Sjogren’s syndrome is an autoimmune disease associated with xerostomia and xerophthalmia. The association of Sjogren’s with hyponatremia has rarely been reported and has been attributed to syndrome of inappropriate antidiuretic hormone secretion. Here, we report a case of polydipsia secondary to xerostomia as a cause of chronic hyponatremia in the setting of Sjogren’s syndrome. Analysis of the patient’s medical record, including medication reconciliation and dietary habits, revealed several underlying causes of her recurrent hyponatremia. A thorough review of the patient’s clinical history and good bedside examination may reduce prolonged hospitalizations and improve the quality of life of a hyponatremic population of patients who are predominantly elderly.

Sjogren’s syndrome is a multisystem autoimmune disease that is characterized by lacrimal and salivary gland inflammation often leading to xerostomia (dry mouth) and xerophthalmia (dry eyes) [1]. It may occur in its primary form in the absence of other autoimmune rheumatologic diseases; however, it can also be present in a secondary form associated with rheumatoid arthritis (RA), systemic lupus erythematosus, or systemic sclerosis [1]. It may also be associated with systemic symptoms of fatigue, musculoskeletal symptoms, pulmonary, renal, hepatic, and neurologic disease; however, this might not always be present. We report a case of a patient with an established diagnosis of RA and Sjogren’s syndrome with keratoconjunctivitis who presents with multiple recurrent episodes of unexplained hyponatremia.

An 85-year-old woman presented to the hospital for acute spontaneous dislocation of the hip and was incidentally found to be hyponatremic. Initial physical examination by the emergency physician was suspicious for volume depletion. There was also evidence of joint deformities and neurologic system was unremarkable with intact alertness and orientation. Review of social history had shown her to live with her son and she was reasonably independent in her activities of daily living although her mobility was limited. She also denied smoking, alcohol use, and recreational drugs.

On admission, serum sodium was 122 mmol/L (normal, 136–145 mmol/L), chloride was 86 mmol/L (normal 98–107 mmol/L), serum osmolality was 274 mOsm/kg (normal 275–305 mOsm/kg), while potassium (4.1 mmol/L), creatinine (0.74 mg/dL), and blood urea nitrogen (13 mg/dL) were within normal limits. Urinalysis was positive for 2+ blood, but negative for glucosuria, bilirubinuria, ketonuria, and proteinuria (Table 1). It also showed urine creatinine of 104.1 mg/dL, sodium 25 mmol/L, potassium 24.6 mmol/L, chloride 21 mmol/L, and urea nitrogen of 316 mg/dL. Fractional excretion of sodium was 0.1% and fractional excretion of urea was 17.3% suggesting prerenal disease. CBC showed a hemoglobin of 11.8 g/dL, C-reactive protein (CRP) was elevated at 157.7 mg/L (normal <5), and sedimentation rate–Westergren was elevated at 23 mm/h (normal 0–14). ECG, free cortisol level, blood glucose level, and thyroid function tests were also found to be within normal limits.

Table 1.

Laboratory data of the patient on admission

Sodium 122 mmol/L Urine blood 2+ Urine creatinine 104.1 mg/dL 
Chloride 86 mmol/L Urine glucose negative Urine sodium 25 mmol/L 
Hemoglobin 11.8 g/dL Urine ketones negative Urine potassium 24.6 mmol/L 
C-reactive protein 157.7 mg/L Urine proteins negative Urine chloride 21 mmol/L 
Sedimentation rate 23 mm/h Urine urea nitrogen 316 mg/dL Urine osmolality 297 mOsm/kg 
Sodium 122 mmol/L Urine blood 2+ Urine creatinine 104.1 mg/dL 
Chloride 86 mmol/L Urine glucose negative Urine sodium 25 mmol/L 
Hemoglobin 11.8 g/dL Urine ketones negative Urine potassium 24.6 mmol/L 
C-reactive protein 157.7 mg/L Urine proteins negative Urine chloride 21 mmol/L 
Sedimentation rate 23 mm/h Urine urea nitrogen 316 mg/dL Urine osmolality 297 mOsm/kg 

Outside previous records were obtained which showed that the patient had an established diagnosis of RA with sicca features receiving treatment with abatacept monthly (started 1 year prior, last dose 3 weeks prior to admission). These records also indicated a prior admission in 2019 where serum sodium was found to be 131 mmol/L. The patient was also admitted to an outside hospital in 2021 which showed a serum sodium of 133 mmol/L.

In addition to abatacept, current medications included amlodipine 5 mg tablet daily, acetaminophen 325 mg, aspirin 81 mg daily, atenolol 25 mg daily, and Restasis 0.05% ophthalmic solution and the patient stated she was compliant with all her medications. Additionally, she was not on any long-term steroid medications. On admission, she received one dose of acetaminophen-hydrocodone (Norco 5 mg–325 mg), celecoxib 200 mg (one dose), gabapentin 300 mg (one dose), and Toradol 15 mg (5 doses) to bring down her pain to a tolerable level.

Upon further investigation, the patient had complaints of progressively worsening dry eyes and dry mouth in the weeks prior to hospitalization. In turn, she admitted to increased water consumption associated with increased urination which she attributed to her dry mouth. There was no history of photosensitivity, musculoskeletal symptoms, renal involvement, or skin rashes. Records did indicate dry eye syndrome of bilateral lacrimal glands and salivary glands were not enlarged. Antinuclear antibodies were 1:640 and fluorescent ANA was positive. Although obtained records confirmed a diagnosis of RA and Sjogren’s syndrome, inpatient ENA screen for anti-sm, antiRNP, anti-Ro (SSA), anti-La (SSB), SCL70, and anti-Jo1 were negative.

Her initial serum sodium was 122 mmol/L. However, she was clinically asymptomatic at the time. The patient’s blood glucose was 114 mg/dL, and serum proteins and lipids were also within normal limits. She had no recent surgeries or IV steroids, and serum osmolality was found to be low at 274 mOsm/kg indicating hypotonic hyponatremia in the setting of normal glomerular filtration rate 98 mL/min/1.73 m2 and creatinine of 0.69 mg/dL. Initial laboratories were obtained approximately within 1 h after administering the nonsteroidal anti-inflammatory drugs. Initial urine osmolality was 297 mOsm/kg and repeat urine studies 46 h later demonstrated a drop of urine osmolality to 162 mOsm/kg with unchanged urine sodium at 25 mmol/L.

Although her physical exam on presentation by the emergency physician was suspicious for volume depletion, she was clinically euvolemic at the time of physical exam by the nephrology team after receiving 1.5 L of isotonic saline by the emergency department. Subsequently, the patient was not placed on IV maintenance fluids after obtaining the second set of labs as per recommendations from our nephrology team. She was put on fluid restriction 1 L/day, a high protein and high salt diet, in combination with 2 g oral NaCl tablets three times daily. Sodium levels corrected to 134 mmol/L while inpatient over a span of 6 days and 9 h and was encouraged to follow up with nephrology and rheumatology for treatment of RA with sicca symptoms.

Hyponatremia is one of the most common clinical electrolytes disorders, more frequent in older patients (>60 years of age) [2]. It is categorized, depending upon its duration, into an acute (<48 h) and a chronic variety (>48 h) [3]. The clinical presentation of the two varieties is quite different, with acute hyponatremia causing predominantly gastrointestinal and neurological symptoms, while the chronic variety is strongly associated with fatigue, poor quality of life in general, cognitive impairment, attention deficits, gait disturbances, frequent falls, and accidental fractures with concomitant morbidity and mortality [4].

Her initial high concentration of urine osmolality indicates that the patient may have been volume depleted as the kidney tries to concentrate the urine. As clinical volume assessment in a noncritical care setup relies mainly on clinical bedside examination and the response to IV fluids trial, there are no objective measures to assess the effective arterial blood volume in a regular medical floor. Although orthostatic vital signs performed on admission would have been beneficial, none were documented and the patient had already received IV fluid repletion by the time she was evaluated by the nephrology team. In addition, the patient’s initial reason for hospitalization was due to a hip fracture, and therefore the patient was unable to stand to obtain the full set of orthostatic vital signs. The patient’s general status did identify a likely need to transfer to the intensive care unit for more invasive and noninvasive methods to assess volume status such as inferior vena cava diameter, pulmonary artery catheterization, and other invasive approaches which will require central venous access insertion. Free water as we know diffuses freely between body compartments and does not conclude hypovolemic states. Also, while her pain on admission was controlled with a number of nonsteroidal anti-inflammatory medications including celecoxib and Toradol, we do not believe that these medications have played any major role in the value of her initial urine osmolality. The physiologic mechanism of these medications causes a hemodynamically prerenal state by constricting the afferent arteriole due to inhibition of synthesis of prostaglandins. Our patient’s initial laboratories including urine osmolality and urine sodium were collected approximately within 1 h of administering these medications and paradoxically, with IV fluids, her urine osmolality decreased from 297 to 162 mOsm/kg.

The differential diagnosis for our patient’s hyponatremia includes syndrome of inappropriate secretion of antidiuretic hormone (SIADH), thiazide diuretics therapy, psychogenic polydipsia, beer potomania, as well as a low protein diet with excessive water intake. The general approach for determining the cause of hyponatremia includes correcting blood glucose and determining whether additional solutes are present. After measuring serum osmolality, a low osmolality (<280 mosmol/kg) indicates hypotonic hyponatremia. TSH and morning cortisol levels are obtained to rule out any coexisting adrenal and thyroid disease, and in the patient described above, both values were within normal limits. To our knowledge and after a detailed literature search, there are no similar case series that report polydipsia secondary to xerostomia as a cause of hyponatremia in the setting of autoimmune disease.

In contrast to polydipsia, SIADH is a disorder of impaired water excretion caused by the inability to suppress the secretion of antidiuretic hormone (ADH) [5]. It is often suspected in patients with hyponatremia, hypoosmolality, a urine osmolality above 100 mosmol/kg, and a urine sodium >40 mEq/L, although serum potassium is usually normal [5]. Causes often include CNS disturbances, malignancies, drugs, surgeries, pulmonary disease, hormone deficiency/administration, hereditary, idiopathic, and HIV. Few cases have been reported of the association of Sjogren’s syndrome and inappropriate ADH secretion [6‒8]. One likely mechanism is the numerous inflammatory cytokines produced in Sjogren’s syndrome including IL-1β, IL-6, IL-12, TNF-α, and interferons [9‒11]. ADH levels have been shown to increase after administration of IL-6 injections, suggesting that IL-6 activated ADH-secreting neurons might be involved in the SIADH [12]. IL-6 was found highly expressed in serum and peripheral circulating lymphocytes of Sjogren’s patients [13]. Additionally, it was found in labial gland biopsies of Sjogren’s syndrome patients but detected at lower levels in healthy controls [13]. This indicates that the likely mechanism of Sjogren’s syndrome is the overproduction and infiltration of IL-6 which activates magnocellular AVP-secreting neurons leading to SIADH.

Other possibilities included beer potomania which is described as excessive alcohol intake (beer), which often leads to fatigue, dizziness, and muscle weakness secondary to poor dietary solute intake [14]. The low solute content and its suppressive effects on proteolysis result in reduced solute delivery to the kidney, which in turn, causes dilutional hyponatremia secondary to reduced clearance of excess fluids from the body [14]. Although our patient denied beer or alcohol consumption, poor salt and poor protein intake as well as a low body mass have most likely contributed to her chronic hyponatremia. Excessively rapid correction of chronic hyponatremia puts patients at risk of demyelinating brain lesions [3, 15]. However, demyelination can be prevented by relowering plasma sodium after rapid correction [3, 15]. Here, hyponatremia was corrected slowly and safely without any neurological sequelae.

In our patient, we think the most likely reason for hyponatremia is the chronic xerostomia which has predisposed her to polydipsia and chronic hyponatremia. This is coupled with her low body mass being an elderly frail female (height: 152 cm, weight: 50 kg, BMI: 21.6) who is chronically immobile, malnourished and surviving on a poor-quality low salt, low protein diet. We think that her suboptimal socioeconomic status was a major barrier to access to an adequate diet. She had established keratoconjunctivitis with severe decreased tear production being treated with Restasis. In addition, she reported severe dry mouth associated with polydipsia and polyuria. Sicca manifestations including dry eyes and dry mouth often occur in the presence of collagen vascular disorders [16]. Likely causes of her hyponatremia included SIADH and polydipsia. While both mechanisms could have been contributing to her chronic hyponatremia, analysis of her urine studies showed a urine osmolality of 162 mOsm/kg. In SIADH, urine osmolality would be expected to be higher indicating that her hyponatremia was likely due to polydipsia and poor diet.

The patient’s elevated CRP and sedimentation rate could be explained by the inflammatory process related to her hip dislocation. Per operative report, general anesthesia was administered prior to the procedure and a revision of total hip arthroplasty was performed. The only medication obtained prior to receiving her initial set of labs was a one-time dose of Norco 5 mg. However, the anesthetic and pain medications received during her hospitalizations do not explain her prior documented values of hyponatremia. Additionally, if both CRP and ESR are elevated inpatient with collagen vascular disorder, this likely indicates a flare-up. But if the sedimentation is normal and the CRP is elevated, causes such as sepsis and infection need to be explored. While her ANA and ENA panel were negative, this is possibly secondary to a false-negative exam as her clinical symptoms could be explained by disease progression.

Urine osmolality may be elevated in hypovolemic states but could also be altered by renal disease that leads to renal sodium wasting, diuretic use, or solute diuresis. States of low urine sodium and high urine osmolality can be found in euvolemic hyponatremic patients. In order to differentiate causes of hyponatremia, normal saline may be administered. In states of hypovolemia, isotonic saline inhibits ADH secretion which in turn promotes the excretion of dilute urine. Meanwhile, in patients with SIADH, the response to saline administration normally demonstrates an increase in urine sodium but urine osmolality remains elevated. Low urine sodium concentrations can also be seen in patients with SIADH in settings of volume depletion or poor sodium intake.

The patient has clinically responded very well to a high protein and normal salt diet combined with free water restriction where she remained clinically euvolemic. Dietary manipulations including high protein intake do not have an immediate effect. They are slow measures which take a few days to take effect. This is in contradiction to pharmacologic medicine such as oral urea, meclocycline, and tolvaptan which have a quicker effect. Unfortunately, the patient was discharged before repeat urine studies were performed. The clinical scenario did not argue against hyponatremia secondary to polydipsia caused by xerostomia in the setting of Sjogren syndrome.

In conclusion, a detailed clinical history (including drug history) as well as a good bedside clinical examination is critically important in guiding work-up and subsequent management of this common, yet challenging, clinical problem. In hospitalized patients, the early detection and optimal treatment of hyponatremia can be quite rewarding as it will have a significant positive impact on reduction of in-hospital mortality, obviates the need for more intensive hospital monitoring, reduces the cost of hospitalization, and last but not least, improves the quality of life of a hyponatremic population of patients who are predominantly elderly. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000530491).

This research work does not contain human or animal subject research material. This review of patient data did not require ethical approval in accordance with local/national guidelines. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

The authors have stated that they have no conflicts of interest.

No funding was received.

Ahmad El-Moussa and Yahya Osman Malik were involved with direct patient care, chart reviewing the case, performing literature review, and writing the manuscript. Syed Umer Mohsin, Omer Alrawi, and Obead Yaseen were involved with performing literature review and editing the manuscript.

Research data are not publicly available as it is contained within a confidential medical record. Further inquiries can be directed to the corresponding author.

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