Parathyroid Disorders. Группа авторов

Preface

      Disorders of the function of parathyroid glands most commonly present with abnormalities of calcium homeostasis. The area of mineral metabolism was not receiving the same attention as diseases affecting other endocrine glands. This was due in part to the lack of targeted medical therapies both in hyperparathyroidism and in hypoparathyroidism. However, recent developments in the medical therapy of hypoparathyroidism has created a renewed interest in parathyroid disorders overall.

      Clinical practice guidelines, which describe the consensus of experts in the field, are available for the management of hyperparathyroidism and hypoparathyroidism. Recognition of the need for more research to optimize care in parathyroid disorders has emerged in recent publications.

      This book puts together the experiences of specialists in the field, as the demands placed upon a clinician’s time are both unrelenting and enormous. As a busy specialist in this field, I believe there is a genuine need for an up-to-date evidence-based overview that is practically oriented. The aim of this book is to serve as a practical guide to the clinical management of common parathyroid conditions.

      The book will be relevant to specialists, general practitioners, undergraduates, postgraduates, and clinical nurse specialists. I am extremely grateful to the contributors who, as experts in their individual areas, have provided authority, experience, and invaluable insight. Finally, we would like to thank Karger for having the trust, determination, and encouragement to carry this project to fruition.

      Maria Luisa Brandi, Florence

      Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs.

      Front Horm Res. Basel, Karger, 2019, vol 51, pp 1–12 (DOI: 10.1159/000491034)

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Primary Hyperparathyroidism

      Laura Masi

      Metabolic Bone Diseases Unit, University Hospital of Florence, AOU-Careggi, Florence, Italy

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      Abstract

      The 4 parathyroid glands derive from the third and fourth pharyngeal pouches and descend caudally to the anterior neck. Through the secretion of parathyroid hormone (PTH), the parathyroid glands are primarily responsible for maintaining extracellular calcium and phosphorus concentrations. Hypercalcemia may be distinguished in parathyroid-hypercalcemia and nonparathyroid hypercalcemia. The most common disorders include primary hyperparathyroidism (PHPT), malignancy, granulomatous diseases, and medications. PHPT is a disease characterized by excessive secretion of PTH. PHPT is most commonly due to a single benign parathyroid adenoma (80%) and with multiglandular disease seen in approximately 15–20% of patients. PHPT is due to multiglandular involvement consisting of either multiple adenomas or hyperplasia of all 4 glands (5–10%), and very rarely parathyroid carcinoma (<1%). In most patients the disease is sporadic, without a personal or family history of PHPT. The genetic syndromes associated with PHPT include multiple endocrine neoplasia type 1 (MEN1), MEN2A, and MEN4, hyperparathyroidism-jaw tumor syndrome, familial isolated PHPT, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. The asymptomatic clinical presentation is most common in countries where biochemical screening is routine. Conversely, target organ involvement at presentation dominates the clinical landscape of PHPT in other countries, such as China and India, where biochemical screening is not routine practice.

      © 2019 S. Karger AG, Basel

The 4 parathyroid glands derive from the third and fourth pharyngeal pouches and descend caudally to the anterior neck. They are embedded in the posterior thymus, with ectopic locations occurring as well. Through the secretion of parathyroid hormone (PTH), the parathyroid glands are primarily responsible for maintaining extracellular calcium and phosphorus concentrations. PTH has well-described effects on bone, kidney, and intestine, which play a role in controlling serum calcium phosphorus levels [1]. Hypercalcemia may be distinguished in parathyroid-hypercalcemia and nonparathyroid hypercalcemia. Parathyroid-hypercalcemia is characterized by an overproduction of PTH and causes pathological disorders as seen in primary, secondary, or tertiary hyperparathyroidism. Primary hyperparathyroidism (PHPT) is a disease characterized by excessive secretion of PTH. The increase of serum calcium is the biochemical hallmark of PHPT. It mainly affects women, with a female to male ratio of 3–4:1 [2, 3]. A single benign parathyroid adenoma is the cause in most people. However, multiglandular disease is not rare and is typically seen in familial PHPT syndromes. The genetics of PHPT is usually monoclonal when a single gland is involved and polyclonal when multiglandular disease is present. The genes that have been implicated in PHPT include proto-oncogenes and tumor-suppressor genes [4]. Usually, the concentration of PTH is frankly increased but can remain within the normal range, which is abnormal in the setting of hypercalcemia. Normocalcemic PHPT, a variant in which the serum calcium level is persistently normal but PTH levels are increased in the absence of an obvious inciting stimulus, is now recognized [4]. The asymptomatic clinical presentation is most common in countries where biochemical screening is routine. Conversely, target organ involvement at presentation dominates the clinical landscape of PHPT in other countries, such as China and India, where biochemical screening is not routine practice [5, 6].

Table 1. Severity of hypercalcemia on the basis of serum calcium

Normal	Serum calcium level is 8–10 mg/dL(2–2.5 mmol/L) with some interlaboratoryvariation in the reference range
Mild	Total calcium 10.5–11.9 mg/dL (2.5–3 mmol/L)orIonized calcium 5.6–8 mg/dL (1.4–2 mmol/L)
Moderate	Total calcium 12–13.9 mg/dL (3–3.5 mmol/L)orIonized calcium 8–10 mg/dL (2–2.5 mmol/L)
Hypercalcemic crisis	Total calcium 14–16 mg/dL (3.5–4 mmol/L)orIonized calcium 10–12 mg/dL (2.5–3 mmol/L)

      Hypercalcemia and Differential Diagnosis

The severity of hypercalcemia may be classified based on total serum and ionized calcium levels, as indicated in Table 1. The differential diagnosis for hypercalcemia includes an extensive group of disorders. The most common disorders include PHPT, malignancy, granulomatous diseases, and medications. Hypercalcemia may be distinguished in parathyroid-hypercalcemia and nonparathyroid hypercalcemia. The PTH-dependent family of hypercalcemic disorders includes primary and tertiary hyperparathyroidism, their inherited variants, and familiar hypocalciuric hypercalcemia [7]. These disorders are described in the Primary Hyperparathyroidism section below.

Malignancy-associated hypercalcemia represents approximately 90% of cases of hypercalcemia among hospitalized patients. About 20–30% of patients with cancer have hypercalcemia during the course of the disease, and its occurrence may signify an unfavorable prognosis [8]. Of the cases that result from malignancy, approximately