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\begin{document}

\title{Polyserositis Caused by Tuberculosis in a Young Female Patient with
Hypothyroidism: A Diagnostic Challenge}



\author[1]{Gashaw Solela }%
\author[1]{Ferhan Kedir}%
\author[2]{Merga Daba}%
\affil[1]{Yekatit 12 Hospital}%
\affil[2]{Addis Ababa University College of Health Sciences}%


\vspace{-1em}



  
  \date{May 21, 2024}


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\textbf{Polyserositis Caused by Tuberculosis in a Young Female Patient
with Hypothyroidism: A Diagnostic Challenge}

Gashaw Solela\textsuperscript{1} Ferhan Kedir\textsuperscript{1} Merga
Daba\textsuperscript{2}

\textsuperscript{1}Department of Internal Medicine, Yekatit 12 Hospital
Medical College, Addis Ababa, Ethiopia.

\textsuperscript{2}Department of Internal Medicine, College of Health
Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Correspondence: Gashaw Solela, Department of Internal Medicine, Yekatit
12 Hospital Medical College, gashawsol@gmail.com, +251-921562995, ORCiD
ID - 0000-0002-2233-9270

\textbf{Abstract}

\textbf{Introduction:} The most frequent causes of polyserositis include
neoplasia, autoimmune diseases, and infections. Polyserositis, an
uncommon feature of disseminated tuberculosis (TB), may delay diagnosis
of TB. Patients with hypothyroidism have a higher risk of developing
tuberculosis compared to those without hypothyroidism.

\textbf{Case presentation:} Here, we report the case of a 32-year-old
female patient who presented with a complaint of abdominal distension of
3 weeks associated with shortness of breath and excessive fatigue.
Thyroid function tests were suggestive of primary hypothyroidism and
sputum GeneXpert~was positive for tuberculosis with exudative pleural
effusion. The polyserositis resolved following the initiation of
levothyroxine and anti-tuberculosis drugs.

\textbf{Conclusion:} Polyserositis is extremely rare in patients with
primary hypothyroidism and it is uncommon presentation of tuberculosis.
Evaluation for tuberculosis should be the rule for any patient
presenting with polyserositis, especially in high tuberculosis burden
countries.

\textbf{Keywords:} Polyserositis, Hypothyroidism, Tuberculosis

\textbf{Key Clinical Messages}

The most frequent causes of polyserositis include neoplasia, autoimmune
diseases, and infections; whereas, polyserositis is extremely rare with
primary hypothyroidism. Though tuberculosis is uncommon cause of
polyserositis, evaluation for tuberculosis should be the rule for any
patient presenting with polyserositis, especially in high tuberculosis
burden countries.

\textbf{Introduction}

According to Losada et al. {[}1{]}, polyserositis is an inflammation of
several serous membranes, such as the pleura, pericardium, and
peritoneum, which causes a buildup of exudates in these body cavities.
The causes of polyserositis are numerous. According to a systemic review
which included 114 patients, the most frequent causes of polyserositis
were neoplasia (30; 26.3\%), autoimmune disorders (19; 16.7\%), and
infections (16; 12.2\%), {[}2{]}. Polyserositis, a rare presentation of
disseminated tuberculosis, may delay diagnosis of tuberculosis {[}3{]}.

Hypothyroidism and tuberculosis (TB) are correlated in both directions.
Patients with hypothyroidism have a roughly 3-fold increased risk of
developing tuberculosis (TB) compared to those without hypothyroidism,
and those already suffering from TB have a 2-fold increased risk of
developing hypothyroidism {[}4{]}. Chemotaxis, phagocytosis, the
generation of reactive oxygen species, and the release of cytokines are
just a few of the immune system processes that thyroid hormones regulate
{[}5{]}. Hypothyroidism may have a negative impact on the immune system,
and recent research has demonstrated that thyroid hormone signaling is
crucial for an effective immunological response to TB infection {[}6{]}.

We report a rare case of polyserositis due to tuberculosis, involving
pleura, pericardium and peritoneum in a young female patient
concomitantly diagnosed to have primary hypothyroidism.

\textbf{Case Presentation}

A 32-year-old female patient presented with abdominal distension of 3
weeks associated with shortness of breath, excessive fatigue, and loss
of appetite. She had no previously known chronic medical illness. She
had blood pressure of 100/70mmHg, pulse rate of 72 beats per minute,
respiratory rate of 28 breaths per minute, oxygen saturation of 85\% at
atmospheric air, signs of bilateral pleural effusion and ascites. She
had coarse and dry skin over her trunk and extremities {[}Figure 1{]}.

Complete blood count showed normal white blood cell (WBC) count,
moderate anemia (hemoglobin: 9.8 g/dL, MCV: 88 fl) and normal platelet
count. Liver enzymes and serum creatinine were within the normal ranges.
Thyroid function tests showed high thyroid stimulating hormone (TSH)
level with low free T3 and T4 (TSH: 49 mU/L, Free T3: 0.1 pg/mL and Free
T4: 0.3 ng/dL). Sputum GeneXpert~MTB/RIF~test was positive for
rifampicin sensitive mycobacterium tuberculosis (TB). Anti-nuclear
antibody (ANA) and rheumatoid factor were negative. Pleural fluid
analysis revealed WBC count of 1200 cells/\selectlanguage{greek}µ\selectlanguage{english}L (neutrophil: 6.7\%,
Lymphocyte: 93.3\%), LDH of 704 IU/L, protein of 5.6 g/dL and glucose of
47 mg/dL. Echocardiography showed pericardial effusion; abdominal
ultrasound showed ascites; and chest x- ray showed bilateral pleural
effusion {[}Figure 2{]}.

The patient was diagnosed with polyserositis due to disseminated
tuberculosis and primary hypothyroidism and started on anti-tuberculosis
medications and oral levothyroxine (100 microgram daily). After a month
of initiation of anti-TB and thyroid hormone replacement, patient showed
marked improvement of her symptoms and repeated imaging confirmed
resolution of the body cavity fluid collections.

\textbf{Discussion}

Infectious infections like tuberculosis have been known to cause
polyserositis. Serosal tuberculosis is a common extrapulmonary
manifestation, particularly in places with a high tuberculosis burden,
whereas polyserositis is a less common form of the disease {[}7, 8{]}.
In an old case series, 50\% of the cases of polyserositis had
mycobacterium tuberculosis {[}9{]}. Certain case reports have shown that
endocrine disorders including hypothyroidism can also be the cause for
polyserositis {[}10{]}. A diagnostic challenge is faced when both
tuberculosis and hypothyroidism are present in a patient who has
polyserositis and microbiologic tests, such as GeneXpert, remain the
most important tools to confirm tuberculosis as a cause for the
polyserositis, like in our case.

The most typical clinical features of hypothyroidism include cold
intolerance, fatigue, weight gain, constipation, and dry skin {[}11,
12{]}. In patients with primary hypothyroidism, ascites, pericardial
effusion, or pleural effusion can all occur alone; however, the
occurrence of all three together is highly uncommon and not well
recognized {[}13{]}. Hypothyroidism-related pericardial and pleural
effusions have features that lie in between exudate and transudate and
exhibit little sign of inflammation {[}14{]}. Different pleural fluid
characteristics including transudate, exudative and bloody pleural
effusions have been reported from patients with multiple body cavity
fluid collections due to hypothyroidism {[}15 -- 18{]}. Our patient had
clinical features and thyroid function tests suggestive of
hypothyroidism; however, the polyserositis was most likely due to
disseminated tuberculosis evidenced by positive GeneXpert~MTB/RIF~test
from sputum and the exudative nature of the pleural fluid.

In a small study of 50 patients with sputum-positive pulmonary TB who
were hospitalized in South Africa, the most prevalent endocrine
dysfunction was a low free T3 state, which was present in almost 90\% of
patients as part of sick euthyroid syndrome. In some hospitalized
individuals recovering from nonthyroidal illnesses, temporary spikes in
blood TSH values (up to 20 mU/L) may occur {[}20{]}. It is typical for
patients to have permanent hypothyroidism when their serum TSH levels
are over 20 mU/L {[}21{]}. Sick euthyroid syndrome might have been
considered as one differential diagnosis for the hypothyroidism in our
patient; but, the very high TSH level (47 mU/L) was suggestive of
permanent hypothyroidism.

Hypothyroidism has been rarely reported to be caused by thyroid
tuberculosis (TB), an uncommon disease with an incidence of 0.1-0.4\%,
even in areas with high rates of pulmonary tuberculosis. Our patient did
not have a thyroid mass or nodule, which contrasts with solitary thyroid
nodule, which is the most common clinical presentation of thyroid TB
{[}22{]}. There are also case reports of hypothyroidism following the
initiation of second-line anti-TB agents, particularly p-amino salicylic
acid and ethionamide, and first-line anti-TB agents such as rifampicin,
which have more significant effects on thyroid physiology {[}23, 24{]}.
Contrary to these findings, our patient did not take any
anti-tuberculous medication before the diagnosis of hypothyroidism.

\textbf{Conclusion}

Polyserositis with combination of ascites, pericardial and pleural
effusions is extremely rare in patients with primary hypothyroidism and
it is uncommon presentation of tuberculosis. Consideration and work up
for tuberculosis should be the rule, for any patient presenting with
polyserositis of indefinite cause, especially in high tuberculosis
burden countries like Ethiopia.

\textbf{Authors' Contributions}

\textbf{Gashaw Solela:} Conceptualization; data curation; resources;
validation; writing -- review \& editing

\textbf{Ferhan Kedir:} Resources; writing -- original draft

\textbf{Merga Daba:} Data curation; writing -- original draft

\textbf{Acknowledgments}

The authors would like to thank the patient for approving the
publication of her case details.

\textbf{Data Availability Statement}

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

\textbf{Funding information}

There was no specific grant received from any funding agency in the
public, commercial, or not for-profit sectors.

\textbf{Conflict of Interest Statement}

The authors declared no potential conflicts of interest.

\textbf{Ethics Approval}

Ethical clearance including publication of this patient's case details
was obtained from Institutional Review Board of Yekatit 12 Hospital
Medical College.

\textbf{Consent for publication}

The patient gave an informed written consent for the publication of her
case details including the history, physical findings, laboratory
reports and images.

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