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1.
Cell ; 170(5): 860-874.e19, 2017 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-28803730

RESUMO

Lower urinary tract infections are among the most common human bacterial infections, but extension to the kidneys is rare. This has been attributed to mechanical forces, such as urine flow, that prevent the ascent of bladder microbes. Here, we show that the regional hypersalinity, required for the kidney's urine-concentrating function, instructs epithelial cells to produce chemokines that localize monocyte-derived mononuclear phagocytes (MNPs) to the medulla. This hypersaline environment also increases the intrinsic bactericidal and neutrophil chemotactic activities of MNPs to generate a zone of defense. Because MNP positioning and function are dynamically regulated by the renal salt gradient, we find that patients with urinary concentrating defects are susceptible to kidney infection. Our work reveals a critical accessory role for the homeostatic function of a vital organ in optimizing tissue defense.


Assuntos
Rim/imunologia , Fagócitos/imunologia , Animais , Linhagem Celular , Quimiocina CCL2/metabolismo , Quimiocinas/imunologia , Diabetes Insípido , Humanos , Rim/citologia , Medula Renal/imunologia , Receptores de Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/citologia , Salinidade , Sódio/metabolismo , Fatores de Transcrição/genética , Infecções Urinárias/imunologia , Infecções Urinárias/microbiologia , Urina/química , Escherichia coli Uropatogênica/fisiologia
2.
Annu Rev Pharmacol Toxicol ; 62: 595-616, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34579536

RESUMO

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing-based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailedframework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia.


Assuntos
Receptores de Vasopressinas , Desequilíbrio Hidroeletrolítico , Aquaporina 2/metabolismo , Teorema de Bayes , Humanos , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo , Biologia de Sistemas
3.
J Cell Mol Med ; 28(8): e18301, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38652212

RESUMO

X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the ß3-adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the ß3-AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X-NDI. Here we demonstrate that the ß3-AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X-NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow-release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X-NDI mice. Taken together, these data suggest that human ß3-AR agonists might represent an effective possible treatment strategy for X-NDI.


Assuntos
Agonistas de Receptores Adrenérgicos beta 3 , Masculino , Animais , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Antidiuréticos/farmacologia , Antidiuréticos/uso terapêutico , Capacidade de Concentração Renal/efeitos dos fármacos , Polidipsia/tratamento farmacológico , Polidipsia/etiologia
4.
Am J Physiol Renal Physiol ; 326(2): F278-F284, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38059298

RESUMO

The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule.NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria.


Assuntos
Anemia Falciforme , Diabetes Insípido Nefrogênico , Diabetes Insípido , Diabetes Mellitus , Humanos , Poliúria , Diurese , Concentração Osmolar , Antidiuréticos , Água
5.
Artigo em Inglês | MEDLINE | ID: mdl-38164825

RESUMO

The elucidation of the underlying cause of polyuria-polydipsia syndrome (PPS) is a challenging-especially in the differentiation of partial defects of arginine vasopressin (AVP) secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated-copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population-incorporating the differences in physiological regulation of water homeostasis, and safety requirements-before there is widespread adoption into clinical practice.

6.
Clin Endocrinol (Oxf) ; 101(1): 23-31, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38291597

RESUMO

OBJECTIVE: Plasma copeptin is a relatively new biomarker for evaluation of arginine vasopressin (AVP) secretion. The aim of this study was to test the diagnostic performance of copeptin in patients with polyuria-polydipsia syndrome. DESIGN, PATIENTS AND MEASUREMENTS: This was a prospective study where 88 patients with polyuria-polydipsia syndrome were evaluated with a water deprivation test (WDT). Weight, urine osmolality, urine specific gravity, and plasma copeptin were collected at baseline, after 8 h, and at termination of the WDT when one of the following had been reached: (i) >3% weight reduction, (ii) urine specific gravity >1.017 or urine osmolality >600 mOsm/kg, or (iii) intolerable adverse symptoms. RESULTS: Of 88 patients (57 women), 21 (24%) were diagnosed with central diabetes insipidus (cDI), 5 (6%) with nephrogenic DI (nDI), and 62 (71%) with primary polydipsia (PP). Median (interquartile range) copeptin at baseline was 1.7 (1.4-2.5) pmol/L in cDI, 22 (18-65) pmol/L in nDI, and 2.7 (2-4) pmol/L in PP. After 8 h of WDT, the highest copeptin in patients with cDI was 4.0 pmol/L. In patients with PP: (i) 41 had urine osmolality <600 mOsm/kg, 7 (17%) of these had copeptin >4.0 pmol/L, (ii) 21 had urine osmolality ≥600 mOsm/kg, 14 (67%) of these had copeptin >4.0 pmol/L. CONCLUSIONS: Copeptin >4.0 pmol/L after an overnight WDT can be used to rule out cDI and copeptin ≥21 pmol/L at baseline to diagnose nDI. The diagnostic performance of copeptin in the context of the WDT is otherwise limited in the diagnostic work-up of patients with polyuria-polydipsia syndrome.


Assuntos
Glicopeptídeos , Polidipsia , Poliúria , Humanos , Glicopeptídeos/sangue , Feminino , Masculino , Estudos Prospectivos , Adulto , Poliúria/diagnóstico , Poliúria/sangue , Poliúria/urina , Polidipsia/diagnóstico , Polidipsia/sangue , Pessoa de Meia-Idade , Biomarcadores/sangue , Concentração Osmolar , Adulto Jovem , Privação de Água
7.
Artigo em Inglês | MEDLINE | ID: mdl-39168952

RESUMO

Secondary adrenal insufficiency (SAI) is an endocrine disorder due to impaired secretion of ACTH resulting from any disease affecting the pituitary gland. Glucocorticoid replacement therapy is mandatory to ensure patient survival, haemodynamic stability, and quality of life. In fact, a correct dose adjustement is mandatory due to the fact that inappropriately low doses expose patients to hypoadrenal crisis, while inappropriately high doses contribute to glucose metabolic and cardiovascular deterioration. This review analyses the current evidence from available publications on the epidemiology and aetiology of SAI and examines the association between glucocorticoid replacement therapy and glucometabolic and cardiovascular effects.

8.
Rev Endocr Metab Disord ; 25(3): 453-455, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38801648

RESUMO

Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of one or more pituitary hormones, including growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH), also called arginine vasopressin (AVP). Symptoms vary widely and are often not, late recognized.Diagnosis typically involves a thorough clinical evaluation, hormone level assessments, and neuroimaging studies to identify underlying causes. Treatment aims to replace deficient hormones and address the underlying cause and related complications when possible. In this special issue we address diagnosis, comorbidities, and management of hypopituitarism. We hope that it will help healthcare professionals to manage their patients.


Assuntos
Hipopituitarismo , Humanos , Hipopituitarismo/terapia , Hipopituitarismo/diagnóstico
9.
BMC Cancer ; 24(1): 572, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720306

RESUMO

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.


Assuntos
Craniofaringioma , Diabetes Insípido Neurogênico , Neoplasias Hipofisárias , Complicações Pós-Operatórias , Humanos , Craniofaringioma/cirurgia , Craniofaringioma/sangue , Craniofaringioma/complicações , Feminino , Masculino , Estudos Retrospectivos , Adulto , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Adolescente , Pessoa de Meia-Idade , Criança , Adulto Jovem , Diabetes Insípido Neurogênico/sangue , Diabetes Insípido Neurogênico/etiologia , Neutrófilos , Biomarcadores/sangue , Linfócitos , Inflamação/sangue , Contagem de Leucócitos , Período Pré-Operatório , Pré-Escolar , Prognóstico , Curva ROC
10.
Am J Med Genet A ; 194(3): e63407, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37909842

RESUMO

Ninety percent of congenital nephrogenic diabetes insipidus (NDI) are X-linked inherited and are caused by mutations in the vasopressin type 2 receptor gene (AVPR2). Most affected individuals are males. Only sporadic female cases have been reported. Here, we first reported a female monozygotic twin with discordant phenotypes for NDI carrying a missense variant c.845T>C (p.Leu282Pro) in exon 4 of AVPR2. Intracellular cAMP concentrations in COS7 cells transfected with AVPR2-L282P were significantly decreased by about 60% compared with those in wild-type AVPR2 plasmid transfected cells, suggesting this variation was pathogenic. The X-inactivation pattern was investigated in peripheral leukocytes and urine sediments in both the unaffected and affected pair. Results showed that the affected pair had a skewed X chromosome inactivation (XCI) pattern in urine sediments and a random XCI pattern in leukocytes, while the unaffected pair showed a random XCI pattern both in leukocytes and urine sediments. This was the first report of monozygotic twins who developed different phenotypes of NDI. Our study suggested that the development of NDI symptoms is more closely associated with the XCI pattern in urine sediments compared with the XCI pattern in peripheral leukocytes. Analysis of XCI in peripheral leukocytes may not be enough to explore possible mechanisms.


Assuntos
Diabetes Insípido Nefrogênico , Gêmeos Monozigóticos , Feminino , Humanos , Diabetes Insípido Nefrogênico/genética , Éxons , Mutação de Sentido Incorreto , Receptores de Vasopressinas/genética , Gêmeos Monozigóticos/genética
11.
BMC Endocr Disord ; 24(1): 120, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044171

RESUMO

BACKGROUND: Sheehan's syndrome is a rare condition, which is classically characterized by anterior pituitary hypofunction following postpartum shock or hemorrhage. While diabetes insipidus (DI) is not commonly associated with Sheehan's syndrome, we present a rare case of a multiparous female developing rapid-onset panhypopituitarism and DI following severe postpartum hemorrhage. CASE PRESENTATION: A previously healthy 39-year-old woman, gravida 5, para 4, presented with hypovolemic shock after vaginal delivery, attributed to severe postpartum hemorrhage, necessitating emergent hysterectomy. Although her shock episodes resolved during hospitalization, she developed intermittent fever, later diagnosed as adrenal insufficiency. Administration of hydrocortisone effectively resolved the fever. However, she subsequently developed diabetes insipidus. Diagnosis of Sheehan's syndrome with central diabetes insipidus was confirmed through functional hormonal tests and MRI findings. Treatment consisted of hormone replacement therapy, with persistent panhypopituitarism noted during a ten-year follow-up period. CONCLUSIONS: Sheehan's syndrome is a rare complication of postpartum hemorrhage. Central diabetes insipidus should be suspected, although not commonly, while the patient presented polyuria and polydipsia. Besides, the potential necessity for long-term hormonal replacement therapy should be considered.


Assuntos
Diabetes Insípido Neurogênico , Hipopituitarismo , Humanos , Feminino , Hipopituitarismo/diagnóstico , Hipopituitarismo/complicações , Hipopituitarismo/tratamento farmacológico , Adulto , Diabetes Insípido Neurogênico/diagnóstico , Diabetes Insípido Neurogênico/etiologia , Diabetes Insípido Neurogênico/tratamento farmacológico , Diabetes Insípido Neurogênico/complicações , Hemorragia Pós-Parto/etiologia , Prognóstico
12.
Neuroradiology ; 66(8): 1405-1416, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38844695

RESUMO

PURPOSE: Malignant intracranial germ cell tumors (GCTs) are rare diseases in Western countries. They arise in midline structures and diagnosis is often delayed. We evaluated imaging characteristics and early tumor signs of suprasellar and bifocal GCT on MRI. METHODS: Patients with the diagnosis of a germinoma or non-germinomatous GCT (NGGCT) who received non-contrast sagittal T1WI on MRI pre-therapy were included. Loss of the posterior pituitary bright spot (PPBS), the expansion and size of the tumor, and the expansion and infiltration of surrounding structures were evaluated. Group comparison for histologies and localizations was performed. RESULTS: A total of 102 GCT patients (median age at diagnosis 12.3 years, range 4.4-33.8; 57 males; 67 in suprasellar localization) were enrolled in the study. In the suprasellar cohort, NGGCTs (n = 20) were noticeably larger than germinomas (n = 47; p < .001). Each tumor showed involvement of the posterior lobe or pituitary stalk. A PPBS loss (total n = 98) was observed for each localization and entity in more than 90% and was related to diabetes insipidus. Osseous infiltration was observed exclusively in suprasellar GCT (significantly more frequent in NGGCT; p = .004). Time between the first MRI and therapy start was significantly longer in the suprasellar cohort (p = .005), with an even greater delay in germinoma compared to NGGCT (p = .002). The longest interval to treatment had circumscribed suprasellar germinomas (median 312 days). CONCLUSION: A loss of the PPBS is a hint of tumor origin revealing small tumors in the neurohypophysis. Using this sign in children with diabetes insipidus avoids a delay in diagnosis.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias Embrionárias de Células Germinativas , Humanos , Masculino , Feminino , Criança , Adolescente , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/patologia , Pré-Escolar , Imageamento por Ressonância Magnética/métodos , Adulto , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Sistema Hipotálamo-Hipofisário/diagnóstico por imagem , Neuro-Hipófise/diagnóstico por imagem , Neuro-Hipófise/patologia , Estudos Retrospectivos
13.
Pediatr Nephrol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842721

RESUMO

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.

14.
Pituitary ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266909

RESUMO

PURPOSE: The desmopressin daily dose requirement is highly variable among patients with arginine vasopressin (AVP) deficiency (i.e. central diabetes insipidus) and few studies to date have evaluated this topic, with often inconclusive results. The aim of our study was to identify clinical and biochemical predictors of such dose requirements in a cohort of patients with a confirmed diagnosis of permanent AVP deficiency who have good and stable control under substitutive treatment. METHODS: We retrospectively analyzed data of all patients with permanent AVP deficiency undergoing regular follow-up at our Division. Inclusion criteria were the presence of stable disease under therapy for at least 12 months and in good biochemical and clinical control. Patients with AVP deficiency who lacked intact thirst or had a disease duration of less than 12 months were excluded from the analysis. RESULTS: Out of the 132 patients initially screened, 96 patients (M/F 44/52; age 51 [37-63] years) met the inclusion criteria. Patients on nasal spray therapy (n = 8) had a significantly longer disease duration (p = 0.002) than patients treated with oral lyophilizate (n = 88). In the bivariate analysis, considering only patients treated with the sublingual formulation, the drug dose was correlated positively with estimated glomerular filtration rate (eGFR) and weight (r = 0.410, p < 0.001; r = 0.224, p = 0.036, respectively) and negatively with age (r = - 0.433, p < 0.001). In the multivariate regression analysis taking into account age, weight, and eGFR, only age emerged as a significant predictor of the required sublingual desmopressin dose (ß = - 1.426, p = 0.044). CONCLUSION: Our data suggest that patient age appears to be the primary factor associated with the daily sublingual desmopressin dose required to achieve adequate clinical and biochemical control in patients with permanent AVP deficiency.

15.
Pituitary ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847919

RESUMO

PURPOSE: Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes in diuresis in individuals with acromegaly undergoing neurosurgery remains unexplored. Our study aimed to assess changes in postoperative fluid balance in acromegaly patients and correlate them with both copeptin and growth hormone (GH) levels. METHODS: This was a secondary analysis of a prospective study involving 15 acromegaly patients undergoing endoscopic endonasal resection at our University Hospital. Fluid balance was assessed daily, and copeptin and GH levels were evaluated preoperatively (T0), and serially on the morning of the first (T2) and second (T3) postoperative day, with an additional measurement of copeptin one hour post-extubation (T1). Patients with pre-existing or post-neurosurgical CDI were excluded from the analysis. RESULTS: Most patients (11/15) exhibited a negative fluid balance on the second postoperative day, with 4 developing polyuria. Postoperative GH levels did not differ significantly between polyuric and non-polyuric patients, but GH measured at T2 correlated significantly with negative total balance (r = -0.519, p = 0.048). Copeptin levels at T1 were significantly higher in those who developed polyuria (p = 0.013), and a copeptin value > 39.9 pmol/L at T1 showed excellent ability (Sensitivity 100%, Specificity 90.9%, p < 0.001) in predicting postoperative polyuria. Additionally, polyuric patients exhibited a higher T1 / T3 copeptin ratio (p = 0.013) and a negative fluid balance was associated with the remission of acromegaly at 12 months (p = 0.046). CONCLUSION: The early assessment of copeptin, in addition to facilitating the rapid identification of individuals at increased risk of developing CDI, could also allow the recognition of subjects with a tendency towards non-pathological polyuria in the postoperative setting, at least in individuals affected by acromegaly.

16.
Endocr Pract ; 30(2): 141-145, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38029928

RESUMO

OBJECTIVE: Adipsic diabetes insipidus (ADI) is a life-threatening disease. It is characterized by arginine vasopressin deficiency and thirst absence. Data about clinical characteristics of ADI were scarce. This study investigated the clinical features of hospitalized ADI patients. METHODS: A retrospective study was conducted of hospitalized ADI patients admitted to the Endocrinology Department of Huashan Hospital between January 2014 and December 2021, and compared with central diabetes insipidus (CDI) patients with normal thirst. RESULTS: During the study period, there were a total of 507 hospitalized CDI patients, among which 50 cases were ADI, accounting for 9.9%. Forty percent of ADI patients were admitted due to hypernatremia, but there were no admissions due to hypernatremia in the control group. The lesions of ADI patients were more likely to be located in the suprasellar area (100% vs 66%, P < .05). Higher prevalence of hypothalamic dysfunction (76% vs 8%, P < .001), central hypothyroidism (100% vs 90%, P = .031), hyperglycemia (66% vs 32%, P < .001), dyslipidemia (92% vs 71%, P = .006), and hyperuricemia (64% vs 37%, P = .003) was found in the ADI group than in the control group. The proportions of hypernatremia were higher in the ADI group both at admission and at discharge (90% vs 8%, 68% vs 8%, respectively, both with P < .001), contributing to higher prevalence of complications, such as renal insufficiency, venous thrombosis, and infection. CONCLUSION: ADI patients were found with higher prevalence of hypernatremia, hypopituitarism, hypothalamic dysfunction, metabolic disorders, and complications, posing a great challenge for comprehensive management.


Assuntos
Diabetes Insípido Neurogênico , Diabetes Insípido , Diabetes Mellitus , Hipernatremia , Humanos , Hipernatremia/etiologia , Hipernatremia/complicações , Estudos Retrospectivos , Diabetes Insípido/etiologia , Diabetes Insípido/complicações , Diabetes Insípido Neurogênico/epidemiologia , Diabetes Insípido Neurogênico/etiologia , Sede
17.
Endocr Pract ; 30(3): 253-258, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092289

RESUMO

OBJECTIVE: Pituitary adenoma (PA) is the most frequent tumor in the sellar region. Arginine vasopressin deficiency (AVP-D), formerly known as central diabetes insipidus, is a common complication after pituitary surgeries. In this study, we reviewed patients with PAs after endoscopic transsphenoidal surgery, evaluated the incidence of postoperative AVP-D, and determined associated risk factors. METHODS: We retrospectively studied 520 patients who underwent endoscopic transsphenoidal surgery for PAs and evaluated perioperative risk factors and their associations with postoperative AVP-D. Patients who developed AVP-D were categorized in 3 groups: (1) early AVP-D, (2) transient AVP-D, and (3) permanent AVP-D. RESULTS: Of the 520 patients, 24.8% experienced early AVP-D, and 1.9% (n = 10) had transient AVP-D. Permanent AVP-D was observed in only 6 patients (1.1%). Gross total resection, hormonal remission, pituitary stalk manipulation, and intraoperative cerebrospinal fluid leak were significantly associated with a higher incidence of AVP-D (P = .027, P = .002, P < .001 and P < .001, respectively). All patients who developed permanent AVP-D had somatotroph adenomas. AVP-D was not found to be related with tumor size. The length of hospital stay was prolonged by AVP-D on average by 1.5 days (P = .018). CONCLUSION: The reported incidence of AVP-D has a considerably wide range. A consistent definition and grading for AVP-D will increase consistency and comparability among studies. Nonetheless, most patients experience AVP-D on a temporary basis, and only a few require long-term treatment. Cerebrospinal fluid leak, gross total resection, and hormonal remission were identified as risk factors for postoperative AVP-D. We believe that the intraoperative risk factors play the main role in postoperative AVP-D. The course of surgery and operative findings help us plan selective postoperative patient monitoring and care.


Assuntos
Adenoma , Diabetes Insípido Neurogênico , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/complicações , Estudos Retrospectivos , Adenoma/complicações , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Arginina , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
18.
Endocr Pract ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39187157

RESUMO

BACKGROUND: Copeptin stimulation tests can be used in the differential diagnosis of polyuria polydipsia syndrome. Current stimulation methods rely on intravenous or subcutaneous administration. Oral stimulus can further simplify the diagnostic approach. The levodopa stimulation test is widely used in the evaluation of growth hormone deficiency (GHD), and the dopamine pathway was reported to be associated with arginine vasopressin secretion. The study aimed to investigate the effect of oral levodopa on copeptin secretion. METHODS: The study was a prospective observational single-center cohort study. Patients < 18 years old with short stature and no symptoms of polyuria or polydipsia undergoing levodopa stimulation test for suspected GHD were recruited from May 2023 to Nov 2023. Copeptin and growth hormone (GH) were measured at 0, 30, 60, 90, and 120min in the levodopa test. The insulin tolerance test with copeptin and GH measured at the same time points was conducted in part of patients. RESULTS: Forty-four participants were included in the final analysis. In the levodopa stimulation test, the median (interquartile range, IQR) copeptin concentration increased from 5.20 (3.51, 8.25) pmol/L to maximum 19.36 (8.97, 108.08) pmol/L (P < 0.001), 3.94 (1.41, 13.88) times of the baseline (P < 0.001). Compared with insulin tolerance test, peak copeptin in the levodopa test was significantly higher (34.61 (13.67, 98.96) vs 8.88 (7.14, 15.42) pmol/L, P = 0.009). Higher copeptin was associated with larger dose of levodopa. CONCLUSIONS: Oral levodopa could be used to stimulate copeptin.

19.
Endocr J ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39198191

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, and various complications have been reported. Furthermore, there have been increasing reports of endocrinopathy related to COVID-19 following the pandemic. We report a 49-year-old healthy woman who developed rapid onset of polydipsia and polyuria three weeks after COVID-19. Laboratory tests indicated low urine osmolarity and increased serum osmolarity, and antidiuretic hormone (ADH) was undetectable. Urine osmolality remained low with water deprivation. Similarly, plasma ADH responses to hypertonic-saline infusion were blunted and urine osmolality increased in response to desmopressin. There was no clear evidence of anterior pituitary dysfunction. T1-weighted magnetic resonance imaging (MRI) showed pituitary stalk thickening and absence of posterior pituitary bright signal spots, suggesting the presence of hypophysitis. Based on these results, we made a probable diagnosis of lymphocytic infundibulo-neurohypophysitis (LINH) which have caused central diabetes insipidus. Positive findings for serum anti-rabphilin-3A antibodies, reported as a potential diagnostic marker for LINH, were also noted. Following oral desmopressin administration, polydipsia and polyuria were quickly improved, though treatment with desmopressin was still required over four months. This is the first report of a patient with a probable diagnosis of LINH after COVID-19 who tested positive for anti-rabphilin-3A antibodies. Positive findings for those antibodies suggest that pituitary dysfunction associated with COVID-19 is hypophysitis involving an abnormal immune mechanism. The presence of anti-rabphilin-3A antibodies may be useful as a non-invasive diagnostic marker of LINH and potentially serve as a valuable diagnostic aid in cases of LINH associated with COVID-19.

20.
Nephrology (Carlton) ; 29(7): 438-441, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38450903

RESUMO

Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder. The condition is characterised by an inability of distal nephron segments to respond to normal or raised concentrations of serum antidiuretic hormone. In this report, we describe the case of a 13-year-old male known with CNDI who experienced a pedestrian vehicle accident leading to coma following a head injury. Intra-operatively, severe hypernatraemia and polyuria were observed. Following an inadequate response to conventional therapy, acetazolamide was prescribed resulting in an immediate response to therapy. To the best of our knowledge, acetazolamide has not been previously documented as a therapeutic option for CNDI. Additional research is necessary before considering the recommendation of acetazolamide for cases of NDI that do not respond adequately to conventional treatments.


Assuntos
Acetazolamida , Diabetes Insípido Nefrogênico , Humanos , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/tratamento farmacológico , Masculino , Acetazolamida/uso terapêutico , Adolescente , Resultado do Tratamento
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