doi:10.1507/endocrj.EJ24-0091

Case Report with Review of Literature

Post-traumatic pituitary stalk transection syndrome(PSTS) expeditiously manifested after a fall from a heightcombined with acute traumatic spinal cord injury: a rarecase report with review of literature
Yohei Ishiki, Atsuko Tamaki, Ken-ichiro Honma, Ken Yonaha, Takamitsu Yabiku, Taiki Teruya,
Moriyuki Uehara, Yoshiro Nakayama, Rei Chinen, Tsugumi Uema, Sawako Nakachi, Shiki Okamoto andHiroaki Masuzaki
Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine,
Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
Abstract. Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitaryhormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalkinterruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to theirsimilar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal
developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies
are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing topanhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally
associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord
injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor.
She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On
postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably,
menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism,
hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal
axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights
endocrinological landscape of transection of the pituitary stalk by acute trauma.
Key words: Post-traumatic pituitary stalk transection syndrome (PSTS), Pituitary stalk interruption syndrome (PSIS), Acutetraumatic spinal cord injury, Secondary adrenal insufficiency, Combined pituitary hormone deficiency

Introduction
Post-traumatic pituitary stalk transection syndrome(PSTS) is a rare cause of combined pituitary hormone
deficiency (CPHD). It has been reported that occurrenceof traumatic brain injury is approximately 235 per
100,000 persons per year, with PSTS accounting for
approximately 4% of all cases [1, 2]. PSTS is an
Submitted Feb. 13, 2024; Accepted Apr. 29, 2024 as EJ24-0091
Released online in J-STAGE as advance publication ??, 2024

Correspondence to: Hiroaki Masuzaki, MD, PhD, Division of
Endocrinology, Diabetes and Metabolism, Hematology andRheumatology, Second Department of Internal Medicine, Graduate
School of Medicine, University of the Ryukyus, 207 Uehara,
Nishihara, Okinawa 903-0215, Japan.
E-mail: hiroaki@med.u-ryukyu.ac.jp©The Japan Endocrine Society

acquired consequence of head trauma, leading to regen‐erative and regressive changes in the hypothalamicpituitary region, which occasionally mimics closely
genetic pituitary stalk interruption syndrome (PSIS) on
magnetic resonance imaging (MRI) findings [3].
PSIS was initially reported in 1987, which is accom‐
panied by both an ectopic posterior pituitary gland (EPP)
and an interrupted stalk [4]. Incidence of PSIS has
recently been increasing due to routine use of MRI as a
primary radiological modality in patients with hypopitu‐
itarism [5]. A previous report demonstrated that PSIS
was found about 7% in approximately 15,000 patientswith growth hormone (GH) deficiency [6]. Nowadays,
MRI reveals numerous anatomical variations in patientswith PSIS, encompassing alterations in the anterior
pituitary lobe (e.g., absence, hypoplasia or normal), the2Ishiki et al.

posterior pituitary lobe (e.g., absence, ectopic along thestalk, ectopic at the hypothalamus base or normal in thesella turcica), and/or the stalk (e.g., interrupted, thin or
normal) [7]. Moreover, molecular pathogenesis of PSIS
caused by genetic defects is widely recognized [8].
Here, we report an extremely rare case of an adultfemale in whom PSTS expeditiously manifested after thefall from heights accompanied by the acute traumatic
spinal cord injury.

Case Presentation
A 34-year-old female (height 164 cm, body weight 64
kg, Body Mass Index 23.8 kg/m2) was transferred to our
hospital two days after jumping from the fourth floor of abuilding (approximately 12 meters) due to a quarrel withher partner. She initially experienced post-traumaticstress disorder stemming from sexual abuse by her father
and was prescribed psychotropic medications, including
Quetiapine at a dosage of 300 mg/day, Trazodone at
50 mg/day, Eszopiclone at 2 mg/day, Flunitrazepam at
2 mg/day, and Lorazepam at 1.5 mg/day. She had no his‐
tory of breech delivery or the delayed development of
secondary sexual characteristics. The patient’s last men‐strual period occurred 13 days before the day of jumping,and her menstruation had not resumed even after 200
days following the event. Her menstruation stopped forthe first time following the fall from the height. Upon
admission, she was fully conscious. However, abrasion
was observed in the occipital region. She sustained bothof lower limb fractures (right talus and fibula fracture aswell as left femur fracture) and vertebral fractures at thelevel of C2, C6, C7, and T2. Preoperatively, all muscle
groups were tested using the manual muscle test (MMT)
according to the International Standards for NeurologicalClassification after Spinal Cord Injury (ISNCSCI). She
presented with incomplete tetraplegic, exhibiting an
MMT of 1 or 2/5 below the C7 myotome level and theloss of anal tone. However, she demonstrated no pares‐
thesia below the T1 dermatomal level. The ISNCSCI
examination results were consistent with C7 ASIA
Impairment Scale C tetraplegia. MRI revealed a dislo‐cated fracture of the C7 vertebral body with mild poste‐rior displacement of T1 (Fig. 1). Fortunately, no apparent
visceral injury was observed throughout the body,
including the liver, spleen, kidney, adrenal gland, aorta,
bladder, ovary, uterus or vagina. She then underwent theoperation of elective posterior spinal fusion (C3–T4) on
the fifth day after the trauma. On the postoperative day(POD) 7, a routine blood test revealed considerable
hyperkalemia (potassium [K] 6.7 mEq/L) and slighthyponatremia (sodium [Na] 133 mEq/L), whereas bloodurea nitrogen (BUN) and creatinine levels were within

Fig. 1

The fracture of the C7 vertebral body is illustrated in MRI.
The T2-weighted sagittal MRI sequence displays adislocated fracture of the C7 vertebral body with mild
posterior displacement of T1 (orange arrow). The 7th
cervical spinal cord is compressed by a dislocated fracture
at C7.

the normal range. She represented with no symptoms ofadrenal insufficiency such as nausea, vomiting, fatigue,
or fever. Value of her blood pressure remained stable ataround 90/50 mmHg.
Laboratory findings of the patient revealed
eosinophilia, anemia, elevated serum levels of liver
enzymes and prolactin (PRL), hypogonadism, hypothy‐
roidism, secondary adrenal insufficiency and low
somatomedin C levels (Table 1). In addition, the level ofplasma arginine vasopressin (AVP) was below the mea‐
surable range (<0.4 pg/mL), while no clinical manifesta‐
tions, including dry mouth, polydipsia, and polyuria,
were noted. Basal value of hormones in Table 1 wasassessed at 31 days after the day of jumping, because she
had undergone antimicrobial and infusion therapy. Sus‐
pecting combined pituitary hormone deficiency (CPHD),
we performed a line of hormone-loading tests to evaluate
pituitary function at 31–35 days after the fall. In thecorticotropin-releasing hormone (CRH) stimulation test,
the response of serum cortisol was apparently blunted(baseline 2.1 μg/dL; peak 12.1 μg/dL), while that ofadrenocorticotropic hormone (ACTH) was within thenormal range (baseline <1.5 pg/mL; peak 29 pg/mL)(Table 2A). The gonadotropin-releasing hormone stimu‐
lation test revealed a delayed response to both luteinizing
hormone (LH) and follicle-stimulating hormone (FSH)(Table 2A). The thyrotropin-releasing hormone test
demonstrated that the response of thyroid-stimulating
hormone (TSH) was within the normal range, while
the response of PRL was slightly blunted (baseline

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PSTS with acute spinal cord injury

Table 1

Laboratory Data

Hematology

Value (Reference range)

Biochemistry

Value (Reference range)

WBC, 103/μL

4.3 (3.3–8.6)

Calcium, mg/dL

8.8 (8.8–10.1)

Neutro, %56.0 (40.7–77.0)

CRP, mg/dL

2.27 (0.00–0.14)

Lymph, %25.5 (16.0–49.5)

TC, mg/dL

152 (142–248)

Eosino, %10.9 (0.0–8.5)

TG, mg/dL

184 (30–117)

Baso, %

1.6 (0.0–2.5)

HDL-C, mg/dL

24 (48–103)

RBC, 106/μL

3.15 (3.86–4.92)

LDL-C, mg/dL

80 (65–163)

Hb, g/dL

9.6 (11.6–14.8)

Ht, %29.7 (35.1–44.4)

Endocrine hormones

PLT, 103/μL

498 (158–348)

GH, ng/mL

1.03 (0.00–2.47)

Somatomedin-C, ng/mL
Biochemistry84 (115–277)

PRL, ng/mL

132.0 (4.91–29.3)

Total protein, g/dL

5.4 (6.6–8.1)

LH, mIU/mL<0.3 (1.13–64.3)

Albumin, g/DL

2.8 (4.1–5.1)

FSH, mIU/mL

0.9 (1.79–113.6)

AST, U/L

41 (13–30)

ACTH, pg/mL

5.0 (7.2– 63.3)

ALT, U/L

28 (7–23)

Cortisol, μg/dL

1.76 (6.24–18.0)

Total bilirubin, mg/dL

0.4 (0.4–1.5)

TSH, μU/mL

1.50 (0.3–4.2)

ALP, U/L

77 (38–113)

Free T3, pg/mL

1.2 (2.3–4.0)

LDH, U/L

280 (124–222)

Free T4, ng/dL

0.47 (1.10–1.80)

Creatine kinase, U/L

228 (41–153)

24h UFC, μg/day

Glucose, mg/dL

80 (73–109)

Urine volume, mL/day

BUN, mg/dL

12 (8.0–20.0)

P-osm, mOsm/L

274 (275–295)

Creatinine, mg/dL

0.66 (0.46–0.79)

U-osm, mOsm/L

294 (100–1,300)

Na, mEq/L

133 (138–145)

AVP, pg/mL<0.4 (0.4–3.5)

K, mEq/L

6.7 (3.6–4.8)

PRA, ng/mL/h

3.8 (0.2–2.7)

Cl, mEq/L

99 (101–108)

PAC, pg/mL (CLEIA)

96 (4.0–82.1)

Lower limit (4.3–176)
1,900

Abbreviations: WBC, White Blood Cells; RBC, Red Blood Cells; Hb, Hemoglobin; Ht, Hematocrit; PLT, Platelet;
Neutro, Neutrophil; Lymph, Lymphocytes; Eosino, Eosinophil; Baso, Basophil; AST, Aspartate aminotransferase;
ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; LDH, Lactate dehydrogenase; Na, Sodium; K,
Potassium; Cl, Chloride; TC, Total cholesterol; TG, Triglyceride; HDL-C, High-density lipoprotein cholesterol;
LDL-C, Loc-density lipoprotein cholesterol; GH, Growth hormone; PRL, Prolactin; LH, Luteinizing hormone; FSH,
Follicle-stimulating hormone; ACTH, Adrenocorticotropic hormone; TSH, Thyroid-stimulation hormone; T3,
Triiodothyronine; T4, Tetraiodothyronine; UFC, Urinary free cortisol; P-osm, Plasma osmolality; U-osm, Urine
osmolality; AVP, Arginine vasopressin; PRA, Plasma renin activity; PAC, Plasma aldosterone concentration; CLEIA,
Chemiluminescent enzyme immunoassay.

132 ng/mL; peak 211 ng/mL) (Table 2A). In the growth
hormone-releasing hormone peitide-2 (GHRP-2) test
(Table 2B), the GH response was substantially blunted(baseline 1.5 ng/mL; peak 7.7 ng/mL) and the responseof serum cortisol was not detected (baseline 0.1 μg/dL;
peak 0.9 μg/dL). Moreover, the rapid ACTH test
revealed that the response of serum cortisol was also
blunted (baseline 1.7 μg/dL; peak 8.3 μg/dL) (Table 2C).
At six weeks after the day of jumping, MRI detected anormal size of anterior pituitary lobe, but no visible pitu‐

itary stalk was identified (Fig. 2A). Of note, hyperintense
signal in the posterior lobe on T1 weighted imaging wasdisappeared, meanwhile, the hyperintense signal of the
distal axon of the hypothalamus was still identified(Fig. 2B). These MRI findings are consistent with thecharacteristics of PSTS [9, 10].
Based on a series of findings above, she was diag‐
nosed as PSTS accompanied by acute traumatic spinal
cord injury. The patient began treatment with hydrocorti‐
sone (15 mg/day) and levothyroxine sodium hydrate

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Ishiki et al.

(125 μg/day). After adequate hormone replacement, herblood test at four months after the day of jumping
revealed as follows: Na 140 mEq/L, K 4.2 mEq/L, TSH<0.10 μU/mL, FT3 2.0 pg/mL, FT4 1.54 ng/dL, ACTH
<1.5 pg/mL, cortisol 0.25 μg/dL, PRL 177.0 ng/mL, LH<0.3 mIU/mL, FSH 0.8 mIU/mL, plasma osmolality

294 mOsm/L, urine osmolality 407 mOsm/L, AVP<0.4 pg/mL without polydipsia and polyuria. At six
months after the day of jumping, she was transferred to a
psychiatric hospital for mental rehabilitation. Fig. 3 pro‐vides an overview of the clinical timeline of this case,delineated based on the day of the incident.

Discussion
Table 2

Hormone-releasing testsA) CRH/TRH/GnRH test (CRH 100 μg, TRH 200 μg, GnRH
100 μg iv.)
Time (min)

0

30

60

90

ACTH (pg/mL)

<1.5

29.0

21.0

14.3

9.5

Cortisol (μg/dL)

2.1

8.8

11.9

12.1

11.5

TSH (μU/mL)

1.5

14.1

15.0

14.6

12.8

T3 (ng/mL)

0.31

T4 (μg/dL)

3.01

PRL (ng/mL)

132

211

183

157

144

LH (mIU/mL)

<0.3

1.6

1.9

2.0

2.5

FSH (mIU/mL)

0.8

2.7

3.6

4.1

4.8

—

120

0.81

—

4.19

B) GHRP-2 test (GHRP-2 100 μg iv.)
Time (min)

0

15

30

45

60

GH (ng/mL)

1.5

7.7

6.6

4.5

2.9

Cortisol (μg/dL)

0.1

0.3

0.9

0.9

0.6

C) ACTH stimulation test (ACTH 250 μg iv.)
Time (min)0ACTH (pg/mL)<1.5

Cortisol (μg/dL)

1.66

30

60
—

6.0

8.3

Abbreviations: CRH, corticotropin releasing-hormone; TRH,
thyrotropin-releasing hormone; GnRH, gonadotropin-releasing
hormone; ACTH, Adrenocorticotropic hormone; PRL, Prolactin;
TSH, Thyroid-stimulation hormone; T3, Triiodothyronine; T4,
Tetraiodothyronine; LH, Luteinizing hormone; FSH, Folliclestimulating hormone; GHRP-2, growth hormone-releasing
hormone peitide-2; GH, Growth hormone.

Fig. 2

PSTS and PSIS are often confused due to their similarnames and resembling images in MRI. PSIS is currently
thought to represent a prenatal developmental event
caused by a couple of genetic aberrations. Mutations inseveral genes (e.g., TGIF, SHH, OTX2, SOX3) have been
identified in approximately 5% of the patients studied[11, 12]. Approximately 50% of patients with PSIS haveextra-pituitary and midline developmental malformations(e.g., microcephaly, hydrocephalus, type 1 Chiari malfor‐
mation and cleft lip and/or palate) [13]. In any cases, it
should be noted that PSIS never occurs as a consequenceof PSTS. Furthermore, distinct hormonal presentations
have been observed between PSIS and PSTS. Typicalclinical manifestations of PSIS include permanent ante‐rior pituitary hormone deficiencies particularly GH andgonadotropin during the pediatric age, which appear
gradually but steadily progress to panhypopituitarism inadulthood. However, very few patients have arginine
vasopressin deficiency (AVP-D) compared to otherhormonal deficiencies, partly because the anterior andposterior lobes have different embryonic origins [7].
On the other hand, hormonal manifestations of PSTS
are temporally related to head trauma, which causes tran‐
section of the pituitary stalk [3]. In our case, the patient’s
menstruation stopped just after the acute traumatic spinal
cord injury caused by a fall from a height. Moreover, she

The findings of post-traumatic pituitary stalk transection syndrome in MRI.
(A) T1-weighted sagittal images after the intravenous injection of gadopentetate dimeglumine MRI sequence demonstrating theloss of the pituitary stalk (blue circled).
(B) The T1-weighted sagittal MRI sequence displays a lack of the hyperintense signal in the posterior lobe (blue arrow) and thehyperintense signal of the distal axon of the hypothalamus (orange arrow).

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PSTS with acute spinal cord injury

Fig. 3

5

The clinical course of the patient.
The timeline in this case is summarized based on the day of jumping.

had no history of severe head trauma, growth retardation,
or delayed development of secondary sexual characteris‐tics. In Fig. 4, we summarize the clinical manifesta‐
tions and pathophysiological differences between PSTS
and PSIS.
In our case, the normal ACTH response to the CRH
test was combined with apparently low levels of basal
ACTH and cortisol, while the cortisol response wasdiminished highly suggesting secondary adrenal insuffi‐
ciency. In addition, the low level of peak cortisol after
GHRP-2 administration also indicates secondary adrenal
insufficiency [14]. A peak value of cortisol <15 μg/dL ina rapid ACTH test indicates primary adrenal insuffi‐
ciency in some cases. However, some patients with trau‐
matic brain injury in the acute phase, just as in our case,are likely to exhibit an attenuated response of cortisol[15]. Taken together, along with the loss of the pituitary
stalk on MRI imaging, a line of hormonal dysregulation
seems to be attributed to the above the pituitary gland.
To the best of our knowledge, neither PSTS nor PSIS
associated with acute traumatic spinal cord injury inadulthood have been reported. In Table 3, we summarize
the clinical characteristics of previously reported cases of
PSTS and PSIS with adrenal insufficiency in adulthood.
As far as our search extended over approximately 20
years of case reports using PubMed with keywords

including “pituitary transection syndrome or invisible
pituitary stalk or ectopic posterior pituitary” and “adrenal
insufficiency” and “adult or adulthood” and “casereport,” there were only five cases reported in literature.
According to previous reports [16-18], more than 20
years had elapsed between the onset of PSTS or PSIS
and their final diagnosis. In contrast, the diagnosis in ourcase was established only three months after the onset.
The measurement of cortisol levels as a cause of theimbalance in circulating electrolytes facilitated the early
diagnosis of PSTS.
Our report has several limitations. First, we could not
perform a serial tetracosactide acetate stimulation test or
insulin tolerance test, mainly because of both time con‐straints in clinical practice and the risk of post-traumatic
epilepsy. However, most of the data, including intact
aldosterone production and MRI imaging findings werehighly suggestive of secondary adrenal insufficiency.
Some researchers have suggested that post-traumatic
hypopituitarism includes not only direct mechanical tran‐
section of the pituitary stalk but also neuroinflammationand vascular mechanisms of injury [19]. The pituitary
gland is suspended on the stalk within the third ventricle,
with hypophyseal vessels descending the stalk andsupplying the anterior pituitary lobe via the latticeworkof the portal vessels. Such perforating vessels are

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Fig. 4

Ishiki et al.

Schematic representation of pathophysiological differences between post-traumatic pituitary stalk transection syndrome (PSTS)
and pituitary stalk interruption syndrome (PSIS).
Schematic view of the clinical course of post-traumatic pituitary stalk transection syndrome (PSTS) and pituitary stalk interruption
syndrome (PSIS). Hormonal manifestations of PSTS are temporally associated to head trauma. Alternatively, the clinicalmanifestations of PSIS include permanent deficiencies in anterior pituitary hormones, particularly growth hormone andgonadotropin during the pediatric age, which appear gradually but steadily progresses to panhypopituitarism in adulthood.

Table 3Characteristics of previously reported five patients with PSTS and PSIS with adrenal insufficiency
Sex

Age ofdiagnosis

CausedDecreased levels ofhormone

MRI findings

female20

Head trauma at
2 months of age

Somatomedin C, LH, FSH,
TSH, Cortisol

Loss of the pituitary stalk
Hypoplasia of anterior lobe
EPP at the infundibular recess

male

19

unknown

Somatomedin C, LH, FSH,
TSH Cortisol

Loss of the pituitary stalk
Hypoplasia of anterior lobe
EPP at posterior optic chiasm

female36

Breech delivery

Somatomedin C, LH, FSH,
TSH, ACTH, Cortisol

Loss of the pituitary stalk
Absence of anterior lobe
EPP at floor of the hypothalamus

Gotyo N et al. [17]

male

38

Breech delivery

Somatomedin C, LH, FSH,
TSH, ACTH, Cortisol

Loss of the pituitary stalk
Normal size of anterior lobe
EPP at the infundibulum

Makino S et al. [18]

male

48

Breech delivery

Somatomedin C, TSH,
ACTH, Cortisol

Loss of the pituitary stalk
Hypoplasia of anterior lobe
EPP at the median eminence

Ioachimescu AG et al.
[16]

Abbreviations: PSTS, post-traumatic pituitary stalk transection syndrome; PSIS, pituitary stalk interruption syndrome; LH, Luteinizing
hormone; FSH, Follicle-stimulating hormone; ACTH, Adrenocorticotropic hormone; TSH, Thyroid-stimulation hormone; EPP, ectopic
posterior pituitary gland.

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PSTS with acute spinal cord injury

vulnerable to shearing injuries from sudden accelerationdeceleration forces. Sudden transection of the pituitary
stalk results in infarction of the anterior pituitary lobe[20]. A previous study demonstrated that anti-pituitary
antibodies are commonly positive after traumatic brain
injury and are associated with pathophysiology ofhypopituitarism [21]. Taken together, it tempts us to
speculate that diminished response of cortisol in the
rapid ACTH test may be attributed to a consequence of
the infarction and neuroinflammation in the anterior pitu‐
itary lobe due to the complete transection of the pituitary
stalk. Infarction and neuroinflammation in the anterior
pituitary lobe are likely to rapidly decrease ACTH pro‐duction and release in the anterior pituitary lobe.
In conclusion, our case highlights endocrinologicallandscape of transection of the pituitary stalk by acutetrauma.

Acknowledgments
We thank E. Kakuta, M. Hirata and C. Noguchi for
their excellent secretarial assistance.

Disclosure
None of the authors has any potential conflicts ofinterest associated with this case report. Hiroaki
Masuzaki is a member of Endocrine Journal’s Editorial
board.

Author’s Contribution
All the authors contributed to this work. Data collec‐
tion was undertaken by Y.I. The draft of the manuscript
was written by Y.I., A.T., K.H., K.Y., T.Y., T.T., M.U.,
Y.N., R.C., T.U., S.N., S.O. and H.M. reorganized thefinal form of the manuscript. All the authors read andapproved the final version of the manuscript.

Informed Consent
Informed consent was obtained from the patient publi‐
cation of this case report, and any accompanying dataand images.

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