Frontiers of Hormone Research

In hypotonic hyponatremia, which is the most common form of hyponatremia, clinical manifestations are largely due to brain swelling caused by entry of water into the cells. In acute and severe hyponatremia, dramatic symptoms, such as seizures, acute psychosis, permanent brain damage, brain-stem herniation, leading to coma and death may occur. In chronic hyponatremia, symptoms are generally less dramatic and may include headache, nausea, vomiting, gait alterations, muscle cramps, restlessness, and disorientation...

Exercise-associated hyponatremia (EAH) refers to below-normal serum sodium concentrations [Na+] that develop during exercise. The pathogenesis of EAH is best described as a spectrum ranging between profound polydipsia to modest sweat sodium losses with hypovolemia and relative dilution. Non-osmotic arginine vasopressin (AVP) remains the unifying pathogenic stimulus to abnormal renal water retention in acute symptomatic EAH. Cases of hyponatremia are mostly reported after endurance sports, but are also observed after shorter duration events and in team sport athletes...

Hyponatremia is a frequent occurrence in patients with neurosurgical disorders. Acute onset hyponatremia is particularly common in patients who have any type of cerebral insult, including traumatic brain injury, subarachnoid hemorrhage, and brain tumors. Furthermore, it is a common complication of intracranial procedures. Acute hyponatremia creates an osmotic gradient between the brain and the plasma, which promotes the movement of water from the plasma into brain cells, causing cerebral edema and neurological compromise...

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...

Numerous observational studies have confirmed that inadequate investigation of hyponatremia leads to diagnostic errors and incorrect treatment. In fact, only one out of five patients diagnosed as having syndrome of inappropriate antidiuresis (SIAD) have had all the tests necessary to meet the diagnostic criteria. Diagnostic errors could help explain why a majority of patients presenting hyponatremia during hospitalization are discharged while still hyponatremic. The correct differentiation of hypovolemic from euvolemic patients is a clinical diagnostic challenge...

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...

Chronic hyponatremia may not cause overt symptoms, and therefore frequently remains untreated. More recently, growing evidence indicate that this condition is not benign, and can lead to unsteady gait, deterioration of bone mass and strength, increased fragility, and increased all-cause mortality. We provided the first evidence for hyponatremia-induced osteoporosis based on markedly reduced bone mineral density and bone structural changes in hyponatremic rats, which is an experimental model of the syndrome of inappropriate antidiuresis (SIAD)...

Hyponatremia is a frequently encountered clinical finding, and by far the most common disorder of electrolyte and water homeostasis throughout the world. Given the complex pathophysiology of hyponatremia as well as its clinical implications, which range from apparently asymptomatic presentations to life-threatening conditions, a comprehensive understanding of its possible causes and of the frequencies of occurrence of the various types of hyponatremia in distinct clinical settings is essential for successful disease management...

Euvolemic hyponatremia is the most common cause of hyponatremia in both hospitalized patients and outpatients. The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD). Diagnosis of SIAD involves evaluation of a set of long-standing clinical and laboratory criteria for this diagnosis. Many treatment options for SIAD exist, and choosing among them should be based on the chronicity of the hyponatremia and neurological symptomatology. Importantly, clinical judgment and risk/benefit analysis that is individualized for specific patients should drive therapeutic decisions, because there is no single treatment that represents the "best" therapy for all patients with SIAD...

Hyponatremia is frequent in cancer patients and potentially deleterious. Cancer patients have specific requirements due to the nature and treatment of their disease, which can directly impact the occurrence and severity of hyponatremia, and limit treatment choices. Although essential for successful hyponatremia management, appropriate diagnostic testing is not routinely performed in the current practice. Despite clear evidence that hyponatremia is associated with poor outcome in oncology patients, most patients are still hyponatremic while under observation...

Menopause is the period of a woman's life that is characterized by the permanent cessation of menses associated to hormonal changes, of which the most important is the decrease of estrogen levels. Following menopause, the concentrations of circulating androgens decrease. However, increased concentrations of luteinizing hormone induce androgens secretion from the ovaries and presumably from the adrenal glands. Peripheral conversion of androgens results to the circulating hormonal androgen profile. Some pathological conditions are associated with greater concentrations of androgens after menopause than in controls, with polycystic ovary syndrome (PCOS) being the commonest...

Congenital Adrenal Hyperplasias (CAH) are genetic diseases transmitted in an autosomal recessive way and these diseases affect many aspects of human health. The majority of CAH cases is due to a deficiency in 21-hydroxylase as a result of the existence of mutations in both alleles of the CYP21A2 gene. Since the identification of mild, non-classic forms of this disease, CAH has been recognized to be one of the most common genetic diseases in human beings. This disease is generally associated with elevated secretion of androgens, sometimes resulting in virilizing syndromes, including genital ambiguity, precocious puberty in both sexes, or milder syndromes of androgen excess like precocious pubarche or the occurrence of hirsutism and oligomenorrhea in women...

Most research efforts addressing the pathophysiology of polycystic ovary syndrome (PCOS) applied targeted approaches focusing on specific genes and/or proteins that were selected on the basis of previous knowledge about their putative roles in metabolic and signalling pathways. On the contrary, the use of nontargeted approaches is not constricted by previous knowledge on the issue and offers the potential advantage of revealing novel associations with unexpected molecules that might lead to new mechanistic explanations for the etiology and the pathophysiology of PCOS...

Androgen-secreting tumors are a rare cause of hyperandrogenism of adrenal origin. Although these tumors are identified in less than 2% of patients, the prevalence of adrenocortical carcinomas is relevant (2/3 of the cases). Those tumors are associated with simultaneous elevation of several androgens, mainly androstenedione, DHEAS, and testosterone, in more than half of the patients, as measured either by immunoassay or mass spectrometry. Despite the recent advances on the pathogenesis of adrenocortical tumors, to date no driver molecular event have been identified in those tumors...

Sex steroids, except for their primary reproductive role, exert key effects on metabolic target tissues. Androgen receptors have been detected in various tissues, participating in both central and peripheral regulation of metabolism and insulin action. The physiological role of androgens in regulating multiple aspects of female insulin signaling and energy metabolism becomes evident early in utero, thus programming how insulin-targeted tissues will behave in later life. Across lifespan, distinct effects of androgens in all insulin-targeted tissues are controlled by their circulating serum levels, within a narrow window, outside of which disturbances in metabolism are observed...

Although polycystic ovary syndrome (PCOS) is the most common androgen excess disorder, screening for Cushing's Syndrome (CS) should be considered in women with PCOS phenotype, particularly if they are also affected by other disturbances that increase their pretest probability (e.g., osteoporosis/bone fractures). Approximately 70-80% of women with CS present menstrual abnormalities, and PCOS findings are found in 46% of these patients. Diagnostic efforts should strengthen if the clinical picture is severe or of rapid onset in order to ensure the earliest and most appropriate treatment...

Unwanted sexual hair growth has a considerable negative impact on a woman's self-esteem and quality of life. Excessive growth of terminal hair in women in a man-like pattern is defined as hirsutism and affects up to 1 in 7 women. Androgens secreted by the ovary and adrenal are the main regulator of physiological and pathological alterations of skin hair. Hirsutism is the result of the interaction between circulating serum androgens and hair follicles. Hirsutism is the most commonly used clinical diagnostic criterion of hyperandrogenism and majority of hirsutism cases are due to androgen excess...

Differences between males and females are commonly attributed to sexual hormones. Androgens are responsible for the development of primary and secondary sexual characteristics in males, whereas they influence sexual behaviour, glycaemic control, lipid profile, bone metabolism and erythropoiesis in both sexes. In this chapter, we discuss preclinical and clinical data on sex-specific androgen metabolism and androgen effect on body composition.

Androgen excess is often associated with obesity states, at any age of life, because of changes in the pattern of secretion or metabolism of androgens and in their actions at the level of target tissues, particularly the adipose tissue. Androgen excess plays an important role in favouring the expansion of visceral fat, which characterize so-called visceral obesity. Moreover, there is evidence that the combination of androgen excess and obesity may favour the development of metabolic disorders, such as the metabolic syndrome and type 2 diabetes...

Adipose tissue is an important target of androgen action in humans. Androgens exert important effects on adipose tissue biology, including fat mass expansion and distribution, insulin signalling and lipid metabolism. In conditions of female androgen excess such as polycystic ovary syndrome (PCOS), androgens exert metabolically deleterious effects on adipose tissue function in a depot-specific manner. Androgen excess in women is metabolically deleterious, and adverse metabolic effects may be mediated by effects on preadipocyte differentiation and adipocyte hypertrophy...