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Copyright: © 2016 Kobayashi T, et al.
http://dx.doi.org/10.19104/crcm.2016.119
Archives of Case Reports in Clinical Medicine
Case Report
Open Access
Panhypopituitarism due to Transection of the Pituitary Stalk Diagnosed
Nine Years after Traumatic Brain Injury
Toshiyuki Kobayashi1*, Takenori Hibino2, Tsuyoshi Odai3, Kanami Waki2, Yumemi Hasegawa2, Naoki Gocho4 and Hiroshi Tadokoro1
Department of General Medicine, Zama General Hospital, Zama City, Kanagawa, Japan
Department of General Medicine, Ebina General Hospital, Ebina City, Kanagawa, Japan
3
Department of Internal Medicine, Yokohama Asahi Chuo General Hospital, Yokohama City, Kanagawa, Japan
4
Diabetes Center, Ebina General Hospital, Ebina City, Kanagawa, Japan
1
2
Received Date: May 13, 2016, Accepted Date: June 20, 2016, Published Date: June 30, 2016.
*Corresponding author: Toshiyuki Kobayashi, Department of General Medicine, Zama General Hospital, 1-50-1, Sobudai, Zama City, Kanagawa 252-0011,
Japan. Tel: 81(46)-251-1311; Fax: 81(46)-251-5050; E-mail: [email protected]
Abstract
Traumatic brain injury is frequently involved in cases of
hypopituitarism. We report a case of panhypopituitarism due to
transection of the pituitary stalk that we diagnosed 9 years after
the traumatic brain injury. If a patient develops unexplained
or non-specific symptoms, the physician should consider the
possibility of hypopituitarism.
Keywords: Panhypopituitarism; Brain Injury; Trauma
Key Clinical Message
Hypopituitarism is frequently associated with traumatic
brain injury, usually presenting acutely post-injury. However, it
may present some years later. Thus, if a patient with a history of
a traumatic brain injury develops unexplained or non-specific
symptoms, hypopituitarism should be considered. Prompt
investigation and treatment are required for optimal outcomes.
Introduction
Traumatic brain injury is frequently associated with the
dysregulation of pituitary hormone secretion during the acute
phase [1-3]. In addition, more than 35% of patients exhibit some
degree of hypopituitarism within three months post-injury [4].
The subsequent decrease in levels of adrenocorticotropic hormone
A
(ACTH), thyroid-stimulating hormone (TSH), and antidiuretic
hormone can be life-threatening. Moreover, the clinical onset can be
acute and severe, requiring intensive in-hospital care [5]. However,
there have been no reports of panhypopituitarism with non-specific
symptoms occurring several years after experiencing a traumatic
brain injury. Herein, we report a case of panhypopituitarism due to
transection of the pituitary stalk, which we diagnosed 9 years after
the patient’s traumatic brain injury occurred. Careful consideration
of hypopituitarism is warranted after a traumatic brain injury, even
when presenting symptoms are non-specific or when the injury
occurred several years prior to presentation.
Case Report
A healthy 68-year-old man sustained a serious head injury
after he fell from heavy machinery and was caught between the
equipment and the ground. He was moved to the hospital, comatose
and with severe epistaxis. Computed tomography (CT) of the head
revealed a basilar skull fracture, cerebral edema with midline shift,
intracranial hemorrhage, and pneumocephalus (Figure 1). The
patient did not have diabetes insipidus. His neurological status
gradually improved with conservative therapy. He was subsequently
transferred to a rehabilitation hospital and was discharged three
months later. However, the patient reported fatigue and excessive
somnolence, which began after his stay in the rehabilitation hospital.
These symptoms led to a diagnosis of higher brain dysfunction.
The fatigue worsened in the two months before being hospitalized
B
C
Figure 1: Computed tomography of the head revealed a basilar skull fracture, cerebral edema with midline shift, intracranial hemorrhage, and
pneumocephalus. (a) Axial view, (b) and (c) Axial image with bone windows.
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at our institution, which was nine years after his head injury. He
became lethargic five days before hospitalization and was ultimately
admitted via the emergency department of our hospital.
His vital signs at presentation were as follows: body temperature
35.1°C, blood pressure 117/77 mmHg, pulse rate 49 beats/min,
respiratory rate 18 breaths/min, and SpO2 value 96 % in room air.
Physical examination revealed a Glasgow Coma Scale score of 14 (E3
V5 M6), with normal pupil size and pupillary light reflex. As sequela
of his previous head injury, he had bilateral ptosis, left ocular medial
deviation, visual loss in his left eye, and hearing loss in his left ear.
We confirmed negative results for the Barre and Mingazzini tests.
Laboratory data were as follows: white blood cell count, 5,440/
µL (neutrophils, 30.0%; lymphocytes, 58.0%; monocytes, 5.4%;
eosinophil granulocytes, 5.9%; basophils, 0.7%); hemoglobin level,
10.1 g/dL; platelet count, 14.2 × 104/µL; blood urea nitrogen level,
15.7 mg/dL; creatinine level, 0.95 mg/dL; aspartate aminotransferase
level, 32 IU/L; alanine aminotransferase level, 12 IU/L; creatine
kinase level, 469 IU/L; C-reactive protein level, 0.65 mg/dL; Na
level, 133mEq/L; K level, 3.9 mEq/L; and Cl level, 98mEq/L. We
suspected adrenal insufficiency and hypothyroidism and performed
stimulation tests to determine the basal levels of various hormones
(Table 1). We assessed the corticotropin-releasing hormone (CRH)ACTH-adrenal axis; the patient’s plasma ACTH level was < 1.0 pg/
mL. The rapid ACTH challenge test demonstrated a poor response
in serum cortisol levels. The lack of an adequate cortisol response
to ACTH was most likely a consequence of adrenal gland depletion
due to longstanding low serum ACTH levels. The CRH challenge
test revealed a poor response in ACTH and cortisol levels. The peak
plasma ACTH concentration was < 30 pg/mL. We assessed the
activity of luteinizing hormone-releasing hormone (LH-RH) and
gonadotropin by measuring serum levels of LH, follicle-stimulating
hormone (FSH), and testosterone. These levels were 0.1 mIU/mL,
0.5 mIU/mL, and < 10 ng/mL, respectively. The LH-RH challenge
test demonstrated poor responses in LH and FSH levels. The TSH
level was elevated and there was a response to thyrotropin releasing
hormone (TRH), although this was delayed. The prolactin (PRL) level
was normal, but displayed a blunted response to TRH. These results
suggested tertiary rather than secondary hypothyroidism. The
level of serum growth hormone (GH) was < 0.02 ng/mL, and that of
serum insulin-like growth factor-1 was 7.2 ng/mL. The GH-releasing
peptide-2 test revealed a poor response in serum GH levels. Given all
these findings, we diagnosed the patient with panhypopituitarism.
Head CT and horizontal magnetic resonance imaging (MRI)
revealed no significant findings. However, sagittal MRI of the
pituitary gland revealed an atrophic anterior lobe, an empty sella, a
pseudo-posterior lobe of the pituitary gland, and transection of the
A
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B
pituitary stalk (Figure 2). Empty sella syndrome is an anatomical
and radiological abnormality that is not always accompanied by
hormonal insufficiency. Therefore, we assumed that the cause of the
panhypopituitarism was transection of the pituitary stalk resulting
from the previous brain injury, and that the hormonal changes
observed were of hypothalamic origin. We treated the patient with
oral hydrocortisone (15 mg daily), and introduced levothyroxine
sodium hydrate (25 μg daily) 1 week later. The patient responded to
this treatment and subsequently completed in-hospital treatment
with notably increased attention and improved functional ability.
Discussion
This case highlights two important clinical issues. First,
hypopituitarism due to transection of the pituitary stalk can be
diagnosed several years after a traumatic brain injury. Second,
hypopituitarism due to transection of the pituitary stalk can
develop without significant symptoms of adrenal insufficiency.
Hypopituitarism may develop because transection of the pituitary
stalk leads to impaired transport of hypothalamic hormones and
nutrients through the hypophyseal portal system. Previous studies of
patients who sustained fatal traumatic brain injuries revealed varying
degrees of hemorrhagic infarction of the pituitary gland in > 70%,
and hypothalamic micro hemorrhages in > 40% of such patients.
However, pituitary stalk lesions are not typically considered a major
cause of brain injury-induced hypopituitarism [6]. In the present
case, T1-weighted MRI revealed anterior lobe atrophy and formation
of a pseudo-posterior lobe of the pituitary gland, suggesting that
the pituitary stalk transection was caused by the head trauma. MRI
revealed an association of the post-injury pituitary stalk lesion with
the skull fractures and brain swelling. Moreover, although the risk
of anterior gland injury is greatest after a basilar skull fracture, the
anterior gland can also be injured after any skull fracture or even due
to brain trauma in the absence of fracture [7,8].
Traumatic brain injury-related hypopituitarism remains largely
Endocrine studies
TSH level (μIU/mL)
fT3 level (pg/mL)
fT4 level (ng/dL)
ACTH (pg/mL)
Cortisol (μg/dL)
Testosterone (ng/mL)
Growth hormone (ng/mL)
Somatomedin-C (ng/mL)
Value
5.72
1.97
<0.40
<1.0
<0.20
<10
≤0.02
7.2
Table 1: Endocrine study.
Range
0.35-4.94
1.71-3.71
0.70-1.48
7.2-63.3
4.5-21.1
236-1037
0.0-0.97
42-250
C
Figure 2: MRI of the pituitary gland revealed an atrophic anterior lobe, empty sella, and a pseudo-posterior lobe of the pituitary gland (the arrow
indicates the lesion). (a) T2W sagittal view, (b) T1W coronal view, and (c) T1W sagittal view.
Citation: Kobayashi T, Hibino T, Odai T, Waki K, Hasegawa Y, et al. (2016) Panhypopituitarism due to Transection of the
Pituitary Stalk Diagnosed Nine Years after Traumatic Brain Injury. Arc Cas Rep CMed 2(2): 119.
Page 2 of 3
Arc Cas Rep CMed
ISSN: 2469-5173
under-diagnosed. This is mostly due to a lack of awareness among
physicians who are likely to care for the affected patients [7].
Thus, many undiagnosed or misdiagnosed patients with traumatic
brain injury-related hypopituitarism exist. These patients likely
experience a lower quality of life and shorter life expectancy,
compared with patients who are correctly diagnosed. In the
literature, approximately 20 % of patients developed pituitary
hormonal deficiencies at 6–9 months after a traumatic brain injury
[9], and most patients developed hypopituitarism within one year
post-injury, with only a few diagnoses confirmed several years postinjury [10]. To the best of our knowledge, this is the first report of
panhypopituitarism due to transection of the pituitary stalk that
was diagnosed several years after the causal brain injury.
Hypopituitarism due to transection of the pituitary stalk can
develop without significant symptoms of adrenal insufficiency,
such as hypotension, hypoglycemia, or hyponatremia. In the case
presented, diabetes insipidus had not developed in the presence
of a pseudo-posterior lobe, because vasopressin secretion was
preserved from the transected part of the stalk. The signs and
symptoms associated with hypopituitarism often mimic the sequela
of traumatic brain injury, and the patient may develop vague
symptoms, such as anorexia, malaise, weight loss, lethargy, and
nausea. A previous study recommended that patients with more
severe forms of brain injury, and especially patients with basilar
skull fractures or early diabetes insipidus, be closely monitored
for signs and symptoms of endocrine dysfunction [11]. However,
symptom severity is not necessarily related to the severity of the
injury. The patient’s medical history can provide important clues
to support a diagnosis of hypopituitarism due to traumatic brain
injury, but patients may not report their history of traumatic brain
injury, particularly if they were not admitted to a hospital or if the
injury caused only mild-to-moderate damage. Therefore, physicians
should obtain a detailed medical history from patients who exhibit
unexplained hypotension, weight loss, fatigue, loss of libido, and/or
depression. Furthermore, physicians should consider questioning
both the patient and their relatives, as well as testing for pituitary
hormone abnormalities [12,13].
Conclusion
Hypopituitarism due to transection of the pituitary stalk
can exist for several years after the causal brain injury without
significant symptoms of adrenal insufficiency, such as hypoglycemia
or hyponatremia. Therefore, given the high incidence of pituitary
dysfunction after traumatic brain injury, physicians should obtain
a detailed history-both of the present illness and past medical
history-and should perform a detailed examination of the patient.
If hypopituitarism is suspected, hormonal testing should be
performed as soon as possible to enable early initiation of hormone
replacement therapy, for all complicated cases of mild, moderate, or
severe traumatic brain injury.
Vol. 2. Issue. 2. 29000119
Acknowledgements
The authors acknowledge Dr. Yuko Ono (Department of
Radiology, Ebina General Hospital) for helpful suggestions
regarding the case.
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*Corresponding author: Toshiyuki Kobayashi, Department of General Medicine, Zama General Hospital, 1-50-1, Sobudai, Zama City, Kanagawa 2520011, Japan. Tel: 81(46)-251-1311; Fax: 81(46)-251-5050; E-mail: [email protected]
Received Date: May 13, 2016, Accepted Date: June 20, 2016, Published Date: June 30, 2016.
Copyright: © 2016 Kobayashi T, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Citation: Kobayashi T, Hibino T, Odai T, Waki K, Hasegawa Y, et al. (2016) Panhypopituitarism due to Transection of the Pituitary Stalk Diagnosed Nine
Years after Traumatic Brain Injury. Arc Cas Rep CMed 2(2): 119.
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Citation: Kobayashi T, Hibino T, Odai T, Waki K, Hasegawa Y, et al. (2016) Panhypopituitarism due to Transection of the
Pituitary Stalk Diagnosed Nine Years after Traumatic Brain Injury. Arc Cas Rep CMed 2(2): 119.
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