Presumed partial aplasia of the hypothalamus and pituitary gland causing central diabetes insipidus in an adult cat

Abstract

Case summary

A 2-year-old castrated male domestic shorthair cat presented with severe lethargy, hyporexia, dehydration and poor body condition. The incidence of polyuria/polydipsia was unknown because of the presence of multiple other cats in the household. Laboratory findings revealed severe hypernatraemia, isosthenuria, haemoconcentration and moderate azotaemia. MRI of the head demonstrated partial hypoplasia/aplasia of the hypothalamus and pituitary gland, confirming congenital central diabetes insipidus; additional endocrine testing excluded other causes. Initial fluid therapy improved the azotaemia and stabilised the haematocrit; however, hypernatraemia persisted until desmopressin therapy was initiated. The cat was successfully managed in the long term with gradually titrated oral desmopressin, achieving normalisation of electrolytes.

Relevance and novel information

This report details the first documented case of central diabetes insipidus in an adult cat, attributed to presumed partial aplasia of the hypothalamus and pituitary gland, with no other hormonal deficiencies.

Plain language summary

Congenital brain abnormality causing central diabetes insipidus in an adult cat: a rare case report

A 2-year-old cat was brought to the veterinarian because it was lethargic, eating poorly and dehydrated. Tests showed very high sodium levels consistent with a rare condition called central diabetes insipidus, which affects the body’s ability to regulate water balance. A brain scan revealed that parts of the cat’s hypothalamus and pituitary gland – areas that help regulate hormones and water – had not developed normally since birth. After treatment with fluids and the medication desmopressin, the cat’s condition improved and was successfully managed over the long term. This is a rare case report of a developmental brain problem in an adult cat that causes signs of diabetes insipidus without any other hormonal issues.

Introduction

Feline central diabetes insipidus (CDI) is a rare condition characterised by a deficiency in the production or secretion of arginine vasopressin (AVP). Accordingly, the Human Endocrine Society recently proposed renaming it arginine vasopressin deficiency (AVP-D).^1,2 AVP is a neurosecretory hormone produced in the hypothalamus by neuronal cell bodies. It is transported through axons of the hypothalamo-hypophyseal tracts to the neurohypophysis, where it is released into the capillary bed. ³ When AVP binds to V2 receptors on the basolateral membrane of principal cells in the renal collecting duct, multiple protein kinase pathways are activated, leading to the accumulation of aquaporin-2 (AQP-2) on the apical membrane. AQP-2 facilitates the entry of water molecules into collecting duct cells, after which water exits into the interstitium through aquaporin-3 and/or aquaporin-4 channels on the basolateral membrane. ¹

CDI is most often caused by head trauma, neoplasia or congenital lesions affecting the pituitary gland. ¹ Cats presenting with CDI usually exhibit polyuria and polydipsia (PU/PD), have low urine osmolarity and increased serum osmolarity, and are hypernatraemic. ¹ Here, we report the case of an adult cat with CDI resulting from presumed partial aplasia of the hypothalamus and part of the pituitary gland, with no other hormonal deficiencies aside from the lack of AVP.

Case description

A 2-year-old, castrated male domestic shorthair cat presented with severe apathy and hyporexia. Reduced appetite and apathy had been present for several days before presentation to the clinic. PU/PD were not thoroughly assessed because there were eight other cats in the household, which made individual monitoring difficult. However, it was noted that this cat may have been drinking more water than the others since being adopted. The cat was originally from a farm, rescued at approximately 2 months of age, and had been kept indoors ever since. The cat was up to date on vaccinations and yearly deworming.

On presentation, the cat was severely dehydrated and lethargic, with a body condition score (BCS) of 2/9, a poor haircoat, generalised scaling and small stature. Cardiopulmonary auscultation was unremarkable (heart rate 200 beats/min, respiratory rate 32 breaths/min). Mucous membranes were pale pink and dry, with a delayed capillary refill time; rectal temperature was 35.7°C. Abdominal palpation was non-painful, and peripheral lymph nodes were normal. The cat was actively warmed and given a shock-dose fluid bolus for stabilisation.

Urinalysis after the fluid bolus for stabilisation showed isosthenuria (urine specific gravity [USG] 1.010) without other abnormalities; urine culture was negative. The haematocrit was markedly high at 72%, consistent with the cat’s dehydration. A biochemistry panel showed moderate azotaemia and increased total protein and globulin levels, consistent with severe dehydration. Electrolyte changes were as follows: mild hyperphosphatemia, mild hyperkalaemia, mild hyperchloraemia and marked hypernatraemia (Table 1). Calculated plasma osmolality [= 2 sodium (Na) + (blood urea nitrogen / 2.8) + (glucose / 18)] was high on the day of presentation (>370 mOsm/kg, reference interval [RI] 280–300). The cat tested negative for feline leukaemia virus and feline immunodeficiency virus.

Table 1

Plasma biochemistry and USG values

Parameter	Initial presentation	After treatment with desmopressin (day 2)	After treatment with desmopressin (day 120)	RI
USG	1.010	NA	>1.035	>1.035
BUN (mmol/l)	28.4	NA	NA	5.7–12.9
Creatinine (µmol/l)	277	NA	166	71–212
Chloride (mmol/l)	144	121	120	112–129
Sodium (mmol/l)	>180	161	160	150–165
Potassium (mmol/l)	6.3	5.3	5.5	3.5–5.8

BUN = blood urea nitrogen; NA = not available; RI = reference interval; USG = urine specific gravity

An abdominal ultrasound examination performed 1 day after presentation under sedation was unremarkable. Three days after the initial presentation, MRI of the head was performed under general anaesthesia, using a 1.5 T MRI machine (GE Signa HD; GE Medical Systems). A standard brain MRI protocol was used, including transverse, sagittal and dorsal T1- and T2-weighted sequences with and without contrast. Abnormal findings were limited to the hypothalamus and the pituitary gland. Specifically, the distal 6 mm of the left part of the hypothalamus were absent. Instead, T2-hyperintense, T1-hypointense and mildly T2*-hyperintense material with clear suppression in the fluid-attenuated inversion recovery sequence was present in that location, consistent with cerebrospinal fluid (CSF) in the resulting cavity with a width of 3.2 mm (asterisk in Figure 1). The pituitary gland was mostly absent; a small, 1.7 mm peripheral rim of tissue remained at the ventral and caudal aspects of the sella turcica (red arrow in Figure 1a,c). In this region, mild gadolinium uptake was evident in the post-contrast sequences (white arrowhead in Figure 1b). The brain hemispheres, the ventricular system, and the remaining cerebral and brainstem structures were symmetrical and of normal architecture. The cerebellum was normal in form, structure and position. In summary, MRI confirmed the suspicion of CDI due to a presumed malformation of the ventral parts of the diencephalon, specifically a presumed partial hypoplasia/aplasia of the hypothalamus and parts of the pituitary gland (Figure 1). CSF, collected via an atlanto-occipital tap, was unremarkable; therefore, an underlying inflammatory condition was unlikely.

Figure 1

(a) Transverse T2W FSE, (b) transverse T1W FSE fs + gadolinium, and (c) sagittal T2W FSE magnetic resonance images at the level of the sella turcica. There is aplasia of the left part of the hypothalamus and pituitary gland, evidence of a left-sided distension of the pars infundibularis of the third ventricle (asterisk) and only partially remaining tissue of the anterior left part of the pituitary gland (red arrow in panels (a,c), white arrowhead in panel (b)). fs = fat saturated; FSE = fast spin echo; T1W = T1-weighted; T2W = T2-weighted

To rule out other hormonal deficiencies, an adrenocorticotropic hormone stimulation test was performed, which was unremarkable. In addition, total free thyroxine and canine thyroid-stimulating hormone levels were measured to exclude hypothyroidism. Fructosamine and insulin-like growth factor-1 were also measured; both were unremarkable.

Before MRI, dehydration and profound hypernatraemia were addressed with intravenous lactated Ringer’s solution and free water (5% dextrose). The free-water deficit (FWD) was calculated using the 2024 American Animal Hospital Association Fluid Therapy Guidelines for Dogs and Cats [FWD = ([measured Na / desired Na] – 1) × 0.6 × body weight]. ⁴ Correction was planned over 48 h, targeting a sodium decrease of 0.5 mmol/l/h or less (maximum 10–12 mmol/l/day). Lactated Ringer’s solution was administered via a separate intravenous line to address dehydration. The cat had limited access to water. Despite serial monitoring, serum sodium remained elevated at 172 mmol/l. Azotaemia improved (creatinine 207 µmol/l after 24 h) and haematocrit stabilised at 32%. Despite calculated FWD replacement, serum sodium did not decrease as expected, likely because of ongoing renal free-water loss in the absence of sufficient endogenous AVP.

After the head MRI, desmopressin was administered (total dose of 4 µg SC q24h), as recommended in Shiel. ¹ Within 12 h, serum sodium decreased to 155 mmol/l. Gradual correction with intravenous fluids alone was ineffective, and after desmopressin administration, sodium decreased more rapidly than recommended. Although frequent neurological monitoring was limited by handling difficulties, the cat remained bright and alert, with no signs of deterioration.

Before transitioning the cat to oral desmopressin, the dose was reduced by 50%. Over the subsequent weeks and months, oral desmopressin (0.1 mg tablets) was gradually increased until sodium levels remained within the RI, starting with a quarter of a tablet twice daily. Ultimately, the cat received three-quarters of a tablet twice daily, and electrolytes remained within the RI by day 120 (Table 1). Two days after initiating desmopressin treatment, the cat showed no further signs of lethargy and remained well hydrated. Four months later, the BCS had improved to 4/9. The owners also reported a noticeable decrease in the cat’s water intake. However, the anxious behaviour and difficulties handling the cat persisted.

Discussion

CDI, also known as AVP-D, is a rare condition in cats, with limited documented cases.^5–11 The cat in this study showed no signs of CDI until later in life, despite a diagnosis of a congenital malformation. Notably, the cat had significant hypernatraemia (172 mmol/l) 1 year before the presentation of severe lethargy. This hypernatraemia was noted during an evaluation for diarrhoea and was not investigated further.

An extensive diagnostic work-up was performed to rule out alternative causes of hypernatraemia. Elevated sodium with hyposthenuria suggests central or nephrogenic diabetes insipidus (NDI). In this cat, the USG was isosthenuric; initial bolus stabilisation may have influenced the USG. AVP-D can be confirmed with a modified water deprivation test or a desmopressin therapeutic trial. ¹ The clinical utility of endogenous AVP measurement is limited by its variable secretion and challenges with sample handling. ¹ In human medicine, serum copeptin has largely supplanted plasma AVP measurement. It is stable in plasma or serum, but its applicability in cats remains unexplored and very limited data are available in healthy dogs. ¹² In this case, desmopressin effectively normalised serum sodium levels within 24 h.

The presence of concurrent mild chronic kidney disease (CKD) contributing to PU/PD and subsequent NDI remains a possibility. Although serum creatinine and symmetric dimethylarginine were within their RIs, early-stage CKD cannot be entirely excluded. ¹³

In young cats, acquired causes of CDI, particularly trauma, hypophysectomy and idiopathic origins, are most prevalent. Congenital anomalies, infections, inflammation, cysts and neoplasia are less common. ¹ Neoplasia is more frequently observed in older cats. Advanced imaging techniques, such as MRI and CSF analysis, are essential for confirming the diagnosis and for further endocrine evaluations. The malformation likely originated during embryogenesis, given the disparate developmental origins of the neurohypophysis and the adenohypophysis. ³ MRI results indicated partial pituitary gland involvement, correlating with AVP deficiency while preserving other hormone levels.

A necropsy study found that about 15% of cats without clinical signs had incidental pituitary lesions. ¹⁴ This suggests that a substantial portion of functional pituitary tissue may remain intact before the onset of clinical signs. ¹ Complete CDI is marked by the absence of AVP secretion and persistent hyposthenuria after correction of dehydration. Conversely, partial CDI permits some AVP production, enabling limited urinary concentration. In this case, the absence of persistent hyposthenuria and urine osmolality exceeding 300 mOsm/kg suggests preserved concentrating ability, which contradicts a complete CDI. Direct measurement was not performed at presentation, which limits interpretation.

Primary NDI is unreported in cats; in this case, secondary NDI was considered less likely given the absence of concurrent systemic disease. Severe dehydration and mild azotaemia may have affected USG. Hence, differentiating between partial CDI, complete CDI and secondary NDI is difficult without further diagnostic evaluation. ¹

Although well tolerated in this case, rapid correction of sodium is inadvisable. A lower initial dose of desmopressin would have been more appropriate. The cat’s tolerance of rapid correction may be related to suspected partial CDI, a shorter duration of severe hypernatraemia, prior sodium reduction and adequate hydration. However, sodium should be decreased gradually to prevent cerebral oedema and central nervous system dysfunction from rapid sodium shifts.^4,15

The cat exhibited significant anxiety and handling resistance, possibly linked to presumed partial hypothalamic aplasia. The hypothalamus, in conjunction with the limbic system, is crucial for modulating aggression, with specific areas governing various aggressive behaviors.^3,16 Oxytocin, which is synthesised alongside vasopressin in the paraventricular and supraoptic nuclei of the hypothalamus, may have contributed to the cat’s behaviour, as reduced oxytocin levels are linked to increased anxiety in humans. ¹⁷ Alternative explanations may include early rescue, which can lead to inadequate human socialisation and affect future interactions. ¹⁸

This case highlights the need to consider congenital CDI in adult cats, particularly when concomitant hypernatraemia and isosthenuria are present. With careful titration, desmopressin therapy can be effective and well tolerated in the long term.

Conclusions

To the authors’ knowledge, this is the first case report of presumed partial aplasia of the hypothalamus and pituitary gland causing CDI in an adult cat without other hormonal imbalances. Although rare, congenital malformation should be considered in the differential diagnosis of young adult cats with signs of pituitary dysfunction.