Hypothalamic adipsia presenting as persistent hypernatremia after aneurysmal subarachnoid hemorrhage

Abstract

A woman in her 50s developed persistent hypernatremia after aneurysmal subarachnoid hemorrhage treated with surgical clipping. During the acute phase, she presented transient hypotonic polyuria requiring desmopressin, initially suggesting arginine vasopressin (AVP) deficiency (AVP-D). However, her subsequent course was characterized by recurrent hypernatremia without persistent polyuria and with complete absence of thirst. Urine output was low or inappropriately normal, with preserved urinary concentrating capacity, making persistent AVP-D unlikely. Neuroimaging showed ischemic changes close to hypothalamic regions involved in osmoregulation. The clinical pattern supported hypothalamic adipsia, with possible partial dysfunction of osmotically stimulated AVP release. Outpatient management focused on structured water intake, family supervision, digital reminder systems, and cautious low-dose desmopressin to minimize osmotic variability. This case emphasizes that hypernatremia following neurovascular injury should not be automatically attributed to AVP-D. Systematic assessment of thirst, urine output, and urine osmolality is key to identifying hypothalamic adipsia, facilitating early diagnosis and the implementation of structured hydration strategies to prevent recurrent severe hypernatremia and its complications.

Introduction

Hypernatremia, defined as a plasma sodium concentration >145 mmol/L, is a clinically relevant complication in patients with acute neurological injury and usually reflects a free water deficit rather than sodium excess [1-3]. In the neurocritical setting, hypernatremia is prevalent and associated with increased mortality, poorer functional outcomes, and a higher risk of neurological complications, especially when sodium levels exceed 155-160 mmol/L (reference range: 135-145 mmol/L) or when correction is suboptimal [1-3]. Its pathophysiology is multifactorial, including impaired access to water, increased renal water losses, arginine vasopressin (AVP) deficiency (AVP-D), osmotic diuresis, and disruption of hypothalamic pathways regulating thirst and osmoregulation [1-4]. Distinguishing among these entities is essential, since management differs substantially. AVP-D is characterized by hypotonic polyuria and requires desmopressin replacement, whereas hypothalamic adipsia is primarily a disorder of thirst perception in which scheduled water intake is central to treatment [4-8].

We describe a patient who developed recurrent hypernatremia after aneurysmal subarachnoid hemorrhage, initially suggesting partial AVP-D, but whose longitudinal course supported hypothalamic adipsia.

Case presentation

A woman in her 50s was first evaluated by the endocrinology service during hospitalization for aneurysmal subarachnoid hemorrhage (SAH) in June 2022, due to early postoperative hypernatremia and transient hypotonic polyuria. After discharge, she continued follow-up in the endocrinology outpatient clinic for persistent hypernatremia. She was an active smoker, with no relevant personal or family medical history, no known cardiovascular risk factors or overweight, and no previous neurological disease.

She initially presented to the emergency department with severe headache, neck stiffness, and hearing loss, while maintaining a preserved level of consciousness (Glasgow Coma Scale 15/15) and without associated focal neurological deficits. Cranial computed tomography (CT) and CT-angiography showed SAH involving the bilateral frontotemporal sulci, basal and interpeduncular cisterns, and perimesencephalic, prepontine, and prebulbar regions, secondary to a 6.7 mm saccular aneurysm arising from the anterior communicating artery (ACoA) (Figs. 1 and 2A). These findings were associated with hypoplasia of the proximal segment of the right anterior cerebral artery (right ACA) (A1 segment) (Fig. 2B).

Figure 1.

Axial noncontrast cranial CT scan demonstrating hyperdense foci consistent with SAH extending through the basal cisterns (white arrows), suggestive of an aneurysmal bleeding pattern. CT, Computed Tomography.

Figure 2.

(A) Axial cranial CT angiography with MIP reconstructions showing a 6 mm saccular aneurysm arising from the anterior communicating artery AcoA (white arrow), identified as the source of hemorrhage. (B) Coronal cranial CT angiography demonstrating the saccular aneurysm arising from the anterior communicating artery (white arrow), as well as an incidental hypoplasia of the right A1 segment of the anterior cerebral artery. AcoA, Anterior Communicating Artery; CT, Computed Tomography; MIP, Maximum Intensity Projection.

Urgent surgical clipping of the ACoA aneurysm was performed, together with clipping of an additional aneurysm at the bifurcation of the left middle cerebral artery (MCA). During dissection, intraoperative aneurysm rupture occurred, which was controlled with temporary clipping of both A1 segments followed by definitive clipping.

Postoperative care was provided in the intensive care unit (ICU) during the immediate postoperative period, where the patient required sedation and analgesia due to episodes of restlessness and agitation, as well as noninvasive mechanical ventilation due to hypoxemic respiratory failure secondary to fluid overload. During the early postoperative period, she developed transient hypotonic polyuria that required desmopressin. Mannitol was not administered at any time during the postoperative course, thereby excluding osmotic diuresis as a likely explanation for the subsequent fluid and electrolyte abnormalities. After this initial phase, however, urine output became inappropriately normal despite persistent hypernatremia.

Diagnostic assessment

During hospitalization, serum sodium remained elevated, ranging from 147 to 156 mmol/L (reference range: 135-145 mmol/L), with urine output of approximately 2.5 L/day and negative fluid balances. Intermittent episodes of severe hypernatremia occurred, reaching 163 mmol/L, in the setting of markedly reduced fluid intake. These episodes were associated with reduced urine output, relatively concentrated urine 552 mOsm/kg (reference range: 300-1000 mOsm/kg), and urinary sodium concentration above 100 mmol/L (reference range: 30-190 mmol/L) (Fig. 3).

Figure 3.

Evolution of serum sodium levels during hospitalization after surgery. Na⁺: serum sodium levels. Reference range: 135-145 mmol/L.

Follow-up neuroimaging showed postoperative changes without rebleeding, with ischemic lesions involving the subcallosal region, the right portion of the corpus callosum, and the left frontotemporal territory (Fig. 4). These findings suggested injury near hypothalamic regions involved in osmoregulation.

Figure 4.

Sagittal noncontrast cranial CT scan showing a hypodense area along the right margin of the genu of the corpus callosum (white arrow), consistent with an established ischemic lesion. Metallic clip material used for surgical treatment of the AcoA aneurysm is also visible. AcoA, Anterior Communicating Artery; CT, Computed Tomography.

One month after surgery, endocrine evaluation demonstrated globally preserved anterior pituitary function, with normal (thyroid-stimulating hormone [TSH] 1.8 µIU/mL [SI: 1.8 mIU/L] [reference range, 0.37-4.20 µIU/mL {SI: 0.37-4.20 mIU/L}], free thyroxine [free T4] 1.04 ng/dL [SI: 13.38 pmol/L] [reference range, 0.90-1.70 ng/dL {SI: 11.58-21.88 pmol/L}], and free triiodothyronine [free T3] 3.42 pg/mL [SI: 5.25 pmol/L] [reference range, 2.00-4.40 pg/mL {SI: 3.07-6.76 pmol/L}]), somatotropic (insulin-like growth factor 1 [IGF-1] 141 ng/mL [SI: 18.43 nmol/L] [reference range, 53-234 ng/mL {SI: 6.93-30.59 nmol/L}]; IGF-1+0.39 standard deviation score [SDS]), adrenal (morning cortisol 15.6 µg/dL [SI: 430.4 nmol/L] [reference range, 4.8-20.0 µg/dL {SI: 132.4-551.8 nmol/L}]), and lactotroph (prolactin 11.9 ng/mL [SI: 11.9 µg/L] [reference range, 4.7-28.2 ng/mL {SI: 4.7-28.2 µg/L}]) axes. The only abnormality involved the gonadal axis, which showed a hypergonadotropic pattern consistent with menopause (follicle-stimulating hormone [FSH] 106.0 mIU/mL [SI: 106.0 IU/L] [reference range, 26.7-133.4 mIU/mL {SI: 26.7-133.4 IU/L}], luteinizing hormone [LH] 53.6 mIU/mL [SI: 53.6 IU/L] [reference range, 5.0-62.0 mIU/mL {SI: 5.0-62.0 IU/L}], and estradiol 5.0 pg/mL [SI: 18.4 pmol/L] [reference range, 1.1-18.2 pg/mL {SI: 4.0-66.8 pmol/L}]), rather than pituitary dysfunction.

After hospital discharge, the patient reported asthenia and persistent absence of thirst. She denied polyuria or polydipsia and described very low spontaneous fluid intake, below 1 L/day. Laboratory testing continued to show hypernatremia, with serum sodium ranging from 150 to 153 mmol/L, elevated plasma osmolality of 323 mOsm/kg (reference range: 280-295 mOsm/kg), and markedly reduced urine output of 350 mL/24 hours. Pituitary magnetic resonance imaging (MRI) showed no structural pituitary abnormalities. The absence of structural pituitary abnormalities on MRI did not exclude hypothalamic osmoregulatory dysfunction, given the postoperative ischemic changes described above.

The absence of polyuria, in conjunction with relatively concentrated urine and impaired thirst, argued against persistent AVP-D as the primary mechanism. The fluctuating pattern of hypernatremia depending on water intake, together with preserved urinary concentrating capacity, was more consistent with hypothalamic adipsia rather than a pure reset osmostat.

Treatment

Management was undertaken in both inpatient and outpatient phases. Throughout hospitalization, treatment required repeated adjustments of intravenous fluid therapy, minimization of sodium load, free water supplementation, and desmopressin during the early polyuric phase. After partial stabilization, sublingual desmopressin was continued at night.

During follow-up, management emphasized structured fluid intake rather than desmopressin alone, as impaired thirst perception, resulting in inadequate spontaneous drinking, was the primary clinical issue. The patient was instructed to increase water intake progressively, initially to at least 1.5 L/day and later to approximately 2 L/day.

Outcome and follow-up

With family support, the patient was able to increase fluid intake to approximately 2 L/day, resulting in partial biochemical improvement, with serum sodium decreasing to 146 mmol/L, plasma osmolality to 300 mOsm/kg, and urine output increasing to 1300 mL/24 hours. This partial improvement enabled an attempt to discontinue desmopressin, while maintaining the previously established hydration regimen.

However, at subsequent follow-up, serum sodium again increased to 151 mmol/L, with plasma osmolality of 312 mOsm/kg, urine output of 700 mL/24 hours, and persistent absence of thirst. Desmopressin was therefore restarted at low nocturnal dose.

At the most recent follow-up, the patient continued to experience recurrent episodes of hypernatremia related to poor adherence to scheduled drinking. These episodes were accompanied by symptoms such as bradypsychia, somnolence, and confusion, temporally associated with worsening hypernatremia. She remains on nocturnal desmopressin and strict scheduled water intake supported by a mobile phone alarm system.

Discussion

Hypernatremia after acute neurological injury should be approached as a syndrome rather than as a single diagnosis. Although AVP-D is often presumed early in patients with brain injury and hypernatremia, the diagnosis requires demonstration of persistent polyuria with inappropriately dilute urine [4, 5]. In patients with unrestricted access to water and preserved thirst, hypernatremia is less common because increased water intake usually compensates for renal water losses [4, 5]. Therefore, the combination of serum sodium concentration, urine output, urine osmolality, thirst perception, and access to water is more informative than serum sodium alone [1, 4, 5].

The main differential diagnosis in this case included AVP-D, reset osmostat, and hypothalamic adipsia. AVP-D was considered during the acute postoperative period because of transient hypotonic polyuria and partial response to desmopressin [4, 5, 9, 10]. However, the subsequent absence of persistent polyuria, together with relatively concentrated urine during hypernatremia, argued against persistent AVP-D as the predominant mechanism.

Reset osmostat was also considered, as hypothalamic injury may shift the osmotic threshold for thirst and AVP secretion [11, 12]. However, this condition typically produces a relatively stable abnormal sodium concentration around a new equilibrium set point [11, 12]. In contrast, our patient had recurrent and clinically significant sodium fluctuations closely linked to inadequate water intake, with persistent absence of thirst. A suggested diagnostic approach to hypernatremia after acute cerebrovascular injury is summarized in Fig. 5.

Figure 5.

Diagnostic algorithm for the evaluation of hypernatremia following acute cerebrovascular accident. AVP-D, Arginine vasopressin deficiency; CSW, Cerebral Salt Wasting; Na+, Sodium; OsmU, Urine osmolality; POST-CVA, Post-cerebrovascular accident. ^aIn a patient presenting with polyuria associated with low urine osmolality and an absent or impaired thirst mechanism, the possibility of partial adipsic AVP-D should be considered; however, longitudinal follow-up is required to confirm the diagnosis.

The overall pattern was therefore most consistent with hypothalamic adipsia. This disorder results from injury to hypothalamic structures involved in osmoregulation and thirst perception, particularly the anterior hypothalamic and preoptic regions [6, 13]. Patients fail to experience thirst despite plasma hyperosmolality and are therefore unable to defend plasma sodium through spontaneous drinking [6-8, 14]. Urine output may be low or inappropriately normal, and urinary concentrating capacity may be preserved if the AVP axis is at least partially intact [15-17]. This explains why hypothalamic adipsia can be misclassified as AVP-D during the acute phase, especially when transient polyuria, fluid shifts, or partial AVP dysregulation coexist [7, 8, 14-17]. Longitudinal assessment was crucial in this case, as the dominant abnormality became evident only after the acute postoperative phase: persistent lack of thirst, low spontaneous fluid intake, recurrent hypernatremia, and absence of sustained hypotonic polyuria.

Copeptin measurement could have provided additional pathophysiological insight, particularly regarding residual AVP secretory capacity. In patients with severe hypernatremia, basal copeptin reliably differentiates AVP deficiency from AVP resistance without the need for osmotic stimulation, and may help distinguish adipsic AVP-D from pure adipsia with preserved AVP secretion [7, 18-20]. However, copeptin is not routinely available at our institution and requires referral to an external laboratory. In this case, the diagnosis was supported by highly characteristic clinical and radiological findings, including chronic hypernatremia, complete absence of thirst, preserved urinary concentrating capacity, and ischemic injury in the anterior communicating artery territory. Therefore, copeptin measurement was unlikely to have altered the diagnostic or therapeutic approach.

Management should be directed at the underlying mechanism. In hypothalamic adipsia, the cornerstone of treatment is scheduled water intake, supported by education, family supervision, and practical tools such as alarms or mobile phone reminders [6-8, 14]. Serum sodium should be monitored closely during unstable phases and after any change in fluid prescription or desmopressin dose [6-10, 21]. Desmopressin should not be interpreted as routine replacement therapy in patients without persistent polyuria [4-10]. Its role is individualized and cautious, mainly when a mixed phenotype is suspected, with partial impairment of osmotically stimulated AVP release or marked osmotic variability. Low-dose nocturnal desmopressin may help reduce sodium fluctuations in selected patients, but dose escalation without close biochemical monitoring may cause excessive water retention and iatrogenic hyponatremia [9, 10, 21].

This case highlights the importance of recognizing absent thirst as a key diagnostic sign and of prioritizing structured hydration over desmopressin-cantered management.

Learning points

• Hypernatremia after neurovascular injury should not be attributed automatically to arginine vasopressin deficiency (AVP-D).

• Persistent AVP-D requires hypotonic polyuria; absence of sustained polyuria and relatively concentrated urine should prompt reconsideration of the diagnosis.

• Absence of thirst despite hypernatremia is a key clinical clue to hypothalamic adipsia.

• Management of hypothalamic adipsia relies primarily on scheduled water intake, adherence strategies, family support, and close sodium monitoring.

• Desmopressin may be useful only in selected mixed phenotypes with suspected partial AVP dysregulation and should be used cautiously.

Contributors

All authors met the International Committee of Medical Journal Editors criteria for authorship. B.R.J. and A.M.M.D. contributed to data collection, diagnostic interpretation, literature review, and drafting of the initial manuscript. M.R.R.G., R.O.R., and E.D.F. were involved in the patient's inpatient and outpatient assessment and management, contributed to the clinical and diagnostic interpretation of the case, and critically revised the manuscript for important intellectual content. M.A.M.B. supervised the clinical interpretation, diagnostic approach, and manuscript development, and critically revised the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work.

Funding

No public or commercial funding.

Disclosures

None declared.

Informed patient consent for publication

Signed informed consent obtained directly from patient.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed. All relevant clinical data are included in the article.