Pulmonary veno-occlusive disease in a patient with a history of Hashimoto's thyroiditis.

Abstract

Pulmonary veno-occlusive disease (PVOD), a rapidly progressive and fatal disorder, is a rare cause of pulmonary hypertension. We report the occurrence of PVOD in a female patient with Hasimoto's thyroiditis. This report emphasises that PVOD can co-exist with Hashimoto's thyroiditis and a high index of clinical suspicion is required to confirm the diagnosis of PVOD.

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CASE REPORT
Pulmonary Veno-occlusive Disease in a Patient with a
History of Hashimoto’s Thyroiditis
Nurdan Kokturk, Nalan Demir, Sedat Demircan1, Leyla Memis2, Cuneyt Kurul1,
Nalan Akyurek2 and Haluk Turktas
Departments of Pulmonary Medicine, Thoracic Surgery1 and Pathology2, School of Medicine, Gazi University,
Turkey
ABSTRACT
Pulmonary veno-occlusive disease (PVOD), a rapidly progressive and fatal disorder, is a rare
cause of pulmonary hypertension. We report the occurrence of PVOD in a female patient with
Hasimoto’s thyroiditis. This report emphasises that PVOD can co-exist with Hashimoto’s
thyroiditis and a high index of clinical suspicion is required to confirm the diagnosis of PVOD.
Key words: Pulmonary veno-occlusive disease, Hashimoto’s thyroiditis.
[Indian J Chest Dis Allied Sci 2005; 47: 289-292]
[Received: July 7, 2004; accepted after revision: January 20, 2005]
Correspondence and reprint request: Dr Nurdan Kokturk, Department of Pulmonary Medicine, School of
Medicine, Gazi University, Kizilirmak Sok 16/10, Besevler/Ankara/Turkey 06510; Tele.: 903124251580; Telefax:
903122129019; E-mail: <nkokturk@gazi.edu.tr>, <nurdank@yahoo.com>.
INTRODUCTION
Pulmonary veno-occlusive disease (PVOD) is
an uncommon cause
hypertension that characteristically leads to
intimal fibrosis of postcapillary pulmonary
vasculature due to vascular thrombosis1. The
disease is extremely rare and less than 200 cases
have been reported so far in the literature1.
Although the viral infections are implicated as a
cause, the aetiology of PVOD is largely
unknown. Autoimmunity has been occasionally
proposed for the development of PVOD1-3.
of pulmonary
In this report, a patient with a history of
Hashimoto’s thyroiditis in whom PVOD was
diagnosed is described. Our observation
suggest that PVOD can co-exist with
Hashimoto’s thyroiditis and confirming the
diagnosis of PVOD needs extensive evaluation
and high index of clinical suspicion.
CASE REPORT
A 54-year-old, non-smoker female was
admitted to our department for the evaluation
of increased shortness of breath and chest pain.
The patient had experienced exertional
dyspnoea for the preceding 10 years. Dyspnoea
had rapidly progressed for the past one year.
Paroxysmal nocturnal dyspnoea and chest pain
appeared during the last three months.
Previously, the patient received several inhala-
tion therapies for these symptoms, but no
improvement occurred. The patient had under-
gone thyroidectomy for goiter five years ago.
The post-operative diagnosis was Hashimoto's
thyroiditis. She had been receiving levothy-
roxine therapy since then. There was no history
of appetite suppressant or antidepressant drug
usage or recent viral infection.
On admission, body temperature was 36 oC,

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290
respiration was 28 per min, pulse was 96 per
min and blood pressure was 100/60 mmHg.
There were telengiectasis on the skin of the neck
and cheeks. Neck veins were bilaterally
enlarged. There was a scar of thyroidectomy in
the neck. Clubbing was not present.Chest
auscultation revealed bilateral inspiratory
crackles at the bases. Pulmonary component
(P2) of the second heart sound was prominent
on cardiac examination. Hepatomegaly and
peripheral oedema were noted in both lower
extremities. Peripheral cyanosis was present.
The arterial blood gas analysis on room air
revealed marked hypoxaemia with respiratory
alkalosis. Electrocardiography (ECG) revealed
sinus rhythm, right axis deviation and
inferolateral ST-T changes. Chest radiograph
(Figure 1) revealed enlarged pulmonary arteries,
cardiomegaly and prominent interstitial
markings in the lower zones. In the echocar-
diogram, right ventricle and right atrium were
dilated. Maximum pulmonary artery pressure
(PAP) was 100 mmHg. Left ventricular
functions and mitral valve appeared to be
normal. Routine blood work up and erythrocyte
sedimentation rate (ESR) were normal.
Antinuclear antibody (ANA) was weakly
positive with a titer of 30 IU/ml. Other markers
of collagen vascular disorders (CVD) including
anti-ribonucleoprotein (anti RNP), anti scl-70
and, anti-centromere antibodies were negative.
Total immunoglobulins, C3 and C4 were
normal. Free T3, free T4 and thyroid stimulating
hormone (TSH) levels were normal. Anti-
thyroid peroxidase (Anti-TPO) antibody was
negative. Anti-thyroglobulin (anti-T) was
positive at the level of 183.5 (upper limit:115).
Anti-streptolysin O(ASO) was 200 IU/ml, C-
reactive protein (CRP) was negative and
rheumatoid factor (RF) was 40 IU/ml. Comp-
uterised tomographic scan (CT scan) of the chest
(Figure 2) revealed multiple enlarged medi-
astinal lymph nodes with the largest one in 2 cm
in diameter. CT scan of the chest (Figure 3) also
demonstrated enlarged main pulmonary artery,
bilateral diffuse ground glass opacities,
Figure 1. Chest radiograph (postero-anterior view )
showing bilateral hilar enlargement, cardiomegaly
and interstitial markings in the lower zones.
Figure 2. CT scan of the chest showing enlarged
mediastinal lymph nodes in prevascular and
pretracheal regions.
Figure 3. CT scan of the chest showing enlargement
of main pulmonary artery.
PVOD and Hashimoto's ThyroiditisNurdan Kokturk et al

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2005; Vol. 47The Indian Journal of Chest Diseases & Allied Sciences291
interlobular septal thickening and minimal
right-sided pleural effusion (Figure 4).
Spirometric evaluation revealed normal
findings. Carbon monoxide diffusion capacity
(DLCO) was reduced to 50 percent. Abdominal
ultrasonography (USG), upper gastrointestinal
endoscopy and lower extremity doppler
ultrasonography examinations were normal.
Perfusion scan of the chest revealed low
probability pulmonary embolism.
biopsy which revealed thickened alveolar septa,
severe congestion of alveolar capillaries,
collection of hemosiderin-laden macrophages in
the alveolar spaces and hemosiderosis of the
interstitium. Examination of small-and
medium-sized pulmonary veins revealed
fibrous thickening by a peculiarly oedematous
laminated loose connective tissue. Narrowing
and occlusion of the small veins by eccentric or
concentric intimal fibrosis was also observed
(Figure 5). Mediastinal lymph node sampling
revealed reactive lymph nodes. Histopatho-
logical findings were consistent with PVOD.
Figure 4. CT scan of the chest showing ground glass
appearance, interlobular septal thickening.
Figure 5. Photomicrograph showing a small
pulmonary vein obstructed by intimal fibrosis (H&E
× 200) (internal scale : 50 µ).
On the basis of above clinical and laboratory
findings; the patient initially underwent the
work-up for the evaluation of pulmonary
arterial hypertension (PAH). In the mean time, it
was noted that the patient’s clinical condition
deteriorated and the patient developed atypical
chest pain and hypotension while receiving
nifedipine. At that time chest radiograph
demonstrated pulmonary oedema. In the
presence of suggestive CT and clinical findings,
the most likely diagnosis was PVOD.
Hemodynamic study was therefore, done to
evaluate pulmonary capillary wedge pressure
(PCWP). On right heart catheterisation, with the
method of catheter tip, PCWP was measured as
12 mmHg. Left sided pressures and valve
gradients were normal. PAP(systolic/diastolic/
mean) was measured as (120/50/83). Vasodi-
lator test with 500 µg sodium nitroprusside was
negative. The patient experienced chest pain
and hypotension after vasodilator test. The
patient underwent confirmatory open lung
On the 17th day of the operation, the patient’s
clinical condition deteriorated and severe
hypoxaemia developed despite high oxygen
supplement. The patient died due to marked
pulmonary oedema.
DISCUSSION
Pulmonary veno-occlusive disease (PVOD) is
a devastating disorder with an unknown
etiology. The disease is characterised by intimal
fibrosis of small veins and venules in the
postcapillary pulmonary vasculature1. The
disease is extremely rare with the estimated
annual incidence of 0.1 per million persons4.
Making a difinitive diagnosis of PVOD requires
an awareness regarding the disease.

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The aetiology of PVOD is largely unknown.
However, viral infections e.g. human immuno-
deficiency virus (HIV), Epstein-Barr virus are
defined associated with the condition. Auto-
immune disorders such as rheumatoid arthritis,
systemic lupus erythematosus and Raynaud’s
phenomenon are found to be associated with
the development of the disease in occasional
case reports1-3. It has been suggested that PVOD
is a syndrome of multiple causes rather than a
single entity5.
Autoimmune features are more frequently
reported in primary pulmonary hypertension
(PPH) even in the absence of clinical
autoimmune disease6. Yanai-Landau et al6
reported that 62.4% of the cases with PPH
showed circulating autoantibodies including
antinuclear and antithyroglobulin antibodies6.
These observations imply that in a subgroup of
patients with PPH the disease might be ascribed
to immune dysregulation6. Although the
association of PVOD and Hashimoto’s
thyroiditis has not been described before, an
association between autoimmune thyroid
diseases and PAH has been reported7. The
underlying machanism of this association has
not been completely elucidated. In a prospective
study7, the prevalence of autoimmune thyroid
disease in PAH was found to be as high as 49
percent. This high prevalence led the authors to
propose that there might be a common
immunogenetic mechanisms shared between
these disorders7.
Co-existence of Hashimoto’s disease and
PVOD also suggests that both diseases may
share common immunogenetic mechanisms.
Clinical for the diagnosis of PVOD criteria
consist of the triad of severe PAH, radiological
findings suggestive of pulmonary oedema and
normal pulmonary capillary wedge pressure4.
Interpretation of radiological findings is
important in the diagnosis of PVOD. The CT
findings such as mediastinal lymphadenopathy,
interlobular septal thickening and diffuse
ground glass opacifications may easily be
misdiagnosed as interstitial lung disease. In our
case it was quite interesting to see that reactive
mediastinal lymph nodes could be as large as 2
cm in diameter. Lymph node enlargement may
be caused by vascular congestion1.
Haemodynamic evaluation has a crucial role in
documenting normal PCWP in suspected cases.
Vasodilator testing may lead pulmonary
oedema or even death in association with
increased transcapillary hydrostatic pressure.
Therefore, a great caution must be taken during
the procedure4. Pulmonary oedema that
becomes manifested after taking calcium-
channel blocker would be a clue for the
suspected diagnosis. The definite diagnosis is
usually made by open lung biopsy1.
Our observation emphasises that PVOD
would co-exist with Hashimoto’s thyroiditis.
Making an exact diagnosis of PVOD needs
extensive evaluation and high index of clinical
suspicion.
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PVOD and Hashimoto's ThyroiditisNurdan Kokturk et al