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JCEM Case Reports Jan 2023Hereditary central diabetes insipidus (CDI) is a genetic disorder characterized by polydipsia and polyuria. Most known mutations are located in the arginine-vasopressin...
Hereditary central diabetes insipidus (CDI) is a genetic disorder characterized by polydipsia and polyuria. Most known mutations are located in the arginine-vasopressin () gene. Here, we describe a Swiss family with an autosomal dominant mutation in the gene region encoding for the carrier protein neurophysin II (P55R). In addition, we discuss the algorithm for diagnosing and treating patients with hereditary CDI based on this Swiss family.
PubMed: 37908243
DOI: 10.1210/jcemcr/luac023 -
JCEM Case Reports Jan 2023Waterhouse-Friderichsen syndrome and central diabetes insipidus are uncommon but potentially fatal endocrine and metabolic diseases. Waterhouse-Friderichsen syndrome is...
Waterhouse-Friderichsen syndrome and central diabetes insipidus are uncommon but potentially fatal endocrine and metabolic diseases. Waterhouse-Friderichsen syndrome is defined as adrenal insufficiency caused by adrenal hemorrhage, which is typically bilateral and most frequently due to meningococcal infection. It is usually diagnosed by necropsy. Central diabetes insipidus in children is often caused by trauma, intracranial lesions, autoimmune diseases, and infections. In addition, it can be caused by mutations in the AVP-NPII gene, although this occurs typically later in childhood rather than in the neonatal period. This report describes a term infant who developed meningitis, which resulted in septic shock and disseminated intravascular coagulation. Abdominal ultrasound led to an early diagnosis of bilateral adrenal hemorrhage and appropriate treatment with corticosteroids. Symptomatic central diabetes insipidus developed a few days after the onset of meningitis. Intravenous vasopressin was effective in resolving hemodynamic instability. In conclusion, sepsis and meningitis may have severely affected the endocrine system in this patient. Early diagnosis and appropriate treatment for both diseases may have resulted in better clinical outcomes for this patient.
PubMed: 37908241
DOI: 10.1210/jcemcr/luac031 -
Case Reports in Nephrology and Dialysis 2023Congenital nephrogenic diabetes insipidus (CNDI), a rare hereditary disorder, is characterized by the inability of the kidneys to concentrate urine in response to the...
Congenital nephrogenic diabetes insipidus (CNDI), a rare hereditary disorder, is characterized by the inability of the kidneys to concentrate urine in response to the antidiuretic hormone arginine vasopressin (AVP); as a result, large volumes of unconcentrated urine are excreted. In addition to the clinical manifestations of CNDI, such as dehydration and electrolyte disturbances (hypernatremia and hyperchloremia), developmental delay can result without prompt treatment. In approximately 90% of cases, CNDI is an X-linked disease caused by mutations in the arginine vasopressin receptor 2 () gene. In approximately 9% of cases, CNDI is an autosomal recessive disease caused by mutations in the water channel protein aquaporin 2 (), and 1% of cases are autosomal dominant. We report a case of CNDI caused by a novel nonsense mutation, c.520C>T (p.Q174X), and cases of siblings in another family who had a different nonsense mutation, c.852G>A (p.W284X). Both cases responded well to treatment with hydrochlorothiazide and spironolactone. If CNDI is suspected, especially in carriers and neonates, aggressive genetic testing and early treatment may alleviate growth disorders and prevent irreversible central nervous system disorders and developmental delay.
PubMed: 37900924
DOI: 10.1159/000533895 -
Cureus Sep 2023Central diabetes insipidus (CDI) is a rare condition characterized by excessive urination and thirst due to vasopressin deficiency. The underlying cause of CDI remains...
Central diabetes insipidus (CDI) is a rare condition characterized by excessive urination and thirst due to vasopressin deficiency. The underlying cause of CDI remains unknown in many cases. Tumors are a leading cause of CDI in young individuals, with germinoma being the most prevalent. We present a case of a 22-year-old male diagnosed with infundibuloneurohypophysitis (INH) of unknown etiology. His pituitary stalk thickening partially responded to high-dose prednisone treatment; however, one year after initial diagnosis, a new pineal region mass was noted on imaging. Further evaluation revealed the mass to be most likely a germinoma. This case emphasizes the importance of ongoing clinical and radiologic follow-up in idiopathic cases of CDI. The patient's symptoms improved with desmopressin, but the presence of the pineal mass necessitates further comprehensive neurosurgical evaluation.
PubMed: 37900440
DOI: 10.7759/cureus.46103 -
Frontiers in Endocrinology 2023Wolfram Syndrome (WS) is a rare condition caused by mutations in , with a poor prognosis and no cure. Mono-agonists targeting the incretin glucagon-like-peptide 1...
AIM
Wolfram Syndrome (WS) is a rare condition caused by mutations in , with a poor prognosis and no cure. Mono-agonists targeting the incretin glucagon-like-peptide 1 (GLP-1) have demonstrated disease-modifying potential in pre-clinical and clinical settings. Dual agonists that target GLP-1 and glucose-dependent insulinotropic polypeptide (GIP-1) are reportedly more efficacious; hence, we evaluated the therapeutic potential of dual incretin agonism in a loss-of-function rat model of WS.
METHODS
Eight-month-old knock-out (KO) and wild-type control rats were continuously treated with either the dual agonist DA-CH5 or saline for four months. Glycemic profile, visual acuity and hearing sensitivity were longitudinally monitored pre-treatment, and then at 10.5 and 12 months. Pancreata and retina were harvested for immunohistological analysis.
RESULTS
DA-CH5 therapy reversed glucose intolerance in KO rats and provided lasting anti-diabetogenic protection. Treatment also reversed intra-islet alterations, including reduced endocrine islet area and β-cell density, indicating its regenerative potential. Although no rescue effect was noted for hearing loss, visual acuity and retinal ganglion cell density were better preserved in DA-CH5-treated rats.
CONCLUSION
We present preclinical evidence for the pleiotropic therapeutic effects of long-term dual incretin agonist treatment; effects were seen despite treatment beginning after symptom-onset, indicating reversal of disease progression. Dual incretins represent a promising therapeutic avenue for WS patients.
Topics: Humans; Rats; Animals; Infant; Incretins; Wolfram Syndrome; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide; Insulin-Secreting Cells
PubMed: 37900147
DOI: 10.3389/fendo.2023.1234925 -
CEN Case Reports Jun 2024Ifosfamide, a cytotoxic antineoplastic drug, can induce rare complications of Fanconi syndrome and nephrogenic diabetes insipidus (DI). Ifosfamide-induced Fanconi...
Ifosfamide, a cytotoxic antineoplastic drug, can induce rare complications of Fanconi syndrome and nephrogenic diabetes insipidus (DI). Ifosfamide-induced Fanconi syndrome tends to occur in patients with certain risk factors including young age, high cumulative ifosfamide dose, and coadministration of cisplatin. Nephrogenic DI causes polyuria from impaired urinary concentrating ability due to resistance to arginine vasopressin (AVP) at the collecting duct. These complications are serious and potentially fatal. Here, we describe a case of a middle-aged man without risk factors who was admitted for the management of acute kidney injury and electrolyte derangements after his fourth cycle of chemotherapy including ifosfamide for synovial sarcoma. He was found to have hypokalemia, hypophosphatemia, renal glycosuria, and aminoaciduria, likely from Fanconi syndrome, which were managed by electrolyte replacement therapy. In addition, polyuria and hypernatremia were considered due to nephrogenic DI, which partially responded to desmopressin treatment. This case highlights the importance of the routine electrolytes monitoring after ifosfamide treatment.
Topics: Humans; Fanconi Syndrome; Male; Ifosfamide; Diabetes Insipidus, Nephrogenic; Acute Kidney Injury; Antineoplastic Agents, Alkylating; Middle Aged; Hypokalemia; Deamino Arginine Vasopressin
PubMed: 37897631
DOI: 10.1007/s13730-023-00829-z -
Endocrine Connections Dec 2023The incidental diagnosis of nonfunctioning pituitary macroadenomas (NFPMAs) is becoming more prevalent with the spread of modern brain imaging techniques. We sought to...
OBJECTIVES
The incidental diagnosis of nonfunctioning pituitary macroadenomas (NFPMAs) is becoming more prevalent with the spread of modern brain imaging techniques. We sought to uncover new data about their natural history and surgical outcome.
DESIGN
This is a retrospective single-center observational study.
METHODS
Among 210 patients seen for a NFPMA between 2010 and 2019, 70 (33%) were discovered incidentally (i-NFPMA). We analyzed outcomes in a total of 65 patients with available follow-up data.
RESULTS
Mean age at diagnosis (± s.d.) was 60 ± 14 years and mean maximal diameter was 20.0 ± 7.3 mm. At diagnosis, 29 patients (45%) had pituitary hormone deficits (LH/FSH 41%, TSH 29%, ACTH 15%) and 12% had visual field deficits. 26 patients underwent initial surgery, while 12 had delayed surgery after initial surveillance. In the surveillance group, the risk of tumor growth was estimated at 10%/year. Patients with hormonal deficits at diagnosis experienced earlier growth at 24 months (P < 0.02). Overall, surgical resection of the i-NFPMA led to stable or improved endocrine function in 91% of patients, with only 6% postoperative permanent diabetes insipidus. Moreover, surgery was more effective in preserving intact endocrine function (10/12) than restoring altered endocrine function to normal (6/22, P = 0.03).
CONCLUSION
About one-third of NFPMAs are now discovered incidentally and a significant subset may be responsible for unrecognized endocrine and visual deficits. Under surveillance the risk of further tumor growth is significant (10%/year) and seems to occur faster in patients already harboring an endocrine deficit. Early surgical removal before onset of endocrine deficits appears to lead to better endocrine outcome.
PubMed: 37887079
DOI: 10.1530/EC-23-0224 -
Frontiers in Endocrinology 2023We present the case of a 15-year-old girl, with a fifth cystic progression of an adamantinomatous craniopharyngioma after multiple surgeries and previous local...
We present the case of a 15-year-old girl, with a fifth cystic progression of an adamantinomatous craniopharyngioma after multiple surgeries and previous local radiotherapy. She had severe visual impairment, panhypopituitarism including diabetes insipidus, and several components of hypothalamic damage, including morbid obesity and severe fatigue. To prevent further late effects hampering her quality of survival, she was treated biweekly with intravenous tocilizumab, an anti-interleukin-6 agent, which stabilized the cyst for a prolonged time. Based on the biology of adamantinomatous craniopharyngioma, this immune-modulating treatment seems promising for the treatment of this cystic tumor in order to reduce surgery and delay or omit radiotherapy.
Topics: Humans; Female; Child; Adolescent; Craniopharyngioma; Pituitary Neoplasms; Hypothalamus; Hypopituitarism
PubMed: 37886643
DOI: 10.3389/fendo.2023.1225734 -
Intracranial germinoma combined with parathyroid adenoma in a male pediatric patient: A case report.SAGE Open Medical Case Reports 2023Cases of young patients combined with intracranial germinoma and parathyroid adenoma are extremely rare. A 6.25-year-old boy was diagnosed with growth hormone deficiency...
Cases of young patients combined with intracranial germinoma and parathyroid adenoma are extremely rare. A 6.25-year-old boy was diagnosed with growth hormone deficiency at his first visit and was then treated with growth hormone substitution. Later, he was clinically diagnosed with central diabetes insipidus (CDI) and primary hyperparathyroidism, whereas no abnormal imaging evidence was identified, except for a thickened pituitary stalk. Due to persistent follow-up, parathyroid adenoma and intracranial germinoma were verified in succession. The patient had derived benefits from parathyroidectomy and chemotherapy plus radiotherapy. We concluded that children and adolescents who present with CDI and pituitary stalk thickening should undergo repeated screenings for underlying intracranial germinoma. Multiple lesions involving the parathyroid gland and pituitary should alert physicians to the possibility of multiple endocrine neoplasia or other inherited diseases; therefore, genetic screening is recommended.
PubMed: 37886631
DOI: 10.1177/2050313X231207561 -
Hormone and Metabolic Research =... Mar 2024Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analogue of...
Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analogue of vasopressin, desmopressin.The primary aim of this retrospective register study was to compare desmopressin dose requirements in patients with acquired and congenital DI, and secondly to assess the influence of BMI on dose requirement and risk of hyponatremia with different drug administrations. We included all patients with suspected DI attending the endocrine department at Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were included whereof 130/222 (58.6%) were females and median age was 53 years (IQR 35 to 63). The etiology included 7/222 (3.2%) congenital and 215/222 (96.8%) acquired. After converting nasal and sublingual doses to equivalent oral doses, the median daily dose requirement was 600 μg in patients with congenital etiology compared to 200 μg in patients with acquired etiology (p=0.005). We found no association between BMI and desmopressin dose requirements (p=0.6). During the past 12 months, 66/215 (30.7%) had sodium levels<136 mmol/l including 20/215 (9.3%) with sodium levels<131 mmol/l. No increased risk of hyponatremia was found, when nasal and oral were compared (p=0.9). Daily desmopressin dose requirements were higher in patients with congenital DI compared to patients with acquired DI. However, this result was associated with uncertainty due to the small congenital group. BMI did not influence daily dose requirements and nor did type of administration influence the risk of hyponatremia.
Topics: Adult; Female; Humans; Middle Aged; Male; Diabetes Insipidus, Neurogenic; Deamino Arginine Vasopressin; Hyponatremia; Antidiuretic Agents; Retrospective Studies; Sodium; Diabetes Mellitus
PubMed: 37879354
DOI: 10.1055/a-2198-7207