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Cancers Jan 2023In recent years, in the context of the increase in the life expectancy of cancer patients, special attention has been given to immunotherapy and, indeed, to immune... (Review)
Review
In recent years, in the context of the increase in the life expectancy of cancer patients, special attention has been given to immunotherapy and, indeed, to immune checkpoint inhibitors. The use of immune checkpoint inhibitors has increased rapidly, and approximately 40% of cancer patients are eligible for this treatment. Although their impact is valuable on cancer treatment, immune checkpoint inhibitors come with side effects, known as immune-related adverse effects. These can affect many systems, including cutaneous, musculoskeletal, cardiovascular, gastrointestinal, endocrine, neural, and pulmonary systems. In this review, we focus on immune-related endocrinopathies that affect around 10% of all treated patients. Endocrine dysfunctions can manifest as hypophysitis, thyroid dysfunction, hypoparathyroidism, insulin-deficient diabetes mellitus, and primary adrenal insufficiency. Currently, there are multiple ongoing clinical trials that aim to identify possible predictive biomarkers for immune-related adverse effects. The design of those clinical trials relies on collecting a variety of biological specimens (tissue biopsy, blood, plasma, saliva, and stool) at baseline and regular intervals during treatment. In this review, we present the predictive biomarkers (such as antibodies, hormones, cytokines, human leukocyte antigens, and eosinophils) that could potentially be utilized in clinical practice in order to predict adverse effects and manage them appropriately.
PubMed: 36672324
DOI: 10.3390/cancers15020375 -
Deutsche Medizinische Wochenschrift... Aug 2019A finely balanced control system keeps the extracellular calcium concentration within narrow limits. Disorders of calcium metabolism are often based on altered... (Review)
Review
A finely balanced control system keeps the extracellular calcium concentration within narrow limits. Disorders of calcium metabolism are often based on altered parathormone levels. Symptoms are not always clear, sometimes they are even missing: the more it is important to know possible associated diseases. The author presents basics, current diagnostics and concrete therapy options. Central hormone for the regulation of the calcium balance is the parathyroid hormone. With decreasing calcium, PTH leads to an increase in extracellular free calcium concentration in three ways. The classic symptoms of pHPT (polyuria, polydipsia, "stone, leg, and stomach pain") are rare now, as the condition is diagnosed much earlier. Treatment of choice in all symptomatic patients with pHPT is surgery. FHH and pHPT are both characterized by hypercalcaemia and increased parathyroid hormone. The differential diagnosis of urinary calcium excretion, which is usually lower in FHH but normal or elevated in pHPT, is crucial. In primary hypoparathyroidism, parathyroid failure interferes with calcium homeostasis at a central location. Consequences are hypocalcaemia, hyperphosphatemia and lack of active vitamin D. Due to increased urinary calcium excretion, patients with ADH are at high risk for kidney stones, nephrocalcinosis and the development of renal insufficiency. Recently, rhPTH 1-84 has been available for the treatment of hypoparathyroidism. However, long-term data is still lacking to provide a safe indication, considering potential effects and side effects.
Topics: Calcium; Calcium Metabolism Disorders; Calcium, Dietary; Humans; Hypoparathyroidism; Vitamin D
PubMed: 31416104
DOI: 10.1055/a-0833-9674 -
Endocrine Connections Sep 2023Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their...
OBJECTIVE
Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy operations for Graves' disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves' disease.
DESIGN
Retrospective cohort study from a single institution.
METHODS
We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves' disease.
RESULTS
We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012-2014 to 6% in 2020-2021. For patients with Graves' disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015-2016 to 2% (1 out of 56) in 2020-2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012-2014 to 10% (10 out of 51) in 2020-2021.
CONCLUSION
Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery.
SIGNIFICANCE STATEMENT
Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoperative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves' disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures.
PubMed: 37487033
DOI: 10.1530/EC-23-0198 -
Journal of Clinical Medicine Jun 2022Growing evidence shows that arterial stiffness measurement provides important prognostic information and improves clinical stratification of cardiovascular risk. Thyroid... (Review)
Review
Growing evidence shows that arterial stiffness measurement provides important prognostic information and improves clinical stratification of cardiovascular risk. Thyroid and parathyroid diseases are endocrine diseases with a relevant cardiovascular burden. The objective of this review was to consider the relationship between arterial stiffness and thyroid and parathyroid diseases in human clinical studies. We performed a systematic literature review of articles published in PubMed/MEDLINE from inception to December 2021, restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and thyroid and parathyroid diseases. For each selected article, data on arterial stiffness were extracted and factors that may have an impact on arterial stiffness were identified. We considered 24 papers concerning hypothyroidism, 9 hyperthyroidism and 16 primary hyperparathyroidism and hypoparathyroidism. Most studies evidenced an increase in arterial stiffness biomarkers in hypothyroidism, hyperthyroidism and primary hyperparathyroidism, even in subclinical and mild forms, although heterogeneity of measurement methods and of study designs prevented a definitive conclusion, suggesting that the assessment of arterial stiffness may be considered in the clinical evaluation of cardiovascular risk in these diseases.
PubMed: 35683533
DOI: 10.3390/jcm11113146 -
Acta Medica Portuguesa Mar 2022Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that increase the efficiency of the immune system in the destruction of neoplastic cells. In recent years,... (Review)
Review
INTRODUCTION
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that increase the efficiency of the immune system in the destruction of neoplastic cells. In recent years, these drugs have been increasingly used in the treatment of many neoplasms in advanced stages. However, the change in the regulation of the immune system induced by these drugs has the potential adverse effect of inducing autoimmunity in practically all organ systems. Endocrinopathies are one of the most common autoimmune adverse eventsof these drugs.
MATERIAL AND METHODS
Non-systematic review of endocrinopathies reported in the context of treatment with ICIs. A search was carried out on PubMed until January 31st, 2020, and articles were selected based on their relevance and excluded in case of redundant content. The following search terms were used: "immune checkpoint inhibitor" and "endocrinopathy" / "endocrine system diseases" / "pituitary" / "thyroid" / "diabetes" / "adrenal" / "parathyroid".
RESULTS
Endocrinopathies with all classes of ICIs (anti-CTLA-4, anti-PD-1, anti-PD-L1) have been reported. Thyroid dysfunction is the most frequently reported endocrinopathy, mainly with anti-PD-1 and anti-PD-L1. Hypophysitis is the most prevalent with anti-CTLA-4. The incidence of autoimmune diabetes in this context is increasing, mainly with anti-PD-1 and anti-PD-L1. Rare cases of primary adrenal insufficiency, Graves' disease and primary hypoparathyroidism have also been reported.
CONCLUSION
Knowing the spectrum of endocrinopathies triggered by ICI, as well as their clinical features, diagnosis and treatment criteria is essential, given its high prevalence and the increasing number of cancer patients treated with these new drugs.
Topics: Antineoplastic Agents, Immunological; Endocrine System Diseases; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms
PubMed: 35077347
DOI: 10.20344/amp.13673 -
The Journal of Clinical Endocrinology... May 2023Taking care of patients with parathyroid disorders during pregnancy requires consideration of the physiological fundamental changes in bone and mineral metabolism...
Taking care of patients with parathyroid disorders during pregnancy requires consideration of the physiological fundamental changes in bone and mineral metabolism occurring in these women. Diagnostic and therapeutic procedures regarding primary hyperparathyroidism (PHPT) and hypoparathyroidism significantly differ from the nonpregnant population. PHPT should preferably be cured by parathyroidectomy before pregnancy since in women with hypercalcemic PHPT, maternal and fetal pregnancy complications seem to increase according to the degree of hypercalcemia. Parathyroidectomy, if needed during pregnancy, is preferentially performed in the second trimester. Conservative treatment is recommended for milder cases and is mainly restricted to hydration, with only limited evidence regarding drug treatment. Women with hypoparathyroidism can be informed that there are no major concerns regarding disease-associated infertility and that the risk of pregnancy complications is low if the disease is properly managed. Regular active surveillance is recommended, as requirements for calcium and active vitamin D may change during the course of pregnancy in either direction, with an overall trend for rather reduced doses. Any woman suffering from parathyroid disorders during pregnancy requires further surveillance in the postpartum period and during lactation, as there is an increased risk of hypercalcemia after delivery. Newborns of mothers with parathyroid diseases should, depending on disease severity, be carefully monitored for calcium levels in the first days (to weeks) after delivery since intrauterine exposure to hyper- or hypocalcemia may impact their postnatal regulation of calcium metabolism.
Topics: Pregnancy; Humans; Female; Infant, Newborn; Calcium; Hypercalcemia; Parathyroid Diseases; Pregnancy Complications; Hypoparathyroidism; Parathyroidectomy; Hyperparathyroidism, Primary
PubMed: 36546344
DOI: 10.1210/clinem/dgac734 -
Annales D'endocrinologie Jun 2021PTH is a metabolic active hormone primarily regulating calcium and phosphate homeostasis in a very tight and short term-manner. Parathyroid disorders in adult patients... (Review)
Review
PTH is a metabolic active hormone primarily regulating calcium and phosphate homeostasis in a very tight and short term-manner. Parathyroid disorders in adult patients reflect a variety of different conditions related either to the parathyroid glands itself or to the effects of the secreted hormone. The clinical spectrum varies from the common disease primary hyperparathyroidism (PHPT) to the orphan conditions pseudohypoparathyroidism (Ps-HypoPT) and chronic hypoparathyroidism (HypoPT). The purpose of this review is to describe the consequences of disturbances in levels or action of PTH for cardiac function and cardiovascular risk in adult patients with these disorders. Most patients with PHPT achieve the diagnose by chance and have minor or no specific symptoms. Still, these patients with mild PHPT do possess cardiovascular (CV) morbidity, however so far not proven ameliorated by surgery in controlled trials. In severe cases, the CV risk is increased and with a potential reversibility by treatment. Patients with Ps-HypoPT have resistance to PTH action, but not necessarily total resistance in all tissues. So far, no clear CV morbidity or risk has been demonstrated, but there are several aspects of interest for further studies. Most patients with HypoPT do get their hormonal deficiency syndrome following neck surgery. These patients do experience multiple symptoms and do have an increased CV-risk before the primary surgery. Based on existing data, their CV mortality do not deviate from the expected when adjusting for the preexisting increased risk. Patients with nonsurgical (NS-) HypoPT do demonstrate increased CV-risk also associated with exposure time. Endocrine disorders with alterations in PTH function have major impact on the cardiovascular system of importance for morbidity and mortality, wherefore management of these specific diseases should be optimized currently, as new data become available, however also avoiding over-treating asymptomatic patients.
Topics: Adult; Aging; Cardiovascular Diseases; Cardiovascular System; Humans; Parathyroid Diseases
PubMed: 32192790
DOI: 10.1016/j.ando.2020.02.003 -
Updates in Surgery Dec 2019Reoperative thyroid surgery is an uncommon procedure that is indicated in recurrent benign or malignant disease. It is associated with a high complication rate,... (Review)
Review
Reoperative thyroid surgery is an uncommon procedure that is indicated in recurrent benign or malignant disease. It is associated with a high complication rate, especially of hypoparathyroidism and recurrent nerve palsy. We retrospectively reviewed our series of patients on whom reoperative thyroid surgery was performed and we compared this group with patients who underwent primary thyroidectomies. From 2002 to 2015, 4572 thyroidectomies were performed at our institution; among these, 152 (3.3%) were for benign or malignant recurrent disease. We observed a higher rate of transient hypoparathyroidism in secondary vs primary surgery (56.6% vs 25.9%; p < 0.0001), of permanent hypoparathyroidism (10% vs 2.0%; p < 0.0001) and of transient recurrent nerve injury (4.6% vs 1.4%; p < 0.05). Reoperative thyroid surgery is a technical challenge with a high incidence of complications. Scarring, edema, and friability of the tissues together with distortion of the landmarks make reoperative surgery hazardous. Careful assessment of patient's risk factors, physical examination, and if necessary fine needle aspiration cytology are crucial for selecting the patients who should undergo reoperation. Research registry n. 2617 registered 5 June 2017 (retrospectively registered).
Topics: Adult; Anatomic Landmarks; Cicatrix; Edema; Female; Goiter, Nodular; Humans; Hypoparathyroidism; Male; Middle Aged; Postoperative Complications; Postoperative Hemorrhage; Recurrent Laryngeal Nerve Injuries; Reoperation; Retrospective Studies; Risk Factors; Thyroid Nodule; Thyroidectomy
PubMed: 30937820
DOI: 10.1007/s13304-019-00647-y -
International Journal of Molecular... Nov 2021The advent of new insights into phosphate metabolism must urge the endocrinologist to rethink the pathophysiology of widespread disorders, such as primary... (Review)
Review
The advent of new insights into phosphate metabolism must urge the endocrinologist to rethink the pathophysiology of widespread disorders, such as primary hyperparathyroidism, and also of rarer endocrine metabolic bone diseases, such as hypoparathyroidism and tumor-induced hypophosphatemia. These rare diseases of mineral metabolism have been and will be a precious source of new information about phosphate and other minerals in the coming years. The parathyroid glands, the kidneys, and the intestine are the main organs affecting phosphate levels in the blood and urine. Parathyroid disorders, renal tubule defects, or phosphatonin-producing tumors might be unveiled from alterations of such a simple and inexpensive mineral as serum phosphate. This review will present all these disorders from a 'phosphate perspective'.
Topics: Bone and Bones; Calcium; Humans; Hyperparathyroidism, Primary; Hypoparathyroidism; Hypophosphatemia; Multiple Endocrine Neoplasia; Osteomalacia; Parathyroid Diseases; Parathyroid Glands; Phosphates
PubMed: 34884774
DOI: 10.3390/ijms222312975