And the problem with low growth hormone? And the solution? Or are survivors supposed to google their medical answers?
Growth Hormone Deficiency Is Frequent After Recent Stroke
Thomas Lillicrap1, Carlos Garcia-Esperon1, 
Frederick Rohan Walker2, Lin Kooi Ong2, 
Michael Nilsson2, Neil Spratt1,2, 
Christopher R. Levi1,2, Mark Parsons1,2, 
Jörgen Isgaard2,3 and 
Andrew Bivard1,2*- 1Department of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, NSW, Australia
- 2Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- 3Department of Internal Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Introduction: The incidence of
pituitary dysfunction after severe ischemic stroke is unknown, however
given the increasing attention to pituitary dysfunction after
neurological injuries such as traumatic brain injury, this may represent
a novel area of research in stroke.
Methods: We perform an arginine and
human growth hormone releasing hormone challenge on ischemic stroke
patients within a week of symptom onset.
Results: Over the study period, 13
patients were successfully tested within a week of stroke (baseline
NIHSS 10, range 7–16). Overall, 9(69%) patients had a poor response,
with 7(54%) of these patients meeting the criteria for had human growth
hormone deficiency. Other measures of pituitary function were within
normal ranges.
Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.
Introduction
Enhancement of recovery after ischemic stroke has been a
challenging area, with no intervention being widely adopted to promote
recovery in clinical practice. In the search for innovative treatment
targets post stroke, we decided to investigate pituitary function after
stroke with a focus on human growth hormone (hGH). Other acute brain
insults such as traumatic brain injury (TBI) and subarachnoid hemorrhage
have demonstrated hypopituitarism in around one quarter of patients
shortly after injury (1).
Although TBI has previously been considered as a rare cause of
hypopituitarism, an increased prevalence of neuroendocrine dysfunction
in patients with TBI has been reported over the last 15 years as
endocrinological testing has become more common in this patient group.
The symptoms of hypopituitarism depend on which hormone is deficient,
but for hGH, they include impaired attention and memory, reduced energy,
cognitive dysfunction, a decrease in muscle mass and strength, reduced
bone mass and density and cardiac dysfunction, all of which are common
in stroke survivors (2).
We hypothesized that patients with a severe ischemic stroke resulting
in significant residual disability would experience hypopituitarism,
particularly affecting hGH secretion. The aim of this study was to
investigate the potential incidence of hGH deficiency from 7 days after
stroke onwards.
Methods
Consecutive patients presenting to the John Hunter
Hospital Emergency Department with first ever clinical diagnosis of an
ischemic stroke were assessed for this study. The acute clinical
diagnosis was confirmed by multi modal computed tomography (CT) which
included CT angiography, CT perfusion and a noncontrast CT. Patients
presenting with symptoms typical of transient ischemic attack or stroke
mimics such as migraine with aura, seizures, acute confusional states,
hypoglycaemia, diabetes, or patients with symptoms related to known
prior stroke, or patients with a known history of conversion disorder
were excluded from the study.
Baseline clinical data recorded included demographics
(age, sex), vascular risk factors (hypertension, diabetes mellitus,
dyslipidemia, atrial fibrillation, smoking history, prior stroke/TIA,
and ischemic heart disease), clinical features such as the baseline and
24 h National Institutes of Health Stroke Scale (NIHSS), and premorbid
modified Rankin Score (mRS), mRS at discharge and 90 days post stroke.
If the patient consented to the study, researchers would
organize a fasting blood assessment for the next morning to be taken
between 8 and 10 a.m. All enrolled patients underwent growth hormone
(GH) provocative test with a GH-releasing-hormone (GHRH) and arginine
infusion (3).
GH reserve was assessed by GHRH (1 μg/kg bolus) plus arginine (ARG; 0.5
g/kg iv up to maximum of 30 g in 60 ml saline, infused over a 30 min
period) testing. A GH response peak < 11 μg/liter in patients with
BMI < 25 kg/m2, < 8 μg/liter in patients with BMI between 25 and
30 kg/m2, and < 4.2 μg/liter in those with BMI 30 kg/m2 or greater
was considered diagnostic for GHD (3).
From the initial 10 mL sample we will also test the levels of serum
insulin-like growth factor 1 (IGF-1), thyroid function with thyroid
specific hormone (TSH) and T1 and T2 and cortisol. In addition to the GH
test, participants were tested for levels of TSH, T3, T4, ACTH, LH,
testosterone, FSH, and cortisol. These tests were processed and analyzed
by the local pathology department on the same day as the GH test.
If the patient was able, study specific assessments were
also performed at the time of blood testing and included the Montreal
Cognitive Assessment (MoCA) and the NIHSS.
Results
From July 2016 to July 2017, 13 patients were enrolled in
this prospective study. Median time of testing was 7 days post stroke
(range 4–10, Table 1)
and median age was 71 (range 54–78). Median hospital admission National
Institutes of Health Stroke Scale (NIHSS) was 10 (range 7–16). Seven
patients had middle cerebral artery stroke, two had lacunar infarction,
two patients had posterior circulation stroke, and two had brain stem
stroke. The mean 24 h post stroke MRI DWI lesion was 55 mL (range 8–92
mL). The median 90 day modified Rankin Score median was 2 (range 1–4).
Of the 13 patients, 7 (54%) fulfill criteria for hGH deficiency when the
GH peak level was related to BMI and two patients had a borderline
response (mean abnormal GH peak 4.4, Table 2).
In the 8 included men, 6 showed low levels of testosterone below the
normal reference range (mean low testosterone result was 3.2 nmol/L),
and two showed normal levels (mean normal testosterone result was 12.8
nmol/L). Lastly, only one of the studies 5 females showed low levels of
luteinising hormone (LH). FSH was elevated in 8 patients (mean abnormal
FSH level 46.3, reference range 1–12) as can be expected in elderly
subjects. Insulin-like growth factor 1 (IGF-1) was mostly within the
normal range in the tested patients, however two patients had low IGF-1
concomitant with GH deficiency. TSH, T3, T4, and cortisol were all
within normal reference ranges.
