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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 -
The Lancet. Diabetes & Endocrinology Jul 2023Disruptions of the hypothalamic-pituitary axis can cause an arginine vasopressin deficiency, also known as central diabetes insipidus. Patients with this condition are... (Randomized Controlled Trial)
Randomized Controlled Trial
Oxytocin in response to MDMA provocation test in patients with arginine vasopressin deficiency (central diabetes insipidus): a single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial.
BACKGROUND
Disruptions of the hypothalamic-pituitary axis can cause an arginine vasopressin deficiency, also known as central diabetes insipidus. Patients with this condition are at high risk of additional oxytocin deficiency owing to the close anatomical proximity of oxytocin-producing neurons; however, no conclusive evidence for such a deficiency has been reported. We aimed to use 3,4-methylenedioxymethamphetamine (MDMA, also known as ecstasy), a strong activator of the central oxytocinergic system, as a biochemical and psychoactive provocation test to investigate oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus).
METHODS
This single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial included patients with arginine vasopressin deficiency (central diabetes insipidus) and healthy controls (matched 1:1 by age, sex, and BMI) and was conducted at the University Hospital Basel, Basel, Switzerland. We used block randomisation to assign participants to receive either a single oral dose of MDMA (100 mg) or placebo in the first experimental session; patients received the opposite treatment at the next session, with a wash-out period of at least 2 weeks between the two sessions. Participants and investigators assessing the outcomes were masked to assignment. Oxytocin concentrations were measured at 0, 90, 120, 150, 180, and 300 min after MDMA or placebo. The primary outcome was the area under the plasma oxytocin concentration curve (AUC) after drug intake. The AUC was compared between groups and conditions using a linear mixed-effects model. Subjective drug effects were assessed throughout the study using ten-point visual analogue scales. Acute adverse effects were assessed before and 360 min after drug intake using a 66-item list of complaints. This trial is registered with ClinicalTrials.gov, NCT04648137.
FINDINGS
Between Feb 1, 2021, and May 1, 2022, we recruited 15 patients with arginine vasopressin deficiency (central diabetes insipidus) and 15 healthy controls. All participants completed the study and were included in the analyses. In healthy controls, median plasma oxytocin concentration was 77 pg/mL (IQR 59-94) at baseline and increased by 659 pg/mL (355-914) in response to MDMA, resulting in an AUC of 102 095 pg/mL (41 782-129 565); in patients, baseline oxytocin concentration was 60 pg/mL (51-74) and only slightly increased by 66 pg/mL (16-94) in response to MDMA, resulting in an AUC of 6446 pg/mL (1291-11 577). The effect of MDMA on oxytocin was significantly different between groups: the AUC for oxytocin was 82% (95% CI 70-186) higher in healthy controls than in patients (difference 85 678 pg/mL [95% CI 63 356-108 000], p<0·0001). The increase in oxytocin in healthy controls was associated with typical strong subjective prosocial, empathic, and anxiolytic effects, whereas only minimal subjective effects were observed in patients, in agreement with the lack of increase in oxytocin concentrations. The most frequently reported adverse effects were fatigue (eight [53%] healthy controls and eight [53%] patients), lack of appetite (ten [67%] healthy controls and eight [53%] patients), lack of concentration (eight [53%] healthy controls and seven [47%] patients), and dry mouth (eight [53%] healthy controls and eight [53%] patients). In addition, two (13%) healthy controls and four (27%) patients developed transient mild hypokalaemia.
INTERPRETATION
These findings are highly suggestive of clinically meaningful oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus), laying the groundwork for a new hypothalamic-pituitary disease entity.
FUNDING
Swiss National Science Foundation, Swiss Academy of Medical Sciences, and the G&J Bangerter-Rhyner Foundation.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Diabetes Insipidus, Neurogenic; Oxytocin; Cross-Over Studies; Case-Control Studies; Double-Blind Method; Arginine; Diabetes Mellitus
PubMed: 37192642
DOI: 10.1016/S2213-8587(23)00120-1 -
Neurosurgery Clinics of North America Oct 2019Sodium perturbations are a common complication after pituitary surgery, with hyponatremia being the most frequent. Postoperative assessments should be tailored to the... (Review)
Review
Sodium perturbations are a common complication after pituitary surgery, with hyponatremia being the most frequent. Postoperative assessments should be tailored to the early and late periods, and monitoring sodium perturbations is recommended. Cerebral salt wasting is rare after pituitary surgery, and diagnosis and management can be challenging. Providing patient counseling and close postoperative follow-up is important to effectively manage diabetes insipidus and reduce hospital readmissions due to sodium perturbations.
Topics: Adenoma; Diabetes Insipidus; Homeostasis; Humans; Hypernatremia; Hyponatremia; Pituitary Neoplasms; Postoperative Complications; Sodium
PubMed: 31471059
DOI: 10.1016/j.nec.2019.05.011 -
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 -
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 -
Annales D'endocrinologie May 2023Lithium is a cation, similar to sodium and potassium, affecting ion transport. It is used in the medical field as a treatment of bipolar disorders. The main endocrine...
Lithium is a cation, similar to sodium and potassium, affecting ion transport. It is used in the medical field as a treatment of bipolar disorders. The main endocrine complications of lithium treatment affect thyroid and parathyroid glands, in association with renal complications. Thyroid adverse effects, which are more frequent in women, comprise hypothyroidism, goiter, or sometimes hyperthyroidism, through interference with the iodine symporter. The increase in thyroid volume is early. Prevalence of goiter is 4 times higher than in the general population and hypothyroidism (8-20%) more frequent in case of pre-existing thyroid autoimmunity. Hyperthyroidism likely to worsen mood is reported in 5% of cases but the causal link to lithium is unproven. An increase in serum calcium and PTH occurs in 30% of cases, as lithium stimulates parathyroid cell proliferation by activating the Wnt pathway. The risk of hyperparathyroidism, by adenoma and especially by hyperplasia, is 5 times higher than in the general population, with the particularity of frequent low urine calcium by action on the calcium-sensing receptor (CaSR). Renal complications include risk of acute or chronic renal failure and nephrogenic diabetes insipidus, which is a factor for hypernatremia and hypercalcemia through dehydration. Nephrogenic diabetes insipidus is not always reversible after lithium therapy discontinuation. Metabolically, weight gain can be observed, but rather less than with other psychotropic drugs, and lithium does not in itself induce diabetes. At pituitary level, corticotropic activation is frequent, but implicating the disease rather than lithium. Lithium treatment induces little or no hyperprolactinemia. Regular monitoring of serum calcium, the ionogram, creatinine and TSH is recommended in lithium treatment.
Topics: Humans; Female; Lithium; Diabetes Insipidus, Nephrogenic; Calcium; Lithium Compounds; Hyperthyroidism; Hypothyroidism; Goiter; Iatrogenic Disease
PubMed: 36963758
DOI: 10.1016/j.ando.2023.03.004 -
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 -
Best Practice & Research. Clinical... Sep 2020In the majority of cases, hereditary neurohypophyseal diabetes insipidus (DI) is a monogenic disorder caused by mutations in the AVP gene. Dominant transmission is by... (Review)
Review
In the majority of cases, hereditary neurohypophyseal diabetes insipidus (DI) is a monogenic disorder caused by mutations in the AVP gene. Dominant transmission is by far the most common form. In these patients, symptoms develop gradually at various ages during childhood, progressing with complete penetrance to polyuria and polydipsia that is usually severe. In autosomal dominant neurohypophyseal DI (ADNDI), the mutant prohormone is folding deficient and consequently retained in the ER, where it forms amyloid-like fibrillar aggregates. Degradation by proteasomes occurs, but their clearance capacity appears to be insufficient. Postmortem studies in affected individuals suggest a neurodegenerative process confined to vasopressinergic neurons. Other forms of genetic neurohypophyseal DI include the very rare autosomal recessive type, also caused by mutations in the AVP gene, and complex multiorgan disorders, such as Wolfram syndrome. In all individuals where a congenital form of DI is suspected, including nephrogenic types, genetic analysis should be performed.
Topics: Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Genetic Predisposition to Disease; Humans; Mutation; Neurophysins; Protein Precursors; Vasopressins
PubMed: 32712149
DOI: 10.1016/j.beem.2020.101432 -
The Ulster Medical Journal Sep 2021The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual... (Review)
Review
The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual field defects, cranial nerve palsies, anterior pituitary dysfunction and/ or diabetes insipidus. Management options include surgery or radiotherapy, chemotherapy/immunotherapy or a conservative approach. The pituitary should not be overlooked as a site for metastasis in patients with known cancer and can be the first presentation of neoplastic disease in some patients. Given that patients are now living longer with cancer, clinicians should be alert to the varied presentation of pituitary metastasis. We provide a clinical overview of pituitary metastasis with the aid of illustrative clinical cases.
Topics: Diabetes Insipidus; Humans; Pituitary Neoplasms
PubMed: 34815592
DOI: No ID Found