Sellar region surgery in Croatia in the first half of 20th century.

Abstract

We reconstructed the historical development of surgical approaches to the pituitary gland, which were used in Croatia in the first half of the 20th century, on the basis of earliest clinical case reports and descriptions of initial surgical attempts. The first published case report on surgical treatment of acromegaly was described, as well as the review of 11 patients with pituitary disease admitted to the Ophthalmology Clinic in Zagreb in the period 1925-1927. The earliest 5 reports on pituitary surgery dating from 1925 were analyzed to reveal the circumstances that led to the development of transsphenoidal approach as a method of choice in Croatia, when this technique was becoming obsolete in other parts of the world. Frequent modifications of surgical approaches to sellar region have been shown a suitable historical-medical model for analysis of changes in surgical trends.

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History of MedicineHistory of Medicine
Although the pituitary gland was first described in
ancient times, its function remained unknown for
centuries afterwards. Some diseases caused by pi-
tuitary dysfunction were also recognized long time
ago, but were not linked to the gland. In 1886,
Pierre Marie (1853-1940) published the first de-
scription of acromegaly, the disease characterized
by overgrowth of the jaws and facial bones, hands,
and feet and the curvature of the spine (1). Oscar
Minkowski (1855-1931) noted that the pituitary
gland was enlarged in fatal cases of acromegaly.
Deducing from this, Woods Hutchinson (1862-
Sellar Region Surgery in Croatia in the First Half of 20th Century
We reconstructed the historical development of surgical ap-
proaches to the pituitary gland, which were used in Croatia in
the first half of the 20th century, on the basis of earliest clinical
case reports and descriptions of initial surgical attempts. The
first published case report on surgical treatment of acromegaly
was described, as well as the review of 11 patients with pituitary
disease admitted to the Ophthalmology Clinic in Zagreb in the
period 1925-1927. The earliest 5 reports on pituitary surgery
dating from 1925 were analyzed to reveal the circumstances
that led to the development of transsphenoidal approach as a
method of choice in Croatia, when this technique was becom-
ing obsolete in other parts of the world. Frequent modifications
of surgical approaches to sellar region have been shown a suit-
able historical-medical model for analysis of changes in surgical
trends.
1Department for the History and Philosophy of
Sciences, Division for the History of Medical
Sciences, Croatian Academy of Sciences and
Arts, Zagreb, Croatia
2Department of Neurosurgery, Sisters of Mercy
University Hospital, Zagreb, Croatia
Stella Fatović Ferenčić1, Živko Gnjidić2
Stella Fatović-Ferenčić
Department for the History and Philosophy of Sciences
Division for the History of Medical Sciences
Croatian Academy of Sciences and Arts
Gundulićeva 24/III
10000 Zagreb, Croatia
stella@hazu.hr
> Received: September 15, 2005
> Accepted: March 8, 2006
> Croat Med J. 2006;47:310-17
> Correspondence to:
310
www.cmj.hr

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Fatović Ferenčić and Gnjidić: Sellar Region Surgery in Croatia
1930) noted that the pituitary gland was like-
ly responsible for the growth of the body, while
Benda proved that acromegaly was always associ-
ated with the presence of eosinophilic pituitary
adenoma (1,2). By recognizing the brain as the
control center for the complex chemical func-
tions of the body, scientists created the fields of
neurology and endocrinology, ushering in the
discipline of neuroendocrinology. Surgery soon
became part of this newly established medical
field, particularly by exploring and developing
different techniques and previously unthinkable
approaches to some brain areas. After the pio-
neering work of Victor Horsly (1857-1916) and
Harvey Cushing (1869-1939) in the field of neu-
rosurgery, technical aspects of surgical approach
to the pituitary gland quickly developed and
were modified in many ways. After the transcra-
nial approach, transsphenoidal pituitary surgery
was developed independently by different groups
of physicians worldwide (3-5).
Several authors reported that the first trans-
sphenoidal pituitary surgery in Croatia was per-
formed in 1922 by Aleksandar Blašković (1882-
1953), a surgeon working in the Sisters of Mercy
Hospital in Zagreb (6,7). Although there are no
written documents containing clinical details of
these earliest operations or operative techniques,
clinical parameters and operative methods used
in the treatment of pituitary tumors during the
first half of the 20th century can be reconstruct-
ed on the basis of reports and review papers pub-
lished by Croatian clinicians.
Oldest Croatian case report on acromegaly
from 1896
The first specialized hospital departments in
Croatia were established at the end of the 19th
century. The departments consisted of differ-
ent units. For example, in 1894, the Sisters of
Mercy Hospital in Zagreb established the Third
Department for patients with diseases of the
skin, genitalia, eyes, throat, and nose. The first
head of the Department was Dragutin Mašek
(1866-1956), otorhinolaryngologist, who was
succeeded by Aleksandar Blašković, the found-
er of Croatian urology (8). The group of sur-
geons working in the Sisters of Mercy Hospital
was important for organizing the basic institu-
tional level of health care in Croatia, and subse-
quent establishment of many university clinics
that we have today (9). Their efforts culminat-
ed with the foundation of the Zagreb School of
Medicine in 1917.
The institutionalization of health care
marked the beginning of organized and sys-
tematic clinical research in Croatia. However,
even before, there had been an evident interest
in obtaining, producing, and promoting medi-
cal knowledge, which can be traced back to the
early pages of Liječnički vjesnik, the oldest Croa-
tian medical journal launched in 1877. Before
the foundation of the Zagreb University School
of Medicine, Liječnički vjesnik had served as the
leading professional communication and educa-
tion medium. Therefore, it is a valuable source of
earliest scientific achievements, clinical case re-
ports, and descriptions of operational techniques
performed in Croatia at the time. It brought
the earliest description of acromegaly in Croatia
from 1896 (10,11), written by a specialist in in-
ternal medicine Pavao Ćulumović (1868-1963).
This paper was published exactly 10 years after
Pierre Marie had published his description of ac-
romegaly in Revue de Médicine (12) and is the
oldest Croatian article published in the field of
neuroendocrinology. Ćulumović described clin-
ical characteristics of a 30-year-old patient who
was admitted to the hospital in Osijek because
of the enlargement of extremities and pain in
both legs. He was twice unsuccessfully operated
for sarcoma. On the right side of his face, there
was an egg-size tumor close to the ear and anoth-
er one located more centrally. A variety of dif-
ferent size nodules were spread all over his body.
Ćulumović also provided detailed measures of
the patient’s head, nose, tongue, neck, extremi-

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Croat Med J 2006;47:310-317
312
ties, fingers, and nails (10). He further updat-
ed the readership on the most recent informa-
tion on acromegaly, referring particularly to the
Pierre Marie’s article, and concluded that around
90 cases of acromegaly had been described world-
wide thus far.
All reported cases of acromegaly brought a
similar description of the symptoms, because the
disease is recognizable rather early. However, the
etiology of the disease remained unknown. In
his report, Ćulumović also mentioned Marie’s
presumption that acromegaly was caused by pi-
tuitary tumor or dysfunction and laid out Ma-
rie’s theory based on an analogy with the thyroid
gland. At the time, Marie probably believed that
the pituitary gland produced unknown factors
influencing the nervous system through circula-
tion. Ćulumović reflected on his patient’s symp-
toms and, since hemianopsia was not found, he
speculated that thymus rather than pituitary tu-
mor was the cause of symptoms in that particular
case and considered its association with sarcoma-
tosis. He finally concluded that “we could specu-
late about all possible hypotheses, but let us end
only with a simple claim that our case of acro-
megaly that developed with sarcomatosis could
be added to the already existing list of published
cases” (11). The patient Ćulumović described
left the hospital without any hope of improve-
ment. Had he developed the symptoms only a
decade later, he would have had some chance
for surgery.
After 1886, when Pierre Marie first described
acromegaly (11), the interest of medical commu-
nity in this condition started to increase. Social
reaction to patients with acromegaly was not in-
different either. Perhaps the most impressive ex-
ample of public fascination by these patients was
the article Uglies, published in Time magazine
in 1927 (13). It brought the picture of a woman
with a typical case of acromegaly and pronounced
her the ugliest woman in the world (13). This ar-
ticle provoked Harvey Cushing (1869-1939),
who was engaged in pituitary gland investigations
for most of his professional life, to send a detailed
explanation of the disease to Time magazine
(13): “She, previously vigorous and good-look-
ing woman, has become the victim of a disease
known as acromegaly. This cruel and deforming
malady not only completely transforms the out-
ward appearance of those whom it afflicts, but is
attended with great suffering and often with loss
of vision. One of Mr. Ringling’s agents prevailed
upon her to travel with the circus and to pose as
the “ugliest women in the world “as a means of
livelihood. Mr. Ringling is kind to his people and
she is well cared for. But she suffers from intol-
erable headaches, has become nearly blind, and
permits herself to be laughed at and heckled by
unfeeling people in order to provide the where-
withal to educate her four children. Beauty is but
skin deep. Being a physician, I do not like to feel
that TIME can be frivolous over the tragedies of
disease.”
Published reports on pituitary tumors
– clinical and surgical case studies
Even though the earliest description of the clin-
ical presentation of pituitary tumor in Croatia
was published by a specialist in internal medi-
cine, the interest for this subject spread to other
medical specialties as well. The First Meeting of
the Yugoslavian Otological-neurological-oph-
thalmological Society in Zagreb in 1927 brought
together ophthalmologists, otorhinolaryngolo-
gists, psychiatrists, and neurologists who pre-
sented their own experiences, findings, and pro-
cedures for the treatment of pituitary tumors
(14). The earliest results of surgical procedures
for pituitary tumor treatment in Croatia were
published in a Czech journal in 1927 by Ante
Šercer (15). Of 10 cases of pituitary adenoma
presented by Šercer, the first two were admit-
ted to the Otorhinological Clinic in Zagreb in
October 1924, but were not operated on. How-
ever, 6 patients admitted during the period
1925-1926 were surgically treated by the trans-

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Fatović Ferenčić and Gnjidić: Sellar Region Surgery in Croatia
septal-endonasal method modified according to
Hirsch-Segura.
The next paper on the subject was a detailed
review, “Addition to the Clinic for pituitary tu-
mors with special attention to dysfunctions of a
sight organ,” published in 1928 by Mira Mašek-
Breitenfeld, from the Ophthalmological Clin-
ic of Albert Botteri in Zagreb (16). In this thor-
ough review, the author described 11 patients
admitted to the Ophthalmology clinic between
1925 and 1927, mostly for visual disturbances.
Seven of them underwent surgery at the Clinic
of Dr Hirsch in Vienna, and the rest were treated
at the Clinic for Otorhinolaryngology in Zagreb.
Four of these patients had been previously de-
scribed by Šercer in his article (15). All patients
underwent transseptal endonasal surgery. There
were 6 women and 5 men patients; the oldest
was 48 and the youngest 14 years old. The age
and sex distribution of the disease at the time did
not significantly differ from that today (17). The
first patient from the series was operated in Dr
Hirsch’s Clinic in Vienna. Removal of the fron-
tal sphenoidal sinus wall allowed for irradiation
treatment of the pituitary gland with radium.
This combination of surgical and radio-therapy
significantly improved the outcome and seems
to represent the very beginning of brachitherapy
as such, since radiotherapy in the pituitary region
was already in use in 1909 (18).
In the second patient, who was not operated
on, a cocainization of the nasal mucosa was done
with the purpose of exploring paranasal sinuses.
The author wondered whether cocainization im-
proved the patient’s condition, considering that
applied cocaine narrowed the blood vessels in the
edematous mucosa of the sphenoid sinus and the
tissue surrounding pituitary tumor, consequently
decreasing the pressure of the tissue and improv-
ing vision. Today, it is clear that such an effect of
cocaine was possible but temporary, and would
have eventually ceased with the breakdown and
elimination of cocaine from the body. It could be
presumed that this patient had a sphenoid sinus
abscess or a mucocoela, which could have been
pressing against the perisellar structures, includ-
ing the optic nerves. By cocainization, sphenoid
sinus could have become open and the puss or
mucus could have leaked out, decompressing the
optic nerves. At the same time, if it was a matter
of pituitary adenoma with preceding “apoplexy”
or hemorrhagic necrosis, its liquid content could
have perforated the mucosa and leaked out after
the cocainization of mucosa.
In the third patient, the symptoms worsened
6 months after the surgery. According to the data
from the patient’s physician from the island of
Brač, the disease had a fatal end. Even though the
histological finding was hyperplasio hypophyseos,
it was likely a pituitary adenoma that showed ex-
pansive growth after the surgery.
Postoperative diagnosis in the fourth patient
was hydrocephalus internus et externus with dys-
trophia adiposo-genitalis. The author concluded
as follows: “This case, although misdiagnosed, is
very educational, since it shows that hydrocepha-
lus can indeed have the same clinical, ophthalmo-
logic, and radiological presentation as pituitary
adenoma. In our case, it wasn’t possible to radio-
logically conclude on the increase of intracranial
pressure or increased pressure of the structures.
The only diagnostic method that would have led
us to the right path in this case is encephalogra-
phy, since that would have been the only way of
seeing the enlargement of cerebral ventricles due
to hydrocephalus. (Nevertheless, in that time,
in our region such method was not in diagnos-
tic use.) Therefore, I believe that every case of pi-
tuitary tumor, especially with unclear etiology,
should be diagnosed with encephalography, thus
avoiding the possibility of incorrect diagnosis.”
This case is interesting for its diagnostic
procedure of pituitary tumor, obviously still in
the developmental phase. The author’s aware-
ness of the importance of diagnostics is im-
pressive; hence she suggests the introduction of
encephalography. The self-criticism is also mer-
itorious.

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Croat Med J 2006;47:310-317
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The fifth patient was not operated on, but
treated with Ricord’s oral solution (iodine and
mercury). In this case, the final diagnosis was not
confirmed. Histological analysis in the sixth pa-
tient confirmed sarcoma. The seventh case was of
special interest since the patient was operated on
11 times over 7 years at Dr Hirsch’s Clinic in Vi-
enna. According to the author, it was a cyst (cur-
rent diagnosis would probably be calcified cra-
niopharingeoma), which resulted in permanent
improvement only after the last surgery when a
large portion of cystic wall was excided.
The eighth case was conservatively treated,
and in the ninth, additional radio-therapy was
performed 6 months after the surgery. In the
tenth case, a pituitary tumor was operated, the
symptoms disappeared thereafter and the width
of visual field doubled. In the last, eleventh case,
the patient did not undergo surgery.
These articles by Ante Šercer and Mira
Mašek-Breitenfeld are good examples of the doc-
trine and surgical practice at the time, with re-
spect to understanding of etiology, diagnostic
approach, and therapy of pituitary tumors. They
show the level of knowledge of Croatian medical
practitioners, their attitudes, doubts, and uncer-
tainties about pituitary disorders, as well as their
firm opinion on specific surgical procedure. The
importance of early diagnostics was pointed out,
as well as the role of the ophthalmologist. The ne-
cessity for interdisciplinary diagnostic and thera-
peutic approach to this complex area was obvi-
ous. The cooperation among ophthalmologists,
radiologists, and otorhinolaryngologists and in-
volvement of other medical specialties eventual-
ly led to the development of new subspecialties,
such as neurosurgery, neuroradiology, or neuro-
endocrinology. The standards in diagnostic and
other procedures, especially in operative tech-
niques, slowly crystallized. All patients with pitu-
itary diseases at the Clinic for Otorhinolaryngol-
ogy in Zagreb were operated by transsphenoidal
approach, obviously the initial approach and the
method of choice from the very beginning. On
the one hand, it is understandable considering
the fact that such surgeries were done by Ante
Šercer, an otorhinolaryngologist, to whom surgi-
cal approach to nose and sinuses was a daily rou-
tine. In his 1926-1927 article, Šercer clearly de-
fined his position on the indication for pituitary
tumors surgery by saying that “absolute indica-
tion for pituitary surgery exists only in presence
of ocular disturbances with signs of increased in-
tracranial pressure. In all other cases, indications
for surgical therapy are relative” (6).
Communication network on pituitary
surgery techniques
The pituitary gland was a strong research chal-
lenge from the standpoint of anatomy, patho-
logical anatomy, pathophysiology and surgery
since the end of 19th century, when significant
improvement was achieved by an Italian doctor
David Giordano (19). He intensively studied
the problem of approaching the pituitary gland
and performed a series of anatomical studies on
corpses between 1890 and 1896. After 1897,
in further anatomical studies, he applied trans-
glabellar transnasal approach to pituitary gland
(19). After Victor Horsley performed the first
pituitary tumor surgery using transcranial ap-
proach in London in 1904, numerous surgeons
accepted this method (20). Austrian surgeon
Schloffer takes the credit for showing a great
practical value of the sinus of the sphenoid bone
through which pituitary gland is easily reachable.
He published his studies in 1906 in Prague (21).
Only a year later, in 1907 in Innsbruck, he had
a brilliant idea to use natural cavities of the nose
and the sphenoid bone, and for the first time,
successfully operated a pituitary tumor in local
anesthesia with cocaine (22). Following this ini-
tial success, a large number of surgeons and oto-
rhinolaryngologist have accepted this method
with some modifications depending on avail-
able resources, equipment, and personal talents.
Šercer expressed his especially positive opinion