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Endocrine Reviews Dec 2020An adrenal incidentaloma is now established as a common endocrine diagnosis that requires a multidisciplinary approach for effective management. The majority of patients... (Review)
Review
An adrenal incidentaloma is now established as a common endocrine diagnosis that requires a multidisciplinary approach for effective management. The majority of patients can be reassured and discharged, but a personalized approach based upon image analysis, endocrine workup, and clinical symptoms and signs are required in every case. Adrenocortical carcinoma remains a real concern but is restricted to <2% of all cases. Functional adrenal incidentaloma lesions are commoner (but still probably <10% of total) and the greatest challenge remains the diagnosis and optimum management of autonomous cortisol secretion. Modern-day surgery has improved outcomes and novel radiological and urinary biomarkers will improve early detection and patient stratification in future years to come.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Humans
PubMed: 32266384
DOI: 10.1210/endrev/bnaa008 -
European Journal of Nuclear Medicine... Aug 2021Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also...
INTRODUCTION
Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration.
METHODS
Over a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT.
CONCLUSION
These guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.
Topics: Humans; Hyperparathyroidism, Primary; Nuclear Medicine; Parathyroid Glands; Positron Emission Tomography Computed Tomography; Radionuclide Imaging; Sensitivity and Specificity; Technetium Tc 99m Sestamibi
PubMed: 33839893
DOI: 10.1007/s00259-021-05334-y -
Journal of the American College of... Dec 2019Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As... (Review)
Review
Primary aldosteronism (PA) is a common, but frequently overlooked, cause of arterial hypertension and excess cardiovascular events, particularly atrial fibrillation. As timely diagnosis and treatment can provide a cure of hyperaldosteronism and hypertension, even when the latter is resistant to drug treatment, strategies to screen patients for PA early with a simplified diagnostic algorithm are justified. They can be particularly beneficial in some subgroups of hypertensive patients, as those who are at highest cardiovascular risk. However, identification of the surgically curable cases of PA and achievement of optimal results require subtyping with adrenal vein sampling, which, as it is technically challenging and currently performed only in tertiary referral centers, represents the bottleneck in the work-up of PA. Measures aimed at improving the clinical use of adrenal vein sampling and at developing alternative techniques for subtyping, alongside recommendations for drug treatment, including new development in the field, and for follow-up are discussed.
Topics: Adrenal Glands; Aldosterone; Diagnosis, Differential; Humans; Hyperaldosteronism; Hypertension
PubMed: 31779795
DOI: 10.1016/j.jacc.2019.09.057 -
Endocrine Dec 2022In recent years, scientific research has increasingly focused on Endocrine Disrupting Chemicals (EDCs) and demonstrated their relevant role in the functional impairment... (Review)
Review
BACKGROUND
In recent years, scientific research has increasingly focused on Endocrine Disrupting Chemicals (EDCs) and demonstrated their relevant role in the functional impairment of endocrine glands. This induced regulatory authorities to ban some of these compounds and to carefully investigate others in order to prevent EDCs-related conditions. As a result, we witnessed a growing awareness and interest on this topic.
AIMS
This paper aims to summarize current evidence regarding the detrimental effects of EDCs on pivotal endocrine glands like pituitary, thyroid and adrenal ones. Particularly, we directed our attention on the known and the hypothesized mechanisms of endocrine dysfunction brought by EDCs. We also gave a glimpse on recent findings from pioneering studies that could in the future shed a light on the pathophysiology of well-known, but poorly understood, endocrine diseases like hormone-producing adenomas.
CONCLUSIONS
Although intriguing, studies on endocrine dysfunctions brought by EDCs are challenging, in particular when investigating long-term effects of EDCs on humans. However, undoubtedly, it represents a new intriguing field of science research.
Topics: Humans; Endocrine Disruptors; Thyroid Gland; Endocrine System Diseases; Pituitary Gland; Pituitary Diseases; Adrenal Glands
PubMed: 35604630
DOI: 10.1007/s12020-022-03076-x -
Frontiers in Endocrinology 2022Over the years, the vaste expansion of plastic manufacturing has dramatically increased the environmental impact of microplastics [MPs] and nanoplastics [NPs], making... (Review)
Review
Over the years, the vaste expansion of plastic manufacturing has dramatically increased the environmental impact of microplastics [MPs] and nanoplastics [NPs], making them a threat to marine and terrestrial biota because they contain endocrine disrupting chemicals [EDCs] and other harmful compounds. MPs and NPs have deleteriouse impacts on mammalian endocrine components such as hypothalamus, pituitary, thyroid, adrenal, testes, and ovaries. MPs and NPs absorb and act as a transport medium for harmful chemicals such as bisphenols, phthalates, polybrominated diphenyl ether, polychlorinated biphenyl ether, organotin, perfluorinated compounds, dioxins, polycyclic aromatic hydrocarbons, organic contaminants, and heavy metals, which are commonly used as additives in plastic production. As the EDCs are not covalently bonded to plastics, they can easily leach into milk, water, and other liquids affecting the endocrine system of mammals upon exposure. The toxicity induced by MPs and NPs is size-dependent, as smaller particles have better absorption capacity and larger surface area, releasing more EDC and toxic chemicals. Various EDCs contained or carried by MPs and NPs share structural similarities with specific hormone receptors; hence they interfere with normal hormone receptors, altering the hormonal action of the endocrine glands. This review demonstrates size-dependent MPs' bioaccumulation, distribution, and translocation with potential hazards to the endocrine gland. We reviewed that MPs and NPs disrupt hypothalamic-pituitary axes, including the hypothalamic-pituitary-thyroid/adrenal/testicular/ovarian axis leading to oxidative stress, reproductive toxicity, neurotoxicity, cytotoxicity, developmental abnormalities, decreased sperm quality, and immunotoxicity. The direct consequences of MPs and NPs on the thyroid, testis, and ovaries are documented. Still, studies need to be carried out to identify the direct effects of MPs and NPs on the hypothalamus, pituitary, and adrenal glands.
Topics: Animals; Male; Microplastics; Plastics; Semen; Endocrine Disruptors; Mammals; Hormones
PubMed: 36726457
DOI: 10.3389/fendo.2022.1084236 -
The American Journal of Psychiatry Aug 2020Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that... (Review)
Review
Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that by 2030, major depression will be the leading cause of disease burden worldwide. While numerous treatments for major depression exist, many patients do not respond adequately to traditional antidepressants. Thus, more effective treatments for major depression are needed, and targeting certain hormonal systems is a conceptually based approach that has shown promise in the treatment of this disorder. A number of hormones and hormone-manipulating compounds have been evaluated as monotherapies or adjunctive treatments for major depression, with therapeutic actions attributable not only to the modulation of endocrine systems in the periphery but also to the CNS effects of hormones on non-endocrine brain circuitry. The authors describe the physiology of the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary thyroid (HPT), and hypothalamic-pituitary-gonadal (HPG) axes and review the evidence for selected hormone-based interventions for the treatment of depression in order to provide an update on the state of this field for clinicians and researchers. The review focuses on the HPA axis-based interventions of corticotropin-releasing factor antagonists and the glucocorticoid receptor antagonist mifepristone, the HPT axis-based treatments of thyroid hormones (T and T), and the HPG axis-based treatments of estrogen replacement therapy, the progesterone derivative allopregnanolone, and testosterone. While some treatments have largely failed to translate from preclinical studies, others have shown promising initial results and represent active fields of study in the search for novel effective treatments for major depression.
Topics: Depressive Disorder, Major; Endocrine Glands; Hormones; Humans; Neurosecretory Systems; Treatment Outcome
PubMed: 32456504
DOI: 10.1176/appi.ajp.2020.19080848 -
Endocrine Reviews Aug 2015Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased... (Review)
Review
Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery, and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease; or as postsurgical treatment, in cases of failure or incomplete surgical tumor resection; or as bridging therapy before, during, and after radiotherapy while waiting for disease control; or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analog pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of Cushing's syndrome when associated with impairment of glucose metabolism in case of the lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.
Topics: Adrenal Glands; Adrenocorticotropic Hormone; Cardiovascular Diseases; Combined Modality Therapy; Humans; Hydrocortisone; Infections; Mental Disorders; Metabolic Syndrome; Morbidity; Pituitary ACTH Hypersecretion; Pituitary Gland; Pituitary Neoplasms; Receptors, Glucocorticoid; Reoperation
PubMed: 26067718
DOI: 10.1210/er.2013-1048 -
JAMA Oncology Feb 2018If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown.
OBJECTIVE
To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens.
DATA SOURCES
A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase."
STUDY SELECTION
Thirty-eight randomized clinical trials evaluating the usage of these ICIs for treatment of advanced solid tumors were identified, resulting in a total of 7551 patients who were eligible for a meta-analysis. Regimens were categorized by class into monotherapy with a PD-1 (programmed cell death protein 1) inhibitor, a CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) inhibitor, or a PD-L1 (programmed cell death 1 ligand 1) inhibitor, and combination therapy with PD-1 plus CTLA-4 inhibitors.
DATA EXTRACTION AND SYNTHESIS
The data were extracted by 1 primary reviewer (R.B.-S.) and then independently reviewed by 2 secondary reviewers (W.T.B. and A.C.G.-C.) following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inferences on the incidence of AEs were made using log-odds random effects models.
MAIN OUTCOMES AND MEASURES
Incidence of all-grade hypothyroidism, hyperthyroidism, hypophysitis, primary adrenal insufficiency, and insulin-deficient diabetes.
RESULTS
Overall, 38 randomized clinical trials comprising 7551 patients were included in this systematic review and meta-analysis. The incidence of both hypothyroidism and hyperthyroidism was highest in patients receiving combination therapy. Patients on the combination regimen were significantly more likely to experience hypothyroidism (odds ratio [OR], 3.81; 95% CI, 2.10-6.91, P < .001) and hyperthyroidism (OR, 4.27; 95% CI, 2.05-8.90; P = .001) than patients on ipilimumab. Compared with patients on ipilimumab, those on PD-1 inhibitors had a higher risk of developing hypothyroidism (OR, 1.89; 95% CI, 1.17-3.05; P = .03). The risk of hyperthyroidism, but not hypothyroidism, was significantly greater with PD-1 than with PD-L1 inhibitors (OR, 5.36; 95% CI, 2.04-14.08; P = .002). While patients who received PD-1 inhibitors were significantly less likely to experience hypophysitis than those receiving ipilimumab (OR, 0.29; 95% CI, 0.18-0.49; P < .001), those who received combination therapy were significantly more likely to develop it (OR, 2.2; 95% CI, 1.39-3.60; P = .001). For primary adrenal insufficiency and insulin-deficient diabetes no statistical inferences were made due to the smaller number of events.
CONCLUSIONS AND RELEVANCE
Our study provides more precise data on the incidence of endocrine dysfunctions among patients receiving ICI regimens. Patients on combination therapy are at increased risk of thyroid dysfunction and hypophysitis.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cell Cycle Checkpoints; Endocrine Glands; Endocrine System Diseases; Humans; Immunotherapy; Incidence; Neoplasms; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 28973656
DOI: 10.1001/jamaoncol.2017.3064 -
Frontiers in Endocrinology 2020Per- and polyfluoroalkyl substances (PFAS) represent a group of synthetic compounds widely used in industry plants due to their low grade of degradation, surfactant... (Review)
Review
Per- and polyfluoroalkyl substances (PFAS) represent a group of synthetic compounds widely used in industry plants due to their low grade of degradation, surfactant properties, thermic and flame resistance. These characteristics are useful for the industrial production, however they are also potentially dangerous for human health and for the environment. PFAS are persistent pollutants accumulating in waters and soil and recoverable in foods due to their release by food packaging. Humans are daily exposed to PFAS because these compounds are ubiquitous and, when assimilated, they are difficult to be eliminated, persisting for years both in humans and animals. Due to their persistence and potential danger to health, some old generation PFAS have been replaced by newly synthesized PFAS with the aim to use alternative compounds presumably safer for humans and the environment. Yet, the environmental pollution with PFAS remains a matter of concern worldwide and led to large-scale epidemiological studies both on plants' workers and on exposed people in the general population. In this context, strong concern emerged concerning the potential adverse effects of PFAS on the thyroid gland. Thyroid hormones play a critical role in the regulation of metabolism, and thyroid function is related to cardiovascular disease, fertility, and fetal neurodevelopment. , data, and epidemiological studies suggested that PFASs may disrupt the thyroid hormone system in humans, with possible negative repercussions on the outcome of pregnancy and fetal-child development. However, data on the thyroid disrupting effect of PFAS remain controversial, as well as their impact on human health in different ages of life. Aim of the present paper is to review recent data on the effects of old and new generation PFAS on thyroid homeostasis. To this purpose we collected information from studies, animal models, and data on exposed workers, general population, and pregnant women.
Topics: Animals; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Fluorocarbons; Humans; Thyroid Gland; Thyroid Hormones
PubMed: 33542707
DOI: 10.3389/fendo.2020.612320 -
Frontiers in Endocrinology 2023Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures,... (Review)
Review
Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and Tc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients' need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described.
Topics: Humans; Parathyroidectomy; Hyperparathyroidism, Secondary; Parathyroid Glands; Parathyroid Hormone; Neck
PubMed: 37152972
DOI: 10.3389/fendo.2023.1169793