Frontiers of Hormone Research最新文献

Heart failure (HF) represents the most common cause of hypervolemic hyponatremia in current clinical practice. The presence of hyponatremia has been independently associated with worse outcomes in this patient population. The pathogenesis of hyponatremia in HF involves complex neurohormonal and cardio-renal interactions, including an increase in non osmotic secretion of arginine vasopressin (AVP) and insufficient tubular flow in the diluting segments of the nephron. The treatment of hyponatremia in HF involves decongestant therapy with diuretics, neurohormonal blockade and in certain occasions the use of AVP antagonists. The aim of this chapter is to summarize the pathophysiology, current evidence, and management recommendations for hyponatremia in patients with HF, with a specific focus on AVP homeostasis.

Hyponatremia is a frequent complication in patients with advanced cirrhosis. Patients with cirrhosis can develop two types of hyponatremia, hypovolemic or hypervolemic (dilutional) hyponatremia. Hypervolemic hyponatremia is the most common type and it develops as a consequence of an impairment in the renal capacity to eliminate solute-free water. The key mechanism leading to solute-free water retention is a non-osmotic hypersecretion of vasopressin (AVP), secondary to a reduction in effective arterial blood pressure existing in patients with advanced cirrhosis. Hypervolemic hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and it has also been associated with increased complications after liver transplantation. Currently, the management of hypervolemic hyponatremia in cirrhosis is based on fluid restriction. Vaptans, oral selective vasopressin V2-receptor antagonists, and particularly tolvaptan, have been investigated as a pharmacological approach for the management of hypervolemic hyponatremia in cirrhosis. However, existing information on its efficacy in cirrhosis is still scarce and a recent warning has been raised about their potential role on inducing liver injury at high doses.

Parathyroid hormone (PTH) is one of the major hormones that regulates serum calcium. Hypoparathyroidism occurs when PTH secretion is insufficient. The main symptoms of hypoparathyroidism are the result of low blood calcium levels, hypocalcemia, which interferes with normal muscle contraction and nerve conduction. As a result, people with hypoparathyroidism can experience paresthesia, an unpleasant tingling sensation around the mouth and in the hands and feet, as well as muscle cramps and severe spasms known as "tetany" that affect the hands and feet. Many also report a number of other subjective symptoms. Hypocalcemia can be the cause of medical emergencies, for example seizures, severe irregularities in the normal heart beat, as well as laryngospasm, stridor, bronchospasm, and wheezing.

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.

The term hypoparathyroidism encompasses a huge group of disorders all characterized by an abnormal mineral homeostasis determined by inadequate secretion of parathyroid hormone. Postsurgical hypoparathyroidism is a complication of neck surgery (thyroidectomy, parathyroidectomy, lymph node, and cancer neck dissection), closely related to the extent of the surgical procedure and the experience of the surgeon. If lasting more than 6 months it is defined as chronic hypoparathyroidism, requiring life-long replacement therapy with active vitamin D metabolites. All the other forms of nonsurgical hypoparathyroidism, previously referred to as idiopathic hypoparathyroidism, have several causes, the majority of them genetic, which can be grouped into 3 main categories: disorder of parathyroid development, disorders of parathyroid function, and acquired damage to the parathyroids. Hypoparathyroidism can manifest as the sole disease in an individual (isolated hypoparathyroidism) or be associated with other manifestations within complex syndromes (syndromic hypoparathyroidism). Functional hypoparathyroidism, which may be caused by magnesium disturbances, has always to be ruled out before commencing the genetic diagnostic workup in nonsurgical forms. The search for signs of autoimmunity can drive the diagnosis towards an autoimmune pathogenesis of the disease, since a routine assessment of parathyroid autoantibodies is neither available nor specific.

Hyponatremia is the commonest electrolyte deficiency in clinical practice. Of the many causes of hyponatremia, syndrome of inappropriate antidiuresis (SIAD) is the commonest. Glucocorticoid deficiency, due to central/secondary adrenal insufficiency, is the key differential diagnosis for SIAD, as it presents with a similar biochemical picture of euvolemic hyponatremia and inappropriate urinary concentration. The underlying mechanisms for the development of hyponatremia in glucocorticoid deficiency are: (1) impaired renal water handling in the absence of circulating cortisol and (2) increased plasma concentrations of arginine vasopressin (AVP), despite hypo-osmolality. The original diagnostic criteria for SIAD emphasized that normal adrenal reserve was essential for its diagnosis, in recognition of the similar biochemical presentation of SIAD and glucocorticoid deficiency. This has been emphasized in all of the recently published clinical guidelines. However, data from the literature suggest that clinicians ignore the measurement of plasma cortisol concentration in both clinical practice and research protocols. The reported prevalence of glucocorticoid deficiency in patients presenting with euvolemic hyponatremia may, therefore, be underestimated and patients with a dangerous, but treatable cause of hyponatremia are inevitably missed. In this chapter, we will review the physiopathology of hyponatremia in the setting of glucocorticoid deficiency. We will discuss the differential diagnosis of euvolemic hyponatremia and review the prevalence of glucocorticoid deficiency in patients with hyponatremia.

The etiology of hyponatremia is often multifactorial. The most common causes include hypovolemia from gastrointestinal (GI) or other fluid losses, thiazide diuretics, and SIAD [1]. In this chapter, we will discuss hypovolemic hyponatremia, as well as the clinical parameters that help distinguish between hypovolemic and euvolemic states. These include not only the urine [Na+] concentration but also the fractional uric acid excretion, a parameter that can be employed even when diuretics have been prescribed [2,3,4,5,6,7]. Among the common causes of hypovolemic hyponatremia are GI fluid loss, a range of endocrinopathies [7], and thiazide-induced hyponatremia, which is best considered as a distinct entity, in particular because recent data suggest that it has a genetic predisposition. Also, the discontinuation of thiazide is a key step in treatment [2,7]. The management of hypovolemic hyponatremia starts with confirming its presence and determining the underlying cause. Correction focuses on the appropriate use of isotonic fluid to effect volume repletion while avoiding an overly rapid rise in serum [Na+] concentration.