Editor's note: Hyponatremia is a common electrolyte disorder in clinical practice, have you ever encountered a situation where blood sodium is getting lower and lower? Recently, at the 2024 East China Endocrine and Metabolic Disease Forum, Professor Su Qing from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine shared two special cases of hyponatremia with us, come and take a look.
1. Diagnosis and classification of hyponatremia
低钠血症定义为血钠＜135 mmol/L。 根据血浆渗透压分为：低渗性低钠血症(血浆渗透压＜275 mOsm/kg)、等渗性低钠血症(275~295 mOsm/kg)、高渗性低钠血症(＞295 mOsm/kg)；依据严重程度分为轻度（130~135 mmol/L）、中度（125~129 mmol/L）、重度(＜125 mmol/L）。
2. Diagnostic algorithm for hyponatremia
Hyponatremia requires a rapid determination of the course and severity of the disease, collection of medical history, combined with medical history, symptoms, signs, auxiliary examinations, etc., to comprehensively analyze the patient's current volume status and the cause of hyponatremia, and the specific diagnosis process is shown in Figure 1.
Figure 1. Diagnostic algorithm for hyponatremia
3. Case analysis
Case 1: Patient, male, 45 years old, complained of "found a decrease in blood sodium level for 2 months"
History and physical examination
History of present illness: the patient was hospitalized in another hospital for head trauma 2 months before admission, with symptoms such as dizziness, nausea and vomiting, no syncope, convulsions, no speech difficulties and unfavorable limb movements, normal blood sodium at the time of admission, dizziness, nausea and vomiting symptoms gradually relieved during treatment, electrolyte examination found that blood sodium gradually decreased, the lowest was 119 mmol/L, accompanied by slight dry mouth, polyuria, increased urine output and urination, about 2700~2800ml/24h, and sodium supplementation (30g/ days), serum sodium can be maintained at normal, and serum sodium is maintained at about 120 mmol/L after intravenous sodium supplementation is stopped. Corticosteroid supplementation, prednisone 5 mg twice a day and gradually increasing the dose to 10 mg a bid, still cannot be weaned off intravenous sodium supplementation. Refer to our hospital for emergency care.
Physical examination, blood, urine, stool routine, liver and kidney function, blood lipids, blood glucose: no obvious abnormalities were found.
Table 1. Electrolyte trends
Clinical thinking
1. Consider the causes of refractory hyponatremia in this case: secondary adrenal insufficiency, syndrome of improper secretion of antidiuretic hormone (SIADH), cerebral salt-wasting syndrome (CSWS), and CSWS should be considered first if the patient has a clear history of traumatic brain injury.
表2. CSWS和SIADH的鉴别
2. Cerebral salt-wasting syndrome (CSWS)
(1) Pathogenesis of CSWS
Brain injury can destroy cells containing ANP and BNP, and damage the blood-brain barrier, resulting in inappropriate secretion of natriuretic peptides and increased urinary sodium excretion. Acute head injury produces an endogenous sodium-potassium pump inhibitor, similar to a digoxin-like substance, which acts on the sodium-potassium pump in the renal tubules, resulting in decreased sodium-potassium exchange and increased urinary sodium excretion.
(2) Clinical manifestations of CSWS
lack of specificity, psychiatric symptoms, state of consciousness, coma, volume depletion, rapid heart rate, decreased blood pressure, increased urine output, decreased serum sodium (less than 130 mmol/L) and blood osmolality, increased urine sodium and urine osmolality, markedly increased urea nitrogen, and increased hematocrit and hemoglobin.
(3) CSWS diagnostic criteria
1996年Uygun等提出CSWS的诊断标准：①中枢神经系统疾病存在；②低钠血症(＜130 mmol/L)；③尿钠排出增加(＞20 mmol/L或＞80 mmol/24h)；④血浆渗透压＜270 mmol/L,尿渗透压:血渗透压＞1 ；⑤尿量＞1800ml/d；⑥低血容量；⑦全身脱水表现（皮肤干燥、眼窝下陷及血压下降等）。
In addition, the following conditions are helpful in diagnosing CSWS: (1) hyponatremia and polyuria, (2) high urinary sodium with increased urine output with normal urine specific gravity, (3) hypovolemia, decreased central venous pressure (often < 6 cm H2O), signs of dehydration, rapid heart rate, orthostatic hypotension, hematocrit, and elevated blood urea nitrogen (BUN), (4) improvement with hydration and sodium, (5) normal kidney, thyroid, and adrenal function, and (6) exclusion of other causes such as edema and diuretic therapy.
(4) CSWS treatment
Most of them are transient, and they are treated according to the cause, and they are mostly recovered in 3~4 weeks, such as refractory hyponatremia: fludrocortisone 0.1~0.4mg/d.
The central venous pressure was monitored, and the results showed that the central venous pressure was about 1~4 cmH2O for 4 times. The patient met the diagnosis of CSWS, and the dose of prednisone acetate (10 mg bid) was gradually reduced to 1 tablet twice a day/morning and half a tablet in the evening. Fludrocortisone 0.1 mg twice a day, and fluid, sodium, and supportive treatments were continued. The patient's blood sodium fluctuates as follows:
Figure 2. Trend of serum sodium (after fludrocortisone treatment)
The patient was discharged after correction of hyponatremia (without rehydration). After discharge: hydrocortisone acetate tablets twice a day/1 tablet in the morning and half a tablet in the evening, fludrocortisone 0.1 mg twice a day.
Follow
After six months of discharge from the hospital (cortisone acetate has been discontinued for 2 months, fludrocortisone has been discontinued for 3 weeks), serum sodium is normal, pituitary hormone is not significantly reduced, and pituitary magnetic resonance: pituitary gland is thin, roughly similar to the old film. Brain MRI: right frontal lobomalacia with localized gliosis.
summary
Cerebral salt-wasting syndrome is a clinical syndrome of hyponatremia and decreased extracellular fluid volume caused by excessive excretion of urinary sodium caused by intracranial diseases.
Case 2: A 75-year-old male complains of "recurrent fever for more than 1 month".
History of present illness (substitute complaint)
The patient had fever for more than one month before admission, with a maximum body temperature of 39.9°C, obvious in the afternoon and evening, and no other uncomfortable symptoms. The patient was hospitalized in a local hospital after the fever did not resolve spontaneously for several days, and the magnetic resonance cholangiography (MRCP) examination showed that: 1) the head of the pancreas was cystic and the main pancreatic duct was slightly dilated, and 2) there were multiple gallstones in the gallbladder and small stones in the common bile duct. Symptomatic supportive treatment such as rehydration and anti-infection was given, and the patient's family felt that the patient's hearing was gradually declining, so he was admitted to the general surgery department with "biliary tract infection" in the emergency department, and after admission, he underwent ultrasound-guided cholecystecesis and endoscopic retrograde cholangiopancreatography (ERCP) stone removal, and the patient recovered well and was discharged from the hospital after surgery. After discharge, the patient developed fever again, up to 38.8 °C, and was admitted to general surgery again for treatment, and daily intravenous and oral supplementation of sodium chloride 16.75g, hyponatremia is still difficult to correct. The patient's mental status gradually deteriorated, and he was transferred to the endocrinology department for drowsiness, slurred speech, and uncooperative examination.
diagnosis
Hyponatremia (SIADH)
Clinical Thinking:
1 Kcriyehk,
①低钠血症：血钠＜130～135 mg/dL；
(2) Hypoosmolality: plasma osmolality < 270 mg/dL, accompanied by increased urinary sodium excretion, urinary sodium > 30~40 mmol/L and abnormal increase in urine osmolality; urine osmolality is greater than or twice as high as blood osmolality;
(3) No clinical dehydration or edema;
(4) The heart, liver, kidney, adrenal cortex and thyroid function are normal.
2. Other diagnostic methods
(1) Water stress test: if the serum sodium > 124 mmol/L and there is no obvious clinical hyponatremia symptoms, the patient is asked to drink 20 ml/kg of water quickly (the maximum amount is 1500 ml), if the urine output is less than 65% of the drinking volume in the following 4 hours, or 80% of the introduced urine cannot be excreted within 5 hours, SIADH can be diagnosed. (Note: Not suitable for patients with acute intracranial disease)
(2) ADH concentration detection: Usually the ADH level of patients with hyponatremia is very low and often undetectable, but in SIADH, the ADH level of patients is often high.
总之,SIADH诊断思路如下:
Figure 3. SIADH diagnostic thinking
3. Treatment of SIADH
(1) Pay attention to the treatment of the primary disease
Continuous water restriction: 500~1000 ml/d for adults and 40~60 ml/kg/d for children until the blood sodium concentration is normal. In more severe, symptomatic patients with hyponatremia, hypertonic sodium chloride solution can be slowly infused with tachydiuretics (eg, furosemide). Monitor the serum sodium level closely, otherwise the rapid rise of serum sodium may cause nerve demyelination, and the rate of sodium elevation should not exceed 8 mmol/L per day.
(2) Others: such as lithium, tetracyclines, urea, vasopressin inhibitors, etc., have been reported, but the efficacy has not been confirmed.
4. Return to this case
Tolvaptan, fluid restriction (1000~1500ml for 24 hours), combined intravenous and oral sodium and potassium supplementation, the results are as follows:
Figure 4. Changes in serum sodium after treatment
Problems that are still faced after treatment
(1) still fluctuating fever, and (2) lethargy after correction of hyponatremia.
Diagnosis is made after discussion with a multidisciplinary consultation (MDT).
(1) Fever, (2) Hyponatremia, (3) Syndrome of inappropriate secretion of antidiuretic hormone, (4) Gallstones with cholecystitis, (5) After bile duct stent implantation, continue empiric anti-infection therapy, and improve PET-CT, lumbar puncture and other related examinations to determine the cause of fever.
Lumbar puncture was performed with the consent of the patient's family in the middle of the process, and the intraoperative puncture was smooth, and the colony stimulating factor (CSF) was pale yellow and translucent (the flow rate was slow and the pressure was not measured). Combined with the biochemical results of cerebrospinal fluid, the central nervous system infection (tuberculous meningitis?) was considered, and he was transferred to the Department of Infectious Diseases of Huashan Hospital.
Diagnosis was discharged from our hospital
(1) central nervous system infection (tuberculous meningitis possible), ;( 2) antidiuretic hormone inappropriate secretion syndrome, (3) bile duct stent implantation, (4) gallstones with cholecystitis, (5) hypertension grade I, (6) hyperlipidemia, (7) hypokalemia (primary aldosteronism), ;(8) impaired glucose tolerance.
After being transferred to Huashan Hospital, cerebrospinal fluid examination and next-generation sequencing (NGS) were further improved, and cryptococcal meningitis was diagnosed with antifungal therapy.
summary
This case is a patient with recurrent fever, with biliary tract infection as the treatment direction, and is characterized by recurrent fever with severe refractory hyponatremia and impaired consciousness after treatment of the cause, SIADH was diagnosed after a series of examinations, but the patient's consciousness level did not recover after correcting hyponatremia, and the fever still existed, and the cerebrospinal fluid puncture was perfected, and the case of cryptococcal meningitis was finally diagnosed. Cryptococcosis is an opportunistic infection in which inhaled cryptococci are effectively eliminated in immunocompetent hosts, but in immunocompromised individuals, cryptococci can proliferate and spread to the central nervous system, crossing the blood-brain barrier, causing meningoencephalitis. There have been anecdotal reports of meningitis (including Cryptococcus neoformans meningitis) complicated by SIADH. When encountering similar situations in clinical practice, it is necessary to be vigilant and carefully identify.