PEDIATRIC DENTISTRY/Copyright ©1986 byThe American Academy of Pediatric Dentistry

Volume 8 Number 1

Pseudohypoparathyroidism: report of case with systemicand oral manifestations

Richard K. Wesley, DDS, MSD Claire L. Cullen, DMD

Arnold L. Golnick, DDS, MS

Abstract

Pseudohypoparathyroidism is a rare sex-linkeddominant disease. The clinical symptoms are associatedwith an end-organ defect manifested by a lack of responsein bone or kidney target cells to parathyroid hormone.Clinical signs are described with emphasis on pertinentoral findings which may be the first signs of the disease.

Pseudohypoparathyroidism (PHP) is a rare dis-

ease of hypocalcemia first described in 1942 as A1-bright’s hereditary osteodystrophy.1,2 He reported 3patients who presented with clinical symptoms of idi-opathic hypoparathyroidism, but whose level ofparathyroid hormone was normal. 3 Further studiesconcluded that the clinical symptoms were not as-sociated directly with parathyroid hormone release,as determined by an unresponsiveness to parathy-roid hormone extract (Ellsworth-Howard test), butwere associated with an end-organ defect.2-s The dis-ease was renamed pseudohypoparathyroidism. Themost common presenting symptom is tetany or con-vulsions, which may be misdiagnosed as epilepsy,especially in infants. 2 A dentist may diagnose thisdisease from changes that affect the dentition --enamel hypoplasia, short blunted roots, and delayederuption. This case report presents the systemic andoral manifestations of the disease in an adolescentmale and reviews the literature.

Case Report

A 13-year-old black male with confirmed pseudo-hypoparathyroidism was admitted as an outpatientto Children’s Hospital of Michigan for evaluation. Hisinitial diagnosis was made following an ophthalmo-

logical examination of his cataracts at age 10 years,10 months.

Physical findings demonstrated a healthy-appear-ing, cooperative child. He weighed 34.7 kg (10th per-centile) and his height was 133.7 cm (<3rd percentile,Fig 1). His facies were coarse, with patchy areas ofhair loss (Fig 2). He manifested bilateral lens opacitiesdue to the presence of cataracts, which were sched-uled for surgical removal. His skin appeared dry andcoarse.

Subcutaneous calcifications were detected just pos-terior and inferior to the right external ear, the leftlower thorax, right axilla and over the lower leftquadrant of the abdomen. He had moderate mentalretardation and was enrolled in both physical therapyand occupational therapy programs within the schoolsystem. The neurological examination revealed a pos-itive Chvostek’s sign. An electroencephalogram wasperformed and revealed mild excessive sharp waveactivity dominant on the left side which resulted inrecurrent seizures.

The radiologic examination indicated diffuse calci-fications in the region of the basal ganglia with athickened calvarium. Radiographs confirmed the pre-senting brachydactyly of the first, fourth, and fifthmetacarpals and the first and fifth metatarsal (Fig 3).

The dental examination revealed delayed eruptionof maxillary first molars and premolars, with impac-tion of the mandibular second permanent molars. Themaxillary permanent right central, left central, andleft lateral incisors were avulsed. The texture of theenamel on all premolars was rough and pitted withcircumferential grooves. Radiographically, the enamelof the second molars appeared hypoplastic. Thesehypoplastic defects were soft and carious in manyareas, requiring extensive restorations. The roots of

48 PSEUDOHYPOPARATHYROIDISM/CASE REPORT: Wesley et al.

FIG 2. Coarse facies with patchy hair loss are characteristic ofthe disease. Postauricular subcutaneous calcifications are seen.

FIG 1. Patient's height falls below the third percentile andweight falls within the tenth percentile.

the premolars and permanent second molars wereshortened and blunted. The lamina dura density wasincreased (Fig 4).

At age 4, the patient exhibited seizure activity whichwas documented poorly. He was treated with phen-obarbital on an intermittent basis due to poor paren-tal compliance. Af ter the diagnosis ofpseudohypoparathyroidism was confirmed, the sei-zures were considered to be hypocalcemic induced.He was maintained on phenobarbital 75 mg b.i.d.,

FIG 3. Right and left hands exhibit brachydactyly of the first,fourth, and fifth metacarpals.

and calcitriol 1.5 mg with calcium carbonate 500 mgb.i.d. to maintain a normal serum calcium level. At

PEDIATRIC DENTISTRY: March 1986/Vol. 8 No. 1 49

4FIG 4a. (above) Panoramic radiograph reveals delayed erup-tion of maxillary and mandibular permanent right first molarand premolars, short roots with open apices, and impactionof the mandibular second molars.FIG 4b. (below) Periapical radiograph reveals areas of enamelhypoplasia, increased density of the lamina dura, and short-ened root of the mandibular left second premolar.

age 14 years, 3 months, his parents discontinuedadministration of the phenobarbital. His physicianagreed with the decision since his serum calcium lev-els were stabilized and he had had no known seizuressince discontinuation of the phenobarbital.

Systemic ManifestationsThe end-organ defect which occurs is a result of

either unresponsiveness in bone or kidney target cellsto parathyroid hormone (Type I), or uneffectivephosphate diureses in the kidney (Type II).3-4-6-7 Theunresponsiveness causes a decreased mobilization ofcalcium in the bones, impaired calcium absorptionfrom the intestine, and failure in the renal tubule toexcrete phosphate.8-9 As a result, serum calcium isreduced from a normal of 9 mg/100 ml to 4-8 mg/100ml and serum phosphate is elevated to 10-12 mg/100ml, accompanied by a decrease in alkaline phospha-tase.9

Clinical tests for latent tetany include checking forChvostek's sign. This twitching of facial muscles nearthe eye and mouth results from tapping the facialnerve at the point of origin anterior to the parotidgland.5-10 Another valuable clinical test is detectionof Trousseau's phenomenon, the induction of a car-pal spasm by inflating a blood pressure cuff abovethe systolic pressure for at least 1 min.10-11

The patient's appearance includes a round headand face, reduced height and stocky build.3-12 Theskin appears dry and coarse and the nails are hypo-plastic and ridged.8 The hair ranges from thin andprematurely gray to partial or complete alopecia.5

Seventy-five per cent of patients exhibit brachydac-tyly of the first, fourth, and fifth metacarpals and thefirst and fifth metatarsals.8-12 Photophobia with len-ticular cataracts is a result of prolonged hypocal-cemia.5-8'10-13 The electrocardiogram may be normalwith the presence of a prolonged Q-T wave. Perni-cious anemia is a rare finding.2-14

Calcium deposits cause bilateral, but asymmetrical,metaplastic bone formation in the subcutaneous tis-sue, particularly in the facial planes.4-5-15 However,there is generalized bone demineralization.8 Cepha-lometric radiographic indications of the disease arethe presence of discrete, symmetrical calcifications inthe basal ganglia area, the dentate nuclei of the cer-ebellum and the falx cerebri, with an increased den-sity of the facial bones.5-8-12 Mental retardation andemotional lability are common.3-16-17 The electroen-cephalogram is usually abnormal, but improves fol-lowing successful anti-tetanic treatment.5

The disease is considered to be sex-linked domi-nant, but the exact genetic basis is unknown.2-3-7-9'11

There is a predilection for females, however malesare affected to a greater degree than females.2-5-7 Whenthe disease is accompanied by candidiasis and adre-nal deficiency, the syndrome is considered autosomalrecessive and referred to as Addison's disease.9-10

Oral ManifestationsChanges affecting the dentition are considered of

diagnostic value in 37-50% of patients withPHP 3,7,9,10,12,15 Teeth exhibit a calciotraumatic re-sponse coinciding with the age of onset and reflectingthe periods of hypocalcemia during tooth develop-ment.5

The wedge-shaped teeth are hypocalcified and ex-hibit random pits and grooves in the enamel. Teethin females are not as thin as in males due to theLyonization effect of sex-linked disorders.7 Becausethe average age of onset is 8l/2 years, primary teethrarely are affected, while premolars and second andthird molars are affected most severely.5-18 Often thereis an overall delay in eruption of permanent teeth

50 PSEUDOHYPOPARATHYROIDISM/CASE REPORT: Wesley et al.

with short, incomplete root formation. 5,14 Periapicalradiographs may reveal increased density of the lam-ina dura.3,s The dentin exhibits interglobular calcifi-cations, with incremental lines being highlighted inall areas, especially at the root apex.8

Discussion

The patient exhibited the classic clinical picture foundin PHP. He presented with hypocalcemia, a positiveTrousseau’s phenomenon, Chvostek’s sign, short-ened height, hair loss, dry skin, brachydactyly, andsubcutaneous calcifications. On the cephalometricradiograph, calcifications in the region of the basalganglia were present with a thickened calvarium. Thelevel of mental retardation was moderate. The pres-ence of cataracts led to the medical evaluation anddiagnosis.

The most striking dental finding in the patient wasenamel hypoplasia as indicated by the dull white color;randomly oriented pits and circumferential grooves;and extensive caries. The hypoplasia was most evi-dent in the canines, premolars, and radiographicallyin the second molars. The premolars and second mo-lars displayed shortened roots and open apices withwidened pulp chambers. The lamina dura was thick-ened in this case. The mandibular second molars wereimpacted with delayed eruption of the maxillary rightmolars and premolars.

Seizures due to tetany from below-normal levels ofserum calcium are often the initial clinical symptom.This patient began seizure activity at age 4 and wastreated with phenobarbital intermittently. An electro-encephalogram is usually abnormal, as in this paotient. Subsequent to establishing normal serum calciumlevels, these hypocalcemic-induced seizures wereeliminated. These seizures frequently are treated withdiphenylhydantoin; this may be inadequate since theseizures are due to reduced serum calcium levels. Inaddition, the diphenylhydantoin will aggravate fur-ther the serum calcium levels due to its rachitic-pro-ducing effects. In order to help maintain normal serumlevels, patients are requested to reduce dietary intakeof food high in phosphorus such as milk, eggs, andcheese. However, complete control may be difficult

due to rapid calcium absorption changes in adoles-cents, and frequent reassessment is necessary.

Recent studies have shown that short stature, de-layed dental eruption, smaller tooth size and short-ened roots, as well as decreased serum calcium levelsmay be caused by the administration of some anti-convulsant drugs. 19-21 Therefore, a dentist may con-clude erroneously that a patient who presents with ahistory of diphenylhydantoin therapy and dental ab-errations may have misdiagnosed PHP.

Summary

The clinical manifestations of PHP have been pre-sented. Systemically, the patient presented with de-creased serum calcium, increased serum phosphorus,shortened height, dry skin, brachydactyly, cataracts,subcutaneous calcifications, and cephalometric evi-dence of basal ganglia calcification. The dental find-ings included enamel hypoplasia, shortened roots withopen apices, thickened lamina dura, delayed erup-tion, and impaction of second molars.

Dr. Wesley is a professor and chairman, pathology, and Dr. Cullenis an associate professor and chairman, pediatric dentistry, Uni-versity of Detroit; and Dr. Golnick is pediatric dentistry residencyprogram director, Children’s Hospital of Michigan in Detroit. Re-print requests should be sent to: Dr. Claire L. Cullen, Dept. ofPediatric Dentistry, University of Detroit School of Dentistry, 2985E. Jefferson Ave., Detroit, MI 48207.

1. Albright F, Burnett CH, Smith PH, Parson W: Pseudohypo-parathyroidism -- an example of Seabright-Bantam syn-drome. Endocrinology 30:922-32, 1942.

2. Witkop CJ: Inborn errors of metabolism with particular ref-erence to pseudohypoparathyroidism. J Dent Res 45:568-74,1966.

3. Jensen SB, Illum F, Dupont E: Nature and frequency of dentalchanges in idiopathic hypoparathyroidism and pseudohy-poparathyroidism. Scand J Dent Res 89:26-37, 1981.

4. Elrick H, Albright F, Barter FC, Forbes AP, Reeves JD: Furtherstudies of pseudohypoparathyroidism: report of four newcases. Acta Endocrinol 5:199-225, 1950.

5. Bronsky D, Kushner DS, Dubin A, Snapper I: Idiopathic hy-poparathyroidism and pseudohypoparathyroidism: case re-ports and review of the literature. Medicine 37:317-52, 1958.

6. Barnicot NA: The local action of the parathyroid and othertissues on bone in intracerebral grafts. J Anat 82:233-48, 1948.

7. Stewart RE, Prescott GH: Oral Facial Genetics. St. Louis: CVMosby Co, 1976 pp 212-18.

8. Croft LK, Witkop CJ, Glas J: Pseudohypoparathyroidism. OralSurg 20:758-70, 1965.

9. Gorlin RJ, Goldman HM: Thoma’s Oral Pathology, Vol. 2. St.Louis; CV Mosby Co, 1970 pp 625-27.

10. Eyre WG, Reed WB: Albright’s hereditary osteodystrophy withcutaneous bone formation. Arch Dermatol 104:634-42, 1971.

11. Rose LF, Kaye D: Internal Medicine for Dentistry. St. Louis;CV Mosby Co, 1983 pp 1196-97.

12. Ritchie GM: Dental manifestations of pseudohypoparathy-roidism. Arch Dis Child 40:565-72, 1965.

13. Laing JK: Pseudohypoparathyroidism: report of a case. NZMed J 59:156-58, 1960.

14. Hurwitz LJ: Spontaneous hypoparathyroidism with megalo-blastic anemia. Lancet 1:234-35, 1956.

15. Steinbach HL, Young DA: The roentgen appearance of pseu-dohypoparathyroidism (PH) and pseudo-pseudohypopara-thyroidism (PPH). Am J Roentgen 97:49-66, 1966.

16. deMowbray RR, Smith SHL, Symonds WJC: Hypoparathy-roidism and pseudohypoparathyroidism. Br Med J 1:903-9,1954.

17. MacGregor ME, Whitehead TP: Pseudohypoparathyroidism.Arch Dis Child 29:398-418, 1954.

18. Witkop CJ: Clinical aspects of dental anomalies. Int Dent J26:378-90, 1976.

PEDIATRIC DENTISTRY: March 1986/Vol. 8 No. 1 51

19.

20.

Robinson PB, Hart’is M, Harvey W: Abnormal skeletal anddental growth in epileptic children. Br Dent J 154:9-13, 1983.Staple PH, Miller WA: Effects of chronic administration ofsodium diphenylhydantoin (dilantin) on bones and teeth the rat and hamster: a preliminary study. Calcif Tissue Res17:235-48, 1975.

21. Robinson PB, Rowe DJ, Harris M: The effects of diphenylhy-dantoin and vitamin D deficiency on developing teeth in therat. Arch Oral Biol 23:137-43, 1978.

Pediatric Dentistry: Reviewers

On behalf of the American Academy of Pediatric Dentistry, the editorial staff wishes to thank those

individuals who have spent valuable time reviewing manuscripts for the Journal. Their professional ex-pertise has contributed greatly to the quality of this publication. Those listed were sent manuscripts from

January I through December 31, 1985.

A H PAlbum, Manuel M. Henderson, Hala Z. Pate, Phillip R.Alexander, Stanley A. Hennon, David K. Patterson, Samuel S.

Hicks, M. John Porter, Donald R.B Houpt, Milton I. Pribisco, Thomas A.Badger, Gary R.Baribeau, Douglas S. j RBarton, Douglas H. Johnsen, David C. Ranly, Don M.Bernick, Sheldon M. Johnson, Bruce Rapp, RobertBinns, William H., Jr. Johnson, Robert V. Ripa, Louis W.Bixler, David Jones, James E. Rovelstad, Gordon H.Bogert, John A. Jong, AnthonyBoraz, Robert A.Boyers, Charles L.

KS

Bruner, Fred W. Sandler, Eugene S.Bugg, James L., Jr.

Katz, Simon Saunders, William A.Burns, James

Kennedy, David B. Setcos, JamesKoerber, Leonard G. Shey, ZiaKopel, Hugh Shoptaw, James T.Krutchkoff, David Shore, Scott W.

Silverstone, Leon M.L Sire, Joseph M.Laswell, Harold Sitzer, Thomas L.LeCompte, E. Joseph Snawder, Kenneth D.Lewis, Jasper L. Snyder, C. WilliamLewis, Thompson M. Spedding, Robert H.Loos, Paul J. Steiner, James F.Lowe, James W. Straffon, Lloyd H.Luke, Larry S. Strange, Evelyn M.

Sullivan, Robert E.

CCamp, Joe H.Carrel, RobertCasamassimo, Paul S.Cisneros, George J.Cooley, RobertCorcoran, John W.Cornell, WilliamCroll, Theodore P.Currier, G. Frans

DDavis, William C. MDilley, Diane C.H. Melton, Robert H.Doykos, John D., II1 Mink, John R.Dummett, Clifton O., ]r. Mourino, Arthur P.

Myers, David R.E McDonald, James L.Earl, Robert D. McDonald, John S.

FMcTigue, Dennis ].

Ferguson, Donald J.Ferguson, Fred S. N

Fields, Henry W., Jr. Nash, David A.

Fippinger, Terrance Nazif, M.M.

Full, Clemens A. Needleman, Howard L.Nelson, Gayle V.

G Nelson, John F.Gellin, Milton E. Nowak, Arthur J.

Goldblatt, Lawrence I.Golnick, Arnold L. OGood, David.L. Oliver, David R.Gutz, Dennis P. Osborne, John W.

TThomas, Joe P.Tinanoff, NormanTomich, Charles E.Troutman, Kenneth

VVann, William F., Jr.Vash, BruceVenham, Larry

WWalker, Jerry D.Wallach, Mark A.Weaver, Richard G.Weber, John D.Williamson, Stanley P.Wright, Gerald Z.

52 PSEUDOHYPOPARATHYROIDISM/CASE REPORT: Wesley et al.