Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage

Subarachnoid Haemorrhage From Cerebral Aneurism Rupture Clinical Trial

— TIRASH  

Official title:

Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02915380
• Other study ID #: TIRASH-1.0
• Status: Not yet recruiting
• Phase: N/A
• First received: September 6, 2016
• Last updated: September 23, 2016
• Start date: January 2017
• Est. completion date: January 2018

Study information

• Verified date: September 2016
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: Chiara Robba, MD
• Email: kiarobba[@]gmail.com
• Is FDA regulated: No
• Health authority: United Kingdom: National Institute for Health Research
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Aneurysm
• Aneurysm, Ruptured
• Hemorrhage
• Intracranial Aneurysm
• Pituitary Diseases
• Pituitary Disfunction
• Rupture
• Subarachnoid Haemorrhage From Cerebral Aneurism Rupture
• Subarachnoid Hemorrhage
• Thyroid Disfunction

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Dr. Rita Bertuetti	Cambridge University Hospitals NHS Foundation Trust

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of thyroid disfunction	Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).	At 2 weeks after aSAH	No
Primary	Incidence of thyroid disfunction	Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).	3 months after aSAH	No
Primary	Incidence of thyroid disfunction	Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).	6 months after aSAH	No
Primary	Incidence of thyroid disfunction	Thyroid-stimulating hormone (TSH), free thyroxin (fT4), free triiodothyronine (fT3).	12 months after aSAH	No
Secondary	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).	At 2 weeks, and at follow up at 3, 6 and 12 months.	No
Secondary	Survival	Modified Ranking Scale	At 2 weeks, and at follow up at 3, 6 and 12 months	No
Secondary	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.	At 2 weeks, and at follow up at 3, 6 and 12 months.	No
Secondary	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.	At 2 weeks, and at follow up at 3, 6 and 12 months	No
Secondary	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.	At 2 weeks, and at follow up at 3, 6 and 12 months	No
Secondary	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.	At 2 weeks, and at follow up at 3, 6 and 12 months	No
Secondary	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.	At 2 weeks, and at follow up at 3, 6 and 12 months	No