pituitrin and Diabetic-Nephropathies

The diabetic kidney disease (DKD) is the major cause of the chronic kidney disease (CKD). Enhanced plasma vasopressin (VP) levels have been associated with the pathophysiology of DKD and CKD. Stimulation of VP release in DKD is caused by glucose-dependent reset of the osmostat leading to secondary pathophysiologic effects mediated by distinct VP receptor types. VP is a stress hormone exhibiting the antidiuretic action in the kidney along with broad adaptive effects in other organs. Excessive activation of the vasopressin type 2 (V2) receptor in the kidney leads to glomerular hyperfiltration and nephron loss, whereas stimulation of vasopressin V1a or V1b receptors in the liver, pancreas, and adrenal glands promotes catabolic metabolism for energy mobilization, enhancing glucose production and aggravating DKD. Increasing availability of selective VP receptor antagonists opens new therapeutic windows separating the renal and extra-renal VP effects for the concrete applications. Improved understanding of these paradigms is mandatory for further drug design and translational implementation. The present concise review focuses on metabolic effects of VP affecting DKD pathophysiology.

Topics: Diabetes Mellitus; Diabetic Nephropathies; Glucose; Humans; Receptors, Vasopressin; Renal Insufficiency, Chronic; Vasopressins

Diabetic nephropathy has become the most common cause of chronic kidney disease (CKD). Despite the progress accomplished in therapy, the prevalence of renal disorders remains high. Some modifiable factors driving the increase in incidence of CKD, in diabetes and other settings, might have been overlooked. Consistent evidence supports a role for vasopressin, hydration state, and urine concentration in kidney health.. Plasma vasopressin is elevated in diabetes, even if metabolic control is good. Several epidemiological studies have pointed to a positive association between markers of vasopressin secretion (24-h fluid intake, urine volume, plasma copeptin concentration) and renal function decline in both the community and populations at high risk of CKD, namely, diabetic patients. Research involving animal models also supports a critical causal role of the V2 receptor antidiuretic effects of vasopressin in the early signs of kidney disease associated with type 1 or type 2 diabetes. Key Messages: Data supporting the detrimental effects of chronic vasopressin action on the kidney is consistent in animal models and human observational studies. Since vasopressin secretion can be modulated by water intake, and its actions by selective receptor antagonists, the vasopressin-hydration system could be a potential therapeutic target for the prevention and treatment of diabetic nephropathy. Intervention studies are needed to examine the relevance of lifestyle or pharmacological interventions.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Drinking; Glycopeptides; Humans; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Vasopressins

The prevalence of diabetic kidney disease (DKD) is increasing worldwide. Despite major therapeutic advances in the last decades in DKD, the current standard of care let many people progress to severe stages. Vasopressin secretion is increased in diabetes, and its potential role in the onset and progression of DKD is being re-investigated.. Recently, observational studies evidenced an association between surrogates of vasopressin secretion (daily fluid intake or urine volume, and plasma copeptin concentration) and chronic kidney disease in the community, but also specifically in type 1 and in type 2 diabetes. Causality is strongly supported by a series of studies in rats conducted more than a decade ago, and by additional recent experimental data. The mechanism underlying these adverse effects likely involves the hyperfiltration induced indirectly as a consequence of the tubular effects of the hormone mediated by the V2 receptor.. If chronic vasopressin action on the kidney is detrimental in diabetes as suggested so far, intervention studies should be designed. Available tools include V2 receptor blockade, and changes in daily water intake in vulnerable patients. Safety and effectiveness should be tested, as it is currently done in patients with CKD (NCT01766687).

Topics: Animals; Diabetic Nephropathies; Drinking; Fluid Therapy; Glycopeptides; Humans; Kidney; Rats; Renal Insufficiency, Chronic; Vasopressins

People with chronic kidney disease (CKD) are at risk of severe outcomes, such as end-stage renal disease or cardiovascular disease, and CKD is a globally increasing health burden with a high personal and economic cost. Despite major progresses in prevention and therapeutics in last decades, research is still needed to reverse this epidemic trend. The regulation of water balance and the state of activation of the vasopressin system have emerged as factors tightly associated with kidney health, in the general population but also in specific conditions; among them, various stages of CKD, diabetes and autosomal dominant polycystic kidney disease (ADPKD). Basic science findings and also epidemiological evidence have justified important efforts towards interventional studies supporting causality, and opening therapeutic avenues. On the basis of recent clinical data, the blockade of V2 vasopressin receptors using tolvaptan in patients with rapidly progressing ADPKD has been granted in several countries, and a long-term randomized trial evaluating the effect of an increase in water intake in patients with CKD is on-going.

Topics: Antidiuretic Hormone Receptor Antagonists; Biomarkers; Diabetic Nephropathies; Fluid Therapy; Glycopeptides; Humans; Kidney; Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Renal Insufficiency, Chronic; Vasopressins

Topics: Animals; Atrial Natriuretic Factor; Biological Transport; Bradykinin; Calcium; Calcium Channels; Cyclooxygenase 2; Diabetes Mellitus; Diabetic Nephropathies; Glomerular Filtration Rate; Humans; Kidney Tubules; Membrane Proteins; Muscle Tonus; Muscle, Smooth, Vascular; Nitric Oxide; Prostaglandin-Endoperoxide Synthases; Renal Circulation; Renin-Angiotensin System; Sodium; Vasopressins

Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Aquaporins; Cardiovascular System; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Diuretics; Humans; Risk Factors; Vasopressins

Arterial hypertension and, less often, postural hypotension are frequently associated with diabetes mellitus, and with diabetic complications and death.. To review data on the relationship between hypertension and nephropathy in diabetes mellitus.. We reviewed data on both retinopathy and nephropathy in hypertensive diabetic patients. Data suggesting that vasopressin levels might affect blood pressure in upright patients with postural hypotension due to cardiocirculatory diabetic neuropathy were also examined. Antihypertensive treatment during different phases of diabetic nephropathy in insulin-dependent diabetes was reviewed.. The data showed that hydrochlorothiazide and nitrendipine reduce urinary protein excretion in parallel with a reduction in blood pressure. However, the decreases in urinary protein excretion induced by captopril are not correlated with a reduction in blood pressure and may be related to decreases in intraglomerular pressure found in patients with mild renal failure taking furosemide. Domperidone, a peripherally acting dopaminergic antagonist is an additional therapeutic option for the treatment of diabetic postural hypotension.

Topics: Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertension, Renal; Hypotension, Orthostatic; Male; Vasopressins

Topics: Adrenal Gland Diseases; Diabetes Insipidus; Diabetic Nephropathies; Diagnosis, Differential; Diuresis; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyponatremia; Kidney; Kidney Concentrating Ability; Kidney Diseases; Natriuresis; Osmolar Concentration; Urologic Diseases; Vasopressins; Water-Electrolyte Balance

Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors.. DKD resistors had lower copeptin (95% CI: 4.0 [3.4-4.8] pmol/l) compared to DKD (5.8 [4.5-7.6] pmol/l, p = 0.02) and HC (4.8 [4.1-5.5] pmol/l, p = 0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: -0.32, p = 0.01) and higher renin concentration (r: 0.40, p = 0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (β ± SE: -6.9 ± 3.4, p = 0.04).. In longstanding type 1 diabetes, copeptin was associated with intrarenal renin-angiotensin-aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.

Topics: Adult; Angiotensin II; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Glycopeptides; Hemodynamics; Humans; Renin; Renin-Angiotensin System; Vascular Resistance; Vasopressins

Arginine vasopressin (AVP) plays an important role in the pathophysiology of Diabetes Mellitus (DM) and its related complications like diabetic nephropathy. Copeptin is considered as a reliable surrogate biomarker of AVP. If raised levels of copeptin in diabetic patients are detected earlier, prognosis of DM can be improved by timely modulating the treatment strategy.. The study is therefore planned to assess copeptin levels in different groups of DM and in healthy controls to suggest a better and reliable biomarker for progressive stages of DM.. Subjects were recruited as controls, pre diabetes, DM without nephropathy and diabetic nephropathy. Serum copeptin levels were measured by ELISA. While, Blood Urea Nitrogen (BUN), creatinine, Glycosylated Hemoglobin (HbA1c) and spot urinary albumin creatinine ratio (UACR) were done using spectrophotometry. Statistical analysis was done using ANOVA and Pearson's correlation tests on SPSS.. The average copeptin levels were 215.096 pg/mL. Copeptin levels were significantly elevated in subjects with positive family history of DM (p = 0.025), levels were also raised in pre diabetes kpatients (252.85 pg/mL) as compared to other groups. Copeptin levels were also correlated with HbA1c r = 0.171 (p = 0.101), BUN r = 0.244 (p = 0.007), creatinine r = 0.215 (p = 0.018), UACR r = 0.375 (p = <0.001) and GFR r = 0.215 (p = <0.019).. The significant correlation of copeptin with diabetic and renal biomarkers, along with its positive association with family history of DM support its' role as an early and reliable biomarker of DM and its associated nephropathy.

Topics: Adolescent; Adult; Aged; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycopeptides; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Neurophysins; Prognosis; Protein Precursors; Vasopressins; Young Adult

In normal rats, vasopressin and hyperosmolality enhance urea permeability (P(urea)) in the terminal, but not in the initial inner medullary collecting duct (IMCD), a process thought to occur through the UT-A1 urea transporter. In the terminal IMCD, UT-A1 is detected as 97- and 117-kDa glycoproteins. However, in the initial IMCD, only the 97-kDa form is detected. During streptozotocin-induced diabetes mellitus, UT-A1 protein abundance is increased, and the 117-kDa UT-A1 glycoprotein appears in the initial IMCD. We hypothesize that the 117-kDa glycoprotein mediates the vasopressin- and osmolality-induced changes in P(urea). Thus, in the present study, we measured P(urea) in in vitro perfused initial IMCDs from diabetic rats by imposing a 5 mM bath-to-lumen urea gradient without any osmotic gradient. Basal P(urea) was similar in control vs. diabetic rats (3 +/- 1 vs. 5 +/- 1 x 10(-5) cm/s, n = 4, P = not significant). Vasopressin (10 nM) significantly increased P(urea) to 16 +/- 5 x 10(-5) cm/s (n = 4, P < 0.05) in diabetic but not in control rats. Forskolin (10 microM, adenylyl cyclase activator) also significantly increased P(urea) in diabetic rats. In contrast, increasing osmolality to 690 mosmol/kg H2O did not change P(urea) in diabetic rats. We conclude that initial IMCDs from diabetic rats have vasopressin- and forskolin-, but not hyperosmolality-stimulated P(urea). The appearance of vasopressin-stimulated P(urea) in initial IMCDs correlates with an increase in UT-A1 protein abundance and the appearance of the 117-kDa UT-A1 glycoprotein in this region during diabetes. This suggests that the 117-kDa UT-A1 glycoprotein is necessary for vasopressin-stimulated urea transport.

Topics: Animals; Biological Transport, Active; Blood Glucose; Cell Membrane Permeability; Colforsin; Diabetic Nephropathies; Kidney Medulla; Kidney Tubules, Collecting; Male; Membrane Transport Proteins; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Renal Agents; Urea; Urea Transporters; Vasopressins

Although secondary end-organ damage in diabetes has generally been thought to result from long-term passive shunting of excess glucose through alternative metabolic pathways, recent studies have elucidated a second mechanism of pathogenesis that involves active changes in gene expression in neurons of the CNS. These changes in gene expression result in molecular and functional changes that can become maladaptive over time. In this review, we examine two neuronal populations in the brain that have been studied in human beings and animal models of diabetes. First, we discuss overactivation of magnocellular neurosecretory cells within the hypothalamus and how it relates to the development of diabetic nephropathy. And second, we describe how changes in hippocampal synaptic plasticity can lead to cognitive and behavioural deficits in chronic diabetes. Changes in neuronal gene expression in diabetes represent a new pathway for diabetic pathogenesis. This pathway may hold clues for the development of therapies that, via the targeting of neurons, can slow or prevent the development of diabetic end-organ damage.

Topics: Animals; Cognition Disorders; Diabetes Mellitus; Diabetic Nephropathies; Gene Expression; Hippocampus; Humans; Hyperglycemia; Hypothalamus; Neuronal Plasticity; Neurons; Vasopressins

Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P < 0.01) but failed to increase in DI-DM. Urinary albumin excretion more than doubled in LE-DM but rose by only 34% in DI-DM rats (P < 0.05). Kidney hypertrophy was also less intense in DI-DM than in LE-DM (P < 0.001). These results suggest that VP plays a critical role in diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

Topics: Albuminuria; Animals; Creatinine; Diabetes Insipidus; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Glomerular Filtration Rate; Glycosuria; Hypertrophy; Kidney; Kidney Failure, Chronic; Male; Nephrectomy; Organ Size; Rats; Rats, Brattleboro; Rats, Long-Evans; Vasopressins

alpha-Human atrial natriuretic peptide (ANP) concentrations were measured in 11 diabetic patients with uremia and in 16 nondiabetic uremic controls undergoing renal transplantation after preanesthetic volume expansion with 1000 ml saline solution within 10 min. Two diabetic and seven nondiabetic patients received grafts from living donors and the rest from cadaveric donors. Volume expansion induced a significant increase in the cardiac filling pressures (P less than 0.001), which were kept at that level especially at declamping, which was preceded by mannitol infusion. The baseline mixed venous ANP levels were significantly higher in the diabetic (252 +/- 6 pg/ml) than in the nondiabetic group (103 +/- 14 pg/ml; P less than 0.05). In the nondiabetic group, ANP increased to 177 +/- 40 pg/ml as a response to volume loading (P less than 0.05); it was not clearly changed in the diabetic group. Arterial ANP increased from 267 +/- 55 to 343 +/- 75 pg/ml in the diabetic group (P less than 0.05 and from 102 +/- 17 to 147 +/- 31 pg/ml in the nondiabetic group (P less than 0.05). During transplantation, mixed venous ANP decreased to 125 +/- 55 pg/ml in the diabetic and to 80 +/- 10 pg/ml in the nondiabetic group (P less than 0.001). About 30% of circulating ANP was taken up by the transplant irrespective of postoperative graft function. Two patients in each group showed delayed diuresis requiring postoperative dialysis therapy (22% of all cadaveric transplantations). ANP levels at declamping had no correlation to the outcome of kidney function.

Topics: Adult; Atrial Natriuretic Factor; Blood Volume; Diabetic Nephropathies; Female; Humans; Kidney Transplantation; Lactates; Lactic Acid; Male; Renin; Uremia; Vasopressins

To define the importance of renal prostaglandins in nephrogenic diabetes insipidus (NDI), diuresis and the urinary excretion of PGE2 and PGF2 alpha were studied in a patient with NDI before and during inhibition of endogenous prostaglandin synthesis with either indomethacin (IND) or acetyl-salicylic acid (ASA). The excretion rates of PGE2 and PGF2 alpha were in the low normal range for the patient's age group, remained unchanged during 6 h of fluid deprivation and were suppressed by IND (150 mg/day), ASA (3 g/day), and by the combination of IND and hydrochlorothiazide (HCT, 50 mg/day). However, whereas IND, HCT, and the combination of IND and HCT reduced diuresis ASA did not. Free water clearance as determined during fluid deprivation remained positive during each phase of therapy. These data fail to demonstrate a direct effect of endogenous ADH on renal prostaglandin synthesis in NDI. The ineffectiveness of ASA to reduce diuresis indicates that indomethacin affects diuresis in NDI by a mechanism other than inhibition of cyclooxygenase.

Topics: Adolescent; Aspirin; Diabetes Insipidus; Diabetic Nephropathies; Dinoprost; Dinoprostone; Diuresis; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Indomethacin; Male; Osmolar Concentration; Prostaglandins E; Prostaglandins F; Sodium; Thirst; Vasopressins

A report is presented of a male infant with nephrogenic diabetes insipidus type I. A low-solute-load diet and large fluid intake were not able to prevent hypertonic dehydration and to control the disease. It responded within 3 days to indomethacin (3 mg/kg body weight), a prostaglandin synthetase inhibitor. The boy is doing well on this regimen and no side-effects have been observed after 2 years of treatment. Hitherto only a few case reports have been published on this therapeutic regimen, but all confirm the high efficacy of prostaglandin synthesis inhibition as the treatment of choice in nephrogenic diabetes insipidus.

Topics: Diabetes Insipidus; Diabetic Nephropathies; Fluid Therapy; Humans; Indomethacin; Infant; Male; Prostaglandin Antagonists; Prostaglandins; Vasopressins

Three generations of a family with nephrogenic diabetes insipidus were studied. Treatment of a male infant patient with hydrochlorothiazide normalized the serum sodium concentration and improved the clinical condition, but did not influence the polyuria. Although indomethacin alone was without long-term effect, combined therapy with hydrochlorothiazide and indomethacin regulated serum sodium better than hydrochlorothiazide alone. The renin-aldosterone system was not activated in healthy carriers or patients with nephrogenic diabetes insipidus neither in infancy during severe hypernatremic dehydration nor in adult patients.

Topics: Adolescent; Adult; Diabetes Insipidus; Diabetic Nephropathies; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Indomethacin; Infant; Male; Renin-Angiotensin System; Sodium; Vasopressins

Topics: Animals; Diabetes Insipidus; Diabetic Nephropathies; Diagnosis, Differential; Drinking; Female; Horse Diseases; Horses; Polyuria; Vasopressins

Nephrogenic diabetes insipidus occurred in a 7-year-old child who had received a high dose of demethylchlortetracycline hydrochloride (DMC). The patient had a relatively elevated urinary sodium concentration in addition to isosthenuria. The nephrogenic diabetes insipidus was completely reversible within one month after cessation of DMC administration.

Topics: Child; Demeclocycline; Diabetes Insipidus; Diabetic Nephropathies; Humans; Male; Vasopressins

The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and (PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.

Topics: Adolescent; Child; Child, Preschool; Cyclic AMP; Diabetes Insipidus; Diabetic Nephropathies; Humans; Infant; Kidney Failure, Chronic; Male; Parathyroid Hormone; Vasopressins

Topics: Animals; Body Weight; Diabetes Insipidus; Diabetic Nephropathies; Female; Food Preferences; Kidney; Potassium; Rats; Rats, Inbred Strains; Vasopressins; Water-Electrolyte Balance

Topics: Blood Volume; Cell Membrane Permeability; Chlorothiazide; Chlorpropamide; Diabetes Insipidus; Diabetic Nephropathies; Furosemide; Glomerular Filtration Rate; Humans; Hypertonic Solutions; Injections, Intravenous; Nicotine; Osmolar Concentration; Sodium Chloride; Urine; Vasopressins

Topics: Adult; Diabetic Nephropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypophysectomy; Insulin; Male; Testosterone; Vasopressins

Topics: Adult; Diabetes Insipidus; Diabetic Nephropathies; Diagnosis, Differential; Female; Humans; Pregnancy; Pregnancy in Diabetics; Urine; Urography; Vasopressins

Topics: Adult; Animals; Child; Diabetes Insipidus; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Infant; Male; Middle Aged; Polyuria; Rats; Vasopressins

Topics: Adrenocorticotropic Hormone; Cushing Syndrome; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetic Nephropathies; Endocrine Glands; Endocrine System Diseases; Hormones; Humans; Hypercalcemia; Hypothyroidism; Liver Diseases; Lung Neoplasms; Neoplasms; Nephrosis; Polycythemia; Pseudopseudohypoparathyroidism; Vasopressins