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hypnatremia Due t Pumnary Tubercusis: Review 200 Cases

Nemata Jnaidi Jaari1, Mrteza Izadi

1, Farad Sarrazade

2, Amir heidari

3, Reza Ran-

jbar4, Amin Saburi

5*

1 heat Researc Center, Baqiyataa University Medica Sciences, Teran, IR Iran2 Department Interna Medicine, Inectius Ward, Azaipur Educatina Medica Center, Kerman University Medica Sciences, Kerman, IR Iran3 Neprgy and Urgy Researc Center, Baqiyataa University Medica Sciences, Teran, IR Iran

4 Mecuar Bigy Researc Center, Baqiyataa University Medica Sciences, Teran, IR Iran5 Cemica Injuries Researc Center, Baqiyataa University Medica Sciences, Teran, IR Iran

* Corresponding author: Amin Saburi, Cemica Injuries Researc Center, Baqiyataa University Medica Sciences, Masadra St, Vanak Sq, Teran, IR

Iran. Te.: +98-9127376851, Fax: +98-2188600067, E-mai: aminsaburi@ya.cm

A B S T R A C T

Background: Pumnary Tubercusis (PTB) is ne te cmmn diseases wit ig prevaence mrtaity and mrbidity in devepingcuntries. Varius cmpicatins ave been reprted ang wit PTB. Te subcinica eectryte imbaances are custmary in cases wit PTB.Objectives: Te aim tis study was te evauatin patients wit PTB and ypnatremia.Patients and Methods:We evauated patients wit diagnsis secndary PTB w ave been admitted t Baqiyataa spita, Teran, Iranrm 2005 ti 2010. Te diagnsis PTB was based n te appearance acid ast bacii in sputum smears r sputum cutures, witut anyevidence miiary TB. Demgrapic and abratry caracteristics reative t eectrytes were recrded accrding incusin and excusincriteria.

Results: Te mean age was 59.22 20.57 years and 91 (45.5%) patients were mae. Te mean serum sdium cncentratin was 134.54 4.95mm/l and mre tan a subjects (51%) ave swn ypnatremia. Te mean age dierence between ypnatremic and eunatremicgrups was statisticay signicant (61.95 versus 56.02 years) (P = 0.047). N signicant reatinsip was und between ypnatremia andgender, anti-TB medicatins and c-mrbidity cnditins.Conclusions: In tis study, an der age was suggested as an imprtant predispsing actr r ypnatremia in patients wit PTB wic adbeen bserved as ess a determinant. We recmmend urter evauatins r ypnatremia in patients presenting wit PTB, particuaryr tse w are der.

Keywords: Tubercusis; hypnatremia; Causaity

Cpyrigt 2013, Kwsar Crp.; Pubised by Kwsar Crp.

Artice type: Researc Artice; Received: 04 Ju 2012, Revised: 28 Aug 2012, Accepted: 10 Sept 2012; DoI: 10.5812/numnty.7091

Impicatin r eat picy/practice/researc/medica educatin:

hypnatremia is a cmmn eectryte imbaance wic is presented in many disrders. Tis disturbance can wrsen te prgn-

sis inpatients w ave been admitted r ter diseases suc as pumnary disease. on te ter and pumnary tubercusis

is ne te mst imprtant and cmmn ung diseases especiay in deveping cuntries. In tis study we assessed patients wit

pumnary tubercusis r ypnatremia.

Pease cite tis paper as:

Jnaidi Jaari N, Izadi M, Sarra zade F, heidari A, Ranjbar R, Saburi A. hypnatremia Due t Pumnary Tubercusis; Review 200

Cases. Nepr-Ur Mn.2013;5(1): 687-691. DoI: 10.5812/numnty.7091

Cpyrigt 2013, Kwsar Crp.; Pubised by Kwsar Crp.Tis is an open Access artice distributed under te terms te Creative Cmmns Attributin license (ttp://creativecmmns.rg/icenses/by/3.0), wic per-mits unrestricted use, distributin, and reprductin in any medium, prvided te rigina wrk is prpery cited.

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1. Background

hypnatremia is cnsidered as ne te mst cm-

mn and imprtant eectryte abnrmaities. hypna-

tremia must be cnsidered in a seriusy i spitaized

patients (1). hypnatremia is dened as depetin in teserum sdium (Na) cncentratin t a eve bew 136

mm/l and severe ypnatremia dened as serum sdi-

um cncentratin esser tan 115 mm/l wic it can be

cnsidered as ie-treatening cnditin (2, 3). Te preva-

ence severe ypnatremia and its nn-severe rm are

estimated 1-4% and 15-30% inpatients, respectivey (4).

Usuay, ypnatremia resuts rm water retentin

secndary t an inabiity t matc water excretin wit

intravenus r ra water absrptin. Eective circuat-

ing vume depetin causing nn-smtic reease an-

tidiuretic rmne (ADh) and te syndrme inappr-

priate ADh secretin (SIADh) are disrders in wic ADh

secretin is nt suppressed despite decrease in pasmasmaity. Tese are te tw mst cmmn causes y-

pnatremia (5).

Te diagnsis SIADh is estabised upn te excu-

sin ter ypnatremia etigy. Tis syndrme as

been reprted in a number cinica cnditins, suc as

maignancies (pumnary, mediastina and extratracic

tumrs), centra nervus system disrders (infammat-

ry r demyeinating diseases, strke and trauma), drugs

(desmpressin, prstagandin-syntesis inibitrs, pe-

ntiazines, tricycics and sertnin-reuptake inibi-

trs) and pumnary diseases (acute respiratry aiure,

psitive-pressure ventiatin and inectins) (2, 5). PTB is

ne te rare pumnary inectins wic can induceypnatremia. Tubercusis (TB) is cnsidered as ne

te cmmn inesses in deveping cuntries suc as

Iran wic can present wit varius cinica maniesta-

tins. TB can induce ypnatremia via severa meca-

nisms cntaining ca invasin t te adrena gands

(adrena insuciency) (6, 7), ca invasin t yptaa-

mus r pituitary gand (8, 9), Tubercuar meningitis (10-

12) and inapprpriate ADh secretin via pumnary in-

ectin (13-15).

2. Objectives

Te aim tis study was t evauate te prevaence ypnatremia in a arge number Iranian patients wit

PTB.

3. Patients and Methods

3.1. Design and Participants

We ave prspectivey evauated patients wit a diagn-

sis secndary PTB w were admitted t te inectius

wards Baqiyataa genera spita, Teran, Iran rm

marc 2005 ti marc 2010. Demgrapic and abrat-

ry caracteristics were recrded. Te cnrmatin sec-

ndary PTB was based n appearance acid ast bacii

n a sputum smear r Mycbacterium tubercusis n a

sputum cuture, in te absence radigica eatures

miiary TB. Te patients wit abnrma menta status,

any evidence tubercuar meningitis, edema-rming

cnditins, uncntred ypergycemia, rena insu-

ciency r aiure, yperipidemia, receiving diuretics r

any medicatins reated t SIADh r induced vaspressin

reease were excuded.

3.2. Assessment and Treatment

In additin, hIV-psitive patients wit diagnsis hIV

by enzyme-inked immuneabsrbent assay (ElISA) were

excuded, wing cunseing and securing written

inrmed cnsent. Any sdium r cacium (Ca) wast-

ing cnditin suc as rena diseases was verrued. A

patients received a reguar spita diet. A patients

received a typica daiy regimen cmpsed Riampin(R), Isniazid (h), Pyrazinamide (Z) and Etambut (E)

r te rsttw mnts, wed by Rh r te wing

4-10 mnts (depending n te prgress te disease

and treatment respnse based n Who guideine). Si-

mutaneusy, bd and urine sampes were gatered t

determine measures eectrytes and smaity. Base-

ine bd sampes and urine specimens were acquired

2 t 3 urs ater breakast. Te sampes were cected

bere any prescriptin intravenus fuids.

3.3 Statistics

Data were cected t cmpare te pre and abra-

try caracteristics PTB patients wit r witut yp-

natremia. Te data were anayzed by using SPSS stware

(17t editin) and P vaue ess tan 0.05 was cnsidered

signicant. Quantitative and quaitative data were re-

prted using mean standard deviatin (SD) and inre-

quency (percentage). Ater cecking nrma distributin

quantitative data, te parametric r nn-parametric

tests were used. Fr te anaysis quaitative data wit

nrma distributin, student t-test, ANoVA, and Pearsn

crreatin and r te abnrma distributed variabes,

MannWitney U, KruskaWais and spearman crrea-

tin tests were used.

4. Results

Tw undred patients tat were diagnsed and treated

r active PTB ave been enred. Te mean age was 59

20 years (in range 13-102 years) and 91 (45.5%) patients

were maes. Femaes ad iger mean age tan maes (60

21 versus 57 19) but tis dierence wasnt statisticay

signicant. Te mean serum Na cncentratin was 134

4 mm/l. Te emaes mean cncentratin serum Na

was 134 4.9 vs. te maes mean cncentratin serum

Na was 134 5 mm/l (P = 0.513).o te grup, 96 (48%)

te patients ad nrma serum Na, wereas 102 (51%)

patients ad ypnatremia (47.1% mae vs. 52.9% emae)

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689Nephro Urol Mon. 2013:5(1)

and tw (1%) patients deveped ypernatremia.

Tere is n signicant reatinsip between gender and

ypnatremia (P = 0.670). Te mean age dierence be-

tween ypnatremic and eunatremic grups was statisti-

cay signicant (61 versus 56 years, respectivey) (P.vaue

= 0.047). Mrever, tere is n signicant crreatin be-

tween anti-tubercusis medicatins and ypnatremia

(P = 0.369). Serum Na cncentratin was enumerated r

a dierent anti-TB drugs in Table 1 .

Table 1. Serum Sdium Cncentratin Based n Dse Anti-TB Drugs

Dosage Usual Dosage, % Max Dosage, %

Serum Na con-centration

Less than 135

meq/L

135-145 meq/L More than 145

meq/L

Less than 135

meq/L

135-145 meq/L More than 145

meq/L

Isoniazid 21 16.5 0 30 31.5 1

Rifampin 19 16 0.5 32 32 0.5

Ethambutol 9.5 11 0 41.5 37 1

Pyrazinamide 24.5 18.5 0.5 26.5 29.5 0.5

Te mean crrected serum Ca cncentratin was 8.8

0.7 mm/l. Te emaes mean serum Ca cncentratinwas 8.9 0.8 vs. te maes mean Ca wic was 8.8 0.6

(P = 0.441). one undred tirty seven (68.5%) patients ad

nrma serum Ca cncentratin, wereas 59 (29.5%) pa-

tients ad ypcacaemia and 4 (2%) patients ad yper-

cacemia.

hTN was te mst cmmn c-mrbid cnditin pres-

ent in 46 patients (23%), wie 42 patients (21%) ad cn-

tred diabetes meitus, 8 (4%) patients ad migraine

eadace, 1 patient ad Parkinsn's disease and anter

patient ad epiepsy. Tere was n signicant reatin-

sip between c-mrbid cnditins and ypnatremia

(P = 0.102). Simutaneusy, pneumnia was dcumented

in 18 patients (9%), wie n patients ad a diagnsis sepsis. hspita mrtaity was dcumented in 13 patients

(6.5%). N signicant crreatin was und between y-

pnatremia and mrtaity (P = 0.218). A te patients

wit ypnatremia became eunatremic ater anti-tuber-

cusis terapy.

5. Discussion

Given te ndings, te prevaence ypnatremia and

ypcacaemia btained as 51% and 29% wic is cm-

patibe wit te rmer reprts. Age was te se vari-

abe wic was dierent between PTB patients wit and

witut ypnatremia. We und tat ypnatremia wasiger tan expected in nn-tubercuar patients accrd-

ing t te previus reprts. In previus studies, te preva-

ence ypnatremia amng inpatients, especiay te

nes w admitted in respiratry wards, was reprted in

a varius range (2.48%-40%) (16, 17). Tis issue can be reat-

ed t te type diseases and age. As reprted in severa

studies, patients w were admitted in cidren r geri-

atric wards, admitted in te intensive care unit r cardiac

care unit, and tse w admitted in te emergency de-

partment were mre susceptibe r ypnatremia. Fur-

termre ypnatremia is mre t be bserved in ne-

pastic, brain, endcrine and pumnary diseases. Te

incidence severe ypnatremia as been estimated as1.1% in spitaized patients wereas in tat reprt, PTB

was te mst cmmn underying disease (24%) wic is

in keeping wit ur ndings (18).

In 1969, Cung and hubbard ave nted tat neary 11%

patients wit active TB (pumnary r nn-pumnary)

are aected wit ypnatremia, and it is apparent tat

te main cause serum sdium depetin in tese pa-

tients is SIADh (19). Vrerr et a. as reprted a case wit

PTB and ypnatremia and und antidiuretic agents in

tubercuus ung tissues (14). Bryant et a. as suggested

te syndrme inapprpriate secretin antidiuretic

rmne r patients wit an inectius pumnary dis-

ease suc as PTB (20). Scrn et a. reprted tw cases PTB and an abnrma inapprpriate antidiuretic r-

mne eve as a justier mecanism (15). Cckcrt et a.,

reprted a 74-year-d wman wit miiary tubercusis

wic ad cmpicated by severe ypnatremia due t

SIADh (21). Usaan et a. reprted a case TB w initiay

presented wit etargy due t ypnatremia evidenty

resuting rm SIADh (22). Finay, lee reprted a case

PTB wit reractry ypnatremia due t SIADh (13).

Atug in tis study we did nt evauate patients r

etigy ypnatremia, it can be benecia i we cn-

cisey review causes ypnatremia in patients wit

PTB; SIADh is a cnsiderabe cmpicatin pum-

nary inectin, infammatry and nepastic disrders,atug its prevaence and mecanism are pry re-

garded. SIADh as been dispayed in inectius situatins

suc as TB. In ne te rst reprts, Weiss et a., reprted

ypnatremia in resuting rm SIADh in patients wit

PTB (23). Ten it was decared tat an increased ADh eve

in te presence ypnatremia in PTB cases is an indi-

catr r ectpic ADh prductin. Few studies demn-

strated tat te ADh eve was nt detectabe wing

u anti-TB terapy (13, 24).

SIADh was usuay demnstrated in patients wit TB

and tere are varius causative actrs r SIADh in tu-

bercusis. SIADh may ccur wing PTB, as we as

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Hyponatremia in Pulmonary TuberculosisJonaidi Jafari N et al.

Nephro Urol Mon. 2013:5(1)690

tubercuar meningitis. Tere are many reprts SIADh

assciated wit pumnary, miiary and centra nervus

system-reated TB. Mre tan 60% te patients wit

tubercuar meningitis may present wit ypnatre-

mia r SIADh at rst presentatin (25). SIADh must be

cnsidered in every case wit ypnatremia wit w

serum smaity cnditin, a nrma acid-base state,

urine smaity ver 100 mosm/kg, and urine sdium

cncentratin mre tan 40 meq/l. As, generaized r

ca inectins are imprtant and unregarded causes

SIADh. Mutipe inectius diseases are assciated wit

tis syndrme (26).

In additin t te disease itse, sme anti-TB drugs can

as be rund anemia. Nakasita et a. as reprted a case

SIADh caused by etinamide in a patient wit PTB

as tey suggested tat anti-TB drugs sud be cnsid-

ered as te pssibe cause SIADh but te resut tis

study was tat te incidence ypnatremia in patients

w received etinamide wit maximum dse was nt

iger tan tse w received a esser ne (27).

Besides, nn-tubercuses pneumnia is a very rare

cause SIADh induced ypnatremia. Cares et a. de-

scribed a patient w ad bar pneumnia presenting

wit cnusin due t severe ypnatremia (28). As,

Rivers et a., expressed a cid wit excessive secretin

ADh in assciatin wit cmmn pumnary inectins

(29).

Endcrine system invvements by TB, as te ter

mecanism, can induce ypnatremia wic is impr-

tant t cnsider in patients wit PTB. TB was reveaed t

invve adrena gands directy (30) and tis invvementead t vert r subcinica adrena insuciency and

ypnatremia (6). Pituitary gand may as be invved

by te tubercusis bacii. hyppituitarism as been re-

prted in 20% cases years ater te treatment tuber-

cuar meningitis in cidd. Te reasn seemed t be

tubercusis esins impressing te yptaamus, pitu-

itary stak and indirecty r directy, te pituitary gand

itse (8).

Te ypnatremia due t PTB is usuay mid t mder-

ate, asymptmatic, and se-imited. SIADh is cmmny

reversibe wit eective PTB treatment in mst cases (25).

Terere, it can be verked i te pysician des nt

give sucient attentin. on te ter and, patientsw aected by ypnatremia were mre ikey t ave

iger mrtaity. Sarma et a. suggested ypnatremia

as predictrs devepment and utcme in patients

wit acute respiratry distress syndrme due t tubercu-

sis (31).

Mrever, ter eectryte disturbances suc as y-

percacemia ave been reprted as ne te mst cm-

mn eectryte imbaance in 25.7% patients wit PTB

atug ypnatremia deveped wer prevaence

(22.15%)(32). Furtermre, te incidence ypnatre-

mia in patients wit AIDS cmpicating wit TB is iger.

Smit et a. reveaed tat ypnatremia was discvered

in 60% AIDS patients wit a diagnsis generaized

tubercusis, wever a tese patients dissemi-

nated tubercusis were ny diagnsed ater deat. In

ur study, we verrued te hIV psitive patients and it

can be te reasn te dierences between ur ndings

and ters.

In te present study, te iger age amng te dem-

grapic caracteristics was bserved in patients wit PTB

and ypnatremia tan as previusy been nted. Few

studies evauated te re age n presenting ypna-

tremia in patients wit neura deects (33). Te age range

in mentined reprts was dcumented widespread and

generay it is impssibe t ceary te re age n y-

pnatremia in patients wit PTB. In additin, it sud be

suggested tat ypnatremic patients sud be evau-

ated r PTB wen an initia investigatin aied t test.

We wud recmmend tat patients wit PTB (especiay

der age patients) sud be csey bserved r eectr-

yte imbaance. We as recmmend urter studies wit

a greater sampe size mainy cused n te predisps-

ing actrs eectryte imbaance in patients suering

rm PTB.

Acknowledgements

Te Autrs appreciate very muc a participants and

teir reatives r teir kind cperatin.

Authors Contribution

Jnaidi-Jaari, Izadi, Sarrazade, Ranjbar and Saburi in-

vved in cncept, idea deveping, study designing, and

interpreting data. heidari and Saburi gatered te data.

Jnaidi-Jaari, Sarrazade and Saburi prepared te drat.

A autrs apprved te na drat.

Financial Disclosure

Nne decared.

Funding/Support

Tere is n nancia supprt.

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