- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02915380
Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage (TIRASH)
Study Overview
Status
Conditions
Detailed Description
The incidence of aneurysmal subarachnoid hemorrhage (aSAH) varies between 6 to 10/100,000 subjects per year and it is a major cause of death and disability. The mortality rate ranges from 40 to 50%, and those who do survive SAH have high rates of functional limitations that could lead to impaired quality of life, including fatigue, depression, and loss of motivation.
Because aSAH affects patients in their most productive years of life, the disease has important social, and economic implications, and early prediction of long-term outcome is based on multiple factors including the primary injury secondary insults as well as neurorehabilitation interventions.
Recently, the occurrence and potential impact of pituitary dysfunction after aSAH has gained increasing interest. Several studies have demonstrated pituitary dysfunction after SAH suggesting that pituitary dysfunction may be a contributing factor for residual symptoms after SAH. However, questions remain about the real prevalence and impact of such dysfunction on patients' outcome both in the acute and chronic phase after these events.
In two recent metanalysis, the prevalence of total pituitary dysfunction was found with pooled frequencies of 0.31 (95% confidence interval CI: 0.22-0.43) [Can et a.] and 49.3.0% (95% CI 41.6%-56.9%) [Robba et al] during the acute phase (< 6 months from aSAH) and decreasing in the chronic phase to 0.25 (95% CI: 0.16-0.36) [Can et al.] and 25.6% (95% CI 18.0%-35.1%) [Robba et al]. However, the authors found high heterogenicity and different results between the available literature; many differences were found in the in the choice of time of pituitary function assessment and SAH, of diagnostic criteria and units of measurement used to establish the diagnosis of hypopituitarism after SAH.
Finally, it is not clear which is the hormone axis more likely to be affected after aSAH.
It is believed that, among the other, the incidence of thyroid dysfunction is the most relevant, as it is associated with severe clinical impairment and symptoms. In literature, the prevalence of thyroid dysfunction after aSAH is reported from 0 to 35%.[Karaka, Tanrivedi].
Hypothyroidism includes a wide variety of symptoms including weakness, fatigue, depression, irritability, memory loss and decreased libido. Should these abnormalities complicate more than one third of the patients, hormone testing and eventually replacement should become "standard of care" to test.
In order to define the actual incidence of these abnormalities, an observational multicentric study to test thyroid abnormalities, including TSH, fT4 (free thyroxine) and fT3 (free triiodothyronine) changes, is warranted.
Secondary endpoints of such study include the prevalence of other neuroendocrinological dysfunction and their influence on the patients' outcome.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Chiara Robba, MD
- Email: kiarobba@gmail.com
Study Contact Backup
- Name: Rita Bertuetti, MD
- Email: rita_zoso@yahoo.it
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- patients with acute aneurysmal SAH aged between 18 and 70 years of age who could be subjected to endocrine evaluation within 10 days of ictus and at follow-up.
Exclusion Criteria:
- be major depression, psychiatric premorbidity, pituitary adenoma or perisellar lesion,preexisting hypopituitarism of any degree, previous hormonal substitution, patients in moribund state, pregnancy, glucocorticoid medication on admission to hospital or during treatment, prior pituitary insufficiency, and unsalvageable aSAH.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of thyroid disfunction
Time Frame: At 2 weeks after aSAH
|
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
|
At 2 weeks after aSAH
|
Incidence of thyroid disfunction
Time Frame: 3 months after aSAH
|
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
|
3 months after aSAH
|
Incidence of thyroid disfunction
Time Frame: 6 months after aSAH
|
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
|
6 months after aSAH
|
Incidence of thyroid disfunction
Time Frame: 12 months after aSAH
|
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
|
12 months after aSAH
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of pituitary- sexual hormones disfunction
Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months.
|
serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (in women), testosterone (in men), sex hormone-binding globulin (SHBG).
|
At 2 weeks, and at follow up at 3, 6 and 12 months.
|
Survival
Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months
|
Modified Ranking Scale
|
At 2 weeks, and at follow up at 3, 6 and 12 months
|
Incidence of pituitary-adrenal axis disfunction
Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months.
|
Serum levels of adrenocortico-tropic hormone (ACTH), cortisol, Na, K; serum and urine osmolality.
Adrenal function will be evaluated through ACTH-stimulation testing with injection of 250 mcg of ACTH, and a peak of cortisol <500 nmol/l will be considered pathologic.
Adrenal or GH insufficiency will be evaluated by insulin tolerance testing (ITT), and peak response of more than 3ng/ml for GH and and 500 nmol/l for cortisol will be considered as normal.
|
At 2 weeks, and at follow up at 3, 6 and 12 months.
|
Incidence of growth hormone insufficiency
Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months
|
serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1).
Adrenal or GH insufficiency will be evaluated by insulin tolerance testing (ITT), and peak response of more than 3ng/ml for GH and and 500 nmol/l for cortisol will be considered as normal.
|
At 2 weeks, and at follow up at 3, 6 and 12 months
|
Incidence of language disorders
Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months
|
Neuropsychological examination focused on verbal comprehension will be evaluated through the application of Token Test . Incidence of impaired scoring will be correlated to incidence of altered hormone levels detected in the blood. |
At 2 weeks, and at follow up at 3, 6 and 12 months
|
Incidence of memory disorders
Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months
|
Verbal and visual short term and working memory visuospatial construction and figural memory will be performed through Rey Osterrieth Complex figure test. Incidence of impaired scoring will be correlated to incidence of altered hormone levels detected in the blood. |
At 2 weeks, and at follow up at 3, 6 and 12 months
|
Incidence of attention disorders
Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months
|
Psychomotor speed attention and concentration will be assessed through Trail Making Test. Incidence of impaired scoring will be correlated to incidence of altered hormone levels detected in the blood. |
At 2 weeks, and at follow up at 3, 6 and 12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Chiara Robba, MD, Addenbrookes Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Wounds and Injuries
- Endocrine System Diseases
- Hypothalamic Diseases
- Intracranial Arterial Diseases
- Intracranial Hemorrhages
- Hemorrhage
- Pituitary Diseases
- Rupture
- Aneurysm
- Subarachnoid Hemorrhage
- Intracranial Aneurysm
Other Study ID Numbers
- TIRASH-1.0
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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