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Anterior Pituitary Hormone Replacement in Traumatic Brain Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00957671
Recruitment Status : Completed
First Posted : August 12, 2009
Results First Posted : May 15, 2018
Last Update Posted : May 15, 2018
Sponsor:
Collaborator:
The Moody Foundation
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Brief Summary:
Fifteen to twenty percent of adults who suffer a traumatic brain injury (TBI) that requires hospitalization and rehabilitation have been found to have growth hormone (GH) deficiency by GH stimulation testing. Moreover, abnormalities have also been established for the cortisol and thyroid axis. The hypothesis of this proposal is that hormone replacement in TBI patients with documented abnormalities in the GH, thyroid, or cortisol axis will improve muscle function, body composition, aerobic capacity (GH) and tests of neuropsychologic function (GH, thyroid, cortisol).

Condition or disease Intervention/treatment Phase
Growth Hormone Deficiency Traumatic Brain Injury Drug: Recombinant human growth hormone Phase 4

Detailed Description:
This protocol is designed to screen and detect evidence of pituitary hormone deficiency in adults following traumatic brain injury. Growth hormone deficiency will be replaced for a period of one year. Subject will not be screened until at least one year following brain injury to allow for natural recovery of hormone function.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Anterior Pituitary Hormone Replacement in Traumatic Brain Injury
Study Start Date : November 2003
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015


Arm Intervention/treatment
Experimental: Human Growth Hormone
recombinant human growth hormone (rhGH) self administered daily for one year
Drug: Recombinant human growth hormone
200 mcg daily for two months, followed by 400 mcg daily for two months followed by 600 mcg daily for term of treatment period (one year total)
Other Names:
  • Genotropin
  • Somatropin
  • hGH



Primary Outcome Measures :
  1. Maximum Oxygen Uptake at Baseline. [ Time Frame: baseline ]
    Maximum Oxygen Uptake was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart.

  2. Maximum Oxygen Uptake After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Maximum Oxygen Uptake was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart.

  3. Minute Ventilation at Baseline. [ Time Frame: baseline ]
    Minute ventilation was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart.

  4. Minute Ventilation After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Minute ventilation was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart.

  5. Respiratory Exchange Ratio at Baseline. [ Time Frame: baseline ]
    Respiratory exchange ratio was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart.

  6. Respiratory Exchange Ratio After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Respiratory exchange ratio was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart.

  7. Oxygen Pulse at Baseline. [ Time Frame: baseline ]
    Oxygen Pulse was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart. Oxygen pulse is calculated by dividing VO2 consumed (mL/min) by heart rate (beats/min) yielding mL/beat. This provides an estimate of cardiac stroke volume.

  8. Oxygen Pulse After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Oxygen Pulse was measured during cardiorespiratory testing using a modified Balke protocol with expired gases collected and analyzed by an automated metabolic cart. Oxygen pulse is calculated by dividing VO2 consumed (mL/min) by heart rate (beats/min) yielding mL/beat. This provides an estimate of cardiac stroke volume.


Secondary Outcome Measures :
  1. Neuropsychological Function as Measured by California Verbal Learning Test-II With Total Recall at Baseline. [ Time Frame: baseline ]
    The California Verbal Learning Test II (CVLT-II) is a comprehensive assessment of verbal learning and memory. Subjects are read a list of 16 words. Total recall is a sum of all word list items correctly recalled immediately on learning trials 1 through 5. Data is reported as raw scores. Score range is 0 (lowest) to 80 (highest).

  2. Neuropsychological Function as Measured by California Verbal Learning Test-II With Total Recall After 1 Year of Human Growth Hormone Replacement Therapy. [ Time Frame: One year ]
    The California Verbal Learning Test II (CVLT-II) is a comprehensive assessment of verbal learning and memory. Subjects are read a list of 16 words. Total recall is a sum of all word list items correctly recalled immediately on learning trials 1 through 5. Data is reported as raw scores. Score range is 0 (lowest) to 80 (highest).

  3. Neuropsychological Function as Measured by California Verbal Learning Test-II With Delayed Recall at Baseline. [ Time Frame: baseline ]
    The California Verbal Learning Test II (CVLT-II) is a comprehensive assessment of verbal learning and memory. Subjects are read a list of 16 words. Delayed recall is a sum of all word list items correctly recalled after a 25 minute delay on learning trials 1 through 5. Data is reported as raw scores. Score range is 0 (lowest) to 80 (highest).

  4. Neuropsychological Function as Measured by California Verbal Learning Test-II With Delayed Recall After 1 Year of Human Growth Hormone Replacement Therapy. [ Time Frame: One year ]
    The California Verbal Learning Test II (CVLT-II) is a comprehensive assessment of verbal learning and memory. Subjects are read a list of 16 words. Delayed recall is a sum of all word list items correctly recalled after a 25 minute delay on learning trials 1 through 5. Data is reported as raw scores. Score range is 0 (lowest) to 80 (highest).

  5. Neuropsychological Function as Measured by Brief Visuospatial Memory Test-R With Total Recall at Baseline [ Time Frame: baseline ]
    The Brief Visuospatial Memory Test is measure of visual memory. The subject views a stimulus page with 6 shapes on it for 10 seconds. The subjects are then asked to draw as many figures as they remember in the correct locations as possible. Total recall is a measure of the subjects memory immediately after viewing the stimulus page. Data is reported as raw scores. Scores range from 0 (lowest) to 36 (highest).

  6. Neuropsychological Function as Measured by Brief Visuospatial Memory Test-R With Total Recall After 1 Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    The Brief Visuospatial Memory Test is measure of visual memory. The subject views a stimulus page with 6 shapes on it for 10 seconds. The subjects are then asked to draw as many figures as they remember in the correct locations as possible. Total recall is a measure of the subjects memory immediately after viewing the stimulus page. Data is reported as raw scores. Scores range from 0 (lowest) to 36 (highest).

  7. Neuropsychological Function as Measured by Brief Visuospatial Memory Test-R With Delayed Recall at Baseline [ Time Frame: baseline ]
    The Brief Visuospatial Memory Test is measure of visual memory. The subject views a stimulus page with 6 shapes on it for 10 seconds. The subjects are then asked to draw as many figures as they remember in the correct locations as possible. The delayed recall is a measure of the subjects memory after a 25 minutes delay. The participants are asked to freely recall and again draw the six figures.Data is reported as raw scores. Scores range from 0 (lowest) to 36 (highest).

  8. Neuropsychological Function as Measured by Brief Visuospatial Memory Test-R With Delayed Recall After 1 Year of Human Growth Hormone Replacement Therapy [ Time Frame: one year ]
    The Brief Visuospatial Memory Test is measure of visual memory. The subject views a stimulus page with 6 shapes on it for 10 seconds. The subjects are then asked to draw as many figures as they remember in the correct locations as possible. The delayed recall is a measure of the subjects memory after a 25 minutes delay. The participants are asked to freely recall and again draw the six figures.Data is reported as raw scores. Scores range from 0 (lowest) to 36 (highest).

  9. Neuropsychological Function as Measured by Digit Span Total at Baseline [ Time Frame: baseline ]

    Digit Span; Wechsler Memory Scale III (WMS III).

    Digits Forward is a test of digit span (range = 3 to 9 digits) consisting of seven items (each with 2 trials). Digits Backward is a test of digit span (range = 3 to 9 digits); however the participant must provide the presented sequence in reverse order. The test consists of seven items (each with 2 trials). Total score is calculated by adding the scores from forward and backward. Data is reported as raw scores. Score ranges are 0 (lowest) to 32 (highest). A higher score indicates a better outcome.


  10. Neuropsychological Function as Measured by Digit Span Total After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Digit Span; Wechsler Memory Scale III (WMS III). Digits Forward is a test of digit span (range = 3 to 9 digits) consisting of seven items (each with 2 trials). Digits Backward is a test of digit span (range = 3 to 9 digits); however the participant must provide the presented sequence in reverse order. The test consists of seven items (each with 2 trials). Total score is calculated by adding the scores from forward and backward. Data is reported as raw scores. Score ranges are 0 (lowest) to 32 (highest). A higher score indicates a better outcome.

  11. Neuropsychological Function as Measured by Processing Speed Index at Baseline [ Time Frame: baseline ]

    Processing Speed Index is a subcategory of the Wechsler Adult Intelligence Scale III (WAIS-III). Processing speed refers to the speed of cognitive processes and response output.

    This index is comprised of performances on two separate tests of visuomotor speed of information processing ability. On one test (Coding) participants refer to a key on top of a page to translate non-verbal symbols to an alpha-numeric digit. The participants then fill in boxes with the correct symbol assigned to a particular number. On the other test (Symbol Search) participants are asked to visually scan and mark items that are identical to one of two targets. If neither target is shown in the array the participant must mark out the work "NO". Total correct responses for both task within 120 seconds are recorded.

    Ranges are 0 (lowest) to 150 (highest) with 100 being the normal average. A higher score indicates a better outcome.


  12. Neuropsychological Function as Measured by Processing Speed Index After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]

    Processing Speed Index is a subcategory of the Wechsler Adult Intelligence Scale III (WAIS-III). Processing speed refers to the speed of cognitive processes and response output.

    This index is comprised of performances on two separate tests of visuomotor speed of information processing ability. On one test (Coding) participants refer to a key on top of a page to translate non-verbal symbols to an alpha-numeric digit. The participants then fill in boxes with the correct symbol assigned to a particular number. On the other test (Symbol Search) participants are asked to visually scan and mark items that are identical to one of two targets. If neither target is shown in the array the participant must mark out the work "NO". Total correct responses for both task within 120 seconds are recorded.

    Ranges are 0 (lowest) to 150 (highest) with 100 being the normal average. A higher score indicates a better outcome.


  13. Neuropsychological Function as Measured by Letter Fluency at Baseline [ Time Frame: baseline ]
    Letter Fluency is a condition measured as part of the subcategory, Verbal Fluency, in the Delis-Kaplan Executive Function System (D-KEFS). Subjects are asked to name as many words as they can starting with a specified letter for 60 seconds. The words can not be names, places, numbers or grammatical variants of previous answers. Repeated answers are not scored as a correct response. There are 3 trials, with 3 different letters. The total number of correct responses is totaled for all 3 trials and a Letter Fluency Score is given. A higher score is considered better. There is no set range as the score depends on how many correct words the subject relays in the given time period.

  14. Neuropsychological Function as Measured by Letter Fluency After One Year of Human Growth Hormone Replacement Therapy [ Time Frame: one year ]
    Letter Fluency is a condition measured as part of the subcategory, Verbal Fluency, in the Delis-Kaplan Executive Function System (D-KEFS). Subjects are asked to name as many words as they can starting with a specified letter for 60 seconds. The words can not be names, places, numbers or grammatical variants of previous answers. Repeated answers are not scored as a correct response. There are 3 trials, with 3 different letters. The total number of correct responses is totaled for all 3 trials and a Letter Fluency Score is given. A higher score is considered better. There is no set range as the score depends on how many correct words the subject relays in the given time period.

  15. Depression as Measured by the Beck Depression Inventory at Baseline. [ Time Frame: baseline ]
    Beck Depression Inventory (BDI-II) is used to measure the severity of depression symptoms. The BDI-II contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs are: 0-13: minimal depression; 14-19: mild; depression; 20-28: moderate depression; 29-63: severe depression.

  16. Depression as Measured by Beck Depression Inventory After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Beck Depression Inventory (BDI-II) is used to measure the severity of depression symptoms. The BDI-II contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs are: 0-13: minimal depression; 14-19: mild; depression; 20-28: moderate depression; 29-63: severe depression.

  17. Fatigue as Measured Using Fatigue Severity Scale at Baseline. [ Time Frame: baseline ]
    Fatigue Severity Scale (FSS) is a measure of fatigue and how that fatigue interferes with life. It is a 9-item scale, with a range from 9 to 63, with a higher number indicating greater severity.

  18. Fatigue Measured Using the Fatigue Severity Scale After One Year of Human Growth Hormone Therapy. [ Time Frame: one year ]
    Fatigue Severity Scale (FSS) is a measure of fatigue and how that fatigue interferes with life. It is a 9-item scale, with a range from 9 to 63, with a higher number indicating greater severity.

  19. Muscle Function in Male Subjects Measured Using Maximum Isometric Leg Extension by Biodex Pro 4 at Baseline. [ Time Frame: baseline ]
    Maximum torque production during isometric contraction of the knee extensor muscles.

  20. Muscle Function in Male Subjects Measured Using Maximum Isometric Leg Extension by Biodex Pro 4 After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Maximum torque production during isometric contraction of the knee extensor muscles.

  21. Muscle Function in Male Subjects Measured Using Maximum Isokinetic Leg Extension by Biodex Pro 4 at Baseline. [ Time Frame: baseline ]
    Maximum torque production during maximal isokinetic contractions at 90 degrees per second.

  22. Muscle Function in Male Subjects Measured Using Maximum Isokinetic Leg Extension by Biodex Pro 4 After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Maximum torque production during maximal isokinetic contractions at 90 degrees per second.

  23. Muscle Fatigue as Measured by Biodex Pro 4 at Baseline. [ Time Frame: baseline ]
    Muscle fatigue is measured using repetitive isokinetic contractions of the knee extensors at 90 degrees per second. Each subject was asked to produce 40 contractions at full force. Data is presented as % of maximum torque at the 40th contraction in the fatigue protocol.

  24. Muscle Fatigue as Measured by Biodex Pro 4 After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Muscle fatigue is measured using repetitive isokinetic contractions of the knee extensors at 90 degrees per second. Each subject was asked to produce 40 contractions at full force. Data is presented as % of maximum torque at the 40th contraction in the fatigue protocol.

  25. Body Mass in Male Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline. [ Time Frame: baseline ]
    Body mass was calculated from whole body scan taken using a GE Lunar iDEXA.

  26. Body Mass in Male Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Body mass was calculated from whole body scan taken using a GE Lunar iDEXA

  27. Lean Body Mass in Male Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline [ Time Frame: baseline ]
    Lean Body mass was calculated from whole body scan taken using a GE Lunar iDEXA

  28. Lean Body Mass in Male Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Lean Body mass was calculated from whole body scan taken using a GE Lunar iDEXA

  29. Fat Free Mass in Male Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline. [ Time Frame: baseline ]
    Fat free mass is calculated from whole body scan measured using a GE Lunar iDEXA.

  30. Fat Free Mass in Male Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Fat free mass is calculated from whole body scan measured on a GE Lunar iDEXA.

  31. Percent Body Fat as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline. [ Time Frame: baseline ]
    Percent body fat is calculated from a whole body scan measured on a GE Lunar iDEXA.

  32. Percent Body Fat in Male Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Percent body fat is calculated from a whole body scan measured on a GE Lunar iDEXA.

  33. Muscle Function in Female Subjects Measured Using Maximum Isometric Leg Extension by Biodex Pro 4 at Baseline. [ Time Frame: baseline ]
    Maximum torque production during isometric contraction of the knee extensor muscles.

  34. Muscle Function in Female Subjects Measured Using Maximum Isometric Leg Extension by Biodex Pro 4 After One Year of Human Growth Hormone Replacement Therapy [ Time Frame: one year ]
    Maximum torque production during isometric contraction of the knee extensor muscles.

  35. Muscle Function in Female Subjects Measured Using Maximum Isokinetic Leg Extension by Biodex Pro 4 at Baseline [ Time Frame: baseline ]
    Maximum torque production during maximal isokinetic contractions at 90 degrees per second.

  36. Muscle Function in Female Subjects Measured Using Maximum Isokinetic Leg Extension by Biodex Pro 4 After One Year of Human Growth Hormone Replacement Therapy [ Time Frame: one year ]
    Maximum torque production during maximal isokinetic contractions at 90 degrees per second.

  37. Perceptual Fatigability as Measured by a Fatigue Rating Scale at Baseline. [ Time Frame: baseline ]
    Perceptual fatigue was measured before and directly after performing the muscle fatigue exercise protocol (40 continuous maximal force isokinetic knee extensions at 90 degress per second). Subjects were asked to rate their fatigue on a scale of 0-10 with 0 being no fatigue at all and 10 being extreme fatigue. Data is presented as change in fatigue rating induced by exercise testing.

  38. Perceptual Fatigability as Measured by a Fatigue Rating Scale After One Year of Human Growth Hormone Therapy. [ Time Frame: one year ]
    Perceptual fatigue was measured before and directly after performing the muscle fatigue exercise protocol (40 continuous maximal force isokinetic knee extensions at 90 degress per second). Subjects were asked to rate their fatigue on a scale of 0-10 with 0 being no fatigue at all and 10 being extreme fatigue. Data is presented as change in fatigue rating induced by exercise testing.

  39. Body Mass in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline. [ Time Frame: baseline ]
  40. Body Mass in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy [ Time Frame: one year ]
    Body mass was calculated from whole body scan taken using a GE Lunar iDEXA

  41. Lean Body Mass in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline [ Time Frame: baseline ]
    Lean Body mass was calculated from whole body scan taken using a GE Lunar iDEXA.

  42. Lean Body Mass in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Lean Body mass was calculated from whole body scan taken using a GE Lunar iDEXA

  43. Fat Free Mass in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline. [ Time Frame: baseline ]
    Fat free mass is calculated from whole body scan measured using a GE Lunar iDEXA.

  44. Fat Free Mass in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy [ Time Frame: one year ]
    Fat free mass is calculated from whole body scan measured on a GE Lunar iDEXA.

  45. Percent Body Fat in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline. [ Time Frame: baseline ]
    Percent body fat is calculated from a whole body scan measured on a GE Lunar iDEXA.

  46. Percent Body Fat in Female Subjects as Measured by Dual Energy X-Ray Absorptiometry (DEXA) After One Year of Human Growth Hormone Replacement Therapy. [ Time Frame: one year ]
    Percent body fat is calculated from a whole body scan measured on a GE Lunar iDEXA.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged 21 and older.
  • Documented moderate to severe traumatic brain injury at least one year post injury.

Exclusion Criteria:

  • The only absolute exclusionary medication will be an anticoagulant (Coumadin) because of the risk of bleeding during the possible muscle biopsy procedure and daily injections of rhGH in the GH arm of the study.
  • Any subject with a history of hepatitis or a 3-fold elevation of liver function tests (Alk phos, alanine aminotransferase (ALT), aspartate aminotransferase (AST)). We are uncertain of the effects of hormone replacement such as rhGH on the liver, so we will exclude any subjects with hepatitis. This exclusion applies only to subjects who would be enrolled in the GH arm of the study.
  • Subjects who are deficient in cortisol or thyroid at screening will be excluded until hormone abnormalities have been corrected.
  • Subjects with chronic pain who are being managed with narcotics will be excluded as the effects of central nervous system depressants may interfere with study test results.

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): NCT00957671


Locations
United States, Texas
Transitional Learning Center
Galveston, Texas, United States, 77550
The University of Texas Medical Branch at Galveston
Galveston, Texas, United States, 77555
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
The Moody Foundation
Investigators
Principal Investigator: Randall J Urban, M.D. The University of Texas Medical Branch at Galveston

Responsible Party: The University of Texas Medical Branch, Galveston
ClinicalTrials.gov Identifier: NCT00957671     History of Changes
Other Study ID Numbers: 03-034
First Posted: August 12, 2009    Key Record Dates
Results First Posted: May 15, 2018
Last Update Posted: May 15, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by The University of Texas Medical Branch, Galveston:
TBI
Traumatic Brain injury
Growth hormone deficiency
Anterior pituitary hormone
Recombinant human growth Hormone
Genotropin

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Craniocerebral Trauma
Trauma, Nervous System
Pituitary Diseases
Endocrine System Diseases
Dwarfism, Pituitary
Central Nervous System Diseases
Nervous System Diseases
Hypothalamic Diseases
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs