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2]

Original Article

General seizures revealing macro-adenomas

secreting prolactin or prolactin and growth
hormone in men
Farida Chentli, Lina Akkache, Katia Daffeur, Said Azzoug
Department of Endocrine and Metabolic Diseases, Bab El Oued Hospital, 5 boulevard Said Touati, Algiers, Algeria 16000

A B S T R A C T
Background: Epilepsy is a heterogeneous condition with numerous etiologies. Pituitary tumors are rarely responsible for generalized
convulsions except when they are very large. Apart from anecdotic cases, only one study concerning epilepsy frequency in male
macroprolactinomas is available in Medline. Our aim was to analyze epilepsy frequency and conditions under which seizures appear
and disappear in men harboring macroprolactinomas or somatolactotroph adenomas. Materials and Methods: We retrospectively
analyzed 90 men with macro-adenomas (>1 cm) secreting prolactin (PRL) (n = 82) or both PRL and growth hormone (n = 8) to look for
generalized seizures. We took into account familial and personal medical history, clinical examination, routine and hormonal analyzes,
and radiological assessment based on cerebral magnetic resonance imaging. Results: Between 1992 and 2012, we collected eight
cases (8.9%): Seven were hospitalized for recent generalized seizures; one had epilepsy after conventional radiotherapy given in 1992
because of neurosurgery failure and resistance to bromocriptine. Their median age was 33.75 years (22-58), median PRL was 9,198
ng/ml and median tumor height was 74 mm (41-110). The temporal lobe was invaded in six cases. After tumor reduction, epilepsy
disappeared and never relapsed after a follow-up varying between 1 and 20 years. Conclusion: Epilepsy, which is a life-threatening
condition, can be the first presentation in men with prolactinomas or somatolactotroph adenomas, especially those involving the supra
sellar area, and the brain. Convulsions can also appear after radiotherapy. That one should be avoided, if possible, before tumor
reduction by surgery or medical treatment.
Key words: Epilepsy, large prolactinomas, male, radiotherapy

INTRODUCTION
Epilepsy is a heterogeneous condition with numerous
etiologies including genetics, cerebral trauma, toxic exposures,
vascular diseases, infections, metabolic abnormalities,
malformations and neoformations.[1] Among the last ones,
pituitary tumors (PT) are exceptionally responsible for
convulsions, except when they are very large involving the
suprasellar area and the nervous system. In English literature
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DOI:
10.4103/2230-8210.131185

apart from anecdotic cases,[2,3] there is only one report about

epilepsy frequency in male macroprolactinomas.[4] Our
aim was to analyze generalized epilepsy frequency and the
conditions under which seizures appear and disappear in men
harboring pure macroprolactinomas (>1 cm) or prolactin
(PRL) and growth hormone (GH) macro-adenomas.

MATERIALS

AND

METHODS

In this retrospective study, we analyzed 90 subjects, collected

between 1992 and 2012, harboring macro PT secreting either
PRL (n = 82) or PRL and GH (n = 8) to seek symptoms of
generalized epilepsy. After asking for family and personal
medical history, we took into account clinical examination,
routine analyzes (especially electrolytes imbalance, glycemias,
kidney and hepatic functions) and hormonal exploration.
That one was based on PRL, GH, insulin growth hormone
(IGF1), cortisol, adrenocorticotropic hormone (ACTH),

Corresponding Author: Prof. Farida Chentli, Department of Endocrine and Metabolic Diseases, Bab El Oued Hospital, 5 Boulevard Said Touati,
Algiers, Algeria. E-mail: chentli.F@gmail.com
Indian Journal of Endocrinology and Metabolism / May-Jun 2014 / Vol 18 | Issue 3

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Chentli, et al.: Pituitary tumors and epilepsy

testosterone, follicle stimulating hormone (FSH), luteinizing

hormone (LH), thyroid stimulating hormone (TSH) and
free thyroxin (FT4). Radiological assessment was based on
cerebral computed tomography scan (CT scan) and magnetic
resonance imaging (MRI). After a significant reduction in
their PT, they were re questioned and re-explored on the
neurological side and then we tried to stop progressively
their antiepileptic drugs. The follow-up varied from 1 to
20 years.

RESULTS
In this study, we found eight subjects who experienced
generalized seizures (8.9%). Before seizures all were
complaining of headaches, decreased visual acuity and libido.
Seven were sent to our department for generalized epilepsy
related to large PT after exclusion by the neurologists of
cerebral malformations and other epileptic etiologies such
as familial, metabolic, traumatic and infectious causes. In the
eighth case, tonic-clonic seizures appeared after conventional
radiotherapy given in 1992 for a huge prolactinoma resistant
to dopamine agonists.

DISCUSSION
Epilepsy is a heterogeneous disorder with numerous
etiologies. The mechanism can be genetic, metabolic,
structural, infectious and tumoral.[1] Concerning tumors,
seizures are a common complication in large intracranial
lesions and clinical symptoms vary according to tumor
localization.
Seizures are extremely rare in people with PT. According
to Kawasaki et al., seizures secondary to PT are exceptional
as they account for only 4% among all intracranial tumors
causing seizures.[5] Convulsions appear when the tumor
invades the suprasellar area and/or the nervous system
creating an epileptic area.[3,4] Deepak et al.[4] found that 6/29
(20%) patients harboring prolactinomas with suprasellar
expansion suffered from epilepsy at diagnosis. Most of
them were men and had a temporal crisis i.e. experiencing
visual, olfactory and auditory hallucinations and psycho
sensory features such as sensation of already seen dj
vu or never seen non vu or derealization.[2] For our

Among the seven spontaneous tonic-clonic seizures, six

were related to macroprolactinomas and one to a mixed
adenoma secreting PRL and GH.
The median age of the eight persons was 33.75 years (22-58)
and all their tumors were giant (height 40 mm) invading
the suprasellar area and or the brain. Median tumor height
was equal to 74 mm (41-110). PRL average (after systematic
dilution) was equal to 9,198 ng/ml. The temporal lobe was
invaded in six cases (75%) as in the Figure 1.
For the outcome, after tumor volume reduction
[Table 1] observed after bromocriptine intake alone (n = 5),
bromocriptine plus somatostatins analogs (n = 1) and after
radiotherapy plus cabergoline and bromocriptine (n = 1),
epilepsy disappeared and epileptic drugs were stopped in all
cases. Seizures never re-appreared for a follow-up varying
between 1 and 20 years.

b
Figure1: (a) Example of a huge multidirectional tumor with an important
invasion of the temporal and frontal lobes, secreting prolactin and
causing epilepsy in a 22 year-old man who consulted for generalized
seizures. (b) MRI after medical treatment leading to tumor reduction and
disappearance of epilepsy

Table 1: Metabolic analyses and tumor volumes before treatment and after the disappearance of epilepsy
Patients
N1: Prolactinoma
N2: Prolactinoma
N3: Prolactinoma
N4: Prolactinoma
N5: Prolactinoma
N6: Prolactinoma
N7: Somatolactotroph adenoma
N8: Prolactinoma
N9: Prolactinoma

362

Natremia
(135-145 meq/l)

Calcemia
(85-110 mg/l)

Glycemia
(0.7-1.10 g/l)

MRI

Tumor size before

treatment (mm)

Tumor size after epilepsy

disappearance (mm)

139
140
143
142
139
137
140
140.6
138

96
92.5
90
98
94
99
107
100
89

0.76
0.93
1.05
0.89
0.84
0.85
0.89
0.75
0.76

Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes

685050
50.968.546
1106078
412734
65.697.162
616345
8010070
415238
505562

455427
253434
605548
181530
315530
123014
234737
213811
182825

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Chentli, et al.: Pituitary tumors and epilepsy

group, generalized epileptic seizures were observed in 8 of

90 (8.9%) men harboring macro adenomas secreting PRL
(82 pure prolactinomas and 8 somatolactotroph adenomas).
If we consider only tumors superior or equal to 4 cm (n = 46)
our percentage will rise to 17.3%! This percentage is slightly
lower than Deepaks.[4] Our frequency is probably under
estimated as we did not take into account partial seizures
and we did not do a systematic electro-encephalography
to all our patients. Epileptic seizures are apparently due to
mass effect on the brain system as convulsions are described
only in people with very large PT or those harboring
pituitary metastasis invading the suprasellar area.[6] But, a
fortuitous association with a miroadenoma or an isoadenoma
is not impossible. To our knowledge high PRL or GH
concentrations are not incriminated in epileptic status, but
after epilepsy crisis hormones influenced by stress such as
PRL, GH, cortisol, and even LH and FSH can raise.[7]
It is also interesting to note that seizures may occur in patients
harboring huge tumors which are treated by dopamine
agonists.[8] In such cases a very rapid reduction in tumor
volume would cause an unintended movement of brain
structures responsible for epileptic seizures.[8] Conventional
and even gamma knife radiotherapy is another cause of
epilepsy in people with large prolactinomas or other PT.[9]
Radiotherapy is generally aggressive for the brain as it
can be responsible for radio-necrosis, gliomas or a mere
change of the mesial temporal lobe mimicking gliomas.[9]
Risks for inflammation and/or hemorrhage in PT and the
brain are also increased by radiation as reported by some
authors in prolactinomas[9] non-functioning adenomas[9]
and somatotropinomas.[9,10]
In some exceptional situations, generalized seizures
may reveal a PT as in seven of our cases. This situation
traduces a very late diagnosis or a rapid progression of the
tumor compressing cerebral structures. In our patients,
convulsions were observed only in invasive prolactinomas
and somatolactotroph adenomas deemed to be the largest
PT. Large pure somatotroph adenomas can also induce
seizures in animals[11] and human beings.[3,12]
Epilepsy secondary to PT is usually resistant to symptomatic
treatment by antiepileptic drugs,[1] but responds to medical
treatment that reduces PT, even if tumor reduction is partial
as observed in our study, and by Deepak et al.[4]. Total
resection of the tumor when possible and/or dopamine
agonists for pure prolactinomas and mixed adenomas avoid

recurrence of the life threatening seizures, lead to control

and even recovery from epileptic crisis as we observed it.
Similar results were observed by Castero Cabezas et al.[12]
in somatotroph adenomas invading temporal lobes.

CONCLUSION
Epilepsy, which is a life-threatening condition can reveal
prolactinomas in men and mixed pituitary tumors,
especially giant ones. Convulsions can also appear under
aggressive treatment such as radiotherapy. That one should
be avoided, if possible, before tumor reduction by surgery
or medical treatment.

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Cite this article as: Chentli F, Akkache L, Daffeur K, Azzoug S. General
seizures revealing macro-adenomas secreting prolactin or prolactin and growth
hormone in men. Indian J Endocr Metab 2014;18:361-3.
Source of Support: Nil, Conflict of Interest: None declared.

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