Slipped capital femoral epiphysis (SCFE) commonly

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1 IJOrtho R EP done on // 0 Cse Report Pseudohypoprthyroidism s rre cuse of ilterl slipped cpitl femorl epiphysis Krthikeyn R Somsundrm, Senthilkumr Snkrrmn, Athr Siddiqui, Hmid Zdeh Astrct Slipped cpitl femorl epiphysis (SCFE) is disorder of dolescent ge. Presenttion of SCFE erlier thn the expected ge rnge should prompt the clinicin to consider the presence of n underlying endocrinopthy. Erly recognition nd ggressive mngement of the predisposing endocrine disorder is crucil to prevent tretment filure nd ssocited moridity. We report the clinicl presenttion nd tretment of n -yer-old girl with ilterl slipped cpitl femorl epiphysis. The unusul ge, persistent hypoclcemi, nd ssocited distl femorl physel deformities prompted further evlutions, which led to the dignosis of pseudohypoprthyroidism (PHP) type. PHP type is n extremely rre cuse of SCFE nd only few cses hve een reported. A dely in dignosis in such cse is not uncommon. Key words: Hypoclcemi, pseudohypoprthyroidism type, slipped cpitl femorl epiphysis Introduction Slipped cpitl femorl epiphysis (SCFE) commonly ffects the overweight nd oese dolescents. SCFE clssiclly presents in the ge group of yers. The pek ge for this condition is yers in oys nd. yers in girls. In pproximtely one-third of the cses, SCFE is ssocited with n underlying endocrine disorder. Presenttion of SCFE erlier thn the expected ge rnge should e considered s significnt risk fctor for n underlying endocrinopthy. We herey report the clinicl presenttion nd tretment of n -yer-old femle with simultneous ilterl SCFE predisposed y pseudohypoprthyroidism (PHP) type. To the est of our knowledge, only one prior cse of PHP type predisposing to SCFE tht required comined medicl nd surgicl mngement hs een reported in the literture. Deprtment of Orthopedics, West Middlesex University Hospitl Isleworth, TW AF, United Kingdom, Deprtment of Peditrics, Louisin Stte University Helth Sciences Center, Shreveport, LA, USA Address for correspondence: Dr. Senthilkumr Snkrrmn, Deprtment of Peditrics, Louisin Stte University Helth Sciences Center, Shreveport, LA, USA. E-mil: drsskumr@gmil.com Quick Response Code: Access this rticle online Wesite: DOI: *** Cse Report An -yer-old femle presented to the emergency deprtment with dy history of right hip pin nd limping. The pin ws of spontneous onset without ny history of trum. She chieved norml milestones till the ge of yers. Her pst medicl history ws significnt for psorisis, controlled y topicl medictions. Dietry history reveled norml intke of lnced nonvegetrin diet. On exmintion, she ws noted to hve skin lesions due to mild psorisis. There were no phenotypic fetures of Alright s hereditry osteodystrophy (AHO) which is PHP type. Her weight ws. kg ( th percentile for ge nd sex), height cm ( th percentile for ge nd sex), with height velocity of. cm/yer. Exmintion of her lower lims showed pinful right hip with miniml shortening nd restricted externl rottion. Biochemicl investigtions reveled low serum clcium nd high lkline phosphtse [Tle ]. The liver enzymes, cogultion screen, renl function tests, serum phosphorus, serum lumin, nd serum mgnesium were ll within norml limits. Rdiologicl investigtions showed grde SCFE on the right side nd grde on the left side ccording to Southwick s clssifiction,, [Figures nd ]. Cliniclly, she hd stle slips ccording to Loder s clssifiction. The opertive tretment plnned ws in situ pinning of oth hips using cnnulted screws. The right hip ws operted on within h of presenttion nd the symptomtic left hip ws operted weeks lter. Due to her smll ony ntomy, mm cnnulted screws were used for fixtion 0 Indin Journl of Orthopedics Novemer 0 Vol. Issue

2 0 on oth sides. The procedure ws otherwise similr to the technique descried y Loder. The erly postopertive recovery ws uneventful nd postopertive rdiogrphs were stisfctory. The ptient ws dischrged with dvice to et clcium rich diet nd to tke clcium supplements nd vitmin D (choleclciferol). As the ptient ws feeling etter, she did not come for the follow up ppointments. At the th postopertive month, she presented with the complint of pin in her left knee. Cliniclly her left knee Tle : Biochemicl investigtions of the ptient Investigtions Prmeters on her first presenttion c d Figure : Rdiogrph showing slipped cpitl femorl epiphysis (Rt) (,) in -yer-old femle child t the initil presenttion; nteroposterior nd frog leg lterl (c,d) showing good remodeling of the hed of the femur fter the surgicl fixtion nd lfclcidol tretment during follow up ( yers fter initil presenttion) hd more vlgus thn her symptomtic right knee. Rdiogrphs of oth knees showed widening of the lterl distl femorl physis with norml ossifiction within the metphysis [Figure ]. Rdiogrphs of the hips reveled similr ppernce to the postopertive rdiogrphs. At this stge, the one profile showed persistent low clcium levels with elevted lkline phosphtse, in spite of tretment with clcium nd vitmin D [Tle ]. This persistent hypoclcemi prompted us to crry out further endocrinologic evlution. Her prthyroid hormone (PTH) c d Figure : Rdiogrph showing slipped cpitl femorl epiphysis(lt) (,) in -yer-old femle child t the initil presenttion; nteroposterior nd frog leg lterl (c,d) showing good remodeling of the hed of the femur fter the surgicl fixtion nd lfclcidol tretment during follow up ( yers fter initil presenttion) Prmeters on her second presenttion ( months lter) One month of tretment with lfclcidol ( months lter) After tretment with high dose lfclcidol ( months lter) Clcium (.. mmol/l).0... Phosphte (.. mmol/l).... Alkline phosphtse ( IU/L) (OH) Vitmin D (0 0 ng/ml) ND Prthyroid hormone ( 0 pg/ml) ND Ure (.. mmol/l).... Cretinine ( µmol/l) Norml levels shown within prenthesis. ND, not done 0 Indin Journl of Orthopedics Novemer 0 Vol. Issue

3 0 Figure : Rdiogrph of knee joint nteroposterior view showing () distl femorl physel chnges widening of distl femorl physis nd ossifiction of metphysic with vlgus deformity in left knee t months fter the initil presenttion () disppernce of the distl femorl physel chnges fter the tretment with lfclcidol level ws pg/ml (norml rnge is 0 pg/ml). Further investigtions reveled norml thyroid function. The comintion of high PTH nd low clcium with no possile explntion led us to suspect end orgn resistnce to PTH, which is known s PHP. The sence of AHO phenotype fvoured the dignosis of PHP type. The ptient ws referred to geneticist nd n endocrinologist for further evlution. Genetic testing reveled GNAS methyltion defects, confirming the dignosis of PHP type. She ws strted on clcium cronte supplements nd lfclcidol (-lph-hydroxyvitmin D ) 0. µg once dily. In week, her sense of generl well eing improved nd there ws mrked reduction in the left lower lim pin. Her serum clcium nd vitmin D level incresed, nd t the sme time, serum lkline phosphtse nd PTH levels decresed. The lfclcidol dose ws slowly incresed t weekly increments of 0. µg to finl dose of. µg once dily. She ws llowed to er weight in month. At her lst follow up, yers fter the in situ fixtion, the ptient remined without symptoms. Rdiogrphs of the hips showed good remodeling of the proximl femur with no evidence of vsculr necrosis [Figures c,d nd c,d]. Rdiogrphs of her distl femur showed improved ossifiction nd nrrowing of the distl femorl physis [Figure ]. The vlgus deformity in her left knee hd lso improved, ut correction with hemiepiphysiodesis my e required in the future. The ptient ws dvised to continue clcium cronte nd lfclcidol lifelong. Follow up till skeletl mturity ws plnned, ut unfortuntely the fmily ws lost to follow up. Discussion Slipped cpitl femorl epiphysis (SCFE) is well known disorder commonly seen in dolescent ge group. The exct etiology of SCFE is still unknown, ut the commonly ssocited risk fctors include oesity, dolescent growth spurt, mechnicl normlities, trum, nd endocrine normlities. - An underlying endocrinopthy ccounts for t lest one-third of the cses of SCFE, nd the common endocrinopthies ssocited with SCFE include hypothyroidism, hyperprthyroidism, growth hormone deficiency, nd hypogondism. Pseudohypoprthyroidism (PHP) is heterogeneous group of rre metolic disorders chrcterized y end orgn resistnce to the ction of prthyroid hormone (PTH). In PHP, kidney consistently demonstrte resistnce to the ction of PTH, ut the skeletl resistnce is vrile. Renl resistnce to PTH results in iochemicl hypoprthyroidism (hypoclcemi, hyperphosphtemi) long with elevted PTH., PHP is further clssified s PHP nd. - Ptients with type PHP show no increse in urinry cyclic denosine monophosphte (camp) fter intrvenous dministrtion of exogenous PTH due to end orgn resistnce, ut ptients with type retin this ility. PHP type is n extremely uncommon sutype. PHP type is further clssified s types,, nd c. PHP type ccounts for mjority of the cses nd the prototype of ll sutypes. PHP type ws first descried y Alright in nd is lso known s Alright s hereditry osteodystrophy (AHO). The chrcteristic phenotype includes short stture, oesity, round fcies, rchydctyly, hyperprthyroid one disese (osteitis firos), nd sucutneous clcifictions. Type c is rre ut phenotypiclly similr to type. Ptients with type hve norml G protein ctivity nd norml phenotype. The pthophysiology of type is cused y pternl disomy of chromosome 0q nd susequent GNAS methyltion., The loss of the mternl GNAS gene results in PTH resistnce in the proximl renl tuules, which leds to hypoclcemi nd hyperphosphtemi. The sence of the conspicuous AHO fetures in PHP type nd its rrity frequently cuse dely in dignosis nd tretment. In PHP type, the ones remins sensitive to the effects of PTH, which results in the ony resorption of clcium in n ttempt to mintin the serum clcium. - The ony effects due to PTH descried in PHP re similr to the ony chnges seen in hyperprthyroidism., SCFE is well documented in renl osteodystrophy due to hyperprthyroidism. PTH impirs the norml enchondrl ossifiction nd dimishes the collgen content of the growth pltes. Similrly in PHP, the upper femorl metphysel resorption due to elevted PTH is thought to e the reson for slippge in SCFE., In ddition to surgicl fixtion, medicl tretment with ctive vitmin D nlogs is therefore required to suppress the PTH nd to prevent susequent tretment filure. In our ptient, the distl femorl physel chnges were seen due to the effects of incresed PTH, 0 Indin Journl of Orthopedics Novemer 0 Vol. Issue

4 0 which hs een documented in previously reported cses of PHP.,- Tretment with clcitriol (,-dihydroxyvitmin D ) is generlly recommended to normlize the elevted PTH ecuse clcitriol does not require PTH for its ctivtion. Alfclcidol (-lph-hydroxyvitmin D ) is synthetic nlog of vitmin D, which is converted in the liver to the ctive metolite,-dihydroxyvitmin D. Similr to clcitriol, lfclcidol hs rpid onset of ction nd reltively short hlf-life. - Clcium supplementtion is lso recommended to increse the serum clcium levels. Generlly PTH level of <00 pg/ml nd serum lkline phosphtse >0 IU/L is recommended with vitmin D therpy. In our ptient, PTH levels normlized quickly with the use of lfclcidol nd demonstrted no recurrence of symptoms in the follow up period. PHP should e considered s n extremely rre cuse for SCFE, especilly if the ge of presenttion is erlier thn the expected rnge. We conducted literture serch in Medline using the terms slipped cpitl femorl epiphysis nd pseudohypoprthyroidism nd found only three cse reports.,, Review of the cittions in these rticles reveled nother pertinent rticle, incresing the totl numer of PHP ptients with SCFE to five (including the ptient reported here). All of these ptients were femles. The youngest ptient ws reported y Aggrwl et l. in -yer-old who lso required surgicl fixtion similr to our ptient. All the other ptients required medicl mngement only. In the sence of AHO phenotype, ll the previous ptients were elieved to hve PHP type. As SCFE predominntly ffects the oese nd overweight popultion, the occurrence of SCFE in children with norml or lower ody mss index my provide nother clue to serch for n underlying endocrinopthy. Further endocrinologic evlution is usully required to confirm the dignosis. As illustrted in our cse, this could e difficult nd tke considerle time if this possiility is not considered in the dignosis. We emphsize tht clinicins should hve high index of suspicion s erly initition of medicl tretment prevents tretment filure nd reduces the moridity. Our cse is unique due to the following resons. To the est of our knowledge, the ptient we descried is the second ptient with PHP type predisposing to SCFE nd required oth medicl nd surgicl tretments. The ptient descried y Aggrwl et l. presented with PHP nd ws strted on clcitriol nd clcium supplements. Due to mediction noncomplince, she developed ilterl SCFE months lter, which required surgicl pinning nd continution of medicl tretment. Interestingly, our ptient presented with SCFE requiring surgicl fixtion, ut her mnifesttions of SCFE nd lter distl femorl physel chnges improved only fter tretment with lfclcidol nd clcium supplementtion, further supporting the importnce of ggressive medicl mngement. Even though clcitriol is the preferred choice, lfclcidol my e used s n lterntive if the PTH levels re not highly elevted. In conclusion, we would like to highlight tht PHP, lthough rre, should e considered s possile cuse for SCFE in children younger thn the expected ge group. Clinicins need to hve high index of suspicion s dignosis my e delyed due to the extreme rrity. Further investigtions re required to estlish the dignosis. With pproprite medicl nd surgicl tretment, stisfctory outcome should e expected. References. Loder RT, Aronsson DD, Dos MB, Weinstein SL. Slipped cpitl femorl epiphysis. Instr Course Lect 00;:-0.. Loder RT, Wittenerg B, DeSilv G. Slipped cpitl femorl epiphysis with endocrine disorders. J Peditr Orthop ;:-.. Wells D, King JD, Roe TF, Kufmn FR. Review of slipped cpitl femorl epiphysis ssocited with endocrine disese. J Peditr Orthop ;:-.. Agrwl C, Siegle R, Agrwl S, Bilezikin JP, Hymn JE, Oerfield SE. Pseudohypoprthyroidism: A rre cuse of ilterl slipped cpitl femorl epiphysis. J Peditr 00;:-.. Ro JP, Frncis AM, Siwek CW. The tretment of chronic slipped cpitl femorl epiphysis y iplne osteotomy. J Bone Joint Surg Am ;:-.. Spiegel AM, Weinstein LS, Shenker A. Anormlities in G protein-coupled signl trnsduction pthwys in humn disese. J Clin Invest ;:-.. Jüppner H, Bstepe M. Different muttions within or upstrem of the GNAS locus cuse distinct forms of pseudohypoprthyroidism. J Peditr Endocrinol Met 00;:-.. Bstepe M, Jüppner H. GNAS locus nd pseudohypoprthyroidism. Horm Res 00;:-.. Alright F, Burnett CH, Smith CH, Prson W. Pseudohypoprthyroidism: An exmple of Seright-Bntm sindrome. Endocrinology ;:-.. Levine MA, Speigel AM. Pseudohypoprthyroidism. Endocrinology. Phildelphi:WB Sunders;. p. -.. Hll FM, Segll-Blnk M, Gennt HK, Kol FO, Hwes LE. Pseudohypoprthyroidism presenting s renl osteodystrophy. Skeletl Rdiol;:-.. Dgh S, Chesney RW, Lnger LO, DeLuc HF, Gilert EF, DeWeerd JH Jr. Renl-nonresponsive, oneresponsive pseudohypoprthyroidism. A cse with norml vitmin D metolite levels nd clinicl fetures of rickets. Am J Dis Child ;:-.. Burnstein MI, Kottmsu SR, Pettifor JM, Sochett E, Ellis BI, 0 Indin Journl of Orthopedics Novemer 0 Vol. Issue

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