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Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage (TIRASH)

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ClinicalTrials.gov Identifier: NCT02915380
Recruitment Status : Unknown
Verified September 2016 by Dr. Rita Bertuetti, Cambridge University Hospitals NHS Foundation Trust.
Recruitment status was:  Not yet recruiting
First Posted : September 27, 2016
Last Update Posted : September 27, 2016
Sponsor:
Collaborator:
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Dr. Rita Bertuetti, Cambridge University Hospitals NHS Foundation Trust

Brief 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. 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.

Condition or disease Intervention/treatment
Thyroid Disfunction Subarachnoid Haemorrhage From Cerebral Aneurism Rupture Pituitary Disfunction Biological: Evaluation of pituitary endocrine function Behavioral: Evaluation of clinical outcome Behavioral: Evaluation of neuropsychological function

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.


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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage
Study Start Date : January 2017
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : January 2018

Resource links provided by the National Library of Medicine



Intervention Details:
  • Biological: Evaluation of pituitary endocrine function

    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)

  • Behavioral: Evaluation of clinical outcome
    Patients' outcome will be assessed as modified Rankin Scale (mRS) at discharge from the hospital, at 3, 6 and 12 months.
  • Behavioral: Evaluation of neuropsychological function
    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.


Primary Outcome Measures :
  1. Incidence of thyroid disfunction [ Time Frame: At 2 weeks after aSAH ]
    Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).

  2. Incidence of thyroid disfunction [ Time Frame: 3 months after aSAH ]
    Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).

  3. Incidence of thyroid disfunction [ Time Frame: 6 months after aSAH ]
    Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).

  4. Incidence of thyroid disfunction [ Time Frame: 12 months after aSAH ]
    Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).


Secondary Outcome Measures :
  1. 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).

  2. Survival [ Time Frame: At 2 weeks, and at follow up at 3, 6 and 12 months ]
    Modified Ranking Scale

  3. 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.

  4. 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.

  5. 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.


  6. 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.


  7. 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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients admitted for aneurysmal subarachnoid haemorrhage
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02915380


Contacts
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Contact: Chiara Robba, MD kiarobba@gmail.com
Contact: Rita Bertuetti, MD rita_zoso@yahoo.it

Sponsors and Collaborators
Dr. Rita Bertuetti
Cambridge University Hospitals NHS Foundation Trust
Investigators
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Study Director: Chiara Robba, MD Addenbrookes Hospital

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Responsible Party: Dr. Rita Bertuetti, Medical Doctor, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02915380     History of Changes
Other Study ID Numbers: TIRASH-1.0
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: September 27, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Aneurysm
Intracranial Aneurysm
Aneurysm, Ruptured
Brain Diseases
Hemorrhage
Subarachnoid Hemorrhage
Rupture
Pituitary Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Intracranial Hemorrhages
Cerebrovascular Disorders
Central Nervous System Diseases
Nervous System Diseases
Wounds and Injuries
Hypothalamic Diseases
Endocrine System Diseases
Intracranial Arterial Diseases