case history of a child who met with a motor vehicle accident and developed hypopituitarism in later years of life.

1. Clinical case presentation
Topic – post traumatic hypopituitarism
Presenter – Dr. Amit Samadhiya

2. CASE SUMMARY –
16 year old girl presents with poor growth for four years. Her growth and
development were normal before this, and her appetite and food intake remain
satisfactory. At age 12, she was a passenger in a motor vehicle collision, where she
suffered a moderate traumatic brain injury ( GCS of 12 ), requiring hospitalization for
around a week. There were no intracranial hemorrhages and she did not require
neurosurgical intervention.
Her family history is unremarkable. Her performance at school satisfactory. She has
not attained menarche yet.
A complete blood count, metabolic panel, liver function tests and urinalysis and ESR
are also within normal limits.
Anthropometric mesurements :
Height – 130 cm (< 3rd percentile)
Weight - 40.5 kg (< 3rd percentile)
Calculated height velocity : 1 cm /year
Vital signs – stable
Heart, Lung, CNS – no abnormalities

3. General examination:
• No Dysmorphic feature.
• Tanner stage – 1(i.e. secondary sexual characteristics absent)
• One Scar in left parietal region, 2cm in length.
Endocrine profile –
TSH – 5.6 mcg/dl (5-12)
FT3 – 71 ng/dl (75-200)
CORTISOL – 1.82 mIU/ml (2-10)
FSH – 0.89 mcg/dl ( 5-23)
LH - 1.08 miu/ml (1-9)
Estradiol – 0.31 miu/ml (2-12)
DHEAS – 0.20 ng/dl (3.4 – 17)
Prolactin - 2.0 ng/ml (3-24)
IGF -1 – 1.45 ng/ml (3-24)
X-ray bilateral wrist –
Both wrists are compatible with a bone
age of ten years.
MRI Brain – T2 weighted axial section
demonstrated a slim pituitary gland
located posteriorly in the sella turcica.
Posterior hypophysis appears normal.
These findings are consistent with
partial empty sella syndrome.

4. (Left) An MRI shows an empty sella, (Right) An MRI with a normal sella.

5. Interpretation of biochemistry laboratory reports –
Hypothyroidism –
Hypothyroidism in patients who have pituitary or hypothalamic disease is the result
of thyrotropin (TSH) deficiency. The serum TSH concentration is usually not low,
except when the hypothyroidism is treated. Screening for hypothyroidism in patients
with pituitary or hypothalamic disease is performed by measuring TSH and free T4.
Gonadotropins (FSH, LH) - Workup varies with the gender of the patient.
 Men — luteinizing hormone (LH) deficiency can best be detected by
measurement of the serum testosterone concentration. If it is repeatedly low at 8 to
10 AM and the LH concentration is not elevated, the patient has secondary
hypogonadism. If fertility is an issue, the sperm count should be determined.
Women — In a woman of premenopausal age who has pituitary or hypothalamic
disease but normal menses, no tests of LH or follicle-stimulating hormone (FSH)
secretion are needed because a normal menstrual cycle is a more sensitive indicator
of intact pituitary-gonadal function than any biochemical test.

7.  If the woman has oligomenorrhea or amenorrhea, serum LH or FSH should be measured. In
addition, the following two tests should be obtained:
• Measurement of serum estradiol
• Administration of medroxyprogesterone
10 mg daily for 10 days (to determine if vaginal bleeding occurs after the 10-day course)
A low serum estradiol concentration and/or absence of vaginal bleeding indicate estradiol
deficiency as a consequence of gonadotropin deficiency and warrant consideration of estrogen
treatment.
Normal results, in association with oligomenorrhea or amenorrhea, could indicate sufficient
gonadotropin secretion to maintain normal basal estradiol secretion but insufficient to cause
ovulation and normal progesterone secretion. This situation should prompt consideration of
intermittent progestin treatment.
The serum LH response to a single bolus dose of gonadotropin-releasing hormone (GnRH)
is not helpful in distinguishing secondary hypogonadism due to pituitary disease from that
due to hypothalamic disease, because patients who have hypogonadism due to pituitary
disease may have normal or subnormal serum LH responses to GnRH, as may those who
have hypothalamic disease.

8. Growth hormone –
Measurement of basal serum growth hormone concentration does not distinguish reliably
between normal and subnormal growth hormone secretion in adults.
Three other criteria, however, are useful:
•Deficiencies of multiple other pituitary hormones
•Serum insulin-like growth factor-1 (IGF-1)
•Provocative tests of growth hormone secretion
Either insulin-induced hypoglycemia or the combination of arginine and growth hormone-
releasing hormone (GHRH) is a potent stimulus of growth hormone release. Subnormal
increases in the serum growth hormone concentration (<5.1 ng/mL for the former and
<4.1ng/ml for latter) confirms the diagnosis of growth hormone deficiency.
PROLACTIN -
Women who have severe hypopituitarism due to hypothalamic or pituitary disease may, in the
postpartum period, have a serum prolactin concentration that is inappropriately low and not be
able to nurse.
•No commercially available prolactin preparation is available for these women.
•No data available about serum prolactin concentrations in women without known pituitary
disease who are unable to lactate.
•There is no standardized test of prolactin reserve.

9. Corticotropin (ACTH) –
Morning serum cortisol — To test basal ACTH secretion, morning serum cortisol (at 8 to 9 AM),
and the results should be interpreted as follows.
• A serum cortisol value of ≤3 mcg/dL (83 nmol/L, normal range 5 to 25, confirmed by a second
determination, is strong evidence of cortisol deficiency, which in a patient with a disorder
known to cause hypopituitarism is usually the result of that disorder.
•Indeterminate — A serum cortisol value >3 mcg/dL (83 nmol/L) but less than <18 mcg/dl is an
indication to evaluate ACTH reserve.
 Metyrapone testing.
 Cosyntropin stimulation test
The test has become less necessary because immunometric plasma ACTH assays in use are very
sensitive and specific.

13. Discussion -
At a first glance, this 16 year old girl’s chief complaint appears to be a potential growth delay.
However a careful review of her history brings another important complaint to light : delayed
menarchy. This combination is most concerning.
Her calculated growth velocity, height and weight are all below the third percentile, while her
pubertal maturation is only Tanner stage 1. this confirms the growth delay is indeed present.
Chronic illnesses, malnutrition, endocrine, metabolic disorders or chromosomal anomalies are
characterized by proportionate short stature.
A question arises : why was not her slow growth velocity assessed until now ? unfortunately,
this can not be answered with the information currently at hand.
Plain radiographs of both wrists reveal that her bone age is markedly less than her
chronological age, strongly favoring an endocrine cause.
Consider the history of traumatic brain injury (TBI). Post traumatic hypopituitarism is a known
complication of moderate to severe TBI, typically first appearing months to years after the initial
insult.
A genetic etiology is made clinically less likely by the lack of dysmorphic features,
unremarkable neurological examination and negative family history. However this possibility
should be revisited if other conditions are excluded.

14.  An endocrine profile demonstrates all anterior pituitary hormones to be below the normal
ranges while follow-up brain MRI reveals a partially empty sella. When considered along with
the clinical findings this is sufficient to diagnose post traumatic hypopituitarism.
 Hypopituitarism is a rare disease, but may be significantly underdiagnosed in people with
previous traumatic brain injury.
 Hormone repalcement therapy is the mainstay of treatment.
 Corticosteriods should be replaced first so as to avoid precipitating an adrenal crisis due to
levothyroxine induced increased metabolism.
 Serious consideration should also be given to contacting social services. As mentioned
earlier, it is concerning that her growth delay has been ignored for such a long period.
 As there is no evidence of hereditary disorder, genetic counseling is not indicated.
Thank You