Thyroid DisfunctionTIRASHNCT02915380
Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage
An observational study of Thyroid Disfunction and Subarachnoid Haemorrhage From Cerebral Aneurism Rupture, run by Dr. Rita Bertuetti.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Thyroid Disfunction, Subarachnoid Haemorrhage From Cerebral Aneurism Rupture, Pituitary Disfunction
- What is being tested?
- Evaluation of pituitary endocrine function, Evaluation of clinical outcome and Evaluation of neuropsychological function
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Jan 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients admitted for aneurysmal subarachnoid haemorrhage
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
Chiara Robba, MD contact
Rita Bertuetti, MD contact
About this study
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. This is an observational multicentric study aimed to test the prevalence of thyroid abnormalities, other neuroendocrinological dysfunction and their influence on outcome of patients affected by aSAH.
Read the 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.
- Conditions
- Thyroid Disfunction, Subarachnoid Haemorrhage From Cerebral Aneurism Rupture, Pituitary Disfunction
- Being tested
- Evaluation of pituitary endocrine function, Evaluation of clinical outcome, Evaluation of neuropsychological function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evaluation of pituitary endocrine functionBiological
The basal thyroid hormone and test to perform will be: TSH, fT4, fT3.
When available, the following hormones will be tested:
FSH, LH, estradiol (in women), testosterone (in men), sex hormone-binding globulin (SHBG), ACTH, cortisol, prolactin, Na, K; serum levels of GH and IGF-1; and serum and urine osmolality.
Adrenal function will be evaluated through ACTH-stimulation testing . Adrenal or GH insufficiency will be evaluated by insulin tolerance testing (ITT)
Evaluation of clinical outcomeBehavioural
Patients' outcome will be assessed as modified Rankin Scale (mRS) at discharge from the hospital, at 3, 6 and 12 months.
Evaluation of neuropsychological functionBehavioural
Neuropsychological examination will be conducted focusing on verbal comprehension (Token Test) and visual neglect. Verbal and visual short term and working memory visuospatial construction and figural memory will be performed through Rey Osterrieth Complex figure test, and psychomotor speed attention and concentration through Trail Making Test.
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of thyroid disfunction
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
Measured: At 2 weeks after aSAH
Incidence of thyroid disfunction
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
Measured: 3 months after aSAH
Incidence of thyroid disfunction
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
Measured: 6 months after aSAH
Incidence of thyroid disfunction
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
Measured: 12 months after aSAH
Secondary outcomes (7)
Incidence of pituitary- sexual hormones disfunction
serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (in women), testosterone (in men), sex hormone-binding globulin (SHBG).
Measured: At 2 weeks, and at follow up at 3, 6 and 12 months.
Survival
Modified Ranking Scale
Measured: At 2 weeks, and at follow up at 3, 6 and 12 months
Incidence of pituitary-adrenal axis disfunction
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.
Measured: At 2 weeks, and at follow up at 3, 6 and 12 months.
Incidence of growth hormone insufficiency
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.
Measured: At 2 weeks, and at follow up at 3, 6 and 12 months
Incidence of language disorders
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.
Measured: At 2 weeks, and at follow up at 3, 6 and 12 months
Incidence of memory disorders
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.
Measured: At 2 weeks, and at follow up at 3, 6 and 12 months
Incidence of attention disorders
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.
Measured: At 2 weeks, and at follow up at 3, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2016 (estimated)
- Study startJan 2017
- Primary completionJan 2018 (estimated)
- Study completionJan 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid DisfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Rita Bertuetti
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Responsible party
- Sponsor-investigator, Dr. Rita Bertuetti, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Chiara Robba, MD, Study director, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02915380
- Sponsor's protocol ID
- TIRASH-1.0
- Acronym
- TIRASH
- Status last verified
- Sep 2016
- First submitted
- 6 Sep 2016
- Last updated
- 27 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT02915380
- Acronym / sponsor ID
- TIRASH / TIRASH-1.0
- Conditions
- Thyroid Disfunction, Subarachnoid Haemorrhage From Cerebral Aneurism Rupture, Pituitary Disfunction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Dr. Rita BertuettiUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Study start
- Jan 2017
- Primary completion
- Jan 2018 (estimated)
- Study completion
- Jan 2018 (estimated)
- First posted
- 27 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. This is an observational multicentric study aimed to test the prevalence of thyroid abnormalities, other neuroendocrinological dysfunction and their influence on outcome of patients affected by aSAH.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted for aneurysmal subarachnoid haemorrhage
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Evaluation of pituitary endocrine functionThe basal thyroid hormone and test to perform will be: TSH, fT4, fT3. When available, the following hormones will be tested: FSH, LH, estradiol (in women), testosterone (in men), sex hormone-binding globulin (SHBG), ACTH, cortisol, prolactin, Na, K; serum levels of GH and IGF-1; and serum and urine osmolality. Adrenal function will be evaluated through ACTH-stimulation testing . Adrenal or GH insufficiency will be evaluated by insulin tolerance testing (ITT) | Biological | – |
| Evaluation of clinical outcomePatients' outcome will be assessed as modified Rankin Scale (mRS) at discharge from the hospital, at 3, 6 and 12 months. | Behavioural | – |
| Evaluation of neuropsychological functionNeuropsychological examination will be conducted focusing on verbal comprehension (Token Test) and visual neglect. Verbal and visual short term and working memory visuospatial construction and figural memory will be performed through Rey Osterrieth Complex figure test, and psychomotor speed attention and concentration through Trail Making Test. | Behavioural | – |
Primary outcome
Incidence of thyroid disfunction
Time frame: At 2 weeks after aSAH
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
Incidence of thyroid disfunction
Time frame: 3 months after aSAH
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
Incidence of thyroid disfunction
Time frame: 6 months after aSAH
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
Incidence of thyroid disfunction
Time frame: 12 months after aSAH
Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).
7 secondary outcomes
Incidence of pituitary- sexual hormones disfunction
Time frame: 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
Incidence of pituitary-adrenal axis disfunction
Time frame: 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
Incidence of language disorders
Time frame: 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
Incidence of attention disorders
Time frame: At 2 weeks, and at follow up at 3, 6 and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2016.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chiara Robba, MD contact
Rita Bertuetti, MD contact
Chiara Robba, MD study director
Cambridge University Hospitals NHS Foundation Trust
Questions about this trial
What is this clinical trial studying?
An observational study of Thyroid Disfunction and Subarachnoid Haemorrhage From Cerebral Aneurism Rupture, run by Dr. Rita Bertuetti.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chiara Robba, MD (kiarobba@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of thyroid disfunction (time frame: At 2 weeks after aSAH). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2016; AzTrials last refreshed its copy on 28 Oct 2026.