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Pathophysiology of Hypercalcemia
Extracellular calcium is normally tightly regulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, as well as by calcium ion (Ca++) itself. Dysregulated PTH production leading to hypercalcemia occurs most commonly in sporadic primary hyperparathryoidism (PHPT) but may also result from select genetic mutations in familial disorders. Parathyroid hormone-related protein shares molecular mechanisms of action with PTH and is the most common cause of hypercalcemia of malignancy. Other cytokines and mediators may also cause resorptive hypercalcemia once bone metastases have occurred. Less commonly, extrarenal production o...
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: David Goltzman Source Type: research

Hypercalcemia in Pregnancy
Hypercalcemic disorders are rare in pregnant women and are usually due to primary hyperparathyroidism. Clinical manifestations of hypercalcemia are nonspecific and can be masked by the physiologic changes of pregnancy. Furthermore, routine antenatal screening does not include serum calcium measurement and a hypercalcemia diagnosis may therefore be delayed until term or even after delivery. Timely recognition and appropriate interventions are essential to decrease maternal and fetal complications. Conservative measures are appropriate in the presence of mild hypercalcemia. Parathyroidectomy remains the mainstay of treatment...
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Karel Dandurand, Dalal S. Ali, Aliya A. Khan Source Type: research

Hypercalcemia
Total serum calcium concentration has three components: (i) ionized serum calcium (about 50%), (ii) serum calcium complexed to anions (about 3%), and (iii) protein-bound (mostly albumin) serum calcium (about 47%). (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Claudio Marcocci, Filomena Cetani Tags: Preface Source Type: research

Drug-Related Hypercalcemia
This review focuses on the commonly prescribed medicaments that can be responsible for hypercalcemia, considering the prevalence, the predominant pathophysiological mechanisms, and the optimal medical management of each drug-induced hypercalcemia. Vitamin D supplements and 1 α-hydroxylated vitamin D analogues increase intestinal calcium absorption, renal calcium reabsorption as well as bone resorption. In patients with hypoparathyroidism receiving recombinant human PTH, transient hypercalcemia can occur because of overtreatment, usually during acute illness. Thiazide-i nduced hypercalcemia is mainly explained by enhanced ...
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Anne-Lise Lecoq, Marine Livrozet, Anne Blanchard, Peter Kamenick ý Source Type: research

Treatment of Hypercalcemia of Malignancy
The treatment of hypercalcemia of malignancy (HCM) consists of enhancing renal calcium excretion, mostly through hydration with isotonic fluids and the use of antiresorptive therapies. Intravenous zoledronic acid is currently the first-line treatment. Subcutaneous denosumab is used for bisphosphonate-refractory hypercalcemia and in patients with renal failure. There is no evidence that bisphosphonates prevent the occurrence of HCM. Conversely, denosumab, compared with zoledronic acid, is associated with a lower risk of HCM, both first episode and recurrence, in patients with breast cancer and multiple myeloma. (Source: End...
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Marlene Chakhtoura, Ghada El-Hajj Fuleihan Source Type: research

Hereditary Primary Hyperparathyroidism
Primary hyperparathyroidism (PHPT) is a commonly encountered clinical problem and occurs as part of an inherited disorder in ∼10% of patients. Several features may alert the clinician to the possibility of a hereditary PHPT disorder (eg, young age of disease onset) whilst establishing any relevant family history is essential to the clinical evaluation and will help inform the diagnosis. Genetic testing should be offered to patients at risk of a hereditary PHPT disorder, as this may improve management and allow the identification and investigation of other family members who may also be at risk of disease. (Source: Endocr...
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Paul J. Newey Source Type: research

Tertiary and Postrenal Transplantation Hyperparathyroidism
This article presents the prevalence and epidemiologic and clinical impact of post-KTx hyper-PTH. The principal biochemical and instrumental investigations and the therapeutic options for these conditions are also reported. (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Carlo Alfieri, Deborah Mattinzoli, Piergiorgio Messa Source Type: research

Vitamin D –dependent Hypercalcemia
Vitamin D metabolism represents a well-integrated, hormonally regulated endocrine unit interlinking calcium and phosphate metabolism. Pathophysiologic processes disturbing vitamin D metabolism comprise classic defects of vitamin D activation and action presenting as different forms of vitamin D –dependent rickets as well as disorders with increased vitamin D activity. The latter may result in hypercalcemia, hypercalciuria, and renal calcifications. Acquired and hereditary disorders causing hypervitaminosis D are discussed, including vitamin D intoxication, granulomatous disease, and idio pathic infantile hypercalcemia th...
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Karl Peter Schlingmann Source Type: research

Hypercalcemia and its Multiple Facets
It is my great pleasure to introduce the Hypercalcemia issue of the Endocrinology and Metabolism Clinics of North America to our readers. The guest editors, Dr Claudio Marcocci and Dr Filomena Cetani from University of Pisa in Italy, are well-known experts in the field. (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Adriana G. Ioachimescu Tags: Foreword Source Type: research

Hypercalcemia
ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Authors: Claudio Marcocci, Filomena Cetani Source Type: research

Copyright
Elsevier (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Source Type: research

Contributors
ADRIANA G. IOACHIMESCU, MD, PhD (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Source Type: research

Contents
Adriana G. Ioachimescu (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Source Type: research

Forthcoming Issues
Hypogonadism (Source: Endocrinology and Metabolism Clinics of North America)
Source: Endocrinology and Metabolism Clinics of North America - November 11, 2021 Category: Endocrinology Source Type: research

100  years of Insulin: Why is Insulin So Expensive and What Can be Done to Control Its Cost?
The discovery of insulin 100 years ago and subsequent improvements in insulin formulations and delivery devices have changed the lives of people with diabetes. Unfortunately, the average price of insulin in the United States has nearly tripled over the past decade, and the high cost of insulin has become a barrier to diabetes treatment. On the 100th anniversary of insulin ’s discovery, this life-saving treatment is financially out of reach for as many as one-third of people with diabetes. The challenge now is to ensure that insulin is available for all people with diabetes who need it. We explore reasons for the high cos...
Source: Endocrinology and Metabolism Clinics of North America - October 13, 2021 Category: Endocrinology Authors: William H. Herman, Shihchen Kuo Source Type: research