Anterior Pituitary Function in Patients With Hydrocephalus

March 1, 2010 updated by: Johns Hopkins University
Hydrocephalus (secondary or idiopathic) is a condition characterized by dilatation of the lateral and third ventricles, and often associated with increased intracranial pressure (ICP). We hypothesize that either the ventricle dilatation or the increased ICP may cause disturbances in the hypothalamic-pituitary axis, resulting in different degrees of hypopituitarism. The goal of this study is to determine the prevalence of hypopituitarism in adult patients with hydrocephalus.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The Johns Hopkins Adult Hydrocephalus Program evaluates approximately 250 new patients per year for hydrocephalus and associated disorders, resulting in the new diagnosis of hydrocephalus in about 100 patients annually. After treatment with either shunt surgery or third ventriculostomy, virtually all patients are followed on a regular basis by physicians in the program (Dr. Michael Williams, neurologist, and Dr. Daniele Rigamonti, neurosurgeon, both involved in this project).

These patients represent an ideal cohort to study the effect of hydrocephalus on anterior pituitary function. In addition, as data on intracranial pressure is available for all of them, evaluation of pituitary function would allow us to determine whether the level of intracranial pressure correlates with the likelihood of pituitary failure.

We propose to study 20 subjects of both sexes with NPH, aged 18-80 years over a period of 18 months. They will be recruited by direct advertising among the patients cared for by the Adult Hydrocephalus Program. Patients with hydrocephalus will be studied twice (6-12 months apart) whether or not they undergo shunting.

STUDY PROTOCOL:

  1. In addition to the comprehensive neurological history and physical examination, further history will be obtained, with particular attention to sexual function and libido in males and menstrual history in women of fertile age, will be collected.
  2. After overnight fasting, an indwelling catheter will be inserted in a peripheral vein. Blood for baseline hormonal evaluation (8-9 AM) including: serum free T4 (FT4), TSH, cortisol, GH, IGF-1, prolactin, LH, FSH, Estradiol (in females) and total testosterone (in males). Menstruating females will be studied during follicular phase. Serum IGF-1, testosterone, estradiol and gonadotropin levels will be interpreted in accordance with the patients' age.
  3. All subjects will undergo GH stimulation test by combination of GHRH (1 mcg/kg bolus) and arginine (0.5 gm/kg over 30', maximal dose 30 gm). Blood will be dawn at time 30', 60', 90' and 120' after the GHRH bolus injection. The GHRH+arginine test is the most widely used test to determine GH reserve in adults, independently from their age (14). Normal response is a peak serum GH > 9 ng/ml. Both GHRH and arginine are FDA-approved for this purpose, and have no significant side effects (GHRH may cause transient itching and flushing).
  4. An AM cortisol below 5 mcg/dl will be considered diagnostic of adrenal insufficiency. Conversely, a value above 15 mcg/dl will be interpreted as indicating normal adrenal function. For serum cortisol values between 5 and 15 mcg/dl, subjects will be studied on a separate day by low-dose (1 mcg) ACTH stimulation test. Blood for serum cortisol measurement will be obtained at baseline and after 30' from ACTH injection. The low-dose ACTH stimulation test is safe, easy to perform, has high sensitivity for partial secondary adrenal insufficiency, and has been recently used in patient with TBI. Normal response is a serum cortisol at 30' > 18.0 mcg/dl.

Subjects who have shunt surgery will undergo a second study of pituitary function not earlier than 6 months and no later than 1 year from the procedure. We will identify the degree of clinical improvement by documenting change in gait with the Tinetti Gait Assessment Tool, and change in dementia with the Mini-Mental-Status exam. If there is sufficient sample size in the clinically improved and unimproved patients, we will compare between-group results.

Patients who have been on systemic glucocorticoids (GC) for longer than 3 weeks during the previous 12 months will be excluded, as GC may cause suppression of hypothalamic-adrenal axis. In subjects who are on phenytoin, unbound T4 will be measured by equilibrium dialysis, as phenytoin may interfere with direct unbound T4 measurement. Subjects already on L-thyroxine replacement will be excluded.

Study Type

Interventional

Enrollment

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • GCRC Johns Hopkins University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Diagnosis of idiopathic hydrocephalus, made by clinical and CT or MRI imaging demonstrating ventricular dilation, and confirmed by an established protocol of continuous CSF drainage via spinal catheter. Patients who are found to be eligible for VP shunt insertion on the basis of improvement in cognition/psychomotor speed, gait, or urinary continence are referred for surgery

Exclusion Criteria:

Known peripheral gland failure (primary hypogonadism, primary adrenal insufficiency, primary hypothyroidism); known history of pituitary tumor, pituitary surgery, pituitary hemorrhage, brain irradiation, or of identified causes of secondary hydrocephalus (subarachnoidal bleeding, meningitis, encephalitis, head trauma).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
anterior pituitary function

Secondary Outcome Measures

Outcome Measure
well being

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

Eli Lilly and Company

Investigators

  • Principal Investigator: Roberto Salvatori, MD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Study Completion

December 1, 2007

Study Registration Dates

First Submitted

September 7, 2005

First Submitted That Met QC Criteria

September 7, 2005

First Posted (Estimate)

September 8, 2005

Study Record Updates

Last Update Posted (Estimate)

March 2, 2010

Last Update Submitted That Met QC Criteria

March 1, 2010

Last Verified

March 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B9R-US-X041 (terminated)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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