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\begin{document}

\title{PULMONARY TUBERCULOSIS IN AN ADULT PRESENTING WITH SEVERE HYPONATREMIA:
A CASE REPORT AND REVIEW OF LITERATURE}



\author[1]{Shailes Paudel}%
\author[2]{Maulik Dhanani}%
\author[3]{Krish Patel}%
\author[4]{Naga Praneeth Vakkalagadda}%
\author[5]{Vivek Sanker}%
\author[6]{Abhiram Rao Damera}%
\author[7]{Umang  Gupta}%
\author[1]{Prakriti Bhandari}%
\affil[1]{Patan Academy of Health Sciences}%
\affil[2]{Southwestern University School of Medicine}%
\affil[3]{Government Medical College Surat}%
\affil[4]{Guntur Medical College}%
\affil[5]{Noorul Islam Institute of Medical Science and Research Foundation Medicity}%
\affil[6]{MediCiti Institute of Medical Sciences}%
\affil[7]{Nepalgunj Medical College}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\textbf{PULMONARY TUBERCULOSIS IN AN ADULT PRESENTING WITH SEVERE
HYPONATREMIA: A CASE REPORT AND REVIEW OF LITERATURE}

\textbf{Shailes Paudel\textsuperscript{1,2} , Maulik Dhanani}
~\textsuperscript{\textbf{2,3}}\textbf{, Krish Hitesh
Patel\textsuperscript{2,4}, Naga Praneeth
Vakkalagadda\textsuperscript{2,5}, Vivek Sanker\textsuperscript{2,6},
Abhiram Rao Damera\textsuperscript{2,7}, Umang
Gupta\textsuperscript{2,8}, Prakriti Bhandari\textsuperscript{1,2}}

\textsuperscript{1}Patan Academy of Health Sciences, Lalitpur, Nepal

\textsuperscript{2} Team Erevnites, India

\textsuperscript{3}Southwestern University School of Medicine, Cebu
City, Philippines

\textsuperscript{4}Government Medical College, Surat, India

\textsuperscript{5}Guntur Medical College, Andhra Pradesh, India

\textsuperscript{6}Noorul Islam Institute of Medical Sciences, Kerala,
India

\textsuperscript{7}Mediciti Institute of Medical Sciences, Ghanpur,
Telangana, India

\textsuperscript{8} Nepalgunj medical college, BP Chowk-12, Nepalgunj
Banke, Nepal

\textbf{Corresponding author:}

Shailes Paudel

Patan Academy of Health Sciences, Lalitpur, Nepal

Email: shailespaudel@gmail.com

ORCID: 0000-0002-2405-6952

\textbf{ORCID Ids:}

Maulik Dhanani:~0000-0001-9419-267X

Krish Hitesh Patel: 0000-0001-6719-8996

Naga Praneeth Vakkalagadda: 0000-0002-3879-1739

Vivek Sanker: 0000-0003-0615-8397

Abhiram Rao Damera: 0009-0009-1693-5648

Umang Gupta: 0000-0002-7911-8663

Prakriti Bhandari: 0009-0002-9689-8742

\textbf{KEY CLINICAL MESSAGE}

Identifying pulmonary pathology while evaluating electrolyte disorders
is crucial for optimal patient management. Physicians working in endemic
regions of tuberculosis should consider this pathology as a differential
for electrolyte imbalances.

\textbf{ABSTRACT}

Hyponatremia, a common electrolyte imbalance, can arise from various
underlying etiologies such as diuretics, diarrhea, vomiting, congestive
heart failure, liver and renal disease. We present a case report of a
74-year-old man highlighting the association between pulmonary
tuberculosis (TB) and the development of hyponatremia. GeneXpert assay
of patients sputum sample led to the identification of underlying active
pulmonary TB as the cause of hyponatremia. The patient was started on
anti-TB therapy, and concurrent fluid restriction and sodium
supplementation were initiated to correct the electrolyte imbalance.
Over the next 3 days, patient demonstrated clinical improvement with the
resolution of hyponatremia. This case also highlights the importance of
considering tuberculosis as a potential etiology in patients presenting
with hyponatremia, especially in endemic areas. Further research is
warranted to explore the mechanistic pathways linking pulmonary TB and
hyponatremia, aiding in the development of targeted therapeutic
interventions.

\textbf{KEYWORDS: Dyselectrolytemia, Hyponatremia, Mycobacterium,
Pulmonary Tuberculosis}

\textbf{INTRODUCTION:}

Hyponatremia is defined as the depletion of sodium levels in the blood
below 135 mEq/L. Sodium is essential for proper nerve and muscle
function and therefore hyponatremia can cause weakness, nausea,
headache, confusion, and in severe cases seizures and coma. Common
causes include diuretics, vomiting, diarrhea, congestive heart failure,
renal, and liver disease {[}1{]}. One of the uncommon causes of
hyponatremia is pulmonary tuberculosis which is caused by the
bacteria\emph{M. Tuberculosis} that commonly affects the respiratory
system but is also known to cause systemic complications.

Tuberculosis can cause hyponatremia by a variety of mechanisms,
including local invasion of the adrenal glands (adrenal insufficiency),
local invasion of the hypothalamus or pituitary gland, Tubercular
meningitis, and incorrect ADH secretion via pulmonary infection {[}2{]}.
Timely diagnosis and early management of hyponatremia in individuals
with pulmonary TB is essential to prevent complications and improve
patient outcomes. We present an unusual case of a 74-year-old man who
presented in the emergency department with decreased consciousness and
weakness of the bilateral lower limb with retention of urine.

\textbf{CASE PRESENTATION:}

A 74-year-old man presented to the emergency department with decreased
consciousness and weakness in both lower limbs for about 6 hours for
which he was brought to the emergency department. The patient had a
history of recurrent urinary retention, but no fever or weight loss. He
had a smoking history of 25 pack-years and was a non-alcoholic. The
patient had a past medical history of pulmonary tuberculosis, which was
successfully treated with antitubercular drugs under Directly Observed
Treatment Short-course (DOTS) 15 years ago.

On examination, the patient was thin build and oriented to place but not
to time and person. Chest examination revealed bilateral scattered
wheeze over most of the lung fields, with bronchial breath sounds heard
over the right upper lung region. Neurological examination showed
bilateral lower limb weakness (power of 3/5) with intact sensations.
Abdominal examination revealed a palpable bladder that was slightly
tender. Other examinations were unremarkable. Bedside glucometer
measurements indicated normal blood glucose levels.

Emergency blood investigations (\textbf{Table 1} ) revealed severe
hyponatremia and an elevated erythrocyte sedimentation rate (ESR). A
computed tomography (CT) head scan was performed to rule out stroke,
which showed age-related cortical atrophy. Magnetic resonance (MR) spine
imaging showed normal findings. Chest X-ray revealed areas of fibrosis
(\textbf{Figure 1} ). Sputum samples were collected for Ziehl-Neelsen
(ZN) stain and Gram stain examinations, which yielded normal results.
GeneXpert testing on the sputum samples detected a low amount
of\emph{Mycobacterial Tuberculosis} . Further, Line Probe Assay (LPA)
was conducted for drug susceptibility testing which didn't show
resistance to Isoniazid and Rifampicin.\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Variables} & \textbf{Values} & \textbf{Laboratory reference
values}\tabularnewline
\midrule
\endhead
Random glucose & 81 mg/dL & 70-100 mg/dL\tabularnewline
Blood Urea Nitrogen & 11 mg/dL & 6-16 mg/dL\tabularnewline
Creatinine & 0.6 mg/dL & 0.6-1.3 mg/dL\tabularnewline
Calcium & 9.4 mg/dL & 8.6-10.3 mg/dL\tabularnewline
Sodium & \textbf{114} mmol/L & 135-145 mmol/L\tabularnewline
Potassium & 4.4 mmol/L & 3.5-5.0 mmol/L\tabularnewline
Erythrocyte Sedimentation Rate (ESR) & \textbf{52} mm in
1\textsuperscript{st} hour & 0-15 mm in 1\textsuperscript{st} hour
(Men)\tabularnewline
\bottomrule
\end{longtable}

Table 1: Routine Lab Investigations\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1: Chest X-ray showing diffuse areas of fibrosis in right
upper lobe with deviation of trachea to the right.}

The patient's hyponatremia was gradually corrected over 3 days, and he
was discharged with antitubercular drugs. At the one-month follow-up,
the patient demonstrated significant improvement in his symptoms and
electrolytes (follow-up Sodium was 142 mmol/L) and tolerated the
medications without experiencing any complications.

\textbf{DISCUSSION:}

The most typical presentation of tuberculosis (TB), an ancient human
disease caused by the bacteria, \emph{Mycobacterium tuberculosis} is
respiratory symptoms {[}3{]}. But TB presents itself in a variety of
ways since it affects multiple systems. The respiratory system,
gastrointestinal (GI) system, lymphoreticular system, skin, central
nervous system, musculoskeletal system, reproductive system, and liver
are the organ systems most frequently impacted {[}4,5{]}. In this case
report, we describe a patient presenting with severe hyponatremia in the
context of pulmonary tuberculosis.

A serum sodium content of less than 135 mEq/L is considered
hyponatremia, albeit this definition may vary slightly depending on the
standards used by different laboratories. A frequent electrolyte
disorder known as hyponatremia is brought on by an excess of total body
water in comparison to total body sodium concentration. A ratio
imbalance known as hyponatremia occurs when the body's total water
content exceeds its total solute content. The two primary compartments
of total body water (TBW) are extracellular fluid (ECF), which makes up
one-third, and intracellular fluid (ICF), which makes up the other
two-thirds. ECF's main solute is sodium, while ICF's main solute is
potassium {[}6{]}.

A Study in 1969 by Chung et al, demonstrated that 11\% of patients with
active TB had Hyponatremia and the main cause was SIADH {[}7{]}.
Cockcroft et al., reported a 74-year-old woman with miliary tuberculosis
which had been complicated by severe hyponatremia due to SIADH {[}8{]}.
Lee et al reported an unusual case of PTB presenting as Hyponatremia
with biochemical evidence of ectopic antidiuretic hormone production as
a possible mechanism causing hyponatremia {[}9{]}.

A few similar cases in the literature are described below (Table 2):\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Study; Country; year\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Demographic features\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Past History\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Duration of illness\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Investigations\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Treatment given\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Miliary Tuberculosis Presenting with Hyponatremia and ARDS in an
82-Year-Old Immunocompetent Female; Spain; 2018 {[}10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
82 years Female\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Type 2 Diabetes Mellitus, Atrial fibrillation\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
6 days\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Normal physical examination, Initial blood sodium=123 mmol/dL, Normal
chest x-ray, Chest CT with ground glass areas, Sputum culture showed M.
TB.\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Ciprofloxacin followed by Meropenem (Patient expired before the
diagnosis was made)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Miliary tuberculosis presenting with hyponatremia and
thrombocytopenia;Canada;1976 {[}8{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
74 years Female\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
None\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
14 days\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Chest x-ray suggestive of pulmonary congestion\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
isoniazid, rifampin, ethambutol, prednisone, vincristine and fluid
restriction\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
A case of mild pulmonary tuberculosis complicated with the syndrome of
inappropriate antidiuretic hormone secretion which caused impaired
consciousness; Japan;2011 {[}11{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
81 years Female\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
None\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Chest x-ray suggestive of unilateral infiltration, Mycobacterium
detected on sputum smear\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Sodium loading with fluid restriction and anti-tubercular therapy\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
A case of pulmonary tuberculosis initially presented with syndrome of
inappropriate secretion of antidiuretic hormone (SIADH);Japan;2003
{[}12{]}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
90 years Male\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
None\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Chest x-ray showed pulmonary infiltration, Mycobacterium detected on
sputum smear\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Sodium loading with fluid restriction and anti-tubercular therapy\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Table 2: List of similar cases published in literature

The underlying pathophysiology of hyponatremia in pulmonary tuberculosis
is likely multifactorial. Firstly, the pulmonary infection can lead to
an excessive release of inflammatory cytokines, such as interleukin-6
and tumor necrosis factor-alpha, which may stimulate the secretion of
antidiuretic hormone (ADH) from the posterior pituitary gland. The
increased ADH levels result in impaired water excretion, leading to
dilutional hyponatremia. Secondly, pulmonary tuberculosis can cause
systemic inflammation and oxidative stress, which may affect the renal
tubules' ability to regulate sodium and water balance. Additionally,
tuberculous involvement of the central nervous system can disrupt the
normal regulation of ADH release, further contributing to hyponatremia
{[}13-15{]}. Patients with PTB who are older and have an increased CRP
level are likely to have hyponatremia {[}16{]}.

\textbf{CONCLUSION:}

In conclusion, we presented a case of a 74-year-old man with a history
of pulmonary tuberculosis who showed signs of impaired consciousness,
lower limb weakness, and severe hyponatremia. Mycobacterium tuberculosis
was detected through GeneXpert. Our case indicates the significance of
considering pulmonary tuberculosis as a possible cause of electrolyte
imbalance. Particularly in regions where tuberculosis is endemic,
healthcare professionals should not undervalue the link between
pulmonary tuberculosis and electrolyte abnormalities. To avoid potential
problems and improve patient outcomes, it is essential to identify and
treat dyselectrolytemia in patients with respiratory symptoms. When
dealing with electrolyte imbalances in cases presenting with these
symptoms, healthcare providers should include tuberculosis in the
differential diagnosis.

\textbf{ACKNOWLEDGEMENT:}

We would like to thank Department of Internal Medicine, Patan Academy of
Health Sciences for their collaboration in this study.

\textbf{CONFLICTS OF INTEREST:}

None declared.

\textbf{AUTHOR CONTRIBUTION:}

All the authors contributed equally in drafting, editing, revising and
finalizing the case report.

\textbf{ETHICAL APPROVAL:~}

The ethical approval was not required for the case report as per the
country's guidelines.

\textbf{CONSENT:}

Written informed consent was obtained from the patient to publish this
report.

\textbf{DATA AVAILABILITY STATEMENT:}

The data that support the findings of this article are available from
the corresponding author upon reasonable request.

\textbf{REFERENCES:}

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