Central diabetes insipidus in a young dog - case reportABSTRACT
This work reports a case of an 11-month-old spayed, female mongrel with polyuria, polydipsia, polakiuria and nocturia. Serum biochemistry (alkaline phosphatase, ALT, urea, creatinine, GGT, globulins, triglycerides, cholesterol, total proteins), hemogram, urinalysis and abdominal ultrasound were requested. Blood exams were within the normal range and the urinalysis resulted in urine density of 1.009. Therefore, SDMA, bile acids, bilirubin (total and fractions), urinary protein: creatinine ratio, urinary GGT, Antinuclear Antibodies (ANA), and a new urinalysis were performed. All the measured parameters were within the normal range, except for the urine density of 1.010, suggesting Diabetes Insipidus. The 12-hour water deprivation test associated with desmopressin acetate revealed an increase in urine density to 1.028 and 1.029, one and two hours after administration of the medicine. Treatment was initiated with 3 drops of DDAVP daily in each eye, resulting in a slight improvement in clinical signs, and the dose was increased to 4 drops daily, resulting in the disappearance of the clinical signs and decreased the daily water intake by over 50%.
Keywords:
urine density; endocrinopathy; polyuria; polydipsia
RESUMO
O presente relato visou reportar o caso de uma cadela, castrada, sem raça definida, de 11 meses de idade, apresentando poliúria, polidipsia e noctúria. Foram solicitados bioquímicas séricas (FA, ALT, ureia, creatinina, GGT, albumina, proteínas totais, globulinas, triglicérides, colesterol total), hemograma, urinálise e ultrassonografia abdominal. Os exames hematológicos não apresentaram alterações dignas de nota, e na urinálise a densidade urinária era de 1.009 . Solicitaram-se exames de SDMA, ácidos biliares, bilirrubina total e frações, cortisol basal, anticorpo antinuclear (ANA), nova urinálise, razão proteína-creatinina urinária e GGT urinária. Com exceção da densidade urinária de 1.010, todos os parâmetros avaliados estavam de acordo com os valores de referência, sendo sugestivo de diabetes inspidus. O teste de privação hídrica de 12 horas, associado à aplicação de acetato de desmopressina (DDAVP), revelou aumento da densidade urinária para 1.028 e 1.029 , uma e duas horas após a aplicação do medicamento. Iniciou-se o tratamento diário com três gotas de DDAVP em cada olho, o que promoveu moderada melhora do quadro clínico, sendo aumentada a dose para quatro gotas ao dia, cessando-se os sinais clínicos e reduzindo-se a ingestão de água diária em mais de 50%.
Palavras-chave:
densidade urinária; endocrinopatia; poliúria; polidipsia
INTRODUCTION
Many diseases can alter thirst and urine excretion mechanisms, including Diabetes Insipidus, a rare endocrinopathy that is still barely understood. DI can originate from the central nervous system (CDI), when the arginine vasopressin (AVP) or anti-diuretic hormone (ADH) is not produced by the supraoptic or paraventricular magnocells neurons from the hypothalamus or inadequately secreted by the neurohypophysis. Nephrogenic Diabetes Insipidus (NDI) occurs when aquaporin channels in the kidney stop responding to AVP (Harb et al., 1996; Mahía and Bernal, 2021; Xu et al., 2023).
Arginine vasopressin, as well as its carrier protein, neurofisin II, are produced by the hypothalamus, stored, and secreted in pulses by the neurohypophysis when plasma osmolality increases. This process occurs when there is an increase in extracellular NaCl, or hypovolemia due to fluid losses. In the kidney the AVP binds with its receptor, AVP receptors type II, in the renal collecting tubules, increasing aquaporin-II channels in cells membranes. Water is reabsorbed into the interstitium through passive diffusion in the aquaporin-III and -IV channels. Hence, animals with DI do not reabsorb water, losing the fluid in the urine, which predisposes to dehydration, hyposthenuria and isosthenuria (Mahía and Bernal, 2021; Valandro et al., 2013; Xu et al., 2023).
Moreover, CDI can be congenital, traumatic, neoplasic, due to hypoxia or idiopathic, (Mahía and Bernal, 2021; Ghizzo et al., 2022). In young animals, CDI is mostly idiopathic, and neoplasic in older dogs (over seven years old). Even though, CDI tends to be traumatic or hereditary in humans, animal models have been used to study this second type (Mahía and Bernal, 2021; Xu et al., 2023).
DI most common clinical signs are related to water mechanism disbalances, which can cause polyuria (PU), polydipsia (PD), polakiura, nocturia, blood osmolality increase, urine density decrease, and in emergencies dehydration, hypernatremia hyerchloremia, as well as azotemy (Evenhuis et al., 2021; Ghizzo et al., 2022; Harb et al., 1996). Due to clinical signs unspecifity CDI diagnosis is made by exclusion of other illness that can promote PD and PU, such as Diabetes Mellitus, chronic kidney disease, psychogenic polydipsia, in addition to the water deprivation test and response of desmopressin (DDAVP), a synthetic analogue to ADH (Ghizzo et al., 2022; Silva and Zanutto, 2021).
However, this test is rarely done due to the low incidence of CDI dogs and cats, even with its relevance regarding PU and PD promotion (Evenhuis et al., 2021; Harb et al., 1996; Paulin et al., 2023; Valandro et al., 2023). Furthermore, even with more research on CDI physiopathogeny in humans, there is also a diminished number of reports of this disease (Mahía and Bernal, 2021; Xu et al., 2023). Thus, this article aims to register a case of congenital CDI in a young dog presenting persisting PU and PD.
CASE REPORT
A female mongrel, neutered, at 11 months of age, 16kg of body weight and body condition score (BCS) 6/9 was attended at the Veterinary Clinic from the School of Life and Medical Sciences at the Pontificial Catholic University of Goiás. During anamnesis the owner said that the dog showed signs compatible with PU, PD (water intake of 150mL/kg/day) nocturia and polyphagia since adoption at 3 months of age. The owner also reported recent weight gain and cystitis, diagnosed and treated at another institution.
Even with the dog agitated during physical exam, all vital parameters were within normal range. Alopecic, round, peeling skin lesions were observed along all body (Fig. 1). As complementary exams, hemogram, serum biochemistry (alkaline phospathase, alanine aminotransferase, urea, creatinine, gamma-glutamyltransferase, globulins, triglycerides, cholesterol, total proteins), skin lesions cytology, urinalysis and abdominal ultrasonography were requested.
Cutaneous cytology showed epithelial cells (++/+++), cellular debris (+/+++), isolated and dispersed round bacteria (+/+++). All hemogram parameters were within reference, while albumin was near the superior value at 3.2g /dL (reference: 2.6 - 3.2g /dL), and total proteins 5.1 g/dL (reference: 5.4 - 7.1 g /dL) as well as globulin 1.9g /dL (reference: 2.7 - 4.4 g /dL) were decreased. Urinalysis, collected through cystocenthesis, results were pH of 6.0, density of 1.009 (indicating isosthenuria), presence of bacteria (rare) and lack of other sediments. Ultrasonographic examination showed a discrete thickening from the urinary bladder wall associated with debris deposition and hyperechoic suspended dots, hyperechoic dots (resembling mud) at the gall bladder, and diffuse wall thickening from the intestines in the regions of duodenum, jejunum and colon (Figure 2).
Skin lesions. A) Round, peeling and alopecic lesions in the interscapular region. B) Zoomed in lesion portrayed in A). C) Round, peeling lesions in the pelvic region.
Ultrasound examination. A) Bladder showing thickening of the wall and hypercogenous spots. B) Left kidney with preserved cochlear-medullary relationship. C) Right kidney with preserved cortico-medullary relationship. D) Duodenum showing thickening of walls. E) Jejunum showing thickening of the walls. F) Descending colon with wall thickening.
Considering the complementary exams results and owner new complaint about sporadic vomiting, topic treatment with chlorhexidine 2% + miconazole 2.5% was prescribed in association with hypoallergenic diet exchange. Billirubine (total and fractions), bile acids, SDMA, protein-creatinine ratio, urinary GGT, Antinuclear Antibodies (ANA), and another urinalysis were requested for diagnosis elucidation.
In this round of exams urine density was 1.010 (indicating isosthenuria), pH 6.0 and bacteria were present (++/+++) at the urinalysis, which also presented granular cylinders and 5 - 15 leukocytes per camp analyzed (reference: 0 - 5 leukocytes per camp). Other test results were within reference and were compiled in Table 1. On subsequent appointment the owner reported resolution of vomiting episodes, however skin lesions did not improve after treatment. Lokivetmab injection (2mg/kg) was prescribed, improving all cutaneous clinical signs for six weeks. Ever since, the patient is treated periodically with the same protocol.
Considering these data, water deprivation test associated with desmopressin acetate (DDAVP) administration was required. The animal was kept under observation to perform the 12-hour hydric fasting, which culminated in a 9% reduction of body weight (14,600 kg). Urine collection was done by cystocentesis before administration of one drop in each eye of DDAVP, followed by two collections at 1 and 2 hours after treatment (Fig. 3). Urine densities (Table 2) confirmed CDI diagnosis. Initial treatment with 1 drop of desmopressin in each eye three times a day, resulted in a slight improvement of polyuria and decrease on daily water intake. Dosage increase was recommended, for 4 drops a day in each eye, promoting all clinical signs resolution. After 45 days of treatment a new urinalysis was requested, and urine density had increased to 1.028 without water deprivation, ph to 6.5 and bacteria were not found, demonstrating treatment efficiency. At submission time, clinical signs are kept under control with patient continuous treatment for 8 months, with the same dosage of 4 drops in each eye per day.
Patient urine sample. A) Urine collected before DDAVP treatment. B) Urine sample collected one hour after DDAVP treatment.
DISCUSSION
The patient presented signs compatible with Central Diabetes Insipidus (CDI), a rare endocrinopathy, without a fully understood pathophysiology. The stimulation with desmopressin acetate (DDAVP) performed is essential to differentiate CDI from psychogenic polydipsia, enabling the supposed diagnosis (Silva and Zanutto, 2021; Valandro et al., 2013).
In a retrospective study the only recurrent signs of CDI were PU and PD, and in 9 out of the 20 cases the dogs presented isosthenuria even when dehydrated, in accordance with what was verified in this report, (Harb et al, 1996). Hence, urine density <1.008 is not enough to discard CDI diagnosis, and water deprivation associated with DDAVP administration, like the one performed in order to enable the definitive diagnosis, is considered the gold standard to evaluate DIC. Since its adoption at 3 months, the animal presented clinical signs, suggesting to the congenital origin of the disease. Magnetic resonance would be an important tool to truly differentiate the disease neurological origin, however due to high financial reasons the exam was not performed. Moreover, the improvement in clinical signs also confirmed the diagnosis of CDI, as well as the increase in urine density to 1.028 after 45 days of treatment (Harb et al, 1996; Schimidt et al., 2009; Silva and Zanutto; 2021).
Due to CDI rarity, it was important to exclude other causes to PU and PD that were attached to clinical signs. The complementary exams performed ruled out diabetes mellitus, hyperadrenocorticism, hyperthyroidism, renal dysplasia, chronic kidney disease, pyelonephritis, glomerulonephritis, liver failure and autoimmune diseases such as Canine Lupus Erythematosus, that could promote PU, PD and be related to the skin lesions (Ghizzo et al., 2022; Paulin et al., 2023; Valandro et al., 2013).
The ultrasound showed hyperechoic dots and wall thickening at the urinary bladder, which in addition to the urinalysis bacteriuria, is suggestive of cystitis. Even though uncommon, one report was found among the literature in which the dog had recurrent infectious cystitis along with urolithiasis and partial CDI. The low urine osmolality, due to CDI could predispose bacterial proliferation, which could develop to cystitis (Harb et al., 1996; Silva and Zanutto 2021). However, since the patient did not display clinical signs of cystitis, such as dysuria, low urine volume or positioning mimic, antibiotics or other drugs therapy was not necessary.
In humans idiopathic and hereditary CDI has been associated with higher chances of developing anxiety and depression (Mahía and Bernal, 2021). Even though no neurological signs were present at the dog's evaluation, she was very aggitated and the owner reported stress signs like pacing and object destruction at home. Additionally, it is important to highlight that the codifying gene for vassopressin production (AVP-neurophysin II) is in close proximity to the ocytocin production regulator gene, having both hormones a close relationship, and diminished levels of serum ocytocin have been found in CDI patients. Studies are also researching the ocytocin and desmopressin association to treat CDI (Harb et al., 1996; Xu et al., 2021).
Since different DDAVP dosages have been recommended as treatment for CDI (Lacqua et al., 2021; Schimidt et al., 2009; Valandro et al., 2013). Initial treatment was done with 3 drops a day of dDAVP in each eye. This protocol resulted only in the patient’s partial improvement. Hence, dosage increase to 4 drops a day, promoting a significant decrease on water intake from 150ml/kg per day to 64mL/kg, and clinical signs resolution. Literature also allows owners the choice to not treat idiopathic CDI, if there is constant access to water in order to avoid complications (Silva and Zanutto, 2021; Valandro et al., 2013). In this report the administration of DDAVP allowed a better quality of life to both the patient and owner, that was aggravated by the PU and PD manifestations, highlighting the importance of listening to owners wishes when practicing small animals’ medical clinic.
CDI prognosis is variable, since some patients survive for years without complications and others perished a few weeks after the diagnosis. This variation is mostly due to CDI diverse etiology and age at diagnosis. From the initial appointment to article publication the dog has completed two years and has not shown other neurological signs or developed complication due to CDI. Acquired CDI associated with neurological signs usually presents a poor prognosis due to its relationship with hypophysis neoplasia (Harb et al., 1996; Paulin et al., 2023). Traumatic CDI prognosis is uncertain, since the disease can cease on its own or not. However, recently a dog developed neurological complications after years of treatment for CDI that caused persistent adipsia (Evenhuis et al., 2021; Harb et al., 1996; Lacqua et al., 2021). In this report the patient presented PU, PD, nocturia since adoption at 3 months old, signs expected in animals with congenital CDI. Congenital CDI usually present a good outcome, and animals can survive for several years without showing clinical signs when treated (Ghizzo et al., 2022; Harb et al., 1996; Silva and Zanutto, 2021).
CONCLUSION
This article presents a case of Central Diabetes Insipidus, an uncommon endocrinopathy in the Veterinary Medicine practice. The dog was diagnosed with congenital CDI after a meticulous evaluation and exclusion of other possible diagnoses that can cause polyuria and polydipsia, as well as associating the water deprivation test with desmopressin acetate administration. Furthermore, the treatment with DDAVP was considered successful, resulting in clinical signs resolution, normalizing daily water intake and raising urine density to 1.028, serving as a good example of Central Diabetes Insipidus diagnosis, management and treatment.
REFERENCES
- EVENHUIS, J.; EPSTEN, S.; DELLA-MAGGIORE, A.; REAGAN, K. Congenital pituitary cyst resulting in adipsic central diabetes insipidus and secondary hypernatremia in a cat. J. Feline Med. Surg. Open Rep., v.7, p.2055116921990294, 2021.
- GHIZZO, J.; KUSER, G.; GHIZZO, J. Central diabetes insipidus in a Yorkshire terrier dog: case report. Pubvet, v.16, p.1-3, 2022.
- HARB, M.; NELSON, W.; FELDMAN, E. et al. Central diabetes insipidus in dogs: 20 cases (1986-1995). JVMA, v.20, p.1884-1888, 1996.
- LACQUA, A.; ROZANSKI, E.; FRY, D. et al. Diagnostic findings and successful management of central diabetes insipidus following a self-inflicted penetrating brain injury in a dog. Braz. J. Vet. Med., v.43, p.e001521-e001521, 2021.
- MAHÍA, J.; BERNAL, A. Animal models for diabetes insipidus. Handbook Clin. Neurol., v.181, p.275-288, 2021.
- PAULIN, M.; GLEASURE, S.; SNEAD, E. Multiple pituitary hormone deficiencies in a kitten: hyposomatotropism, hypothyroidism, central diabetes insipidus and hypogonadism. Can. Vet. J., v.64, p.245-251, 2023.
- SCHIMIDT, C.; EMANUELLI, M.; CARGNELUTTI, J.F. et al. Centrally-inspired diabetes in a dog. Ciênc. Rural, v.39, p.922-925, 2009.
- SILVA, D.; ZANUTTO, M. Diabetes insipidus central em dois cães. Med. Vet., v.15, p.357-362, 2021.
- VALANDRO, M.; PIETRO, A.; MARTINS, D. Diabetes insipidus in a dog. Acta Sci. Vet., v. 41, p.1-5, 2013.
- XU, H.; HAO, H.; WANG, S. et al. A dog carrying mutations in AVP-NPII exhibits key features of central diabetes insipidus. J. Genet. Genomics, v.50, p.280-283, 2023.
Publication Dates
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Publication in this collection
14 July 2025 -
Date of issue
Jul-Aug 2025
History
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Received
27 Sept 2024 -
Accepted
19 Dec 2024
