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Pflugers Archiv : European Journal of... Aug 2022Saving body water by optimal reabsorption of water filtered by the kidney leading to excretion of urine with concentrations of solutes largely above that of plasma... (Review)
Review
Saving body water by optimal reabsorption of water filtered by the kidney leading to excretion of urine with concentrations of solutes largely above that of plasma allowed vertebrate species to leave the aquatic environment to live on solid ground. Filtered water is reabsorbed for 70% and 20% by proximal tubules and thin descending limbs of Henle, respectively. These two nephron segments express the water channel aquaporin-1 located along both apical and basolateral membranes. In the proximal tubule, the paracellular pathway accounts for at least 30% of water reabsorption, and the tight-junction core protein claudin-2 plays a key role in this permeability. The ascending limb of Henle and the distal convoluted tubule are impermeant to water and are responsible for urine dilution. The water balance is adjusted along the collecting system, i.e. connecting tubule and the collecting duct, under the control of arginine-vasopressin (AVP). AVP is synthesized by the hypothalamus and released in response to an increase in extracellular osmolality or stimulation of baroreceptors by decreased blood pressure. In response to AVP, aquaporin-2 water channels stored in subapical intracellular vesicles are translocated to the apical plasma membrane and raise the water permeability of the collecting system. The basolateral step of water reabsorption is mediated by aquaporin-3 and -4, which are constitutively expressed. Drugs targeting water transport include classical diuretics, which primarily inhibit sodium transport; the new class of SGLT2 inhibitors, which promotes osmotic diuresis and the non-peptidic antagonists of the V2 receptor, which are pure aquaretic drugs. Disturbed water balance includes diabetes insipidus and hyponatremias. Diabetes insipidus is characterized by polyuria and polydipsia. It is either related to a deficit in AVP secretion called central diabetes insipidus that can be treated by AVP analogs or to a peripheral defect in AVP response called nephrogenic diabetes insipidus. Diabetes insipidus can be either of genetic origin or acquired. Hyponatremia is a common disorder most often related to free water excess relying on overstimulated or inappropriate AVP secretion. The assessment of blood volume is key for the diagnosis and treatment of hyponatremia, which can be classified as hypo-, eu-, or hypervolemic.
Topics: Aquaporin 2; Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Humans; Hyponatremia; Water
PubMed: 35678906
DOI: 10.1007/s00424-022-02712-9 -
Pituitary Apr 2021Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt... (Review)
Review
PURPOSE
Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but can also reflect several physiological adaptive mechanisms in the postoperative phase. These may be difficult to distinguish from and might coincide with DI. The difficulty to distinguish DI from other causes of postoperative polyuria might explain the high variation in incidence rates. This limits interpretation of outcomes, in particular complication rates between centers, and may lead to unnecessary treatment. Aim of this review is to determine a pathophysiologically sound and practical definition of DI for uniform outcome evaluations and treatment recommendations.
METHODS
This study incorporates actual data and the experience of our center and combines this with a review of literature on pathophysiological mechanisms and definitions used in clinical studies reporting of postoperative DI.
RESULTS
The occurrence of excessive thirst and/or hyperosmolality or hypernatremia are the best indicators to discriminate between pathophysiological symptoms and signs of DI and other causes. Urine osmolality distinguishes DI from osmotic diuresis.
CONCLUSIONS
To improve reliability and comparability we propose the following definition for postoperative DI: polyuria (urine production > 300 ml/hour for 3 h) accompanied by a urine specific gravity (USG) < 1.005, and at least one of the following symptoms: excessive thirst, serum osmolality > 300 mosmol/kg, or serum sodium > 145 mmol/L. To prevent unnecessary treatment with desmopressin, we present an algorithm for the diagnosis and treatment of postoperative DI.
Topics: Diabetes Insipidus; Humans; Pituitary Neoplasms; Postoperative Period; Vasopressins
PubMed: 32990908
DOI: 10.1007/s11102-020-01083-7 -
Handbook of Clinical Neurology 2021Central diabetes insipidus (CDI) occurs secondary to deficient synthesis or secretion of arginine vasopressin peptide from the hypothalamo-neurohypophyseal system (HNS).... (Review)
Review
Central diabetes insipidus (CDI) occurs secondary to deficient synthesis or secretion of arginine vasopressin peptide from the hypothalamo-neurohypophyseal system (HNS). It is characterized by polydipsia and polyuria (urine output >30mL/kg/day in adults and >2l/m/24h in children) of dilute urine (<250mOsm/L). It can result from any pathology affecting one or more components of the HNS including the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, and median eminence of the hypothalamus, infundibulum, stalk or the posterior pituitary gland. MRI is the imaging modality of choice for evaluation of the hypothalamic-pituitary axis (HPA), and a dedicated pituitary or sella protocol is essential. CT can provide complimentary diagnostic information and is also of value when MRI is contraindicated. The most common causes are benign or malignant neoplasia of the HPA (25%), surgery (20%), and head trauma (16%). No cause is identified in up to 30% of cases, classified as idiopathic CDI. Knowledge of the anatomy and physiology of the HNS is crucial when evaluating a patient with CDI. Establishing the etiology of CDI with MRI in combination with clinical and biochemical assessment facilitates appropriate targeted treatment. This chapter illustrates the wide variety of causes and imaging correlates of CDI on neuroimaging, discusses the optimal imaging protocols, and revises the detailed neuroanatomy required to interpret these studies.
Topics: Adult; Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Humans; Magnetic Resonance Imaging; Neuroimaging; Pituitary Gland; Pituitary Gland, Posterior
PubMed: 34238459
DOI: 10.1016/B978-0-12-820683-6.00016-6 -
Annales D'endocrinologie Oct 2016Diabetes insipidus is a syndrome that associates both hypotonic polyuria and polydipsia, due to insufficient or ineffective arginine vasopressin (AVP) synthesis, or to... (Review)
Review
Diabetes insipidus is a syndrome that associates both hypotonic polyuria and polydipsia, due to insufficient or ineffective arginine vasopressin (AVP) synthesis, or to AVP resistance. The diagnosis between central/renal origin, or an abnormal thirst regulation (primary polydipsia) is required to organize an adapted management. Because water deprivation tests are not reliable, it's often based on medical history, response to treatment and MRI. Copeptin is an AVP precursor which could be very helpful for the diagnosis. Its basal dosage may identify nephrogenic DI whereas osmotic stimulated dosage would discriminate central DI and primary polydipsia. Central DI is quite frequent after pituitary surgeries or traumatic brain injuries, and often transient. In case of early diagnosis and familial history of DI, a mutation of AVP gene is suspected, most of the time autosomal dominant. MRI is required to identify the other causes, i.e. tumors and inflammatory diseases (sarcoidosis, histiocytosis, hypophysitis). An advanced evaluation is required before idiopathic DI be retained, especially if a thickening of pituitary stalk is observed. The treatment of central DI is mainly based on lyophilisate of desmopressin administration.
Topics: Arginine Vasopressin; Diabetes Insipidus; Humans; Postoperative Complications
PubMed: 28645353
DOI: 10.1016/S0003-4266(17)30073-2 -
Annales D'endocrinologie Aug 2022Lithium is an efficient treatment of bipolar disorder. Besides renal insufficiency, many endocrine side effects are described such as the occurrence of thyroid... (Review)
Review
Lithium is an efficient treatment of bipolar disorder. Besides renal insufficiency, many endocrine side effects are described such as the occurrence of thyroid disorders, hypercalcaemia and nephrogenic diabetes insipidus. Lithium inhibits the secretion of thyroid hormones. The prevalence of goiter is 4 times more common in Lithium-treated patients compared as to the general population. Hypothyroidism (8-20%) is more frequent in women and in case of pre-existing thyroid autoimmunity. Grave's disease and other hyperthyroidisms are sometimes reported. Lithium stimulates the proliferation of parathyroid cells by activating the Wnt pathway. An increase in serum calcium and PTH is described in patients treated with Lithium with a 4 to 6-fold higher risk of primary hyperparathyroidism than in the general population. Nevertheless, 24-hour urine calcium is not often increased, and the phenotype can mimic a hypercalcemia-hypocalciuria syndrome that may regress with Lithium discontinuation. Surgery should be cautious since parathyroid hyperplasia is more common than parathyroid adenoma. Nephrogenic diabetes insipidus is frequently reported and may be debilitating, sometimes intricated with severe dehydration, hypernatremia, and acute renal insufficiency. Nephrogenic diabetes insipidus is not generally reversible after Lithium discontinuation, especially in patients who have chronic kidney disease due to interstitial tubule nephritis. In conclusion, clinical assessment (goiter, diuresis) and biological monitoring of serum calcium, sodium creatinine, TSH and lithium are recommended in patients receiving Lithium therapy. The risk of Lithium discontinuation in case of side effects should be weighed against the psychological risk, and must be discussed with the psychiatrist.
Topics: Calcium; Diabetes Insipidus, Nephrogenic; Endocrinologists; Female; Goiter; Humans; Hypercalcemia; Hyperparathyroidism; Lithium; Lithium Compounds
PubMed: 35074396
DOI: 10.1016/j.ando.2022.01.001 -
Current Opinion in Pediatrics Apr 2017In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite elevated concentrations of the antidiuretic hormone arginine-vasopressin. In... (Review)
Review
PURPOSE OF REVIEW
In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite elevated concentrations of the antidiuretic hormone arginine-vasopressin. In congenital NDI, polyuria and polydipsia are present from birth and should be immediately recognized to avoid severe episodes of dehydration. Unfortunately, NDI is still often recognized late after a 'diagnostic odyssey' involving false leads and dangerous treatments.Once diagnosed, appropriate treatment can be started. Moreover, laboratory studies have identified promising new compounds, which may help achieve urinary concentration independent of vasopressin.
RECENT FINDINGS
MAGED2 mutations caused X-linked polyhydramnios with prematurity and a severe but transient form of antenatal Bartter's syndrome.We distinguish two types of hereditary NDI: a 'pure' type with loss of water only and a complex type with loss of water and ions. Mutations in the AVPR2 or AQP2 genes, encoding the vasopressin V2 receptor and the water channel Aquaporin2, respectively, lead to a 'pure' NDI with loss of water but normal conservation of ions. Mutations in genes that encode membrane proteins involved in sodium chloride reabsorption in the thick ascending limb of Henle's loop lead to Bartter syndrome, a complex polyuric-polydipsic disorder often presenting with polyhydramnios. A new variant of this was recently identified: seven families were described with transient antenatal Bartter's syndrome, polyhydramnios and MAGED2 mutations.Multiple compounds have been identified experimentally that may stimulate urinary concentration independently of the vasopressin V2 receptor. These compounds may provide new treatments for patients with X-linked NDI.
SUMMARY
A plea for early consideration of the diagnosis of NDI, confirmation by phenotypic and/or genetic testing and appropriate adjustment of treatment in affected patients.
Topics: Combined Modality Therapy; Dehydration; Diabetes Insipidus, Nephrogenic; Female; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Infant; Male; Mutation; Rare Diseases; Receptors, Vasopressin; Risk Assessment
PubMed: 28134709
DOI: 10.1097/MOP.0000000000000473 -
Medicina 2022Lithium carbonate is a commonly prescribed drug for bipolar disorders. In addition to its action on the central nervous system, lithium has systemic effects on multiple...
Lithium carbonate is a commonly prescribed drug for bipolar disorders. In addition to its action on the central nervous system, lithium has systemic effects on multiple organs such as kidney, heart, motor end plate, thyroid and parathyroid glands. It can cause hypothyroidism, hyperthyroidism, goiter and ophthalmopathy by different mechanisms. It increases intrathyroid iodine content or compete for iodine transport, resulting in low iodine uptake by the thyroid. It also inhibits the coupling of iodotyrosine residues to form iodothyronines and inhibits the release of T4 and T3. Lithium has direct actions on parathyroid glands by antagonizing the calcium sensing receptor, which may induce hypercalcemia or even hyperparathyroidism, requiring surgery in some cases. Furthermore, it inhibits the expression of aquaporins, mainly aquaporin 2, in the renal collecting tubule by unknown mechanisms leading to nephrogenic diabetes insipidus. This adverse effect is usually reversible after drug withdrawal. However, some patients may present irreversible kidney damage due to chronic interstitial nephropathy.
Topics: Diabetes Insipidus, Nephrogenic; Humans; Hypercalcemia; Hyperparathyroidism; Lithium; Parathyroid Glands; Thyroid Gland
PubMed: 35037871
DOI: No ID Found -
Best Practice & Research. Clinical... Jun 2015Central diabetes insipidus (CDI) is a complex and heterogeneous clinical syndrome affecting the hypothalamic-neurohypophyseal network and water balance. A recent... (Review)
Review
Central diabetes insipidus (CDI) is a complex and heterogeneous clinical syndrome affecting the hypothalamic-neurohypophyseal network and water balance. A recent national surveillance in Denmark showed a prevalence rate of twenty-three CDI patients per 100,000 inhabitants in five years. The differential diagnosis between several presenting conditions with polyuria and polydipsia is puzzling, and the etiological diagnosis of CDI remains a challenge before the identification of an underlying cause. For clinical practice, a timely diagnosis for initiating specific treatment in order to avoid central nervous system damage, additional pituitary defects and the risk of dissemination of germ cell tumor is advisable. Proper etiological diagnosis can be achieved via a series of steps that start with careful clinical observation of several signs and endocrine symptoms and then progress to more sophisticated imaging tools. This review summarizes the best practice and approach for the diagnosis and treatment of patients with CDI.
Topics: Antidiuretic Agents; Brain Injuries; Brain Neoplasms; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Disease Management; Histiocytosis, Langerhans-Cell; Humans; Magnetic Resonance Imaging; Neoplasms, Germ Cell and Embryonal
PubMed: 26051300
DOI: 10.1016/j.beem.2015.04.013 -
Molecular and Cellular Endocrinology Jan 2023Nephrogenic diabetes insipidus is defined as an inability to concentrate urine due to a complete or partial alteration of the renal tubular response to arginine... (Review)
Review
Nephrogenic diabetes insipidus is defined as an inability to concentrate urine due to a complete or partial alteration of the renal tubular response to arginine vasopressin hormone, resulting in excessive diluted urine excretion. Hereditary forms are caused by molecular defects in the genes encoding either of the two main renal effectors of the arginine vasopressin pathway: the AVPR2 gene, which encodes for the type 2 vasopressin receptor, or the AQP2 gene, which encodes for the water channel aquaporin-2. About 90% of cases of nephrogenic diabetes insipidus result from loss-of-function variants in the AVPR2 gene, which are inherited in a X-linked recessive manner. The remaining 10% of cases result from loss-of-function variants in the AQP2 gene, which can be inherited in either a recessive or a dominant manner. The main symptoms of the disease are polyuria, chronic dehydration and hypernatremia. These symptoms usually occur in the first year of life, although some patients present later. Diagnosis is based on abnormal response in urinary osmolality after water restriction and/or administration of exogenous vasopressin. Treatment involves ensuring adequate water intake on demand, possibly combined with thiazide diuretics, non-steroidal anti-inflammatory drugs, and a low-salt and protein diet. In this review, we provide an update on current understanding of the molecular basis of inherited nephrogenic insipidus diabetes.
Topics: Humans; Aquaporin 2; Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; Mutation; Receptors, Vasopressin
PubMed: 36460218
DOI: 10.1016/j.mce.2022.111825 -
JAAPA : Official Journal of the... Aug 2022Each year, nearly one-fifth of adults in the United States are prescribed at least one psychotropic medication. An increased trend in psychiatric polypharmacy has...
Each year, nearly one-fifth of adults in the United States are prescribed at least one psychotropic medication. An increased trend in psychiatric polypharmacy has heightened awareness of drug-drug interactions and the tracking of adverse drug reactions. This article describes a patient who developed concomitant neuroleptic malignant syndrome (NMS) and nephrogenic diabetes insipidus during cross-titration of his antipsychotics while on lithium. The patient's mild form of NMS in turn caused hypovolemia and acute kidney injury. This case study highlights the dangers of polypharmacy and how it can obscure the presentation of even classic adverse reactions.
Topics: Adult; Antipsychotic Agents; Diabetes Insipidus; Diabetes Mellitus; Drug Interactions; Humans; Neuroleptic Malignant Syndrome; Polypharmacy
PubMed: 35881715
DOI: 10.1097/01.JAA.0000840488.74228.46