CASE REPORT |
https://doi.org/10.5005/jp-journals-11010-1112 |
Syndrome of Inappropriate Antidiuretic Hormone and Antituberculosis Treatment-induced Hepatitis: A Case Report
1,2Department of Respiratory Medicine, Dr D. Y. Patil Medical College, Hospital & Research Centre, Dr D. Y. Patil Vidyapeeth (Deemed to be University), Pimpri, Pune, Maharashtra, India
Corresponding Author: Manosri Mandadi, Department of Respiratory Medicine, Dr D. Y. Patil Medical College, Hospital & Research Centre, Dr D. Y. Patil Vidyapeeth (Deemed to be University), Pimpri, Pune, Maharashtra, India, Phone: +91 9666097992, e-mail: manosrireddy@gmail.com
Received: 27 October 2023; Accepted: 21 May 2024; Published on: 18 June 2024
ABSTRACT
Pulmonary tuberculosis (PTB) is a widespread respiratory infection predominantly found in developing countries, known for its high mortality and morbidity rates. The standard initial treatment for drug-sensitive PTB involves a 2-month regimen of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE), followed by 4 months of isoniazid, rifampicin, and ethambutol (HRE). Hepatitis is a prevalent side effect linked to this treatment, emphasizing the need for close monitoring of liver enzymes at the beginning of the regimen. Hyponatremia, a common metabolic abnormality, is frequently observed in tuberculosis (TB) patients.
We present a case of a 54-year-old female with drug-sensitive PTB who developed treatment-induced hepatitis and presented with unresponsive hyponatremia. Extensive investigations and radiological examinations revealed no structural anomalies. Laboratory results pointed to elevated serum antidiuretic hormone (ADH) levels, ultimately leading to the diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) due to ectopic ADH production.
How to cite this article: Mehta K, Mandadi M. Syndrome of Inappropriate Antidiuretic Hormone and Antituberculosis Treatment-induced Hepatitis: A Case Report. Indian J Respir Care 2024;13(2):128–131.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Keywords: Antituberculosis treatment, Case report, Hepatitis, Hyponatremia, Syndrome of inappropriate antidiuretic hormone secretion, Tuberculosis
INTRODUCTION
Pulmonary tuberculosis (PTB) is one of the most commonly seen respiratory infections in developing countries. According to the global tuberculosis (TB) report in 2021, 10.6 million people were infected with TB worldwide.1 The treatment coverage is estimated to be 61% in 2021.1 Despite the availability of highly efficient treatments for decades, a high prevalence of mortality and morbidity is still noted among TB patients.1 The standard treatment protocol for drug-sensitive TB includes a total of 6 months: isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) for 2 months, followed by isoniazid, rifampicin, and ethambutol (HRE) for 4 months.2 A few of the antituberculosis treatment (ATT)-related adverse effects include neurological disorders, hepatotoxicity, skin reactions, and gastrointestinal issues. Among all, hepatotoxicity is the most common of all the adverse effects, accounting for 5–28% of the cases worldwide and is considered the most common reason for drug discontinuation in 11% of the patients treated with fixed dose combination regimen.3 Endocrine and metabolic abnormalities are rare in TB, but they are important as and when they arise. Hyponatremia is considered a fall in the serum sodium levels below 136 mmol/L, while severe hyponatremia is a fall in sodium levels below 115 mmol/L, which can be life-threatening. A fall in serum sodium concentration is of multifactorial origin, leading to an increase in antidiuretic hormone (ADH).4 ADH regulates the water balance in the body by reducing the excretion of water through urine. Excessive release of ADH causes increased water retention with the dilution of sodium levels in the blood, leading to hyponatremia. TB can induce hyponatremia via various mechanisms, such as local invasion of the adrenal glands (adrenal insufficiency), invasion of the hypothalamus, invasion of the pituitary gland, tubercular meningitis, and inappropriate ADH secretion.5 Here, we discuss a case report of a 54-year-old female diagnosed with PTB and syndrome of inappropriate antidiuretic hormone secretion (SIADH) due to ectopic ADH production with ATT-induced hepatitis.
CASE DESCRIPTION
A 54-year-old Asian hypertensive woman, a case of drug-sensitive PTB, presented to the hospital with complaints of confusion, altered sensorium, itching, persistent nausea, and vomiting for 7 days. The patient was started on a drug-sensitive fixed dose combination regimen of HRZE for PTB for 15 days. On admission, biochemistry investigations reported sodium levels to be 105 mmol/L (normal range: 136 and 145 mmol/L), and bilirubin 6.18 mg/dL (normal range: 0.2–1.2 mg/dL), with a random blood glucose level found to be 108 mg/dL. The rest of the laboratory parameters were found to be in the normal range.
At first, the patient was conservatively managed by switching to an alternative treatment of streptomycin, levofloxacin, and ethambutol regimen in view of ATT-induced hepatitis. As the liver enzymes showed improvement (Fig. 1), individual drugs of HRZE were reintroduced one at a time over a period of 1 month. Clinically, the patient’s symptoms such as itching, nausea, and vomiting subsided. Sodium correction with close monitoring was also done. In spite of several corrections, there was a persistent drop in the sodium levels (Fig. 2).
Fig. 1: The line chart shows the serum bilirubin levels of the patient over 1 month
Fig. 2: The line chart shows the serum sodium levels of the patient over 1 month
The patient was biochemically euvolemic, euthyroid, and had morning cortisol levels of 15.5 µg/dL (normal range: 6–23 µg/dL), and was never on any diuretics. Biochemistry showed high serum osmolarity (240 mmol/L), high urine concentration (285.6 mmol/L), and high urine sodium (49 mEq/L). Radiological investigations such as magnetic resonance imaging (MRI) brain and computed tomography (CT) abdomen–pelvis were also done to look for pituitary and adrenal gland involvement (Fig. 3).
Figs 3A and B: Contd...
Figs 3A and B: Magnetic resonance imaging brain suggestive of age-related cerebral atrophic changes
Contrast-enhanced abdomen revealed no abnormality. On further investigation, serum ADH levels were found to be elevated, measuring 9 pg/mL (normal range: 1–5 pg/mL). Thus, a diagnosis of SIADH due to ectopic production of ADH was made. The patient was given a trial of fluid restriction to about 1000 mL/24 hours) for 3 days. Later, the patient was started on intravenous (IV) conivaptan, a selective vasopressin antagonist receptor with an initial loading dose of 20 mg over 30 minutes, followed by a continuous infusion at a rate of 20 mg/day for 4 days. On normalizing liver enzymes, serum sodium levels and symptomatic improvement, the patient was discharged with HRZE and oral tolvaptan 15 mg OD for 3 weeks. On follow-up, the patient had normal sodium levels and liver parameters.
DISCUSSION
In our case, we put forward the challenges faced while treating SIADH in a case of drug-sensitive PTB, along with ATT-induced hepatitis. ATT-induced hepatitis was managed in a stepwise manner with introduction of one drug at a time and close monitoring of liver function parameters. On symptomatic improvement and normalized liver function tests, the full dose ATT was reintroduced. The diagnosis of SIADH due to ectopic production of ADH was made by laboratory and radiological investigations. Hyponatremia has been commonly reported in patients with TB but in our case of hyponatremia, we were not able to establish the cause of SIADH. About 60% of the patients with tubercular meningitis may present with hyponatremia or SIADH at first presentation.5 In this case, the patient’s CT and MRI did not show any structural abnormality. The elevated levels of ADH in a long-standing case of hyponatremia and PTB presents a rare cause of ectopic ADH production. Weiss et al. reported hyponatremia as a result of SIADH in patients with PTB.6 Later, it was reported that an increased ADH level in the presence of hyponatremia in PTB cases is an indicator of ectopic ADH production.7
CONCLUSION
Our case lies in the rare combination of ATT-induced hepatitis and unresponsive hyponatremia. The diagnostic challenges it presented, the meticulous management strategy employed, and the identification of ectopic ADH production without structural anomalies need the right approach and patient–doctor synergy. Stepwise, single drug reintroduction and close monitoring of liver function parameters is the safest way to resolve this issue. Every case of hyponatremia in a tubercular patient should be thoroughly evaluated, and thus TB as a cause of SIADH due to ectopic production of ADH should be considered. An early diagnosis of these conditions and initiation of treatment accordingly may have a good prognosis and outcome.
ORCID
Manosri Mandadi https://orcid.org/0000-0001-7734-1370
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