Post Traumatic Hypopituitarism (PTHP)

Reference

Quinn et al 2018

General

High rate of pituitary gland dysfunction following moderate or severe TBI with evidence that post-traumatic hypopituitarism (PTHP) contributes significantly to the morbidity and possibly mortality in those patients

PTHP can masquerade as a post-concussional syndrome and can be overlooked leading to delayed recovery and impaired rehabilitation

Numbers

Prevalence

27%
The variations in the reported frequency of PTHP is due to

Patient selection
Timing of testing
Methodological heterogeneity in the ascertainment of hypopituitarism.

Among the pituitary hormone deficiencies, growth hormone (GH) deficiency, as with other forms of hypopituitarism, appears to be the commonest deficiency in those who were tested 6 months or more following the event

Natural history

Occurs early after acute TBI.

Most clinically significant abnormalities in the acute phase of TBI are ACTH-cortisol deficiency and salt and water imbalance

Some of these early abnormalities are transient and recover fully within days or weeks after TBI while new pituitary hormone deficiency may become apparent in the post-acute phase

Clinical features

Hormone deficiency	Symptoms	Findings
ACTH	Life-threatening adrenal crises especially during acute illness, weakness, lethargy, weight loss	Hypotension, hypoglycemia, hyponatremia, hypercalcemia, anemia
Growth hormone	Decreased energy, low mood, neuropsychiatric symptoms, poor quality of life	Decreased lean body mass, increased fat mass, altered metabolic profile, decreased exercise capacity, reduced BMD
LH/FSH	Oligo/amenorrhea, mood disturbances, decreased libido, seating, erectile dysfunction	Decreased lean body mass, reduced secondary sexual characteristics, infertility
TSH	Fatigue, weakness, weight gain, constipation, neuropsychiatric problems	Myopathy, bradycardia, skin/hair changes, hypothermia
Vasopressin	Polyuria, polydipsia, nocturia, incontinence	Dehydration, hypernatremia

What is the Clinical Significance of PTHP?

Acute-phase cortisol deficiency

Life threatening
Association between increased morbidity and mortality in acute post-traumatic hypoadrenalism

Long-term adult GH deficiency

Associated with decreased quality of life
Reduced lean body mass
Reduced bone mineral density
Impaired cardiac function

Recent data seem to confirm that anterior pituitary hormone deficiency has a negative impact on functional outcome at 6 months post TBI as assessed by mini-mental state exam and functional independence measure scores

Correlation between PTHP vs

Unfavorable metabolic and body composition profiles
Lower quality of life scores
Decreased exercise capacity
Neuropsychiatric complications

Pathophysiology

Mechanisms of injury

Vascular injury to the hypothalamus, stalk, or the pituitary gland resulting in infarction

Most common
43% in autopsy study

Direct traumatic injury to the pituitary from base of skull fractures
Secondary insults from, hypoxia, hypotension, or raised intracranial pressure

Predictors of post head injury hypopituitarism

Controversial

Possible has to do with

Severity of head injury

Defined by post-resuscitation and pre-intubation Glasgow Coma Scale (GCS) Score. A score of 3–8 indicates severe, 9–12 moderate, and 13–15 mild injury.
Not fully accurate because

GCS is limited by significant inter-observer variability
GCS scores can fluctuate over time.

Some studies show even mild head injury are associated with PTPH

Radiological (CT)

Significant pathological findings like cerebral edema or hemorrhage on cranial imaging may infer a more severe TBI.

Who to Screen?

NICE

In people admitted to hospital with a head injury who have persistently abnormal low sodium levels or low blood pressure, consider investigations for hypopituitarism. [2023]
In people presenting to primary or community care with persistent symptoms consistent with hypopituitarism in the weeks or months after a head injury, consider investigations or referral for hypopituitarism

Screening every patient with a TBI for PTHP is clearly not feasible. This approach does not meet the criteria for an appropriate screening tool due to the high cost and the complexity of testing which often requires dynamic and sometimes repeat assessments.

For patients with moderate or severe TBI

Not really for mild TBI for pituitary dysfunction unless there are specific symptoms suggestive of hypopituitarism

Screening for mild cases of TBI remains controversial.
Schneider et al. demonstrated a high rate (16.8%) of PTHP following a mild TBI although most of the endocrine abnormalities on mild TBI cases were not confirmed by second dynamic tests.
In one well-executed study, the frequency of PTHP after simple mild TBI was found to be very low
However, it has been suggested that “complicated” cases labeled as mild TBI should also be included in the screening process such as

Patients admitted to hospital for >24 h,
Patients admitted to the ICU or those requiring neurosurgical intervention,
Patients suffering pituitary dysfunction within 2 weeks of their TBI, or
Patients with new anatomical changes on their brain scans.

Features that seem to confer an increased risk of PTHP include

Diffuse axonal injury on brain imaging,
Prolonged admission to ICU,
Basal skull fracture,
Increasing age

Assessment

Acute-Phase Assessment

Only treat

ACTH deficiency

Do serial morning cortisol levels to check for ACTH deficiency.

An acute-phase cortisol level below 300 nmol/l is suggestive of adrenal insufficiency

Treatment with glucocorticoids should be instituted

Levels of 300–500 nmol/l should be interpreted in the clinical context.

Features suggestive of adrenal insufficiency should alert the clinician and treatment with GC replacement may be warranted.

Do not do

Dynamic test of the adrenal axis

Insulin stress test
Corticotrophin test

Inappropriate (the insulin stress test)
Unreliable (the corticotrophin test)

Early assessment of (Acute GH, thyroid hormones or gonadotropins deficiencies, or hyperprolactinemia) axes is unnecessary because

No evidence to support the treatment of in the acute phase following TBI.
Interpretation of the results in the acute phase is difficult.

Chronic Phase Assessment

All patients with moderate and severe TBI should have an assessment of their adrenal, thyroid, and gonadal axes in the post-acute phase,

At 3–6 months post TBI.

Dynamic test for adrenal reserves

Depends on the preference of the endocrinologist
Corticotrophin test (Synacthen test) as a simple and reliable test

Thyroid function tests (free T4 and TSH)

Sex steroids test + corresponding gonadotrophins levels (and menstrual history in premenopausal women)

1 year

Early GH deficiency post TBI can be transient
Assessment of the GH axis is also more complex due to the need to perform dynamic testing which is often only available in specialist centers.
Deferring GH assessment until 1 year post TBI.
Assessment of GH reserves should ideally be done with the gold standard insulin tolerance test provided no contraindications (especially seizures and heart disease) are present.
Other dynamic tests for GH can also be used (37)

If a deficiency is detected, we recommend replacement as appropriate and repeating the assessment at 1 year as early deficiencies may recover

Algorithms for diagnosis of pituitary function after TBI

Januszewska 2020.pdf

628.3 KiB

Proposed algorithm for diagnosis of pituitary function after traumatic brain injury (data from Glynn & Agha (105), Czeiter et al. (111), Fernandez-Rodriguez et al. (126), and Herrmann et al. (127)). TBI, traumatic brain injury; GCS, Glasgow coma scale; TSH, thyroid-stimulating hormone; GH, growth hormone; FSH, follicle stimulating hormone; LH, luteinizing hormone.