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Puumala han a i us and
polyendoc inopa hy
M Ta ainen and o he s
Au oimmune polyendoc inopa hy and
hypophysi is a e Puumala han a i us
in ec ion
Ma leneTa ainen1, Sa uMäkelä1,2, JukkaMus onen1,2 and PiaJaa inen1,2,3
1School o Medicine, Uni e si y o Tampe e, Tampe e, Finland, 2Depa men o In e nal Medicine,
Tampe e Uni e si y Hospi al, Tampe e, Finland, and 3Di ision o In e nal Medicine, Seinäjoki Cen al
Hospi al, Seinäjoki, Finland
Summa y
Puumala han a i us (PUUV) in ec ion causes neph opa hia epidemica (NE), a ela i ely mild o m o haemo hagic e e wi h
enal synd ome (HFRS). Hypophyseal haemo hage and hypopi ui a ism ha e been desc ibed in case epo s on pa ien s
wi h acu e NE. Ch onic hypopi ui a ism diagnosed mon hs o yea s a e he acu e illness has also been epo ed, wi hou
any signs o a haemo hagic ae iology. The mechanisms leading o he la e-onse ho monal de ec s emain unknown. He e,
we p esen a case o NE-associa ed au oimmune polyendoc inopa hy and hypopi ui a ism p esumably due o au oimmune
hypophysi is. Thy oid pe oxidase an ibody se ocon e sion occu ed be ween 6 and 12mon hs, and o a ian as well as
glu ama e deca boxylase an ibodies we e ound 18mon hs a e acu e NE. B ain MRI e ealed an a ophic adenohypophysis
wi h a he e ogeneous, low signal in ensi y compa ible wi h a sequela o hypophysi is. The pa ien de eloped cen al (o
mixed cen al and pe iphe al) hypo hy oidism, hypogonadism and diabe es insipidus, all equi ing ho monal eplacemen
he apy. This case epo sugges s ha la e-onse ho monal de ec s a e PUUV in ec ion may de elop by an au oimmune
mechanism. This hypo hesis needs o be con i med by p ospec i e s udies wi h su icien numbe s o pa ien s.
ID: 16-0084; No embe 2016
DOI: 10.1530/EDM-16-0084
10.1530/EDM-16-0084
ID: 15-0028; XXX 2016
Co espondence
should be add essed
o P Jaa inen
Email
[email p o ec ed]
Lea ning poin s:
•Pi ui a y haemo hage esul ing in hypopi ui a ism has been epo ed du ing acu e HFRS caused by PUUV and o he
han a i uses.
•Cen al and pe iphe al ho mone de iciencies de eloping mon hs o yea s a e HFRS ha e also been ound, wi h
an incidence highe han ha in he gene al popula ion. The pa hogenesis o hese la e-onse ho monal de ec s
emains unknown.
•This case epo sugges s ha he la e-onse hypopi ui a ism and pe iphe al endoc ine de ec s a e HFRS could
e ol e ia au oimmune mechanisms.
•The sensi i i y o cu en an i-pi ui a y an ibody (APA) es s is low. A cha ac e is ic clinical cou se, oge he
wi h ypical b ain MRI and endoc ine indings may be su icien o a non-in asi e diagnosis o au oimmune
hypophysi is, despi e nega i e APAs.
Backg ound
Han a i uses cause haemo hagic e e wi h
enal synd ome (HFRS) in Eu asia and han a i us
ca diopulmona y synd ome (HCPS) in he Ame icas (1).
Puumala han a i us (PUUV) causes a mild HFRS called
neph opa hia epidemica (NE). In Finland, annually
1000–3000 cases o NE a e se ologically diagnosed. The
M Ta ainen and o he s Puumala han a i us and
polyendoc inopa hy
ID: 16-0084; No embe 2016
DOI: 10.1530/EDM-16-0084
h p://www.edmcase epo s.com 2
ypical ea u es o NE a e inc eased capilla y pe meabili y,
enal in ol emen and h ombocy openia, he la e
a ely causing se ious haemo hages (1). The pa ien s
commonly su e om high e e , headache, educed
isual acui y, abdominal pain, nausea and backache (1).
Hypophyseal haemo hage and panhypopi ui a ism
ha e been desc ibed in case epo s on pa ien s wi h
NE (2, 3, 4, 5, 6, 7, 8). De ec s o he gonadal and/o
hy oid axis ha e been ound in mo e han hal o he
pa ien s du ing he acu e phase o NE (9). We ha e also
epo ed ch onic hypopi ui a ism in 5 o 54 pa ien s,
p ima y hypo hy oidism in 5 pa ien s and ch onic
subclinical es icula ailu e in 5 o 37 men du ing
a median ollow-up o 5 yea s a e NE (9). Ch onic
hypopi ui a ism was also iden i ied in 18% o pa ien s
wi h a p e ious HFRS in a e ospec i e Se bian s udy
o 60 adul s who had eco e ed om HFRS yea s ago
(10). Thus, pa ien s wi h HFRS may be a high isk o
de eloping hypopi ui a ism o pe iphe al ho mone
de iciencies la e on (8, 9, 10). Howe e , no ob ious
la e-onse hypopi ui a ism was diagnosed in a coho o
47 pa ien s e-examined 4–8yea s a e NE in No he n
Finland (11). The pa hophysiological mechanisms o
hypopi ui a ism de eloping as a la e complica ion o NE
emain unclea .
We p esen a pa ien who de eloped an au oimmune
polyendoc ine synd ome and hypopi ui a ism possibly
due o au oimmune hypophysi is six o wel e mon hs
a e he acu e NE. We also e iew p e ious case epo s on
HFRS-induced hypopi ui a ism.
Table1 Basic labo a o y es esul s du ing acu e neph opa hia epidemica and a he 1-mon h ollow-up isi .
Pa ame e
Lowes le el a
hospi al
Highes le el a
hospi al A discha ge A 1-mon h ollow-up Re e ence ange
WBC (109/L) 5.5 45 5.8 6.8 3.4–8.2
Pla ele coun (109/L) 5 207 207 260 150–360
Haemoglobin (g/L) 90 202 97 114 117–155
CRP (mg/L) 8.7 57.4 8.7 <1 0–10
ALT (U/L) 13 35 13 N/A 10–45
C ea inine (µmol/L) 206 891 206 89 50–90
U ea (mmol/L) 12.9 35.2 12.9 N/A 2.6–6.4
Po assium (mmol/L) 3.7 5.1 3.9 N/A 3.3–4.8
Sodium (mmol/L) 121 132 130 N/A 137–144
ALT, alanine ansaminase; CRP, C- eac i e p o ein; N/A, no assessed; WBC, whi e blood cells.
Table2 Summa y o he ho monal es esul s du ing acu e NE and a he ollow-up isi s.
Va iables (uni s) Acu e NE 1-mon h ollow-up 6-mon h ollow-up 12-mon h ollow-up
24-mon h
ollow-up Re e ence ange
T4 (pmol/L) 10.7 7.7 7.8 18.1116.7111.0–22.0
TSH (mU/L) 9.1 0.64 4.1 <0.0110.2510.27–4.2
Oes adiol
(nmol/L)
1.09 0.04 <0.02 0.1720.172*
FSH (U/L) 3.0 2.8 4.1 1.521.72*
LH (U/L) 12.2 0.9 1.5 0.821.52*
GH (mU/L) 59.4 0.5 0.5 0.3 0.33 0.0–11.0
IGF-1 (nmol/L) 13 17 12 16 9** 12–46
10–37**
Co isol (nmol/L) 1284 277 356 253 249** 180–680
170–500**
ACTH (ng/L) 12 11 19 20 10 0.0–46.0
PRL (mU/L) 439 366 256 283 240 102–496
TPOAb (kU/L) <5 13 23 85 66 <34
1On le o hy oxine subs i u ion, 2on oes ogen–p oges e one subs i u ion, *oes adiol, FSH and LH alues we e e alua ed acco ding o he phase o he
mens ual cycle, **IGF-1 and co isol labo a o y es me hods changed du ing he ollow-up. The new e e ence anges and he alues measu ed wi h
he new me hods a e ma ked wi h as e isks (**).
M Ta ainen and o he s ID: 16-0084; No embe 2016
DOI: 10.1530/EDM-16-0084
Puumala han a i us and
polyendoc inopa hy
h p://www.edmcase epo s.com 3
Case p esen a ion
A 25-yea -old p e iously heal hy woman p esen ed
wi h e e o 39°C, oligu ia and lowe back pain. A
p esen a ion, he plasma C- eac i e p o ein (CRP)
concen a ion was 39 mg/L and u inalysis e ealed
p o einu ia (+++) and haema u ia (++). Pyeloneph i is
was suspec ed, and she was admi ed o a wa d in he
p ima y heal h ca e cen e. In a enous ce u oxime
was s a ed. The pa ien began o su e om nausea,
omi ing, and isual dis u bances, and she was
ans e ed o Tampe e Uni e si y Hospi al. NE was
suspec ed, and a poin -o -ca e an i-PUUV an ibody es
(Reascan Puumala IgM, Reagena In e na ional, Toi ala,
Finland) was e u ned posi i e. The pa ien was anu ic
and hypo ensi e, and i. . luids we e adminis e ed.
Du ing he nex ew days, she expe ienced headache and
dizziness. Diu esis es a ed on day six a e he onse
o e e . The highes daily u ina y ou pu was 3700 mL
in he polyu ic phase. The mild headache was cu ed by
pa ace amol and he isual dis u bances soon subsided.
The pa ien was discha ged 14days a e admission.
In es iga ions
The diagnosis o NE was e i ied by high le els o
speci ic an i-PUUV IgM and IgG an ibodies. O he
labo a o y indings (Table1) ypical o NE included se e e
h ombocy openia, leukocy osis and ele a ed plasma
c ea inine and u ea concen a ions, as well as p o einu ia
and haema u ia. On he i s ew days o hospi alisa ion,
se um le els o co isol and g ow h ho mone (GH) we e
high, and ee hy oxine ( T4) was low (Table2).
Ou come and ollow-up
The pa ien pa icipa ed in a p ospec i e s udy o he
ho monal consequences o NE, and w i en in o med
consen was ob ained. A he i s ollow-up isi one
mon h a e he acu e illness, he pa ien was sligh ly
anaemic, bu o he labo a o y indings we e no mal
(Table1). She s ill had a igue and an i egula mens ual
cycle. Th ee mon hs a e he NE, he pa ien s a ed o
su e om ho lushes, mild headache, sleeping diso de s,
oedema and ameno hea. Six mon hs a e he acu e
illness, cen al hypo hy oidism and hypogonado ophic
hypogonadism we e de ec ed (Table 2). The e we e
no symp oms o labo a o y indings compa ible wi h
diabe es insipidus (DI). Le o hy oxine and oes ogen–
p oges e one eplacemen he apy we e s a ed.
B ain magne ic esonance imaging (MRI, 3 Tesla) was
pe o med 9mon hs a e he acu e NE and showed an
a ophic adenohypophysis wi h a he e ogeneous, low
signal in ensi y, compa ible wi h a sequela o hypophysi is
(Fig.1). The e we e no signs o haemo hage, umou s o
o he abno mal indings on he MRI scan.
A he 12-mon h ollow-up isi , he pa ien epo ed
cons ipa ion, abno mal hi s , polyu ia and loss o
appe i e. The labo a o y es s showed high plasma
sodium le el (145 mmol/L). DI was suspec ed, and a
he apeu ic ial wi h desmop essin p.o. was commenced.
Desmop essin subs i u ion (60 µg b.i.d.) co ec ed he
polyu ia and o he symp oms and no malised he plasma
sodium concen a ion.
Plasma hy oid pe oxidase an ibody (TPOAb) le els
we e no mal du ing acu e NE and a one-mon h and six-
mon h ollow-up isi s, bu inc eased by he 12-mon h
ollow-up isi (Table2). Due o he clinical signs o DI
Figu e1
B ain MRI scan (T1-weigh ed) 9mon hs a e he acu e NE, showing an
a ophic adenohypophysis (a ow) wi h a he e ogeneous, low signal
in ensi y, compa ible wi h a sequela o hypophysi is. (A) Co onal plane.
The heigh o he hypophysis is 2mm. (B) Sagi al plane. The pa ien
de eloped diabe es insipidus la e on, bu a his poin , he ‘b igh spo ’
is s ill isible in he pos e io pi ui a y.
M Ta ainen and o he s Puumala han a i us and
polyendoc inopa hy
ID: 16-0084; No embe 2016
DOI: 10.1530/EDM-16-0084
h p://www.edmcase epo s.com 4
Table3 Summa y o p e ious case epo s on HRFS- ela ed panhypopi ui a ism.
S udy
Type o ho monal de iciency Time om HFRS o
hypopi ui a ism
Radiological o
his ological
indings
(imaging
modali y)
Follow-up
ime
Ho monal
eco e y
ACTH TSH LH/FSH GH* AVP
Fo slund e al.
(2)
x x x N/A – 15yea s Emp y sella (CT) N/A No
Se e g en
e al. (5)
x x x xa,c – 6mo – N/A No
Suh e al. (14) x x x xcN/A 3mo Haemo hage,
la e a ophy
(MRI)
3mo No
Pa k and Pyo
(15)
x x x xcN/A Acu e – N/A N/A
Kim e al. (16) x x N/A xcN/A 13yea s – 1mo No
Hau ala e al.
(3)
x x x N/A N/A 5mo Acu e: Enla ged
pi ui a y
gland,
haemo hage
10mo No
10mo:
Dec eased
pi ui a y
gland size and
pa ial
eso p ion o
haemo hage
(MRI)
x x x – N/A Acu e Acu e: Enla ged
pi ui a y
gland,
haemo hage
2mo No
2mo:
Dec eased
pi ui a y
gland size and
pa ial
eso p ion o
haemo hage
(MRI)
Sane and
Fä kkilä (4)
x x x xb– 10mo Dec eased
pi ui a y
enhancemen
(CT)
17mo No
Pekic e al. (8) x x x xa,b,c N/A 1.5yea s A ophy, emp y
sella (MRI)
N/A No
x x x xa,b,c N/A 2yea s 1mo No?
x x x xbN/A 2yea s 15days No?
Jos e al. (6) x x x N/A N/A Acu e Acu e: Enla ged
pi ui a y
gland
5mo Pa ial**
5mo: No mal
(MRI)
Sa igüzel e al.
(17)
x x x xb– Acu e Haemo hage,
a ophy (MRI)
16mo No
Kaybas e al.
(18)
x N/A x – N/A Acu e No mal (MRI) N/A N/A
ACTH, ad enoco ico opic ho mone; AVP, a ginine asop essin; d, days; FSH, ollicle-s imula ing ho mone; GH, g ow h ho mone; LH, lu einizing
ho mone; mo, mon hs; N/A, da a no a ailable; TSH, hy oid-s imula ing ho mone; y, yea s.
*GH/IGF-1 axis de iciency was diagnosed by de e mining ase um GH le el, o bse um IGF-1 le el o by conduc ing a cGH axis s imula ion es .
**Ad enoco ical and hy oid axis eco e ed, and gonadal axis did no .
M Ta ainen and o he s ID: 16-0084; No embe 2016
DOI: 10.1530/EDM-16-0084
Puumala han a i us and
polyendoc inopa hy
h p://www.edmcase epo s.com 5
and b ain MRI indings, hypophysi is was suspec ed and
u he e iological in es iga ions we e scheduled. Se um
calcium, angio ensin-con e ing enzyme, lysozyme,
an inuclea an ibody (ANA) and IgG4 le els we e no mal.
An i-pi ui a y an ibodies (APA) we e measu ed by a line blo
and a adioimmuno-p ecipi a ion assay (MVZ Labo a o y
D Volkmann and Colleagues, Ka ls uhe, Ge many), and
he es s yielded no mal esul s. Glu ama e deca boxylase
an ibody (GADAb 892.7 IU/mL, e e ence <10 IU/mL),
TPOAb (53 kU/L, e e ence <34 kU/L) and o a ian an ibody
(O a Ab i e 10, e e ence <1) es s we e all posi i e. The
an i-ad enal an ibody (Ad Ab) i e was no mal (<1). The
GADAbs we e measu ed by an enzyme immunoassay
(Eu oimmune an i-GAD-ELISA, Luebeck, Ge many),
whe eas he O a Abs and he Ad Abs we e measu ed by
indi ec immuno luo escence (PhD 1xSys em, Bio-Rad
Labo a o ies) on sec ions o p ima e o a y and ad enal
gland espec i ely, a he ce i ied Huslab Labo a o ies,
Helsinki, Finland. O he measu emen s we e pe o med
by he ou ine labo a o y me hods o he ce i ied Fimlab
Labo a o ies, Tampe e, Finland.
A he la es isi , 2 yea s a e NE, he pa ien
was asymp oma ic on desmop essin, l- hy oxine and
oes ogen–p oges e one subs i u ion. Despi e he
oes ogen subs i u ion, he IGF-1 le el was bo de line low
and co isol was in he low no mal ange (Table2). The
ollow-up is con inued a he Endoc inology Ou pa ien
Clinic.
Discussion
To ou knowledge, his is he i s case epo ed wi h
au oimmune polyendoc inopa hy and hypopi ui a ism
de eloping soon a e acu e NE. Ou pa ien s a ed o
su e om symp oms sugges i e o ho monal de iciencies
h ee mon hs a e he NE. Labo a o y es s e ealed
hypopi ui a ism six mon hs a e he discha ge om
hospi al. Pa ial DI was diagnosed one yea a e NE. Nine
mon hs a e he NE, b ain MRI showed a ophy o he
adenohypophysis wi h a he e ogeneous, low signal in ensi y,
compa ible wi h a sequela o hypophysi is. Au oan ibodies
eme ged du ing he i s 18mon hs a e he NE. The APAs
we e nega i e, bu he diagnos ic sensi i i y and speci ici y
o APA es s a e known o be low (12, 13).
P e iously, only one case epo has been published on
NE-associa ed hypophysi is (6). The pa ien had ansien
panhypopi ui a ism, equi ing ho monal eplacemen
he apy wi h l- hy oxine and hyd oco isone du ing
he acu e NE. In con as wi h he p esen case, he
ho mone le els soon no malised wi h he esolu ion o
he acu e PUUV in ec ion and emained no mal du ing
he ollow-up o 5 mon hs. In ha case epo , b ain
MRI showed enla gemen o he pi ui a y gland, bu no
pi ui a y haemo hage o nec osis and no hypo halamic
al e a ions (6). Bo h he clinical cou se and he adiological
cha ac e is ics o he p e ious case sugges a di ec e ec
o he i al in ec ion, a he han an au oimmune
mechanism, causing he ansien pi ui a y de ec .
Table 3 summa ises ele en p e ious case epo s (2,
3, 4, 5, 6, 8, 14, 15, 16, 17, 18) wi h 14 well-cha ac e ised
cases o HFRS- ela ed panhypopi ui a ism. Fi e pa ien s
we e diagnosed wi h hypopi ui a ism equi ing ch onic
ho monal eplacemen , s a ing om he acu e phase o
HFRS (3, 6, 15, 17, 18). Nine pa ien s de eloped la e-onse
panhypopi ui a ism mon hs o yea s a e HFRS (2, 3, 4,
5, 8, 14, 16). A le hal case o hypophyseal haemo hage
du ing acu e NE was also epo ed (3). In addi ion o
he cases o panhypopi ui a ism ep esen ed in Table3,
we ound i e cases o ch onic hypogonado ophic
hypogonadism, wo wi h cen al hypo hy oidism and
h ee isola ed ones, in he p e ious e ospec i e analysis
o 54 NE pa ien s (9). In he e ospec i e se ies o 60
pa ien s wi h p e ious HFRS, he e we e six cases o a
single pi ui a y ho mone de ici and i e cases o mul iple
pi ui a y ho mone de iciencies espec i ely (10).
The pa hophysiology o ch onic ho mone de iciencies
a e HFRS is s ill unclea . Vi al in ec ions ha e been linked
o he pa hogenesis o se e al au oimmune diseases. Fo
example, many i uses such as en e o i uses ha e been
associa ed wi h ype 1 diabe es (19). I is possible ha
an acu e PUUV in ec ion may a ec he pi ui a y and
pe iphe al endoc ine glands, as well as he immune sys em,
enhancing he p oduc ion o au oan ibodies agains he
endoc ine o gans. In ou pa ien , TPO se ocon e sion
appea ed be ween 6 and 12mon hs a e NE. Measu ed
18mon hs a e HFRS, TPO, o a ian and GAD an ibody
es s we e all posi i e.
Se e al lines o e idence sugges ha p ima y
hypophysi is may de elop by an au oimmune mechanism
(12, 20). P egnancy and childbi h a e known isk ac o s
o hypophysi is. Lymphocy ic hypophysi is is commonly
associa ed wi h au oimmune diseases, such as Hashimo o’s
hy oidi is, G a es’ disease, Addison’s disease, ype 1
diabe es, a ophic gas i is and Sjög en’s synd ome. Such
an associa ion has been epo ed in 25–50% o he cases
(12, 20).
Hypopi ui a ism is he mos common p esen a ion o
au oimmune hypophysi is. The ypical o de o ophic
ho mone de iciency has been epo ed as ACTH > TSH > FSH/
LH > PRL > GH (12). Howe e , he ecen epo wi h 76 cases

M Ta ainen and o he s Puumala han a i us and
polyendoc inopa hy
ID: 16-0084; No embe 2016
DOI: 10.1530/EDM-16-0084
h p://www.edmcase epo s.com 6
om Ge many ound hypogonado ophic hypogonadism,
he mos equen ho monal de ec in p ima y
hypophysi is (13). Ou pa ien i s s a ed o expe ience
symp oms sugges i e o hypogonadism, h ee mon hs
a e NE. Cen al hypo hy oidism and hypogonado ophic
hypogonadism we e diagnosed six mon hs a e he acu e
NE, and ho monal subs i u ions we e s a ed. He co isol
le els ha e been in he low no mal ange, which is likely
o e lec an impai ed co isol p oduc ion, in iew o he
oes ogen eplacemen he apy inc easing he co isol-
binding globulin concen a ion.
A he acu e phase o hypophysi is, a sella mass e ec
may de elop, p o oking headache, diplopia and isual
ield de ici s. In undibula o pos e io pi ui a y de ec s
may cause an idiu e ic ho mone (ADH and asop essin)
de iciency and cen al DI, p esen ing wi h polyu ia and
polydipsia in 20–48% o pa ien s wi h au oimmune
hypophysi is (12). In mos cases o hypophysi is, he le el o
PRL is no mal o e en low (21), as in ou pa ien . Du ing he
anu ic phase o acu e NE, he pa ien had hypona aemia.
Fluid e en ion associa ed wi h acu e kidney inju y was
p obably an impo an cause o low sodium concen a ion
a ha ime. Ne e heless, hypona aemia migh also be
caused by excessi e sec e ion o ADH, i.e. an acu e SIADH.
The pa ial DI o he pa ien , diagnosed one yea a e NE,
e lec ed a sligh de ec o he hypo halamic-in undibulo-
neu ohypophyseal sys em, as he in ense signal o he
pos e io pi ui a y was s ill isible on MRI, and he e
was no isible pa hology in he in undibulum o he
hypo halamus, 3mon hs be o e he diagnosis o DI.
The b ain MRI o ou pa ien e ealed an a ophic
adenohypophysis wi h a he e ogeneous, low signal
in ensi y nine mon hs a e acu e NE. These indings
a e compa ible wi h a sequela o hypophysi is
(12). Haemo hage may also cause a ophy o he
adenohypophysis (13). Howe e , ou pa ien p esen ed no
symp oms o clinical indings indica i e o hypophyseal
haemo hage ei he du ing acu e NE o du ing he
ollow-up. A de ini i e diagnosis o hypophysi is equi es
his ological e i ica ion om a biopsy specimen, bu a
cha ac e is ic clinical cou se, oge he wi h ypical MRI
and ho monal indings ha e been sugges ed o su ice o
a non-in asi e diagnosis (12, 13). Dis inc i e adiological
ea u es in acu e au oimmune hypophysi is a e symme ic
enla gemen o he pi ui a y gland, homogenous pos -
gadolinium enhancemen , hickened in undibulum in
he midline, loss o pos e io ‘b igh spo ’ on T1 imaging
and in ac sella loo (12, 22). A cen al hypoin ensi y,
ep esen ing nec osis o cys o ma ion, has been epo ed
in up o one- hi d o he pa ien s (13, 21). A la e s ages
o hypophysi is, pi ui a y a ophy and emp y sella a e
ypical indings on MRI (12).
Ci cula ing an i-pi ui a y au oan ibodies (APA) may be
de ec ed in au oimmune p ocesses o he pi ui a y gland.
The low diagnos ic sensi i i y and speci ici y o p esen APA
es s un o una ely limi hei diagnos ic u ili y (12, 20).
The p esen pa ien was nega i e o APAs, bu he clinical
pic u e and he p esence o se e al o he au oan ibodies
make au oimmune hypophysi is a plausible cause o he
hypopi ui a ism. A di ec e ec o he PUUV in ec ion,
inc eased capilla y pe meabili y o a mino haemo hagic
damage a e o he possible mechanisms ha may ha e led
o he pi ui a y a ophy and panhypopi ui a ism obse ed.
In conclusion, we epo he i s case o NE-associa ed
au oimmune polyendoc inopa hy and a possible
au oimmune hypophysi is. An au oimmune mechanism
could explain he la e-onse hypopi ui a ism ha has
been epo ed o de elop mon hs o yea s a e HFRS (8,
9, 10). Au oimmune in lamma ion could also explain
he insu iciencies o pe iphe al ho monal glands, which
seem o be mo e equen a e NE han in he gene al
popula ion (9). The case epo s and e ospec i e coho s
published so a call o p ospec i e s udies, o cla i y
he epidemiology and he mechanisms o ho monal
de iciencies a e NE and o he ypes o HFRS.
Decla a ion o in e es
The au ho s decla e ha he e is no con lic o in e es ha could be
pe cei ed as p ejudicing he impa iali y o he esea ch epo ed.
Funding
This s udy was inancially suppo ed by he Compe i i e Resea ch Funding
o he Special Responsibili y A ea o Tampe e Uni e si y Hospi al (9P031)
and he Sig id Jusélius Founda ion.
Pa ien consen
W i en in o med consen has been ob ained om he pa ien o he
publica ion o he submi ed a icle and accompanying images.
Au ho con ibu ion s a emen
D Ma lene Ta ainen examined he pa ien du ing acu e NE and a he
ollow-up isi s and d a ed he manusc ip . D Sa u Mäkelä and P o Pia
Jaa inen we e in ol ed in he ea men o he pa ien and con ibu ed
o he w i ing o he manusc ip . P o Jukka Mus onen con ibu ed o
manusc ip w i ing and edi ing.
Acknowledgemen s
The au ho s hank Esko Väy ynen, MA, o e ising he language o he
manusc ip and D Ma ia Juujä i, D Riikka Mäkelä and D Tapio Seiska i,
M Ta ainen and o he s ID: 16-0084; No embe 2016
DOI: 10.1530/EDM-16-0084
Puumala han a i us and
polyendoc inopa hy
h p://www.edmcase epo s.com 7
Fimlab Labo a o ies, Tampe e Uni e si y Hospi al o a anging he
au oan ibody es s.
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Recei ed in inal o m 3 Oc obe 2016
Accep ed 21 Oc obe 2016