Congenital Adrenal Hyperplasia:A Case Report With Premature TeethExfoliation and Bone ResorptionMatina V. Angelopoulou, DDS, MSa, Elias Kontogiorgos, DDS, PhDb, Dimitris Emmanouil, DDS, MS, PhDc

abstract Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive disordercharacterized by insufficient production of cortisol. The aim of this case reportwas to present a child with CAH, premature exfoliation of primary teeth andaccelerated eruption of his permanent teeth related to bone resorption. A4.5-year-old Caucasian boy with CAH and long-term administration of glucocorticoidswas referred for dental restoration. Clinical examination revealed primarymolars with worn stainless steel crowns, severe attrition of the upper canines,and absence of the upper incisors. Before the completion of treatment,abnormal mobility of the first upper primary molars and the lower incisorswas detected, and a few days later the teeth exfoliated prematurely. Histologicexamination revealed normal tooth structure. Alkaline phosphatase and bloodcells values were normal. Eruption of the permanent dentition was alsoaccelerated. Tooth mobility was noticed in the permanent teeth as soon asthey erupted, along with bone destruction. Examination revealed an elevatedlevel of receptor activator of nuclear factor-kB ligand and lower-than-normalosteoprotegerin and vitamin D levels. The patient was treated with vitaminD supplements, and his teeth have been stable ever since. CAH is a seriouschronic disorder appearing in children with accelerated dental developmentand possibly premature loss of primary teeth.

Congenital adrenal hyperplasia (CAH)is an inherited disorder that leads toinsufficient production of cortisolcaused by abnormality in 1 of the5 enzymes that are necessary for itsbiosynthesis.1–3 Glucocorticoid andmineralocorticoid administration is thetherapy of choice.4 However, chronicadministration of corticosteroids maycause growth retardation, drug-induced osteoporosis, glucoseintolerance, and infectionsusceptibility.5

Increased bone resorption in patientswith CAH has been noted in the pastand has been related to alterations inreceptor activator of nuclear factor-kBligand (RANKL) and osteoprotegerin(OPG).6 This effect might be caused bythe long-term administration of

corticosteroids or the excessivesecretion of adrenocorticotropichormone.7 Also, bone resorption hasbeen related with loss of teeth inpatients with osteolytic diseases.8

In addition, adrenal hyperactivation hasbeen found to increase infectionsusceptibility9 and increase the risk fordevelopment of periodontal disease.10

Periodontal disease is related to loss ofteeth.11

Accelerated tooth eruption has beenreported in patients with CAH.12–15

Long-term therapy withglucocorticoids15,16 and excessivehormonal secretion13,14 have beenassociated with the acceleration of dentaldevelopment. Recently, bone resorptionhas been found to be correlated withaccelerated eruption of teeth in mice.17

aDivision of Pediatric Dentistry, Marquette University Schoolof Dentistry, Milwaukee, Wisconsin; bDepartment ofRestorative Sciences, Texas A&M Baylor College ofDentistry, Dallas, Texas; and cDepartment of PaediatricDentistry, Dental School, University of Athens, Greece

Matina V. Angelopoulou treated the patient anddrafted the initial manuscript; Elias Kontogiorgosanalyzed the RANKL and osteoprotegerin levels andedited the manuscript; Dimitris Emmanouil designedthe treatment plan for the patient, supervised thetreatment and follow-up, and edited the manuscript;and all authors approved the final manuscript assubmitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-3577

DOI: 10.1542/peds.2014-3577

Accepted for publication Feb 25, 2015

Address correspondence to Matina Angelopoulou,415 East Vine St #304, Milwaukee, WI 53212. E-mail:matinangelop@yahoo.gr

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,1098-4275).

Copyright © 2015 by the American Academy ofPediatrics

FINANCIAL DISCLOSURE: The authors have indicatedthey have no financial relationships relevant to thisarticle to disclose.

FUNDING: RANKL and osteoprotegerin tests wereconducted at the Department of ExperimentalSurgery and Surgical Research, Medical School,University of Athens, Greece with supplies providedby the department.

POTENTIAL CONFLICT OF INTEREST: The authors haveindicated they have no potential conflicts of interestto disclose.

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Premature exfoliation of teeth has notbeen reported in patients with CAH.However, susceptibility to periodontaldisease and bone resorption can bethe cause for primary exfoliation ofprimary teeth and acceleratederuption of its successors.

The aim of this case report is to presenta child with CAH with prematureexfoliation of primary teeth andaccelerated eruption of his permanentteeth caused by bone resorption.

CASE REPORT

A 4.5-year-old white boy was referredin June 2010 to the postgraduate clinicof pediatric dentistry of the DentalSchool, University of Athens, for dentalrestoration. The patient had a BMI of13.5, which is below the 5th percentilefor boys of that age. Medical historyincluded preterm birth with normalkaryotype (46 ΧΥ). Medical historyincluded asthma controlled withmedication and history of pneumoniaat the age of 9 months. The child hadbeen hospitalized several times forviral infections and surgical procedures(eg, hypospadias, cryptorchism, andhydrocele). The main medical conditionwas congenital hyperplasia of adrenalcortex, treated with systematic intakeof hydrocortisone (9 mg/m2 per day)and potassium levothyroxine(Τ4, 5 mg/kg) daily. Dental historyincluded uncooperative behavior withthe dentist, toothbrushing once a dayby the mother, and severe bruxismduring the day and night.

Clinical examination revealed thepresence of worn primary dentitionand absence of the maxillary primaryincisors. Parents reported extractionof the upper incisors due to abscesscaused by pulp exposure after severeattrition. Patient had no signs ofcaries or enamel hypomineralization.

The treatment plan included anindividualized preventive programand rehabilitation of dentition withstainless steel crowns applied undergeneral anesthesia (GA). Dentaltreatment under GA was a necessity

not only because the child wasuncooperative but also becausepatients with CAH needadministration of supplementaldoses of glucocorticoids to cope withdental anxiety.

Before the scheduled appointment fordental treatment under GA, the patientpresented for emergency care becauseof gingival swelling, halitosis, andabnormal mobility of first upperprimary molars. The patient receiveda triple daily dose of supplementalsteroids, and the teeth were extractedunder local anesthesia. In addition,abnormal mobility of the primarylower left central incisor was recorded,and radiographic examination revealedsevere bone loss (Fig 1). The incisorfell off during the examination. All teethwere sent for histologic examination to

define the cause of the multiple toothloss, and laboratory blood tests wererequested.

Regarding premature exfoliation ofprimary teeth, the patient waschecked for aggressive periodontitis,immunodeficiency (neutropenia,leukocyte adhesion deficiency,leukemia), hypophosphatasia,Langerhans histocytosis,Papillon–Lefèvre syndrome, diabetesmellitus, hyperthyroidism, dentinaldysplasia, acatalasia, Singleton–Mertensyndrome, Hajdu–Cheney syndrome,Coffin–Lowry syndrome, andChediak–Higashi syndrome.

Histologic examination of the teethrevealed normal tooth structure(Fig 2). Hematologic examinationshowed periodic alteration of alkalinephosphatase and normal blood

FIGURE 1Periapical radiograph of the lower anterior teeth, revealing severe bone loss around the lower leftcentral incisor and accelerated eruption of its successor.

FIGURE 2Histologic examination of lower left central incisor, revealing normal tooth structure. Differenttissues are marked with letters: C, cementum; D, dentine; F, periodontal fibers.

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values. Plaque test results showeda pattern of colonization relevant tothe patient’s age. Aggregatibacteractinomycetemcomitans was notdetected. These findings wereinconclusive for a final diagnosis ofthe conditions and syndromesmentioned earlier.

At the scheduled appointment fordental treatment under GA,

periodontal examination revealedmild gingival inflammation andplaque accumulation but noattachment loss. Permanentrehabilitation of the patient wasperformed (Fig 3), followed by toothcleaning and fluoride treatment. Asshown in Fig 3, all teeth had normalenamel structure. A panoramicradiograph was acquired to evaluate

bone structure (Fig 4). Throughclinical and radiographic evaluation,vertical bone loss and accelerateddental development were observed.More specifically, the first permanentlower right molar, which normallyerupts at 6 years old, and the firstupper left premolar, which normallyerupts at 11 years old, were eruptingat the age of 4.5 years.

At 1-year follow-up, the permanentteeth that had erupted showed class1 mobility. The anterior teeth werevital, and no inflammation wasobserved in the gingival tissues.Radiographic examination revealedexcessive bone destruction in theanterior region (Fig 5), and eruptionof permanent upper and lowercentral incisors, first molars, andupper premolars at the age of5.5 years was also recorded (Fig 6). Ablood test for bone metabolismmarkers revealed an elevated RANKLserum level (1459 pg/mL vs RANKLnormal values of 983–1207 pg/mL)and a lower-than-normal OPG serumlevel (3213 pg/mL vs OPG normalvalues of 3996–5808 pg/mL).Vitamin D deficiency was alsoapparent. The patient’s genome waschecked for RANK mutations, but nofindings were reported.

After consultation with theendocrinologist, the child was treatedwith 25(OH) vitamin D3 supplementsdaily (30 ng/mL) for 6 months, andthe tooth mobility has been absentever since. The patient is monitoredby the endocrinologist to avoid futurebone destruction.

DISCUSSION

This report suggests that earlyexfoliation of primary teeth can bea side effect of bone resorption inpatients with CAH. Early exfoliation ofthe primary dentition and bone loss isan uncommon finding in children.However, whenever it occurs isimportant to diagnose the patientearly because it is usually correlatedwith serious systematic diseases.18

FIGURE 3Clinical examination of upper (A) and lower (B) arch after rehabilitation under general anesthesia.The left permanent central incisor and the right permanent first molar are present in the mandible.The left second premolar has started erupting in the upper jaw (shown in circle).

FIGURE 4Panoramic radiograph at the age of 4.5 years. Severe bone destruction is seen in the upper jaw andthe lower anterior zone. Accelerated eruption of permanent teeth is apparent.

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Premature loss of primary teeth hasnot been reported in the past ina case of CAH. However, CAH shouldbe included in the differentialdiagnosis of premature loss of teethbecause disturbance in dentaldevelopment may be the firstsymptom of this disorder.13 Othersystematic diseases that may cause

premature exfoliation of teeth includehypophosphatasia, aggressiveperiodontitis, Papillon–Lefèvresyndrome, Singleton–Mertensyndrome, Hajdu–Cheney syndromeimmunodeficiency (neutropenia,leukocyte adhesion deficiency,leukemia), Langerhans histocytosis,diabetes mellitus, hyperthyroidism,cherubism, dentinal dysplasia,Ehlers–Danlos syndrome, Coffin–Lowrysyndrome, Chediak–Higashi syndrome,acatalasia, acrodynia, mucocutaneousdyskeratosis, and erythromelalgia.18–20

Hypophosphatasia,immunodeficiency, diabetes mellitus,hyperthyroidism, and acatalasia canbe excluded with hematologicexamination.18,21 In the present case,blood tests revealed normal bloodvalues in all tested enzymes,hormones, or cell numbers.Langerhans histocytosis, cherubism,and dentinal dysplasia present withbone lesions or dental morphologycharacteristic for these type ofdiseases.18 Acrodynia is usuallycorrelated with mercury poisoning,which was not recorded in thepatient’s medical history.18

Papillon–Lefèvre syndrome,Ehlers–Danlos syndrome,mucocutaneous dyskeratosis, anderythromelalgia present specificdermatologic findings that wereabsent in the presentpatient.19,20,22,23

Children with Coffin–Lowrysyndrome have mental retardation,distinguishing facial characteristics,and skeletal abnormalities that werenot present in this child.24 Moreover,none of the clinical features ofChediak–Higashi syndrome, such asalbinism, strabismus, and nystagmus,infections of the skin and respiratorytract, and characteristic alterations inblood cell values and cell morphology,were found in the present patient.25

Patients with Singleton–Mertensyndrome usually present withskeletal and joint defects, glaucoma,and calcification of the aortic arch,whereas Hajdu–Cheney syndrome ischaracterized by joint problems andmultiple osteolytic lesions.18 None ofthese defects were apparent in thispatient.

Aggressive periodontitis is a rarecondition characterized by rapid lossof periodontal attachment anddestruction of the bone.26 Usually thepatients have an unrevealing medicalhistory and present with minorinflammation of gingival tissuesand minimal plaque accumulationthat is incompatible with theseverity of periodontal damage.26

Sometimes high levels ofA. actinomycetemcomitans aredetected.26 In the present patient,A. actinomycetemcomitans was notdetected in the plaque microflora.The patient presented withbone destruction and gingivalinflammation, but loss of attachmentwas not observed. However,attachment loss measurement cannotbe clinically reliable in childrenbecause of continuous growth andtooth eruption.27

The present case reported a child withsevere bruxism. Current literaturesuggests a prevalence of 5.9% to49.6% of bruxism in children.28

However, tooth loss due to bruxismhas not been reported in the literaturein either children or adults despite thehigh prevalence of bruxism.

Bone destruction has been correlatedwith adrenal gland hormone

FIGURE 5Panoramic radiograph at the age of 5.5 years. Severe bone destruction is seen in the upper jaw andthe lower anterior teeth. Erupted permanent teeth have immature apices.

FIGURE 6Clinical examination of the maxilla at the age of5.5 years. Left permanent molars and pre-molars are seen.

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alterations.7 Usually children withCAH present with accelerated bonegrowth caused by androgenoverproduction.7 However,osteoclastogenesis has also beenreported in these children as a sideeffect of long-term glucocorticoidtherapy.6,29 This might have causedthe bone destruction in this patient.In addition, osteoclastogenic activitycan be monitored by testing theRANKL and OPG levels in the patient’sserum.17 In patients with CAH,RANKL levels are elevated whereasOPG levels are lower than normal.6

The findings in the present casereport are consistent with theliterature and suggest that patienthad elevated osteoclastic activity. Forthis reason, the endocrinologistsuggested a serum test for vitamin D,which was found to be lower thannormal, and the patient was givensupplements to increase bone density.

Other conditions presenting withbone destruction have been reportedin the literature.30 In particular,familial expansive osteolysis andPaget disease of the bone have beenrelated to mutations in the generesponsible for receptor activator ofnuclear factor-kB (RANK).31 However,in the present case no RANKmutations were detected in thegenome.

Moreover, RANKL levels have beencorrelated with disturbances in tootheruption.17 Accelerated developmenthas been reported in children withCAH,12–15 as was observed for thispatient. Accelerated eruption ofpermanent teeth may have beencaused by corticosteroid- orandrogen-induced bonedestruction14–16 and can be a sign ofbone metabolism disturbances.However, premature exfoliation in thepresent case may have been a sideeffect of accelerated eruption ofpermanent teeth.

Additional case–control studies willbe needed to define the correlation ofpremature exfoliation and boneresorption in patients with CAH.

ACKNOWLEDGMENTS

The authors thank the Department ofExperimental Surgery and SurgicalResearch, Medical School, Universityof Athens, Greece, assistant professorApostolos Tsolakis, and Dr YannisLyros for conducting the RANKL andOPG tests. Also, we thank assistantprofessor Christina Kanaka for themedical records and follow-up of thepatient.

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DOI: 10.1542/peds.2014-3577 originally published online May 25, 2015; 2015;135;e1524Pediatrics 

Matina V. Angelopoulou, Elias Kontogiorgos and Dimitris EmmanouilExfoliation and Bone Resorption

Congenital Adrenal Hyperplasia: A Case Report With Premature Teeth

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DOI: 10.1542/peds.2014-3577 originally published online May 25, 2015; 2015;135;e1524Pediatrics 

Matina V. Angelopoulou, Elias Kontogiorgos and Dimitris EmmanouilExfoliation and Bone Resorption

Congenital Adrenal Hyperplasia: A Case Report With Premature Teeth

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