This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Currently, pituitary hormone function is rarely considered in the care of patients with bleeding into or over the surface of the brain as the result of a ruptured blood vessel (aneurysm). This type of brain bleeding is called aneurysmal subarachnoid hemorrhage (SAH). Yet, aneurysmal SAH poses risk to hormonal function controlled by the pituitary gland (a structure at the base of the brain and connected to the brain by blood vessels) given its delicate blood supply and connections to the brain that are sensitive to a variety of insults including the initial aneurysm bleeding, narrowing of blood vessels as a result of the bleeding (cerebral vasospasm), increased cerebrospinal fluid in the brain (hydrocephalus) and increased pressure in the brain. It is the primary hypothesis of this study that many SAH patients suffer from unrecognized pituitary hormone loss that acutely and chronically worsens the effects of the initial brain bleeding and may prevent maximal recovery of brain function. The major hypotheses being tested in this study are that i) pituitary hormonal loss after SAH results primarily from an inadequate blood supply to the pituitary gland and/or its connections to the brain; ii) that SAH can result in a lack of stress hormone (cortisol) production (acute secondary adrenal insufficiency), iii) that SAH-induced low growth hormone worsens vasospasm after SAH and iv) that SAH can cause chronic loss of pituitary hormone production (hypopituitarism). These hypotheses will be tested in a two-part pilot study of two aneurysmal SAH patient groups (Acute SAH Cohort and Chronic SAH Cohort) at UCLA and Harbor-UCLA Medical Centers. The results of this pilot project will be used as preliminary data for a more comprehensive NIH grant application addressing SAH-induced pituitary hormonal loss and its treatment. Acute SAH: During the first 14 days after SAH, patients (while in the ICU only) will undergo daily hormonal blood draws to assess for cortisol and growth hormone dysfunction, sodium levels and proteins that cause inflammation (cytokines). Daily studies {transcranial Doppler (TCD)} will be performed to document development of cerebral vasospasm. The frequency of acute cortisol and growth hormone insufficiency and the risk factors associated with the development of these acute hormonal insufficiencies will be determined. If patients have a catheter in place to measure the pressure in the brain (ventriculostomy), samples of cerebrospinal fluid (fluid in the brain) will be collected to measure growth hormone and proteins that cause inflammation. Patients with low cortisol levels (< 5 ug/dL) will be treated with a similar stress hormone (hydrocortisone). The role of growth hormone loss in the development of vasospasm will also be studied. On hospital day 6, the patient will also have a stimulation study using growth hormone releasing hormone (GHRH) and arginine (an amino acid) to further assess for growth hormone loss. Chronic Hypopituitarism after SAH: Aneurysmal SAH patients who suffered a SAH 6 to 12 months prior, will undergo i) pituitary hormone stimulation testing to assess for pituitary failure and ii) neurobehavioral testing and quality of life assessment (tests for memory, concentration, attention, depression, anxiety and fatigue). All patients diagnosed with pituitary hormonal loss will be referred to an endocrinologist. Those diagnosed with low cortisol or low thyroid will be treated by replacement of these essential hormones. Men diagnosed with low testosterone (male sex hormone) and women who have not gone through menopause, diagnosed with low estrogen (female sex hormone), will be recommended to start replacement therapy of these hormones. Patients with low growth hormone will be offered GH-replacement therapy. The results of the neurobehavioral and quality of life tests will be correlated with the rate of hormonal insufficiencies. Patients will be consented separately for the Acute and the Chronic Phases of the study. If patients are unable to consent because of an altered mental state, proxy consent will be obtained from the legal guardian or next of kin. If the patient becomes able to be consented during the acute phase (i.e., the blood draws in the first 14 days after the SAH), consent will be obtained from the patient. The benefit of the study for individual patients is that they may be diagnosed with a treatable hormonal loss that would otherwise have gone undetected had they not participated in the study. Given that the acute and chronic studies only involve well-established hormonal testing and blood draws, the potential benefits of study participation outweigh the risks.
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