Slipped Upper Femoral Epiphysis following Treatment with Human

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Slipped Upper Femoral Epiphysis following Treatment with Human
Growth Hormone
M. W. FIDLER and C. G. D. BROOK
J Bone Joint Surg Am. 1974;56:1719-1722.



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              Slipped                                       Upper                                   Femoral                                                Epiphysis                                           following
                      Treatment                                                with                            Human                                          Growth                                       Hormone
              BY       M.         W.            FIDLER,                   F.R.C.S.*,                AND          C.        0.           D.           BROOK,                 M.D.t,                 LONDON,                        ENGLAND

                                               From          the     Hospitalfor                       Sick       Children                      and        the      Institute            of Child             Health,
                                                                                            University                of        London,                    London


              Although                         Harris,               in 1950,                   described                         the           anatomical                        basis           for slipped                     epiphysis                   in rats
treated    with                          growth                    hormone,                      slipping                        of       the upper   femoral                                      epiphysis        during                               treatment
with    human                            growth                    hormone                     in children                              has not previously                                        been    reported.

                                                                                                           Case                 Reports
          CASE           I   .   In 1962 a seven-year-old                              boy           who       had      signs             of puberty                 when          he was           four       years       old        was       first     seen at
the      Hospital                for      Sick          Children.             Craniopharyngioma                                       was        diagnosed,                and       the        child       was         treated          with         radiotherapy
followed                by administration                            of cortisone                     and      thyroxine.                       In     I 963,        progressive                  spastic         paraplegia                developed              from
an intramedullary                               expanding                  lesion           which           was        treated               successfully                   with         radiotherapy.
          The          patient’s                 growth             ceased             in      1966.           Growth-hormone                                    deficiency               was        revealed             by       the      insulin-induced
hypoglycemia                           test,      and        in May            197 1 he began                         receiving                   injections              of ten         milligrams               of human                 growth           hormone
twice           weekly.
          In September                          197 ,1 the patient                   was            referred          to the             Royal             National             Orthopaedic                   Hospital            for     a complaint                 of
stiff.         painful             hips          and         a waddling                     gait.         present               for       eight            weeks.           Clinical              and                   examinations
                                                                                                                                                                                                            roentgenographic
revealed               bilateral               slipped             upper        femoral               epiphysis                 (Figs.               I-A      and         I-B).          His     chronological                    age       was         sixteen        and
his      skeletal                age,          fourteen            years.            The       epiphyseolyses                            were           stabilized                with         Newman’s                  pins      and          the     deformities
were           corrected                  by          bilateral           biplane             trochanteric                      osteotomy His
                                                                                                                                        .                        subsequent                    progress            was          satisfactory:                the
epiphyses                    and osteotomies                         united            (Fig.            2) and              normal                   physical
                                                                                                                                                          activities                   were         resumed.                Growth-hormone
therapy               was        discontinued                      in April             1972.

          CASE           2.      An        eight-year-old                     girl      had           a craniopharyngioma                                     removed               in     1964         and      postoperative                     radiotherapy
was       administered.                          In      1968,        at the          age       oftwelve                   years,             she       was        seen       at the           Hospital           for      Sick         Children           because           of
poor          growth.              Her          skeletal           age      at that          time          was        nine            years          and      growth-hormone                            deficiency              was       diagnosed               by the




                                                                                                                    FIG.              1-A

   Figs.               1-A and                   I-B:        Case     .    Anteroposterior
                                                                           1                                          and             lateral          roentgenograms                          showing             bilateral              slipped           upper
femoral               epiphysis.
          *     University                     College             Hospital,                Gower           Street,              London,                   WCIE            6AU,            England.
          t Middlesex                          Hospital,             London,                 W1N            8AA,             England.

VOL.          56-A,          NO. 8,            DECEMBER                     1974                                                                                                                                                                 1719
1720                                                           M.      W.         FIDLER         AND         C.      G.      D.      BROOK




                                                                                                        ;.




insulin-induced                  hypoglycemia                  test.        She    began      to receive          human          growth      hormone.           ten milligrams                 twice       weekly.
on     October           22.      1969.
          On November                   26.       I 969,      she was         admitted         to the      Royal          Portsmouth         Hospital          with         a history        of a limp         and      a
painful         left     hip    of one          week’s        duration.           Examination            disclosed          slipping       of the       left   upper         femoral         epiphysis         (Figs.
3-A.       3-B,        and      3-C).      which   was stabilized   by Moore’s           pins.
          In November,                 1970. the patient   had a urinary-tract        infection.                                  The right hip           was painful     and roentgenograms
showed          slight         slipping     of the right upper femoral       epiphysis.        Her                               hip symptoms             receded   during   bed rest and there
was       no      further        displacement                 of    the      epiphysis.         Thereafter           her     progress        was    satisfactory.                 By       August        1973,       the
epiphyseolyses                 were     healing.            The     pins      were        removed         in October              1973    because        of    irritation          ofthe       skin.      At     that
time      the      patient        was         still   receiving             growth         hormone.


                                                                                           Discussion
           Hypopituitarism                                 causes       delayed                 maturation        of                 epiphyseal     growth                         plates.    Bilateral
slipped         upper      femoral                            epiphysis        has              been     reported                   in six patients      so                     affected Both
                                                                                                                                                                                “‘‘.


children               reported                here         had        retardation              of skeletal                age      when        their          epiphyseolyses                          occurred.




     Case I . Anteroposterior          roentgenogram                                 showing          the united.          stabilized      epiphyses           and correction                of deformities
by    suhtrochanteric         osteotomles.

                                                                                                                    THE      JOURNAL           OF BONE             AND         JOINT         SURGERY
                                                       SLIPPED    UPPER        FEMORAL                EPIPHYSIS                                             1721




                                                                          FIG.     3-A




                                      FIG.     3-B                                                                  FIG.   3-C
   Figs.           3-A,    3-B,     and 3-C: Case 2. Anteroposterior                and     lateral      roentgenograms           showing     the   left     slipped      upper
femoral            epiphysis.        The right epiphysis is undisplaced.


The         boy         (Case        I ) had         a skeletal   age     of     fourteen             years      at the       chronological                age     of sixteen
years,              and the         girl (Case     2) had           a skeletal            age      of         ten years      at the         chronological                 age         of
thirteen              years.        Skeletal   ages were             determined                 from          roentgenograms                of the left            hand         and
wrist       2   Apart    from   delayed   maturation                         these          epiphyses              appeared         normal.
            Harris    noted   that in rats growth                          hormone              causes           changes          in the epiphyseal                    growth
plate         within         four weeks.     There     is increased     proliferation                             ofthe    second      ofthe            four layers                of
cells         in the         growth   plate,    followed       by thickening          and                        decreased      shearing             strength     of              the

VOL.       56-A,       NO.    8,   DECEMBER          1974
1722                                                                 M.     W.        FIDLER             AND           C.     G.      D.        BROOK


third     layer                  through               which     the                slipping    occurs.    These                             changes   may be reversed       by                                            the ad-
ministration                        of sex             hormones.                       The patient      in Case                             1 had been    receiving    human                                               growth
hormone      for                        two months       before    bilateral  hip symptoms       developed;                                                                      the patient    in Case                                  2
had a history                           of minor   injury     on the left side thirteen    weeks    before                                                                   admission.      The slipping
could                   have     been   initiated                           at that              time,    but it                    was        not until    four    weeks     after   starting
human                    growth-hormone                                treatment                that   significant                         symptoms      developed.       There     was no
history                     of injury           to the          right         hip,         in which              the        slipped             epiphysis             was           noted            thirteen             months
after           the             start      of        human                 growth-hormone                        therapy.                       A      decrease               in shearing                         strength     in
human                       epiphyses                similar              to that shown                       by Harris                    in       rats would                be consistent                           if human
growth                      hormone             were           administered                     for      longer             than       four         weeks,            as in our                  two        patients.              The
bilateral     epiphyseal                                displacement                        in these         children could,    therefore,       have  been related    not
only      to the effects                               of hypopituitarism,                                but also to the relative        excess    of growth   hormone
following                       treatment.                   Involvement                     of both             hips        suggests                a systemic                cause               for      the      displace-
ment.
       Of                    267 hypopituitary                              children             taking            part         in the Medical                      Research                     Council                  trial of
human                        growth-hormone                               treatment,                only           the         two    patients                   reported                    here    had                  bilateral
slipped       epiphysis.          Although     the incidence                                                      of bilateral      slipped      upper    femoral                                             epiphysis               in
hypopituitary            children      not receiving     human                                                     growth      hormone       is unknown,          the                                         incidence              in
hypopituitary            children       being   treated   with                                                   human      growth       hormone       is relatively                                              high.            The
over-all                     annual           incidence                   of slipped              upper            femoral             epiphysis                has     been           variously                    estimated
at between                       two          and       thirteen              per         100,000          and         it was         bilateral               in only         twenty-three                          of the
100          cases              reported                by          Burrows.

       NOTE:      We wish to thank Mr.                   G. C. Lloyd-Roberts    for his help and advice     in he preparation      of this article.                          We would             also like to thank       Professor
J. M.     Tanner.      Mr. J. D. Allison                and Mr. A. Catterall     for permission  to publish     details    of the children    under                          their care.           and the Medical         Research
Council         Working    Party controlling            the trial of human   growth    hormone.  for permission         to publish   this report.



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