Hypophysitis caused by M. gordonae

1. Neurology International 2009; volume 1:e18
Granulomatous hypophysitis and inflammatory processes.1 Granulomatous
hypophysitis (GH) is an inflammatory disorder Correspondence: José Luis Ruiz Sandoval,
by Mycobacterium gordonae characterized by the formation of granulomas Servicio de Neurología y Neurocirugía, Hospital
in a non HIV-infected patient frequently associated with tuberculosis, sar- Civil de Guadalajara “Fray Antonio Alcalde”.
coidosis, syphilis, and lymphocytic adenohy- Hospital 278, Guadalajara, Jalisco, México.
Juan José Padilla-Martínez,1 pophysitis. This entity usually presents with CP: 44280. E-mail: jorulej-1nj@prodigy.net.mx
Salvador González-Cornejo,1 systemic symptoms such as high fever and
Key words: granuloma, hypophysis, non-tubercu-
Lucía Elizabeth Álvarez-Palazuelos,1 hormonal disturbances.2
lous Mycobacteria, panhypopitituarism, pituitary
Jesús Alejandro Villagómez-Méndez,1 We describe a post-mortem case of granulo- gland.
Erwin Chiquete,2 matous hypophysitis secondary to infection
caused by Mycobacterium gordonae. To our Contributions: all authors have substantially con-
José Alfredo Domínguez-Rosales,3,4
knowledge, only two other cases of GH caused tributed to the conception and design of the work
Ismael Espejo-Plascencia,3 and data analysis, take responsibility for the final
by non-tuberculous mycobacteria infection
Esteban González-Díaz,5 version of the manuscript aapproved it for publi-
(Mycobacterium malmoense and Mycoba-
José Rodrigo Torres-Baranda,6 cation.
cterium tokaiense) in non-compromised hosts
José Luis Ruiz-Sandoval,1,7
have been reported to date.3,4 Conflict of interest: authors of this paper declare
1
Department of Neurology and that the paper is original and has not been pub-
Neurosurgery; 2Department of Internal lished or submitted for publication elsewhere,
and that there is no affiliation with any organiza-
Medicine; 3Department of Pathology;
tion with a direct or indirect financial interest in
4
Department of Molecular Biology; Case Report the subject matter discussed in the manuscript
5
Department of Infectious Diseases, from that may affect the reporting of the work submit-
ly
the Hospital Civil de Guadalajara “Fray A 45-year-old man presented with a six- ted.
month history of weight loss, anorexia, vomit-
on
Antonio Alcalde”; 6Department of
ing, malaise and apathy. In the last month his Received for publication: 10 October 2009.
Molecular Biology and Genomics;
7 condition worsened and headache, diplopia Accepted for publication: 19 October 2009.
Department of Neurosciences, from the
and left ptosis appeared. Neurological exami-
e
Centro Universitario de Ciencias de la This work is licensed under a Creative Commons
nation showed a person with slow mental pro- Attribution 3.0 License (by-nc 3.0).
Salud (CUCS), Universidad de
Guadalajara, Jalisco, México us
cessing, slow speech, affective flattening and
left ophthalmoplegia (partial III cranial nerve
palsy). No visual field disturbances, papillede-
©Copyright J.J. Padilla-Martínez et al., 2009
Licensee PAGEPress, Italy
al
ma or meningeal signs were observed. General Neurology International 2009; 1:e18
doi:10.4081/ni.2009.e18
Abstract physical examination was unremarkable.
ci
Laboratory analyses only showed a low sodium
er
Lymphocytic or granulomatous hypophysitis blood level (114 mmol/L). A chest x-ray and a
is a rare entity with a difficult diagnosis. Our head CT scan were inconclusive and cere- hormones revealed a panhypopituitarism
m
objective was to report a patient with non- brospinal fluid (CSF) was normal. After six state. Based on the neuroimaging and hor-
tuberculous granulomatous hypophysitis. An days of hospitalization, fever, diarrhea and stu- monal findings, a presumptive diagnosis of
om
HIV-negative 45-year old man with confusional por appeared. A cranial MRI showed a sellar hypophysitis was made. The patient was treat-
state, subacute ophthalmoplegia, and clinical and parasellar heterogeneous mass, which in ed with steroid replacement, as well as with
and laboratory findings of panhypopituitarism T1-weighted phase revealed a lesion with first- and second-line antituberculous drugs.
-c
was seen in the emergency unit. A cranial MRI hypointense areas. In a T2-weighted phase Other laboratory studies were unremarkable,
this lesion was predominantly hyperintense including serological tests for B and C hepati-
on
showed a sellar mass suggestive of hypophysi-
tis. After an unsuccessful attempt with steroids with a hypointense center. After gadolinium tis viruses, HIV, VDRL and Brucella, as well as
and antituberculous drugs the patient died. administration, the lesion appeared heteroge- erythrocyte sedimentation rate, C-reactive pro-
N
Post-mortem histopathology revealed granulo- neous with a parasellar extension toward the tein, antinuclear antibodies and rheumatoid
matous lesions and restriction fragment left cavernous sinus (Figure 1). factor.
length polymorphism analysis confirmed the The measurement of plasma hypophysis Despite management, the patient died on
presence of Mycobacterium gordonae’s DNA. In
conclusion, we should consider granulomatous
hypophysitis in the differential diagnosis of
non-secreting hypophyseal tumors. The etiolo-
gy of a pituitary granuloma by a non-tubercu-
lous mycobacteria is best reached by
histopathological techniques and molecular
assays. The optimal therapy is yet to be estab-
lished.
Figure 1. A cranial magnetic resonance imaging showed an intrasellar mass. (A) A sagit-
Introduction tal T1-weighted image revealed a sellar lesion with hypointense areas. (B) A gadolinium-
enhanced sagittal image showed an enhancing lesion with a hypointense center. Axial (C)
The pituitary region is susceptible to and coronal (D) images demonstrated parasellar extension toward the left cavernous
involvement by cystic, neoplastic, infectious sinus.
[Neurology International 2009; 1:e18] [page 63]

2. Case Report
day 11 of hospitilization. The autopsy showed tious material.8 In our patient, the critical sys- is best reached by histopathological tech-
an enlarged, fibrous and thickened pituitary temic and neurological condition made this niques and molecular assays. The optimal
gland. Microscopically, a granulomatous cellu- surgical approach impossible. therapy is yet to be established.
lar reaction suggestive of mycobacterial dis- The other2 reported cases of GH due to non-
ease was observed; however, Ziehl-Neelsen, tuberculous mycobacteria with no history of
modified Kinyoun and Auramine-Rodamine immunosupression included a 32-year-old
staining of the specimen did not identify any woman who presented with fever, headaches, References
acid-fast bacteria (AFB). Molecular diagnostic nausea, vomiting and a six-month history of
testing for potential mycobacterial pathogens diabetes insipidus and amenorrhea.3 In the 1. Lipscombe L, Asa SL, Ezzat S. Management
was then performed. Total DNA was extracted second case, a 36-year-old man presented with of lesions of pituitary stalk and hipothala-
from the hypophysis specimen using a modifi- diabetes insipidus beginning three months mus. Endocrinologist 2003;13:38-51.
cation of the lysis method described by prior, without other hormonal disturbances or 2. Honegger J, Fahlbusch R, Bornemann A, et
Sritharan and Barker.5 A PCR assay and any symptoms of mycobacterial meningitis. In al. Lymphocytic and granulomatous
restriction fragment length polymorphism both cases, Gd-MRI revealed an enhanced hypophysitis: Experience with nine cases.
(RFLP) analysis originally described by Roth et intrasellar mass of heterogeneous appearance Neurosurgery 1997;40:713-23.
al. with oligonucleotide primers of the 16S-23S with suprasellar extension and thickening of 3. Florakis D, Kontogeorgos G, Anapliotou M,
spacer was conducted.6 DNA amplification the pituitary stalk.4 In both patients, a mass et al. Isolated pituitary granuloma by atyp-
experiment included positive controls (for M. lesion was completely removed and histologi- ical Mycobacterium in a nonimmunosup-
tuberculosis H37Rv, M. chelonae, and M. cal examination of the surgical specimen pressed woman. Clin Endocrinol 2002;56:
kansasii) and a blank as well as negative con- showed an epithelioid cell granuloma with 123-6.
trols. The amplified products were digested caseous necrosis, but the acid-fast staining did
4. Kondo A, Mori K, Iwata J, et al. Caseus
ly
separately with 2 IU of the restriction enzyme not identify any AFB organisms. PCR and DNA
necrotic granuloma in the pituitary stalk
HaeIII and CfoI, (Sigma, St. Louis, MO, USA), sequencing to detect the non-tuberculous
due to nontuberculous mycobacteria
on
according to the manufacturer’s recommenda- mycobacteria infection were used.
(Mycobacterium Tokaiense) infection.
tions. Fragment band sizes were estimated M. gordonae has been referred to as a tap
Neur Med Chir 2006;46:80-3.
visually by comparison with appropriate con- water bacillus. It is also found in soil,
5. Sritharan V, Barker RH. A simple method
e
trols (those positive for M. tuberculosis H37Rv, whirlpools, and swimming pools. In healthy
for diagnosis M. tuberculosis infection in
M. chelonae, and M. kansasii) in parallel with
an extract of a whole hypophysis specimen and
a 50 bp ladder (Fermentas, Hanover, USA).
us
people it can be isolated from mucous mem-
branes, urine, and gastric fluid. In the light of
the widespread presence of this pathogen,
clinical samples using PCR. Mol Cell
Probes 1991;5:385-95.
6. Roth A, Reischl U, Streubel A, et al. Novel
al
RFLP assay identified the genotypic character- infection with M. gordonae seems exclusively
istics of M. gordonae. diagnostic algorithm for identification of
determined by host characteristics, and not by
ci
pathogen or exposure variables. M. gordonae mycobacteria using genus-specific ampli-
has often been involved in pseudo-epidemics, fication of the 16S-23S rRNA gene spacer
er
where positive cultures were caused by con- and restriction endonucleases. J Clin
Discussion taminated tap water, fountains, ice machines, Microbiol 2000;38:1094-104.
m
antimicrobial and laboratory solutions, aerosol 7. Cheung CC, Ezzat S, Smyth HS, Asa SL.
The spectrum and significance of primary
om
Even after the HIV pandemics and the great devices and bronchoscopes.9-11 Despite this
use of immunosuppressive drugs, GH by non- apparent vulnerability for our report, we hypophysitis. J Clin Endocrinol Metab
tuberculous mycobacteria remains an uncom- believe this mycobacteria was responsible for 2006;86:1048-53.
8. Sinha S, Singh A, Tatke M, Singh D.
-c
mon disorder.7 The recognition of this entity in this condition in view of all the clinical, radio-
the differential diagnosis of abnormal sellar logical and histopathological test results. Hypophyseal tuberculoma: Direct radio-
surgery is contraindicated for a lesion with
on
masses is important. In cases of GH it has been The optimal therapy for patients with GH
reported a disproportional degree of hormonal due to non-tuberculous mycobacteria is not a thickened pituitary stalk: Case report.
disturbances in relation to the size of the sell- defined in the literature. Although it is univer- Neurosurgery 2000;46:735-8.
N
ar mass.8 The most common manifestations sally accepted that chemotherapy is essential 9. Griffith DE, Aksamit T, Brown-Elliott BA, et
are hypopituitarism, hyperprolactinemia, dia- for a successful treatment of intracranial gran- al. An official ATS/IDSA statment:
betes insipidus, visual field disturbances or ulomas, there is no consensus regarding the Diagnosis, treatment, and prevention of
aseptic meningitis. Nevertheless, none of regimen of drugs or the duration of therapy.10 nontuberculous mycobacterial diseases.
these disorders is specific for this condition.1 Antituberculous treatment must be opportune- Am J Respir Crit Med 2007;175:367-410.
Adequate diagnostic evaluation includes ly initiated in patients who are thought to have 10. den Broeder AA, Vervoort G, van Assen S,
assessment of pituitary gland function, head GH since the mortality rate for mycobacterial et al. Disseminated Mycobacterium gor-
magnetic resonance imaging and the investi- central nervous system infection remains donae infection in a renal transplant recip-
gation of the potential systemic disease. The high.8 ient. Transpl Infect Dis 2003;5:151-5.
trans-sphenoidal approach is the ideal method In conclusion, we should consider GH in the 11. Arnow PM, Bakir M, Thompson K, Bova JL.
for diagnosis and local cure in masses sugges- differential diagnosis of non-secreting hypo- Endemic contamination of clinical speci-
tive of intrasellar granulomas, as it avoids physeal tumors. The etiology of a pituitary mens by Mycobacterium gordonae. Clin
cerebrospinal fluid contamination by infec- granuloma by a non-tuberculous mycobacteria Infect Dis 2000;31:472-6.
[page 64] [Neurology International 2009; 1:e18]