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Therapeutics and Clinical Risk... 2021Autosomal dominant polycystic kidney disease constitutes the most prevalent hereditary kidney disease, associated with high rates of morbidity leading eventually to... (Review)
Review
Autosomal dominant polycystic kidney disease constitutes the most prevalent hereditary kidney disease, associated with high rates of morbidity leading eventually to end-stage renal disease. Tolvaptan is a selective vasopressin antagonist and has emerged as a promising therapeutic option for patients with autosomal dominant polycystic kidney disease. The present review summarized current evidence regarding the safety profile of tolvaptan in patients with the disease. Consistent with its pharmacological action, aquaretic adverse events represent the most common side effects of tolvaptan, consisting of polyuria, pollakiuria and polydipsia. Gradual dose titration based on urinary osmolality, as well as dietary interventions aiming to reduce solute excretion, have been proposed as potential strategies to mitigate polyuria. In addition, tolvaptan administration may be complicated by liver injury, characterized by alanine aminotransferase and bilirubin elevations. Hepatotoxicity has been suggested to be triggered by impaired biliary clearance, activation of innate immunity and increased oxidative stress. Frequent monitoring of liver function tests has been shown to be effective in preventing Hy's Law and liver failure cases. Uric acid elevation due to reduced renal excretion may lead to hyperuricemia and gout, although no drug discontinuations have been linked to these events. Future studies should confirm the safety profile of tolvaptan in large-scale real-world studies, clarify the pathogenetic pathways leading to hepatotoxicity and define its role in special populations, especially pediatric patients.
PubMed: 34234441
DOI: 10.2147/TCRM.S286952 -
Case Reports in Ophthalmology 2023Lymphocytic hypophysitis (LH) is a primary inflammatory disorder of the pituitary gland and infundibulum that commonly manifests in both mass effect and endocrinologic...
Lymphocytic hypophysitis (LH) is a primary inflammatory disorder of the pituitary gland and infundibulum that commonly manifests in both mass effect and endocrinologic symptoms. Although the exact pathophysiology remains unclear, it has been increasingly linked to an autoimmune process. Complications arise by two separate mechanisms. Inflammation in the sella can lead to headaches and visual field defects. Pituitary inflammation and, chronically, fibrosis interfere with the gland's hormone-secreting capacity, often resulting in various endocrinopathies such as polyuria, polydipsia, amenorrhea, and others. While final histologic classification requires pathologic evaluation, diagnosis can often be made clinically with appropriate imaging. Treatment often consists of conservative management but can also include glucocorticoids or surgical resection. We present a case of biopsy-proven LH involving the entire pituitary, dubbed lymphocytic panhypophysitis (LPH) that was misdiagnosed for years as glaucoma due to the lack of endocrinopathy as well as delay in magnetic resonance imaging. After imaging revealed the sellar mass, the patient responded symptomatically to surgical resection and glucocorticoid treatment. LPH may present without endocrinologic symptoms and therefore mimic alternate diagnoses such as glaucoma. Clinicians should be suspicious of a diagnosis of glaucoma in the setting of a temporal field defect and lack of response to traditional therapy. A personal or family history of autoimmune disease in such patients should prompt further imaging and investigation. Therefore, endocrinopathy is supportive but not present in every case of LPH.
PubMed: 37485239
DOI: 10.1159/000531445 -
The Veterinary Record Jul 2019
Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Polydipsia; Polyuria
PubMed: 31346113
DOI: 10.1136/vr.l4865 -
Endocrinology, Diabetes & Metabolism... May 2020The etiology of hyponatremia is assessed based on urine osmolality and sodium. We herein describe a 35-year-old Asian man with pulmonary tuberculosis and perforated...
SUMMARY
The etiology of hyponatremia is assessed based on urine osmolality and sodium. We herein describe a 35-year-old Asian man with pulmonary tuberculosis and perforated duodenal ulcer who presented with hyponatremia with hourly fluctuating urine osmolality ranging from 100 to 600 mosmol/kg, which resembled urine osmolality observed in typical polydipsia and SIADH simultaneously. Further review revealed correlation of body temperature and urine osmolality. Since fever is a known non-osmotic stimulus of ADH secretion, we theorized that hyponatremia in this patient was due to transient ADH secretion due to fever. In our case, empiric exogenous glucocorticoid suppressed transient non-osmotic ADH secretion and urine osmolality showed highly variable concentrations. Transient ADH secretion-related hyponatremia may be underrecognized due to occasional empiric glucocorticoid administration in patients with critical illnesses. Repeatedly monitoring of urine chemistries and interpretation of urine chemistries with careful review of non-osmotic stimuli of ADH including fever is crucial in recognition of this etiology.
LEARNING POINTS
Hourly fluctuations in urine osmolality can be observed in patients with fever, which is a non-osmotic stimulant of ADH secretion. Repeated monitoring of urine chemistries aids in the diagnosis of the etiology underlying hyponatremia, including fever, in patients with transient ADH secretion. Glucocorticoid administration suppresses ADH secretion and improves hyponatremia even in the absence of adrenal insufficiency; the etiology of hyponatremia should be determined carefully in these patients.
PubMed: 32408271
DOI: 10.1530/EDM-19-0155 -
Endocrinology, Diabetes & Metabolism... Dec 2019Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes...
SUMMARY
Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200-1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40-4.80) and low free T4: 5.9 pmol/L (reference range: 8.0-16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI).
LEARNING POINTS
Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA. Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored. Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor. Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.
PubMed: 31829972
DOI: 10.1530/EDM-19-0098 -
Pediatric Nephrology (Berlin, Germany) Jun 2024An 11-year-old male child who presented with increased frequency of urination, thirst and feeling of incomplete void was initially diagnosed with diabetes mellitus (DM)...
An 11-year-old male child who presented with increased frequency of urination, thirst and feeling of incomplete void was initially diagnosed with diabetes mellitus (DM) based on elevated blood sugar. Polyuria and polydipsia were confirmed even after normalisation of blood sugar. A standardised water deprivation test showed presence of central diabetes insipidus (DI) and patient was started on desmopressin. Presence of DM and DI led to suspicion of DIDMOAD/Wolfram syndrome and ophthalmic examination confirmed bilateral optic atrophy. Despite treatment for DM and DI the urinary complaints persisted, and ultrasound showed persistent bilateral hydronephroureterosis. Bladder workup including voiding cystourethrography (VCUG) and urodynamic study reported thickened trabeculated bladder wall along with overactivity, poor compliance and high bladder pressure. Bladder dysfunction has been documented to be associated with Wolfram syndrome and often may lead to chronic kidney disease which can be prevented by early diagnosis and appropriate management. The case highlights the need for comprehensive evaluation of children with urinary symptoms.
PubMed: 38842721
DOI: 10.1007/s00467-024-06424-3 -
La Revue Du Praticien Apr 2023
Topics: Humans; Carbon Monoxide Poisoning
PubMed: 37289160
DOI: No ID Found -
Journal of Veterinary Internal Medicine Sep 2021Glucocorticoids are used for a variety of purposes in veterinary medicine but often are associated with clinically important adverse effects. Polyuria and polydipsia are...
BACKGROUND
Glucocorticoids are used for a variety of purposes in veterinary medicine but often are associated with clinically important adverse effects. Polyuria and polydipsia are the most frustrating adverse effects noted by owners.
OBJECTIVE
To determine whether administration of desmopressin ameliorates polyuria and polydipsia associated with prednisolone administration.
ANIMALS
Seven healthy adult Walker Hounds.
METHODS
Prospective hypothesis testing study. Daily water intake and urine specific gravity (USG) were measured in dogs under 4 separate sequential conditions: no medications (C), prednisolone only (P), prednisolone and desmopressin (PD), and prednisolone after discontinuation of desmopressin (PAD).
RESULTS
When compared to baseline, 6 of 7 dogs became polydipsic after administration of prednisolone (0.5 mg/kg PO q12h). When desmopressin (5 μg/dog SC q12h) was administered to dogs receiving prednisolone, significant decreases in water intake and serum sodium concentration occurred, and USG increased significantly.
CONCLUSIONS AND CLINICAL IMPORTANCE
Administration of desmopressin to dogs receiving prednisolone significantly decreased water intake and serum sodium concentration, and increased USG. Our results suggest that, in some dogs, desmopressin ameliorates the most important adverse effect of prednisolone noted by owners, but that hyponatremia is an important complication associated with desmopressin use.
Topics: Animals; Deamino Arginine Vasopressin; Dog Diseases; Dogs; Glucocorticoids; Polyuria; Prednisolone; Prospective Studies
PubMed: 34448503
DOI: 10.1111/jvim.16250 -
The Journal of Veterinary Medical... Aug 2023We present the report of trismus due to hyperadrenocorticism-associated myotonia diagnosed by electromyography in a dog. An intact female Miniature Dachshund, 13 years...
We present the report of trismus due to hyperadrenocorticism-associated myotonia diagnosed by electromyography in a dog. An intact female Miniature Dachshund, 13 years and 9 months old, presented with stiff gait and trismus as well as polyuria and polydipsia. Abdominal ultrasonography showed enlarged adrenal glands. An adrenocorticotropic hormone stimulation test revealed an exaggerated response. Based on these findings, this case was diagnosed with hyperadrenocorticism. Electromyography revealed myotonic discharge in the temporalis muscle and limbs. Therefore, trismus was considered to be caused by hyperadrenocorticism-associated myotonia, and the case was treated with oral trilostane (1.3 mg/kg, once daily). During the 4-month follow-up period, despite the partial improvement in stiff gait, trismus did not recover. Long-term data on more cases are warranted to assess the prognosis and clinical characteristics of trismus due to hyperadrenocorticism-associated myotonia.
Topics: Dogs; Female; Animals; Myotonia; Trismus; Dog Diseases; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone
PubMed: 37357395
DOI: 10.1292/jvms.23-0103 -
Scars, Burns & Healing 2022Diabetes insipidus (DI) is characterized by polyuria and polydipsia. In most cases, the condition results from either an inadequate release or resistance to the activity...
UNLABELLED
Diabetes insipidus (DI) is characterized by polyuria and polydipsia. In most cases, the condition results from either an inadequate release or resistance to the activity of antidiuretic hormone in the renal collecting tubules. The underlying pathophysiology may be related to destruction the destruction or degeneration of neurons from inflammatory, autoimmune diseases, vascular diseases, Langerhans cell histiocytosis, sarcoidosis, or trauma. However, a large majority of diabetes insipidus cases (50%) are considered idiopathic. An exceedingly rare cause of idiopathic central DI occurs in burn injuries, which has only been reported in eight cases. We present an extremely rare case of idiopathic DI in a 15-year-old male with 76% total body surface area (TBSA) burns with the development of idiopathic central DI. An extensive literature review was accomplished to compare this case with the small number of previously reported case reports of idiopathic DI in burn patients.
LAY SUMMARY
Diabetes insipidus (DI) is a rare complication of burn injuries that results from the destruction of neurons involved in the secretion of antidiuretic hormone from the pituitary gland. Only eight cases of DI have been reported in the literature in association to burn injuries. The patient in this case report received immediate fluid resuscitation, burn treatment, and intensive observation after the initial burn injury. The rapid response was likely the main reason for the absence of neurological damage as reported in the CT image. Therefore, the treatment of burn injuries remains an important step for reducing neurological damage and hormonal dysregulation leading to diabetes insipidus.
PubMed: 36274672
DOI: 10.1177/20595131221122312