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Malaise, Body Aches in an 88-Year-Old – What Can It Be?

An 88-year-old woman presents to an emergency department in New York City with overall body aches. She explains that for the past 4 days, she has also been suffering from nausea, loss of appetite, and general malaise.

Her medical history indicates high blood pressure, depression, and osteoarthritis of both shoulders and both knees. She notes that before this, she was able to walk indoors with the help of a cane and travel outside with a walker. She says that she manages her activities of daily living independently, but needs her family’s help to manage her finances, prepare meals, perform housework, and maintain her home (i.e., instrumental activities of daily living).

She says that for the past 5 years, she has been taking acetaminophen for her osteoarthritis, but with no relief. When she reported her ongoing pain to her family physician 2 weeks previously, he suggested a switch to naproxen to manage the pain.

The patient has no history of heart or liver failure, hypothyroidism, adrenal insufficiency, malignancy, or HIV, and has had no other recent changes in medications, recent surgeries, or vomiting or diarrhea.

Her current home medications include:

  • Amlodipine 10 mg daily
  • Losartan 50 mg daily
  • Citalopram 20 mg daily
  • Naproxen 250 mg every 8 h daily (for the past 2 weeks)

Vital signs are:

  • Blood pressure 169/82 mm Hg
  • Heart rate 82 beats per minute
  • Respiratory rate 16 breaths per minute
  • Temperature 37.3°C

Findings of a neurological exam are unremarkable. She is able to walk about 10 meters with a cane, and is euvolemic with no evidence of peripheral swelling or ascites. No other signs of heart failure, liver failure, or physical evidence suggestive of hypothyroidism are noted.

On the first day of hospital admission, laboratory test results are as follows:

  • Fasting early morning cortisol 18 μ/dL
  • Thyroid-stimulating hormone 3.5 mU/L
  • Pro-B-type natriuretic peptide 221 pg/mL
  • Creatinine 0.47 mg/dL
  • Serum albumin 4 g/dL
  • Cholesterol 192 mg/dL
  • Triglyceride 44 mg/dL
  • Serum sodium 113 mmol/L
  • Urine sodium 120 mmol/L
  • Urine osmolality 487 mOsm/kg

Medical records show that the patient’s sodium level 10 months previously was 129 mmol/L.

Clinicians order imaging and microbiology tests, which show no evidence of infectious causes. Computed tomography of the neck, chest, and abdomen with contrast, and brain magnetic resonance imaging all prove to be unremarkable.

Based on the physical exam and laboratory testing, clinicians consider the differential diagnosis to be syndrome of inappropriate antidiuretic hormone (SIADH). They discontinue treatment with the offending agents, citalopram and naproxen, and start the patient on fluid restriction (i.e., fluid intake limited to 1 L per day).

On the third day, the patient’s serum sodium level remains at 113 mg/dL and clinicians note that her mental status is deteriorating. She is able to protect her airway, but becomes drowsy and unable to follow commands. Endocrinology recommends that she be started on 2 g sodium chloride tablets twice a day, along with more aggressive fluid restriction to 0.5 L/day.

Her sodium level gradually increases, concurrent with an improvement in her mental status.

On day 10, the patient’s serum sodium reaches 131 mmol/L, and clinicians discontinue the sodium chloride tablets.

On day 14, she is discharged to a subacute rehabilitation center, with the following medications:

  • Amlodipine 10 mg daily
  • Losartan 100 mg daily
  • Meloxicam 15 mg daily

Clinicians assess the patient’s need for an antidepressant, and on questioning, she reports that she has not had any depressive symptoms; she is cleared by the hospital inpatient psychiatry team.

Because hyponatremia on its own can induce psychological symptoms, clinicians hold the selective serotonin reuptake inhibitor (SSRI) and advise the patient to follow up with an outpatient psychiatrist. They also instruct the patient and her family to limit her fluid intake to 1 L per day.

A follow-up assessment at the Endocrinology Clinic on day 30 shows improvement in the patient’s serum sodium level to 137 mmol/L. She has also recovered her previous level of mobility – she walks into the clinic with her cane and reports no persisting nausea, decreased appetite, or malaise.

She notes that her long-standing pain over bilateral knees and bilateral shoulder joints is also improving, and since her serum sodium is within normal range, clinicians request a re-evaluation by Psychiatry, and the team decides to discontinue the antidepressant.

Discussion

Clinicians presenting this case of hyponatremia due to SIADH note that the diagnosis was based on laboratory evaluation prompted by the patient’s clinical and medication history.

Given that hyponatremia in the elderly is associated with neurocognitive decline, gait instability, falls, increased hospital readmission rate, increased need for long-term care, and increased mortality, medication reconciliation should be an initial step in assessment of an elderly patient with hyponatremia, the case authors state.

They note that rather than managing the patient with hypertonic saline, they began with fluid restriction alone, due to the patient’s advanced age (which entails a higher risk for osmotic demyelination syndrome), chronic hyponatremia, and relatively stable clinical condition.

When the hyponatremia failed to respond to fluid restriction and her neurological symptoms worsened despite discontinuation of the offending medications upon her presentation at the ED, she was started on oral sodium supplement 2 g twice daily with increasing restriction on fluids, leading to adequate improvement in her sodium level.

The syndrome occurs when autoregulation of ADH is lost, causing impaired water excretion and hyponatremia. Differential diagnoses to consider include hypothyroidism, glucocorticoid deficiency, hyperglycemia, hyperlipidemia, and thiazide use.

The authors note that there is no universal laboratory definition for SIADH, and ADH level is not part of the diagnostic criteria, nor is this assessment warranted in routine practice. A diagnosis of SIADH should be considered in patients who are euvolemic hyponatremic with lab values as follows:

  • Urine osmolality >100 mOsm/kg
  • Urine sodium >40 mmol/kg
  • Plasma osmolality <280 mOsm/kg

Drug-induced SIADH may be related to two proposed mechanisms, the case authors explained:

  • Increased secretion of ADH
  • Increased renal response to ADH

SSRIs work on the neurotransmitter norepinephrine, which normally stimulates the alpha-1 adrenergic receptor; this induces release of ADH, subsequent degradation of norepinephrine, and termination of this signal. In patients taking an SSRI, norepinephrine reuptake is inhibited, and the signal may continue to be generated, thus increasing release of ADH.

In contrast, nonsteroidal anti-inflammatory drugs (NSAIDs) appear to induce hyponatremia by potentiating the effects of ADH rather than by increasing its secretion. Normally, prostaglandin inhibits water reabsorption in the thick ascending limb and in the collecting tubules, the case authors explained, adding that while the mechanism has yet to be clearly described, it may be that NSAIDs inhibit renal prostaglandins synthesis, disturbing sodium and water homeostasis.

There is as yet no universal standardized protocol for assessment or management of patients with SSRI-induced SIADH or NSAID-induced SIADH, the authors said.

A 2015 study of the incidence, risk factors, and consequences of hyponatremia in 608 elderly (mean age of 84), primarily female and African-American community-dwelling individuals followed for over approximately 3.5 years, comorbidities found were:

  • Hypertension (86.7% of the total)
  • Diabetes mellitus (35.4%)
  • Dementia (44.1%)
  • Psychiatric disease (32.5%)
  • Chronic kidney disease (26.6%)
  • Cerebrovascular disease (32.2%)
  • Congestive heart failure (26.3%)
  • Hypothyroidism (13.8%)
  • Frailty by Fried Index (44.4%)

The cases of hyponatremia in the study were found to be primarily due to SIADH and the medications the patients were taking — mostly thiazides and SSRIs.

In general, the association between SSRIs and hyponatremia appears to be elevated in the elderly, in females, in those also taking diuretics, in those of low body weight, and in those with baseline low levels of sodium serum, and the effect typically develops within the first few weeks or months of beginning treatment.

While development of hyponatremia has been suggested to be due to inhibition of norepinephrine reuptake, this does not fully explain the higher incidence of SIADH noted with SSRIs compared with serotonin and norepinephrine reuptake inhibitors (SNRIs) or noradrenergic and specific serotonergic antidepressants (NaSSAs), the case authors said.

The incidence of SIADH in patients taking SSRIs varies, ranging from about 0.5% to 32% as shown in a 2016 retrospective study of 638,352 patients using antidepressants. In this group, hyponatremia incident rate ratios were highest with the SSRI citalopram at 7.8 (CI 7.42 to 8.20), compared with the SNRIs duloxetine at 2.05 (CI 1.44 to 292) and venlafaxine 2.90 (CI 2.43 to 3.46), the NaSSA mirtazapine at 2.95 (CI 2.71 to 3.21), and the first-generation tricyclic antidepressant clomipramine at 4.93 (CI 2.72 to 8.94).

The case authors note that while asymptomatic mild hyponatremia (<130 mmol/L) may not trigger investigation, recent studies suggest that treating even mild hyponatremia and addressing any reversible cause of SIADH may improve quality of life. Re-evaluation of ongoing use of these agents is crucial, therefore, even in minimally affected patients, the authors emphasize.

While most cases of hyponatremia resolve within 2 weeks of SSRI discontinuation, a return to a normal serum sodium level may take up to 6 weeks. In the absence of guidelines for managing SSRI-induced SIADH, providers often rely on their own clinical experience. This can include another trial of the same antidepressant, switching to a different medication within the same class, or using an alternative medication from a different class.

In small trials, SIADH has also been reported secondary to NSAIDs and in patients using ibuprofen or diclofenac, but as with SSRIs, there is no guideline for choosing, switching, or rechallenging of NSAIDs in SIADH patients.

Conclusion

The case authors conclude that since hyponatremia in the elderly is associated with neurocognitive decline, gait instability, falls, increased hospital readmission and need for long-term care, and mortality, medication reconciliation is vital. In this particular patient, laboratory evaluation led to the diagnosis of SIADH, and after ceasing the relevant medication and providing appropriate treatment, the hyponatremia resolved.

Disclosures

The case report authors noted having no conflicts of interest.

Source: MedicalNewsToday.com