U.S. Department of Health and Human Services

2009 Meeting Minutes



Meeting of the
Interagency Coordinating Committee on
Human Growth Hormone and Creutzfeldt-Jakob Disease on

November 16, 2009

National Institutes of Health
Bethesda, Maryland

Committee Members Attending
Dr. Judith Fradkin, NIDDK
Dr. Ellen Leschek, NIDDK
Dr. James Mills, NICHD
Dr. Griffin Rodgers, NIDDK, Chairman
Dr. Lawrence Schonberger, CDC (by speakerphone)
Dr. Diane Wysowski, FDA

Also Attending
Joseph Abrams, CDC (by speakerphone)
Ms. Joan Chamberlain, NIDDK
Ms. Kathy Kranzfelder, NIDDK
Mr. Ryan Maddox, CDC (by speakerphone)
Dr. B. Tibor Roberts, NIDDK
Dr. Julie A. Wallace, NIDDK
Dr. May Wong, NINDS

The meeting began at 1:30 p.m.

1. Welcome

Dr. Rodgers welcomed the group and the members introduced themselves.

2. Epidemiology Study Status Report

As described in last year’s minutes, Dr. Leschek reviewed both confirmed and possible U.S. cases of CJD in the following categories:

  1. Neuropathologically confirmed CJD
  2. Clinically confirmed CJD
  3. Clinically suspicious—neurologic findings of uncertain etiology with insufficient information to confirm or exclude CJD
  4. Deaths under investigation

Case Categories I, II and III:

In 2009, no cases were added to either category I or II (confirmed CJD). Therefore the total number of deaths in the cohort attributable to CJD remains 28, including 13 in category I (neuropathologically confirmed) and 15 in category II (clinically confirmed). All deaths confirmed as CJD received at least some of their hGH treatment prior to 1977, when Dr. Parlow’s laboratory began producing hGH for the National Hormone and Pituitary Program. No deaths were added to categories I or II since the 2008 meeting of the Committee.

The number of cases regarded as “clinically suspicious—insufficient information to confirm” (category III) remains 4. Cases are placed in category III when there is a difference of opinion among members of the Neurologic Review Group (NRG) about the likelihood of CJD, and no further clinical information is likely to become available.

Case Category IV:

The Committee discussed four cases under investigation, and decided that three of these did not justify further study (inclusion in Category IV). The one case remaining under investigation is that of a man whose father called to report that his son had been treated with hGH from 1976-1979 and had died in September 2005. The father reported neurologic symptoms consistent with CJD, including loss of balance, impaired gait, shaking, depression, and diminished hearing and vision. The son was diagnosed with schizophrenia, which predated the other neurologic symptoms, and had been in and out of psychiatric wards but had not been under a doctor’s care for several years. No autopsy was performed. The father has not released the medical records, and the death certificate lists the cause of death as “unspecified natural disease process altered by decomposition.” Although the father believes his son died of CJD, the reported capacity of this person to live alone up to death is inconsistent with that diagnosis. Dr. Leschek will provide Dr. Schonberger with the death certificate so that he can attempt to obtain additional information and/or a release of medical records from the state where the man died.

In the second case discussed, the death certificate cites “aspiration pneumonia (2 days duration) due to dementia (1 year duration) due to radiation treatment for craniopharyngioma” as cause of death. Attempts to locate next of kin have been unsuccessful. Thus, additional information will not likely be found. The presence of dementia in a relatively young person is the basis for considering this as a possible CJD case, but given the individual’s neurological history, alternate explanations are certainly possible, and the Committee agreed that there was no strong reason to suspect CJD, or justification to pursue further investigation of this case.

A third case was listed as having died of “glioblastoma” at 42 years of age, while living in a “care center.” The person had signs of mental deterioration and progressive cerebellar issues in the weeks prior to death. MRI and CT scans 1.5 years before the individual’s death indicated the presence of a glioblastoma. NRG review notes were somewhat inconsistent, but no member of the NRG felt that CJD was a likely cause of death. The Committee agreed that there was no strong reason to suspect CJD or to pursue further investigation of this case.

The fourth individual was listed as having died of “cardiovascular collapse and CNS dysfunction of unknown nature” at age 39. The hGH treatments, from 1980-1982, were indicated for multiple pituitary hormone deficiencies due to surgery, chemotherapy, and possibly radiation for a pinealoma. Adrenal insufficiency could explain the “cardiovascular collapse.” The mother of this individual has expressed unwillingness to provide release of medical records. The Committee felt that additional information will not likely be found. Given the available information, the Committee felt there was no strong reason to suspect CJD, or to pursue further

investigation of this case.

Case Summary by Category (resulting from adjudication during this meeting):

Category # Cases Net change since 2008
I 13 0
II 15 0
III 4 0
IV 1 -3

3. Report on CJD in foreign GH recipients

Dr. Schonberger reported that five additional cases of CJD linked to hGH treatment have been reported in France. This brings the total number of CJD cases outside the United States that are attributable to hGH to 184. The Committee discussed the sixth New Zealand case added last year. The first five New Zealand cases were of special interest because the patients were treated with American-purified hormone, and Dr. Schonberger confirmed that the same was true for the sixth case. Dr. Fradkin asked Dr. Schonberger to try to find a contact in New Zealand in order to determine, if possible, the dates of treatment of this individual. Dr. Schonberger explained that the mention of the sixth New Zealand case came from a draft manuscript from by Ms. Alison Boyd, which also corrected the number of known New Zealand hGH recipients to 159 from the previously reported number of 184. Dr. Schonberger promised to send a copy of the relevant paragraph from the manuscript to Dr. Fradkin for her records. The fact sheet should note that there have been six cases from New Zealand, and indicate for now that we have treatment dates for five of them.

Reported cases by country as of November 2009:

France 115
United Kingdom 56
New Zealand 6
Brazil 2
Holland 2
Australia 1
Austria 1
Qatar 1
Non-U.S. Total 184

Dr. Schonberger also reported that 217 vCJD cases are known to him as of the meeting date. That total includes eight additional cases in the last year: three in the UK, two in France, one in Italy, one in the Netherlands, and one in Spain. Dr. Fradkin asked Dr. Schonberger to update the vCJD section in the fact sheet.

4. Update on Public Inquiries

Ms. Chamberlain reported that in 2009, as of the date of the meeting, she had handled 12 public inquiries pertaining to the NHPP. Most of these were fairly routine, such as inquiries to determine whether an individual was in the cohort.

5. Comprehensive Fact Sheet Update

The Committee suggested several edits for the fact sheet:

  1. New Zealand reported 49 people who received pituitary hGH made by the U.S. lab that supplied most NHPP pituitary hGH before 1977. 159 people in New Zealand received pituitary hGH. 6 out of 47 is 12.2 percent.
  2. The number of hGH/CJD cases in France needs to be updated to 115.
  3. The person with CJD in Austria should be noted to have received hGH from a commercial firm.
  4. The number of vCJD cases should be 217 under the section titled “Mad Cow” Disease.
  5. Committee members suggested adding “as of [DATE]” to the international numbers.
  6. Dr. Schonberger suggested adding information about four vCJD cases associated with infection with blood via transfusions under the section titled “Mad Cow” Disease and editing the first sentence under “Why can’t I donate blood or organs?” to read “Four cases of transmission of the agent that causes variant CJD (vCJD) through blood have been reported.”
  7. Dr. Schonberger recommended that the line “It is important to prevent donation by people from families with rare genetic forms of CJD,” (found under “Why can’t I donate blood or organs?”) be removed.
  8. Dr. Schonberger suggested revising the first line of the third paragraph under “How is CJD diagnosed?” to read: “Researchers from several countries, including the United States, reported success using magnetic resonance imaging (MRI) to diagnose CJD and variant CJD in people with symptoms of these diseases.”
  9. Under “Why should people treated with pituitary hGH know about CJD?” the sentence should read “Any parent of someone who received pituitary hGH who has not received any mailings from the HHS…”
  10. Dr. Schonberger recommended that the fifth bullet under #2 in “What is my risk for getting CJD?” read: “The proportion of those who began treatment before 1977 is about 1 in 100 people or about 1 percent.”
  11. After discussion about a lack of direct link between hGH and colon cancer, the Committee decided to remove the paragraph on colon cancer from the Fact Sheet.
  12. The Committee suggested adding “to date” to the first sentence of the first bullet under “When a person was treated.” Under the second bullet in the same section, Dr. Mills recommended editing the first sentence to reflect that at least one case of CJD has resulted from commercial hGH. However, because industry has not conducted a rigorous study to identify cases, there are insufficient data to determine how many cases may have resulted from exposure to commercial growth hormone.
  13. Dr. Fradkin asked Dr. Schonberger to update the references cited in the Fact Sheet and the vCJD section.
  14. The Committee recommended including that there has been only one case of CJD in the cohort since 2003
  15. Dr. Schonberger suggested clarifying that “The longest reported time from the start of NHPP-provided pituitary hGH treatment to first signs of CJD is 33 years.”
  16. Ms. Kranzfelder will provide Dr. Leschek with additional edits.

The summary version of the fact sheet will also need to be updated to be consistent with these revisions to the comprehensive version.

The question was raised whether the risk of CJD among the post-1977 hormone recipients was now statistically significantly lower than the risk for the earlier hormone recipients. Earlier analyses were hampered by too short a period of follow-up available in the study for the more recent hormone recipients. Dr. Schonberger indicated that he would work with Drs. Abrams and Maddox to address this question in a brief report intended for publication in a peer reviewed medical journal.

6. Brief Highlights of Progress in CJD Research

Dr. Schonberger highlighted a UK case of vCJD transmission via plasma* to a hemophilia patient, reported at the 2009 Prion Meeting. This case is the first and only known transmission via a plasma product. (Four known cases of vCJD transmission have occurred via whole blood.)

Dr. Schonberger also discussed a paper by Jackson et al. (Neuron 2009; 63: 438-450) that demonstrated for the first time that mutations associated with prion disease are sufficient to cause a transmissible neurodegenerative disease in mice. He noted that this paper provides support for the protein-only hypothesis of prion disease transmission.

7. New Business and Information Items

Dr. Rodgers asked Dr. Roberts to provide the historical background for the establishment of the Committee. In February, 1985, PHS officials were notified of a case of CJD in an individual who had received hGH from the National Hormone and Pituitary Program (NHPP). The NHPP notified physicians participating in the program, asked them to stop using NHPP-distributed hormones for non-therapeutic purposes, and inquired about other deaths from apparent CJD. That inquiry brought to light two additional CJD deaths. At that point, in April of 1985, a decision was made to halt temporarily the distribution of hGH for all clinical use, except to patients with life threatening hypoglycemia, and to initiate epidemiological studies to assess the full extent of the problem. The following is excerpted from the Seventeenth Report of the Interagency Coordinating Committee on Human Growth Hormone and Creutzfeldt-Jakob Disease (emphasis added):

To facilitate the scientific review of this issue, the then Acting Assistant Secretary for Health formally established the Interagency Coordinating Committee on Human Growth Hormone and Creutzfeldt-Jakob Disease. The purpose of the Committee is to advise the Assistant Secretary for Health regarding a coordinated PHS response to the scientific questions surrounding hGH distribution in relation to CJD. The Committee originally reported at three-month intervals, and it now reports annually or as significant new information becomes available.

In 2001, the Committee was notified that future reports were not needed unless an increase in the rate of new cases occurs. Since that time, the Committee has served as a coordinating body for continuing surveillance of CJD incidence and epidemiology within the cohort. In addition, the Committee provides updated information via the fact sheets on the NIDDK web site to recipients of pituitary-derived human growth hormone supplied through the NHPP to keep them informed of the progress of the study and of new developments with regard to growth hormone administration and CJD.

The meeting was adjourned at 3:20 p.m.