecia was first described over a century ago. However, the high prevalence of the role of thyroid autoimmune disease in the pathogenesis of alopecia has only recently come to light, together with a strong association between the two. Therefore, this review focuses on articles published between 2011 and 2022 on alopecia's association with thyroid autoimmune disease, and the mechanism behind it. In addition, it highlights the link between alopecia and thyroid cancer, as patients with alopecia have increased risk of thyroid cancer. In conclusion, this comprehensive, focused, scoping review will serve as a reference highlighting recent information on alopecia, exploring its association with thyroid autoimmune diseases.
Various studies, conducted since 2007, have reported a total of eight boys with prepubertal gynaecomastia and four girls with premature thelarche following exposure to lavender and/or tree tea oil. All patients experienced regression of the breast tissue after they stopped using these oils. Both of these essential oils, and several of their constituents, have oestrogenic and antiandrogenic activity in vitro. However, limited dermal penetration of some of the components means that the in vitro findings cannot be extrapolated to the in vivo situation. There are unanswered questions as to how much lavender or tea tree oil was actually present in the skincare products used by the children and a lack of information about exposure to other agents. Furthermore, since both prepubertal gynaecomastia and premature thelarche often spontaneously regress, it cannot be concluded that the use of lavender and/or tree tea oil is the cause of the gynaecomastia and thelarche in these children.
The American Diabetes Association and the European Association for the Study of Diabetes consensus statement 2022 effectively captures the changing paradigm of modern diabetes care. As emphasized in the guidelines, a person-centered decision cycle focusing on preventing complications and improving quality of life is the driving principle behind modern diabetes management. Other notable features of the document are its emphasis on self-management education, therapeutic behaviour, sleep hygiene, nonalcoholic fatty liver disease and weight loss. Focus on individualization of care, social determinants of health, and ethnic variations are pertinent from an Afro-Asian perspective. The “language matters” section is a welcome addition that will help to overcome several barriers in diabetes care.
The most common symptom of menopause is vasomotor symptoms (VMS), which occur in more than 80% of postmenopausal women. Furthermore, VMS are the manifestation of menopause for which women most commonly seek treatment, namely, to address their impacted quality of life, including sleep, and work- and non-work-related productivity. VMS vary in frequency, intensity and duration. Hormone therapy (HT) has been our most effective treatment for VMS and has been approved for this indication by the United States Food and Drug Administration (FDA). Despite being a safe and effective treatment option, many patients and providers are hesitant to consider HT. Moreover, HT is contraindicated for some women. While many over-the-counter and non-HT options are available, we lack data on the efficacy and safety of most of these. This has left a void for women. Fezolinetant was recently approved by the FDA for the treatment of moderate-to-severe VMS. So far, clinical trials have shown positive results in terms of safety and efficacy. Fezolinetant is a non-hormonal, neurokinin 3 receptor antagonist that works in the hypothalamus at the thermoregulatory centre. Blocking the non-hormonal neurokinin 3 receptor antagonist modulates hot flashes and night sweats. As early as 4 weeks from initiating fezolinetant, women experienced a statistically significant reduction of both severity and frequency of VMS per day, resulting in an improved quality of life.
Background: Enhanced external counter-pulsation (EECP) therapy is approved for refractory angina in coronary artery disease (CAD). EECP is being explored as a treatment modality in type 2 diabetes mellitus (T2DM). Methods: The Embase, Web of Science, Cochrane Library, MEDLINE (PubMed), ClinicaltTrials. gov, CNKI database, Clinical Trials Registry-India (CTRI), and Google Scholar databases were searched for randomized controlled trials (RCTs) involving patients receiving EECP therapy in the intervention arm. The primary outcome was the changes in glycated haemoglobin (HbA1c). The secondary outcomes were the changes in blood glucose parameters, inflammatory markers and any adverse events. Results: Data from 3 RCTs involving 71 people with T2DM/prediabetes was analysed to find out the impact of EECP therapy compared with placebo. As compared with placebo, patients receiving EECP had significantly lower HbA1C immediately after completion of therapy (mean difference [MD] -0.70%, 95% confidence interval (CI) -0.95. -0.45;p<0.00001), at 2–4 weeks post completion of therapy (MD -1.04%, 95%CI -1.32. -0.77; p<0.00001) and 7–12 weeks after therapy completion (MD -0.98%, 95% CI -1.22, -0.74; p<0.00001). EECP therapy was well tolerated without any increased side effects (risk ratio 2.36, 95% CI 0.11–52.41; p=0.59. Conclusion: EECP therapy is effective in blood glucose and pressure lowering over at least 7–12 weeks of therapy completion. Blood glucose and pressure should be monitored with suitable modulation of drug doses to prevent hypoglycaemia and hypotension in patients with angina undergoing EECP therapy. The PROSPERO registration number is CRD42023434533
Background: The coronavirus disease 2019 (COVID-19) pandemic was associated with an increased incidence of mucormycosis globally. However, the clinical pattern, epidemiologic features and risk factors for adverse outcomes are not well established. Methods: We performed a retrospective analysis of the data from patients hospitalized with proven mucormycosis between April 2021 and August 2021. Patients were managed with a multi-disciplinary approach involving medical, surgical, and comorbidity treatment. The clinical presentation, management details, complications and outcomes, including mortality, were reviewed from clinical records. Results: The mean age of presentation was 53.7 (± 11.8) years, and 88 (84.6%) were men. Of the 104 cases with COVID-19-associated mucormycosis, 97 (93.27%) patients had diabetes, and 80.8% had a haemoglobin A1C (HbA1c) of ≥6.4% at diagnosis. Seventy percent of diabetes cases experienced steroid-induced hyperglycaemia during treatment. Even with appropriate treatment, 17 (16.35%) patients died. High HbA1c and creatinine levels, presence of chronic kidney disease (CKD), need for intensive care unit admission, and orbital evisceration were the risk factors associated with high mortality on multivariate logistic regression analysis. Cox regression analysis revealed that the overall mortality increased by a factor of 12% with each 1 percentage point increase in HbA1c ≥6.4% (hazard ratio 1.12; 95% confidence interval 0.95–1.31). The mortality risk was even higher when diabetes was associated with CKD (hazard ratio 1.82; 95% confidence interval 0.24–14.00). Conclusion: High HbA1c and creatinine levels, intensive care unit admission, CKD, and aggressive disease requiring orbital evisceration are the predictors of mortality in patients with COVID-19-associated mucormycosis. Patients with these risk factors should be managed more actively to reduce morbidity and mortality.
Hypertension affects about 1.28 billion adults globally, and significantly increases the risk of chronic morbidity and mortality among sufferers. About 15% of these individuals have secondary hypertension, the majority of whom have dysfunction of one or more endocrine systems as the cause of hypertension. Although adrenal disorders are often identified as the cause of endocrine hypertension, extra-adrenal disease and pituitary disorders also can cause the disease. Timely diagnosis is of paramount importance, because of the potential for a surgical cure or optimal disease control with pharmacotherapy to prevent hypertensive complications. Even with its relatively high prevalence compared with many other chronic illnesses, the diagnosis of endocrine hypertension is often delayed or never made because of poor awareness about the disease among physicians. This review attempts to provide an overview of the disease, with some practical aspects of diagnosis and management of a few of the important disorders causing endocrine hypertension.
Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be resistant to treatment. The aim of this review is to report the recently identified biomarkers that might have possible prognostic value. Studies evaluating potentially prognostic biomarkers or a therapeutic target in invasive/recurrent PTs compared with either non-invasive or non-recurrent PTs or normal pituitaries are included in this review. In the 28 included studies, more than 911 PTs were evaluated. A systematic search identified the expression of a number of biomarkers that may be positively correlated with disease recurrence or invasion in PT, grouped according to role: (1) insensitivity to anti-growth signals: minichromosome maintenance protein 7; (2) evasion of the immune system: cyclooxygenase 2, arginase 1, programmed cell death protein 1 (PD-1)/ programmed death ligand 2, cluster of differentiation (CD) 80/CD86; (3) sustained angiogenesis: endothelial cell-specific molecule, fibroblast growth factor receptor, matrix metalloproteinase 9, pituitary tumour transforming gene; (4) self-sufficiency in growth signals: epidermal growth factor receptor; and (5) tissue invasion: matrix metalloproteinase 9, fascin protein. Biomarkers with a negative correlation with disease recurrence or invasion include: (1) insensitivity to anti-growth signals: transforming growth factor β1, Smad proteins; (2) sustained angiogenesis: tissue inhibitor of metalloproteinase 1; (3) tissue invasion: Wnt inhibitory factor 1; and (4) miscellaneous: co-expression of glial fibrillary acidic protein and cytokeratin, and oestrogen receptors α36 and α66. PD-1/ programmed cell death ligand 1 showed no clear association with invasion or recurrence, while cyclin A, cytotoxic T lymphocyte-associated protein 4, S100 protein, ephrin receptor, galectin-3, neural cell adhesion molecule, protein tyrosine phosphatase 4A3 and steroidogenic factor 1 had no association with invasion or recurrence of PT. With the aim to develop a more personalized approach to the treatment of PT, and because of the limited number of molecular targets currently studied in the context of recurrent PT and invasion, a better understanding of the most relevant of these biomarkers by well-designed interventional studies will lead to a better understanding of the molecular profile of PT. This should also meet the increased need of treatable molecular targets.
