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Expert Review of Endocrinology &... 2023Immune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and... (Review)
Review
INTRODUCTION
Immune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and the PD-1/PD-L1 pathways. ICI therapy can trigger autoimmune adverse effects, known as immune-related Adverse Events (irAEs).
AREAS COVERED
This review focuses on irAEs which affect the endocrine system. This review elucidates the pathways used by these drugs with a focus on the hypothetical pathogenesis at their basis. In fact, the pathophysiology of irAEs concerns the possibility of an interaction between cellular autoimmunity, humoral immunity, cytokines, chemokines, and genetics. The endocrine irAEs examined are thyroid dysfunctions, immune related-hypophysitis, diabetes, peripheral adrenal insufficiency, and hypoparathyroidism.
EXPERT OPINION
There is still much to investigate in endocrine irAES of checkpoint inhibitors. In the future, checkpoint inhibitors will be increasingly utilized therapies, and therefore it is crucial to find the proper diagnostic-therapeutic program for irAEs, especially as endocrine irAEs are nonreversible and require lifelong replacement therapies.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Immunotherapy; Endocrine System; Endocrine System Diseases; Drug-Related Side Effects and Adverse Reactions
PubMed: 37682107
DOI: 10.1080/17446651.2023.2256841 -
Journal of Bone and Mineral Research :... Dec 2022
Topics: Humans; Hypoparathyroidism; Parathyroid Hormone
PubMed: 36375811
DOI: 10.1002/jbmr.4671 -
Diagnostics (Basel, Switzerland) Jun 2023Hungry bone syndrome (HBS), severe hypocalcemia following parathyroidectomy (PTX) due to rapid drop of PTH (parathormone) after a previous long term elevated... (Review)
Review
UNLABELLED
Hungry bone syndrome (HBS), severe hypocalcemia following parathyroidectomy (PTX) due to rapid drop of PTH (parathormone) after a previous long term elevated concentration in primary (PHPT) or renal hyperparathyroidism (RHPT), impairs the outcome of underlying parathyroid disease.
OBJECTIVE
overview HBS following PTx according to a dual perspective: pre- and post-operative outcome in PHPT and RHPT. This is a case- and study-based narrative review.
INCLUSION CRITERIA
key research words "hungry bone syndrome" and "parathyroidectomy"; PubMed access; in extenso articles; publication timeline from Inception to April 2023.
EXCLUSION CRITERIA
non-PTx-related HBS; hypoparathyroidism following PTx. We identified 120 original studies covering different levels of statistical evidence. We are not aware of a larger analysis on published cases concerning HBS (N = 14,349). PHPT: 14 studies (N = 1545 patients, maximum 425 participants per study), and 36 case reports (N = 37), a total of 1582 adults, aged between 20 and 72. Pediatric PHPT: 3 studies (N = 232, maximum of 182 participants per study), and 15 case reports (N = 19), a total of 251 patients, aged between 6 and 18. RHPT: 27 studies (N = 12,468 individuals, the largest cohort of 7171) and 25 case reports/series (N = 48), a total of 12,516 persons, aged between 23 and 74. HBS involves an early post-operatory (emergency) phase (EP) followed by a recovery phase (RP). EP is due to severe hypocalcemia with various clinical elements (<8.4 mg/dL) with non-low PTH (to be differentiated from hypoparathyroidism), starting with day 3 (1 to 7) with a 3-day duration (up to 30) requiring prompt intravenous calcium (Ca) intervention and vitamin D (VD) (mostly calcitriol) replacement. Hypophosphatemia and hypomagnesiemia may be found. RP: mildly/asymptomatic hypocalcemia controlled under oral Ca+VD for maximum 12 months (protracted HBS is up to 42 months). RHPT associates a higher risk of developing HBS as compared to PHPT. HBS prevalence varied from 15% to 25% up to 75-92% in RHPT, while in PHPT, mostly one out of five adults, respectively, one out of three children and teenagers might be affected (if any, depending on study). In PHPT, there were four clusters of HBS indicators. The first (mostly important) is represented by pre-operatory biochemistry and hormonal panel, especially, increased PTH and alkaline phosphatase (additional indicators were elevated blood urea nitrogen, and a high serum calcium). The second category is the clinical presentation: an older age for adults (yet, not all authors agree); particular skeleton involvement (level of case reports) such as brown tumors and osteitis fibrosa cystica; insufficient evidence for the patients with osteoporosis or those admitted for a parathyroid crisis. The third category involves parathyroid tumor features (increased weight and diameter; giant, atypical, carcinomas, some ectopic adenomas). The fourth category relates to the intra-operatory and early post-surgery management, meaning an associated thyroid surgery and, maybe, a prolonged PTx time (but this is still an open issue) increases the risk, as opposite to prompt recognition of HBS based on calcium (and PTH) assays and rapid intervention (specific interventional protocols are rather used in RHPT than in PHPT). Two important aspects are not clarified yet: the use of pre-operatory bisphosphonates and the role of 25-hydroxyitamin D assay as pointer of HBS. In RHPT, we mentioned three types of evidence. Firstly, risk factors for HBS with a solid level of statistical evidence: younger age at PTx, pre-operatory elevated bone alkaline phosphatase, and PTH, respectively, normal/low serum calcium. The second group includes active interventional (hospital-based) protocols that either reduce the rate or improve the severity of HBS, in addition to an adequate use of dialysis following PTx. The third category involves data with inconsistent evidence that might be the objective of future studies to a better understanding; for instance, longer pre-surgery dialysis duration, obesity, an elevated pre-operatory calcitonin, prior use of cinalcet, the co-presence of brown tumors, and osteitis fibrosa cystica as seen in PHPT. HBS remains a rare complication following PTx, yet extremely severe and with a certain level of predictability; thus, the importance of being adequately identified and managed. The pre-operatory spectrum of assessments is based on biochemistry and hormonal panel in addition to a specific (mostly severe) clinical presentation while the parathyroid tumor itself might provide useful insights as potential risk factors. Particularly in RHPT, prompt interventional protocols of electrolytes surveillance and replacement, despite not being yet a matter of a unified, HBS-specific guideline, prevent symptomatic hypocalcemia, reduce the hospitalization stay, and the re-admission rates.
PubMed: 37296804
DOI: 10.3390/diagnostics13111953 -
Current Opinion in Endocrinology,... Feb 2024Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have... (Review)
Review
PURPOSE OF REVIEW
Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have clinical features that are distinct from the more common forms. We provide an overview of mitochondrial disorder genetics and phenotypes, focusing on recent studies regarding identification and treatment of associated endocrinopathies.
RECENT FINDINGS
Known endocrine phenotypes of mitochondrial disorders continue to expand, and now include growth hormone deficiency, hypogonadism, precocious puberty, hypoparathyroidism, hypo- and hyperthyroidism, diabetes, and adrenal insufficiency. Recent studies suggest several genotype-phenotype correlations, including those related to nuclear variants. Diagnosis is important, as special considerations should be made in the management of endocrinopathies in mitochondrial patients. Finally, new mitochondrial replacement strategies may soon be available for women interested in preventing mitochondrial disease transmission to offspring.
SUMMARY
Patients with multiple endocrinopathies or atypical endocrinopathies should be evaluated for primary mitochondrial disease, as a diagnosis may impact management of these individuals.
Topics: Humans; Female; Endocrine System Diseases; Diabetes Mellitus; Puberty, Precocious; Mitochondrial Diseases; Hyperthyroidism; Adrenal Insufficiency
PubMed: 38047549
DOI: 10.1097/MED.0000000000000848 -
Journal of Clinical Medicine Apr 2023Breast cancer (BC), the most commonly diagnosed malignancy, frequently metastasizes to the bone, lungs, brain and liver at advanced stages, whereas the thyroid gland... (Review)
Review
Breast cancer (BC), the most commonly diagnosed malignancy, frequently metastasizes to the bone, lungs, brain and liver at advanced stages, whereas the thyroid gland represents a rare target site for secondary disease. We examined the most recent literature about thyroid metastasis (TM) from BC after we encountered a peculiar case of a 71-year-old woman who developed sudden dysphagia, severe hypothyroidism and hypoparathyroidism due to TM 18 years after the diagnosis of her primary cancer. Based on published data, the prevalence of TM in BC ranges from 3% to 34%, with a median onset time of 48.2 months, although longer time intervals are not infrequent. TM negatively impacts the prognosis of these patients, however thyroid surgery can limit the local disease burden. Therefore, we suggest that clinicians involved in the follow-up care of BC patients should consider a differential diagnosis of secondary thyroid malignancy when incidental lesions are diagnosed during radiological evaluations or local symptoms affect the cervical region, even many years after the diagnosis of the primary cancer.
PubMed: 37048792
DOI: 10.3390/jcm12072709 -
Reviews in Endocrine & Metabolic... Dec 2021Both hypoparathyroidism (HypoPT), as well as its pathological counterpart, primary hyperparathyroidism (PHPT), can lead to skeletal abnormalities. Chronic deficiency of... (Review)
Review
Both hypoparathyroidism (HypoPT), as well as its pathological counterpart, primary hyperparathyroidism (PHPT), can lead to skeletal abnormalities. Chronic deficiency of PTH in patients with HypoPT is associated with a profound reduction in bone remodeling, with consequent increases in bone density, and abnormalities in microarchitecture and bone strength. It is still not clear whether there is an increase in fracture risk in HypoPT. While standard therapy with calcium supplements and active vitamin D does not restore bone homeostasis, treatment of HypoPT with PTH appears to correct some of those abnormalities. In PHPT, the continuous exposure to high levels of PTH causes an increase in bone remodeling, in which bone resorption prevails. In the symptomatic form of PHPT, patients can present with fragility fractures, and/or the classical radiological features of osteitis fibrosa cystica. However, even in mild PHPT, catabolic skeletal actions of PTH are evident through reduced BMD, deterioration of bone microarchitecture and increased risk of fragility fractures. Successful parathyroidectomy improves skeletal abnormalities. Medical treatment, such as bisphosphonates and denosumab, can also increase bone density in patients with PHPT who do not undergo surgery. This article reviews skeletal involvement in HypoPT and in PHPT, as assessed by bone remodeling, DXA, trabecular bone score, and quantitative computed tomography, as well as data on bone strength and fracture risk. The effects of PTH replacement on the skeleton in subjects with HypoPT, and the outcome of parathyroidectomy in patients with PHPT, are also reviewed here.
Topics: Bone Density; Bone Remodeling; Bone and Bones; Humans; Hyperparathyroidism, Primary; Hypoparathyroidism; Parathyroid Hormone
PubMed: 33200346
DOI: 10.1007/s11154-020-09614-0 -
FP Essentials Mar 2022Parathyroid hormone (PTH) helps regulate calcium homeostasis in a complex relationship with the gastrointestinal tract, kidneys, bone, and parathyroid glands....
Parathyroid hormone (PTH) helps regulate calcium homeostasis in a complex relationship with the gastrointestinal tract, kidneys, bone, and parathyroid glands. Abnormalities in PTH production can result in many conditions, including hypoparathyroidism, and primary, secondary, and tertiary hyperparathyroidism. Management of each abnormality centers on maintaining normal or near-normal serum calcium values to prevent complications. Most cases of hypoparathyroidism are caused by neck surgery and may result in acute hypocalcemia. Patients with chronic hypoparathyroidism are treated with a combination of calcium, vitamin D analogs, and, occasionally, exogenous PTH. A single parathyroid adenoma causes most cases of primary hyperparathyroidism, with multiglandular disease and cancer as other possible etiologies. All patients with symptomatic primary hyperparathyroidism and many with asymptomatic hyperparathyroidism undergo partial or full parathyroidectomy to correct the underlying condition. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is the most common cause of secondary and tertiary hyperparathyroidism, in which hypocalcemia stimulates PTH production. Most patients with CKD-MBD are treated medically with phosphate binders, vitamin D analogs, and calcimimetics, but rare cases are managed with parathyroidectomy. Severe calcium or vitamin D deficiency also causes secondary hyperparathyroidism and is managed with calcium and vitamin D replacement.
Topics: Calcium; Humans; Hyperparathyroidism, Secondary; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Thyroid Gland; Vitamin D
PubMed: 35235284
DOI: No ID Found -
Nuklearmedizin. Nuclear Medicine Aug 2019We present a patient with a history of thyroid cancer, presumably following radiochemotherapy of a childhood medulloblastoma, who developed a primary hyperparathyroidism...
We present a patient with a history of thyroid cancer, presumably following radiochemotherapy of a childhood medulloblastoma, who developed a primary hyperparathyroidism 10 years after long-term postsurgical hypoparathyroidism. All established imaging modalities failed to detect the origin and only selective neck sampling could identify the suspected parathyroid adenoma causing hyperparathyroidism. This encourages the use of selective neck vein catheterization, particularly in patients with only slightly elevated parathyroid hormone-levels or suspected small ectopic adenoma.
Topics: Diagnosis, Differential; Humans; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Positron Emission Tomography Computed Tomography; Postoperative Period
PubMed: 31140182
DOI: 10.1055/a-0914-2451 -
Frontiers in Immunology 2021Inborn errors of immunity (IEI), caused by hereditary or genetic defects, are a group of more than 400 disorders, in which the immune system, including lymphocytes,... (Review)
Review
Inborn errors of immunity (IEI), caused by hereditary or genetic defects, are a group of more than 400 disorders, in which the immune system, including lymphocytes, neutrophils, macrophages, and complements, does not function properly. The endocrine system is frequently affected by IEI as an associated clinical feature and a complex network of glands which regulate many important body functions, including growth, reproduction, homeostasis, and energy regulation. Most endocrine disorders associated with IEI are hypofunction which would be treated with supplementation therapy, and early diagnosis and appropriate management are essential for favorable long-term outcomes in patients with IEI. In this review, we aimed to comprehensively summarize and discuss the current understanding on the clinical features and the pathophysiology of endocrine disorders in IEI. This review is composed with three parts. First, we discuss the two major pathophysiology of endocrinopathy in IEI, autoimmune response and direct effects of the responsible genes. Next, the details of each endocrinopathy, such as growth failure, hypothyroidism, hypoparathyroidism, adrenal insufficiency, diabetes mellitus (DM) are specified. We also illustrated potential endocrinopathy due to hematopoietic stem cell transplantation, including hypogonadism and adrenal insufficiency due to glucocorticoid therapy.
Topics: Animals; Autoimmunity; Disease Models, Animal; Endocrine System Diseases; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Primary Immunodeficiency Diseases
PubMed: 34887872
DOI: 10.3389/fimmu.2021.786241