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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 -
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 -
Therapeutic Advances in Chronic Disease Jan 2018In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the... (Review)
Review
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches. X-linked hypophosphataemia (XLH) is the most common heritable form of osteomalacia and rickets caused by a mutation in the phosphate regulating endopeptidase gene resulting in elevated serum fibroblast growth factor 23 (FGF23) and decreased renal phosphate reabsorption. The traditional treatment is phosphate replacement. We discuss the development of a human anti-FGF23 antibody (KRN23) as a promising development in the treatment of XLH. The current management of primary hypoparathyroidism is replacement with calcium and active vitamin D. This can be associated with under or over replacement and its inherent complications. We review the use of recombinant parathyroid hormone (1-84), which can significantly reduce the requirements for calcium and vitamin D resulting in greater safety and quality of life for individuals with hypoparathyroidism. The use of receptor activator of nuclear factor κB ligand infusions in the treatment of a particular form of osteopetrosis and enzyme replacement therapy for hypophosphatasia are also discussed.
PubMed: 29344330
DOI: 10.1177/2040622317739538 -
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 -
Clinical Endocrinology Oct 2022Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary... (Review)
Review
Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary hyperparathyroidism (PHPT) or hypoparathyroidism (HP), which have a monogenic aetiology in 5%-10% of cases, and may occur as an isolated endocrinopathy, or as part of a complex syndrome. The recognition and diagnosis of these disorders is important to facilitate the most appropriate management of the patient, with regard to both the calcium-related phenotype and any associated clinical features, and also to allow the identification of other family members who may be at risk of disease. Genetic testing forms an important tool in the investigation of PHPT and HP patients and is usually reserved for those deemed to be an increased risk of a monogenic disorder. However, identifying those suitable for testing requires a thorough clinical evaluation of the patient, as well as an understanding of the diversity of relevant phenotypes and their genetic basis. This review aims to provide an overview of the genetic basis of monogenic metabolic bone and mineral disorders, primarily focusing on those associated with abnormal calcium homeostasis, and aims to provide a practical guide to the implementation of genetic testing in the clinic.
Topics: Calcium; Calcium, Dietary; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Phenotype; Receptors, Calcium-Sensing
PubMed: 34935164
DOI: 10.1111/cen.14644 -
Progress in Medicinal Chemistry 2018The extracellular calcium receptor (CaR) is a G protein-coupled receptor (GPCR) and the pivotal molecule regulating systemic Ca homeostasis. The CaR was a challenging... (Review)
Review
The extracellular calcium receptor (CaR) is a G protein-coupled receptor (GPCR) and the pivotal molecule regulating systemic Ca homeostasis. The CaR was a challenging target for drug discovery because its physiological ligand is an inorganic ion (Ca) rather than a molecule so there was no structural template to guide medicinal chemistry. Nonetheless, small molecules targeting this receptor were discovered. Calcimimetics are agonists or positive allosteric modulators of the CaR, while calcilytics are antagonists and all to date are negative allosteric modulators. The calcimimetic cinacalcet was the first allosteric modulator of a GPCR to achieve regulatory approval and is a first-in-class treatment for secondary hyperparathyroidism in patients on dialysis, and for hypercalcemia in some forms of primary hyperparathyroidism. It is also useful in treating some rare genetic diseases that cause hypercalcemia. Two other calcimimetics are now on the market (etelcalcetide) or under regulatory review (evocalcet). Calcilytics stimulate the secretion of parathyroid hormone and were initially developed as treatments for osteoporosis. Three different calcilytics of two different chemotypes failed in clinical trials due to lack of efficacy. Calcilytics are now being repurposed and might be useful in treating hypoparathyroidism and several rare genetic diseases causing hypocalcemia. The challenges ahead for medicinal chemists are to design compounds that select conformations of the CaR that preferentially target a particular signalling pathway and/or that affect the CaR in a tissue-selective manner.
Topics: Animals; Calcimimetic Agents; Calcium; Drug Discovery; Gene Expression Regulation; Humans; Receptors, Calcium-Sensing; Signal Transduction
PubMed: 29680147
DOI: 10.1016/bs.pmch.2017.12.001 -
Clinical Endocrinology Jan 2018Little is known about the natural changes in parathyroid function after successful parathyroid surgery for primary hyperparathyroidism. The association of intact...
OBJECTIVE
Little is known about the natural changes in parathyroid function after successful parathyroid surgery for primary hyperparathyroidism. The association of intact parathyroid hormone (iPTH) and calcium (Ca) with "temporary hypoparathyroidism" and "hungry bone syndrome" (HBS) was evaluated.
DESIGN
Potential risk factors for temporary hypoparathyroidism and HBS were evaluated by taking blood samples before surgery, intra-operatively, at postoperative day (POD) 1, at POD 5 to 7, in postoperative week (POW) 8 and in postoperative month (POM) 6.
PATIENTS
Of 425 patients, 43 (10.1%) had temporary hypoparathyroidism and 36 (8.5%) had HBS.
MEASUREMENTS
The discriminative ability of iPTH and Ca on POD 1 for temporary hypoparathyroidism and HBS.
RESULTS
Intact parathyroid hormone (IPTH) on POD 1 showed the highest discriminative ability for temporary hypoparathyroidism (C-index = 0.952), but not for HBS. IPTH was helpful in diagnosing HBS between POD 5 and 7 (C-index = 0.708). Extending the model by including Ca resulted in little improvement of the discriminative ability for temporary hypoparathyroidism (C-index = 0.964) and a decreased discriminative ability for HBS (C-index = 0.705). Normal parathyroid metabolism was documented in 139 (32.7%) patients on POD 1 and in 423 (99.5%) 6 months postoperatively, while 2 (0.5%) patients had persistent hyperparathyroidism, one diagnosed between POD 5 and 7 and another at POW 8. No patients suffered from permanent hypoparathyroidism.
CONCLUSIONS
The necessity for Ca and vitamin D3 substitution cannot be predicted with certainty before POD 5 to 7 without serial laboratory measurements. Based on the results, a routine 8-week course of Ca and vitamin D3 treatment seems reasonable and its necessity should be evaluated in a follow-up study.
Topics: Adult; Calcium; Female; Humans; Hyperparathyroidism, Primary; Hypoparathyroidism; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Postoperative Period; Risk Factors; Time Factors; Vitamin D
PubMed: 28906021
DOI: 10.1111/cen.13476 -
Problemy Endokrinologii Aug 2021Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied... (Review)
Review
Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied by impaired calcium-phosphorus metabolism.The main etiology of hypoparathyroidism remains damage or removal of the parathyroid glands during neck surgery. In view of the incidence of thyroid cancer, primary hyperparathyroidism and other pathologies of the neck organs, which radical treatment can lead to the parathyroid gland impairment, an increased number of patients with hypoparathyroidism is expected. Autoimmune hypoparathyroidism is the second most common form of the disease, usually occurring as part of type 1 autoimmune polyglandular syndrome. Autoimmune hypoparathyroidism usually occurs in childhood and is characterized by a severe course of the disease, especially in the case of concomitant malabsorption syndrome.Chronic hypoparathyroidism of any etiology requires lifelong multicomponent therapy, as well as careful monitoring and an individual approach to choose the optimal treatment strategy. In the absence of adequate follow-up, the risks of long-term complications significantly increase, particularly in the renal, cardiovascular systems; in the soft tissues and in the brain, it could lead to visual disturbances; pathology of the musculoskeletal system with a decreased bone remodeling and a potential risk of fractures, as well as to the neurocognitive disorders and an impaired health-related quality of life.Timely diagnosis, rational medical therapy and management strategy may reduce the risks of short-term and long-term complications, frequency of hospitalizations and disability of patients, as well as improve the prognosis.This review covers the main issues of Russian guidelines for the management of chronic hypoparathyroidism, approved in 2021, including laboratory and instrumental evaluation, treatment approaches and follow-up. This guidelines also include the recommendations for special groups of patients: with acute hypocalcemia, hypoparathyroidism during pregnancy.
Topics: Humans; Hypocalcemia; Hypoparathyroidism; Parathyroid Glands; Parathyroid Hormone; Quality of Life
PubMed: 34533015
DOI: 10.14341/probl12800 -
Journal of Equine Veterinary Science Apr 2021Hypoparathyroidism is an uncommon endocrine disorder in the horse characterized by a transient or permanent parathyroid hormone insufficiency. Hypoparathyroidism is...
Hypoparathyroidism is an uncommon endocrine disorder in the horse characterized by a transient or permanent parathyroid hormone insufficiency. Hypoparathyroidism is associated with hypocalcemia and hyperphosphatemia, primarily presenting with clinical signs consistent with hypocalcemia. This case report describes clinical presentation and treatment of a horse with severe hypocalcemia due to primary hypoparathyroidism. A 17-year-old, 542 kg Quarter Horse gelding presented for shaking and tremors. Significant findings include generalized muscle fasciculations, synchronous diaphragmatic flutter, and a markedly hypermetric hindlimb gait. Hematology revealed a moderate hyperkalemia, hyperphosphatemia, hypomagnesemia, and severe hypocalcemia. Initial treatment consisted of oral and intravenous calcium supplementation and fluid therapy. Thirty-six hours after presentation, clinical signs resolved, and treatment was discontinued. Clinical signs reoccurred after the discontinuation of treatment. A presumptive diagnosis of primary hypoparathyroidism was made based on low parathyroid hormone in the presence of low ionized calcium. The patient was maintained on oral calcium carbonate (feed grade lime) and vitamin AED supplementation. Hypoparathyroidism is rare but oral supplementation of calcium with calcium carbonate resulted in a favorable outcome with no apparent decrease in performance. Long-term supplementation may be required to prevent disease recurrence.
Topics: Animals; Horse Diseases; Horses; Hyperphosphatemia; Hypocalcemia; Hypoparathyroidism; Magnesium; Male; Parathyroid Hormone
PubMed: 33781415
DOI: 10.1016/j.jevs.2021.103398