Medical and Health Science Journal, Vol.3., No.

2, August 2019

ORIGINAL ARTICLE

UNCONTROLLED TYPE 1 DIABETES MELLITUS WITH LUNG

TUBERCULOMA AND BILATERAL HYDRONEPHROSIS IN 13-YEAR-
OLD GIRL

Anggia Rarasati Wardhana1*, Sukartini2, Annisa Muhyi3

1,2,3
Department of Child Health, University of Mulawarman Medical School, Abdul Wahab Sjahranie
Hospital, Samarinda-Indonesia
*Correspondent Author: [email protected]

ARTICLE INFO ABSTRACT

Article history: Diabetes Mellitus (DM) is an important risk factor for the development of active
Submitted: July 09 2019 tuberculosis (TB). DM is a chronic disease that weaken the immune system which
Received in revised form increased the risk of tuberculosis up to three-fold. We present a case of 13-year-
August 2019 old girl with chest pain and cough. She has a previous history of type 1 DM.
Accepted: August 12 2019 Laboratory findings showed hyperglycemic state. Thoracic CT showed
tuberculoma at inferoposterior lobe of left lung. The abdominal CT showed
Keywords: bilateral hydronephrosis. She was then administered TB treatment of
Type 1 diabetes mellitus, 2HRZE/10RH, corticosteroid, and insulin regiments with strict monitoring of
tuberculosis, tuberculoma, blood glucose. Clinical symptoms and blood glucose levels were significantly
improved after treatment for 20 days.
hydronephrosis, blood glucose
@2019 Medical and Health Science Journal. All rights reserved

BACKGROUND all cases of the disease. In 2015, there were an

estimated 1 million new cases of childhood
Type 1 Diabetes Mellitus (T1DM) is a
tuberculosis and an estimated 210.000 deaths from
chronic illness characterized by the insufficient
tuberculosis in children.4 Children carry a huge
production of insulin due to autoimmune
tuberculosis disease burden, particularly in endemic
destruction of beta cells in the pancreas. T1DM is
areas.5 According to the WHO, the three regions
chiefly occurred following an autoimmune
where most pediatric tuberculosis cases are
demolition of the pancreatic β cells through cell-
concentrated are Southeast Asia, Africa, and the
mediated immunity as well as a humoral immune
Western Pacific, which respectively accounted for
response. While the disease may develop in adults,
35%, 30%, and 20% of the new cases reported in
the onset most often occurs in childhood. T1DM can
2015. It is estimated that tuberculosis caused the
be considered as one of the most frequent endocrine
death of 210.000 children worldwide in 2015. Based
and metabolic dysfunction in children. T1DM in
on those estimates, tuberculosis might be the sixth
children and teenagers represents 80%-90% of
leading cause of death in the 1- to 5-year age group.4
diabetes. In the US, the prevalence of T1DM in
The possibility of association between DM
youth under 20 years was 1.93 /1000 in 2009 with
and TB represents an important and growing
2.6 - 2.7% relative annual increase.1
challenge to the global control of TB. Patients with
Tuberculosis (TB) is still one of the main
these two conditions may present high rates of
causes of morbidity and mortality worldwide. 3
treatment failure of TB and increased risk of death.
Children are particularly vulnerable to tuberculosis.
Cases of TB with DM have higher probability of
Pediatric cases of tuberculosis account for 10% of
treatment failure of TB and may develop resistance

Correspondence: Anggia Rarasati Wardhana

@2019 Medical and Health Science Journal. All rights reserved
Available at http://journal2.unusa.ac.id/index.php/MHSJ
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 Medical and Health Science Journal, Vol.3., No.2, August 2019

to the drugs used in the treatment. On the other Figure 1. Chest X-ray
hand, TB can induce glucose intolerance and hinder Acid Fast Bacilli sputum smear was negative.
the glycemic control in individuals with DM.6 A Laboratory findings revealed leukocytosis (WBC
systematic review of 13 observational studies found 23.580/mm3), anemia (9,7 gr/dl), Hematocrit was
that DM increases the risk of TB by three-fold.7 30,4%, Platelets were 364.000/mm3, and blood
Thus, patients with DM comorbidity may pose a glucose of 463 mg/dL. Chest X-ray showed
greater challenge the control of TB.8 bronchopneumonia (Fig 1), while thoracic CT
showed: hypodense lesion with slight hyperdense
CASE PRESENTATION on inferior-posterior lobe of left lung; suspicion of
left lung abscess; solid and cystic mass of inferior-
A 13-year-old girl presented to A. W.
posterior lobe of left lung; and minimal effusion on
Sjahranie Hospital with left chest pain for three days
posterior right lung (Fig 2). Fine Needle Aspiration
which felt like being punctured and burned. The
Biopsy revealed granulomatous suppurative
pain was exacerbated when she laid down. She also
inflammations with squamous dysplasia (TB with
had cough for two months with yellow-green
secondary infection and squamous dysplasia).
phlegm and fever which appeared simultaneously
Abdominal USG showed bilateral hydronephrosis
with cough, night sweats, weight loss, and
(Fig 3), while abdominal X-ray showed unclear
hematuria. The patient has a history of a lump in the
kidney contours (Fig 4). Abdominal CT revealed
neck for one year which was sometimes felt painful,
left grade II hydronephrosis and right grade I
and was getting bigger. She also had prolonged
hydronephrosis (Fig 5). After complete
fever, and no cough in that time. Her grandmother
examination, the final diagnosis in this patient is
was diagnosed with lung tuberculosis and had
T1DM with lung tuberculosis and bilateral
passed way. Her BCG vaccine history were
hydronephrosis.
positive. She was diagnosed with lymphadenitis TB
and had been treated in declared cured in 2017 and
was diagnosed with T1DM at the age of 10. Her
father had been diagnosed with DM and stroke. Her
mother had a history of breast cancer.

INVESTIGATIONS
Physical examination revealed asymmetrical
chest movement, decreased tactile fremitus on left
chest, dull percussion on the inferoposterior left
chest, and decreased breath sound on posterior left
chest with rhonchi on both sides of lung bases. Both
kidneys were palpable. Early diagnosis when
admitted to the hospital for this patient was pleural
effusion and T1DM with hematuria. The differential Figure 2. Thoracic CT.
diagnosis were pleuritic TB and pleural abscess
with urinary tract infection or nephrolithiasis.

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 Medical and Health Science Journal, Vol.3., No.2, August 2019

Figure 3. Abdominal USG 1027 AD) over one thousand years ago. In recent
decades, with the increasing prevalence of TB,
particularly Multi Drug Resistant TB (MDR-TB),
and DM cases in the world, the relationship is re-
emerging as a significant public health problem.
The link of DM and TB is more prominent in
developing countries where TB is endemic and the
prevalence of DM is rising.9
Our patient had diseases that were mutually
incriminating one to another. Associated with this
case, patients with T1DM may have an even higher
risk of developing TB compared to those with type
2 diabetes (T2DM).10 DM patients exhibit
Figure 4. Abdominal X-ray. alterations in the immune response against
Mycobacterium tuberculosis (Mtb), making them
more susceptible to infection or progression
towards active TB disease and less responsive to
treatment. DM patients have been associated with
dysregulated cytokine responses to Mtb, including
T-helper 1 (Th1) along with several cytokines
(TNF-𝛼, IL-1𝛽, and IL-12), lymphocytes,
monocytes, natural killer T cells, and B
Figure 5. Abdominal CT. lymphocytes.11 Thus, DM is likely to reduce the
efficiency of anti-mycobacterial treatment.
TREATMENT Hyperglycemia may also compromise Mtb killing
by affecting the microvasculature and reducing lung
On admission she was given antibiotics and
tissue perfusion for optimal immune surveillance.7
the symptomatic theraphy such as antipyretic,
In addition, Arce-Mendoza et al (2008) reported that
antiulcer through injection. Treatment for TB was
DM also affects the expression of receptors like
initiated with 2HRZE/10RH and corticosteroid,
CD64, CD206 and RAGE in monocytes.12
with strict blood glucose monitoring. Insulin
Other possible factors that may impact the
regiment consists of both long-acting insulin and
host response in patients with DM are short-chain
rapid acting insulin with dose adjusted to the
fatty acids (SCFAs). SCFAs modulate immune and
patient’s condition.
inflammatory responses, thereby influencing the
Outcome and follow up
host response to Mtb. SCFAs act on immune and
Clinical symptoms were improved
endothelial cells via at least two mechanisms:
significantly after 20 days of hospitality. The
activation of G-protein coupled receptors (GPCRs)
complaints were reduced. The chest pain were
and inhibition of histone deacetylase (HDAC). They
eased, cough were missing arise, and vanished
affect the function of various cell types such as
fever. After one month, the patient’s blood glucose
lymphocytes, neutrophils, and macrophages.13
becomes normal. The chest examination was
The immunological source of susceptibility
improved lung spot and no effusion on the affected
to TB among those with DM is not well understood.
side.
Enhanced susceptibility to TB in patients with DM
has been attributed to several factors, including
DISCUSSION
direct effects related to hyperglycemia and insulin
The first report of the association between
resistance and indirect effects related to macrophage
DM and TB was documented by Avicenna (980-
and lymphocyte function. The impaired immune

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 Medical and Health Science Journal, Vol.3., No.2, August 2019

response in patients with DM, which facilitates support systems, treatment of patients with double
either primary infection with TB or reactivation of disease, research and innovation. Optimizing DM
latent TB, may be the possible reason for these management during TB treatment should therefore
defective immune responses. Studies probing the be a high priority in patients with TB to improve the
innate and adaptive immune response to microbial general health status of the patient. Management of
antigens in patients with DM suggest that these DM in TB should be aggressive, since an optimal
responses are compromised, particularly in patients glycemic control results in a better patient outcome.
with chronic hyperglycemia.12 The optimal approach might consist of avoiding
Active TB disease may present atypically sulphonylurea derivates and treating DM with diet,
with altered symptoms and signs in those with DM. lifestyle modifications, metformin and insulin, as
Among persons with DM, TB may progress faster, these last two medications have few interactions
present with more chest and systemic symptoms and with TB drugs.15 The American Association of
more frequent and higher-grade smear and culture Clinical Endocrinologists recommends the use of
positivity. Severity at presentation seems to be modern insulins or insulin analogues, as they are
related to the degree of uncontrolled hyperglycemia. more predictable in action and cause less
The effects of DM on chest radiograph findings are hypoglycemia.16 A successful treatment can only be
inconsistent.14 There is also some evidence that DM achieved by ensuring good compliance to treatment
prolongs smear and culture positivity.14 both for TB and DM.15
Patients with DM comorbidity may pose a
greater challenge to control the TB, since DM CONCLUSION
adversely affects TB treatment outcomes. The
A case of 13-year-old girl with T1DM and
reasons are not completely understood but include
tuberculoma and bilateral hydronephrosis was
the immunosuppressive effects of DM itself, drug-
reported. The diagnosis was based on patient’s
drug interactions, adverse effects from medications,
history, physical examination, laboratory findings,
suboptimal adherence to medication, reduced bio-
and imaging. The patient was admitted with chest
availability of the drugs and other unlisted factors.
pain and chronic cough with a history of T1DM.
There is also a doubling of the risk of death during
Standard regiment of anti-tuberculosis treatment
TB treatment among those with DM with the risk
was initiated, in conjunction with corticosteroid and
increasing to about five times.6,14 Diabetic patient
insulin therapy. Clinical and laboratory
with TB has a higher probability of failure of the
improvement were shown after treatment. This
sputum smear conversion after 2 months of therapy
report highlighted that aside from the comorbidities
than patients without DM. Patients with DM also
between diseases, there existed additional
are more likely to be lost to follow-up than patients
complexity in managing T1DM patient with DM.
who are non-diabetic, thus, increased duration of
Patients with DM comorbidity may pose a greater
treatment and weight-adjusted doses of anti-TB
challenge to control the TB, since DM adversely
drugs might be necessary.15 In addition, Lee et al
affects TB treatment outcomes. The reasons are not
(2014) revealed that the presence of DM was
completely understood but include the
independently associated with the risk of TB
immunosuppressive effects of DM itself, drug-drug
relapse.8
interactions, adverse effects from medications,
Currently, there is not sufficient evidence to
suboptimal adherence to medication, reduced bio-
recommend alternative anti tuberculosis regimen
availability of the drugs and other unlisted factors.
for diabetics. Consequently, treatment of TB is
There is also a doubling of the risk of death during
similar between diabetics and nondiabetics.9 There
TB treatment among those with DM with the risk
are a number of actions that can be taken to mitigate
increasing to about five times. A successful
the effect of DM to decrease the burden of TB, such
treatment can only be achieved by ensuring good
as prevention by addressing the underlying
compliance to treatment both for TB and DM. The
determinants, screening, early diagnosis, adequate

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 Medical and Health Science Journal, Vol.3., No.2, August 2019

success of the therapy will later provide a good Patients With Type 1 Diabetes Mellitus : Results
prognosis to the patient. From a Population-Based Cohort Study in
Taiwan. Medicine (Baltimore). 2014;93(16):1–6.
9. Baghaei P et al. Diabetes mellitus and
CONFLICTS OF INTEREST
tuberculosis facts and controversies. J Diabetes
There is no conflict of interest in this article. Metab Disord. 2013;12(58):1–8.
10. Lachmandas E et al. Patients with type 1 diabetes
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