- Email: [email protected]
Pseudohypoparathyroidism: report of case
Pseudohypoparathyroidism: report of case P arathyroid fu n c tio n A . Norman Cranin, DDS Howard E. Katz, DDS, New York
More research is needed to determine the dis tinction between pseudohypoparathyroidism and pseudopseudohypoparathyroidism. Both conditions, however, present orocranial prob lems pertinent to the dental profession. The patient discussed in this report demonstrates most of the classic clinical and laboratory findings.
Pseudohypoparathyroidism (PH) and pseudo pseudohypoparathyroidism (PPH) are formidable terms. The conditions are rare. Data, however, are accumulating in sufficient amounts to warrant alerting the dental profession to orocranial problems. This report includes a discussion of parathyroid function, a survey of the literature, and a report of a case.
Parathormone is a protein with a molecular weight of about 7,000. The protein is a chain of 83 amino acid residues of 17 amino acids.1 If the normal calcium levels are thought of as 100 percent, about 70 percent of the level is main tained by a simple solubility mechanism. The re maining 30 percent is controlled by a feedback mechanism of the parathormone. Parathormone is involved with the regulation of serum calcium levels and serum phosphorus levels, elimination of both into the urine, in creased activity of serum phosphatase, and migration of calcium from the bony depots if there is insufficient calcium in the diet. Parathormone release raises the blood calcium and lowers the blood phosphorus. It acts, primarily, in two regions. In bone, parathormone promotes the release of calcium from more sol uble intercrystalline substance and from the hydroxyapatite crystals.2 In the kidneys, para thormone increases urinary elimination of phos phates by inhibiting tubular reabsorption. Pure 741
hyperfunction could cause osteitis fibrosa cys tica.3 Parathormone secretion is governed by the calcium ion level in the blood. Normal levels vary from 9.5 to 11 mg./100 ml. Below this level, parathormone secretion is increased. Higher levels are, in part, balanced by the kidneys, which have a renal threshold of about 9 mg./100 ml. Serum calcium levels affect neuromuscular ir ritability. Levels below 5 to 7 mg./100 ml. cause tetany. Thus, pure hypofunction would result in pedocarpal spasm. Excretion of calcium is partly through the kidneys; but most calcium excretion is through the small intestinal mucosae. Vitamin D has a major role in preventing excessive loss of calcium through the intestinal wall. Review o f lite ra tu re In 1942, Albright4 reported on a group of pa tients who suffered the clinical and laboratory manifestations of hypoparathyroidism but who failed to respond to parathormone. Most of the patients were mentally retarded, short and stocky, with rounded faces, shortened metacarpals or metatarsals or both, subcutaneous calcinosis, and calcification of the basal ganglions. Although Boorstein5'8 reported bilaterally sym metrical brachymetacarpalia and brachymetatarsalia as early as 1916, the term “pseudohypopara thyroidism,” was not used until Albright’s report4 in 1942. The term, “pseudopseudohypoparathy roidism,” was used 10 years later in a paper by Albright, Forbes, and Henneman.7 In that report, the diséase of a 29-year-old patient was described. The subject had all the characteristics of PH but no corroborating laboratory evidence of hy pocalcemia. Since that time, 42 cases with vary ing additional characteristics have been added to the medical literature.8'10 Additional clinical findings reported are epi physeal dysplasia, osteochondromas, defective or delayed dentition and dental eruption, thick ened calvarium, osteoporosis, corneal or lentic ular opacities, blue scleras, mental retardation, and abnormal electrocardiograph tracings. Some of these characteristics have been observed in other independent congenital or hereditary syn dromes, such as brachydâctylia, or in other meta bolic disorders. Consistencies appear as more cases are report ed. Twice as many females as males are affected 742 ■ JADA, Vol. 74, March 1967
by the disease, and classic clinical and radiographic features have appeared. The term pseudopseudohypoparathyroidism has been criticized11 because it does not défine the syndrome it identifies. For example, there appears to be no dysfunction of the parathyroid glands. Changing the names of pseudohypopara thyroidism and pseudopseudohypoparathyroidism to Albright’s hereditary osteodystrophy has been discussed. As a more definitive term, we suggest hereditary osteopleiotropy. Chemically, PH may show hypocalcemia, whereas PPH does not. In three cases, early-age hypocalcemia spontaneously changed to normocalcemia as the subjects matured. This change seems to indicate a change from PH to PPH. Therefore, it has been suggested that PH and PPH are two forms of the same syndrome be cause of the similarities of symptoms and find ings, and because both diseases were reported in members of the same family, suggesting genetic relationships. The most recent review by Papaioannou and Matsas12 introduced evidence that hypocalcemia and hyperphosphatemia should not be consid ered pathognomonic features to distinguish PH from PPH. Papaioannou and Matsas suggest that PH is the extreme form of the less severe. Some of the reported characteristics, such as méritai re tardation, disturbed dental development, and ectopic calcinosis, which are common in idio pathic hypoparathyroidism, suggest metabolic dis turbance of calcium and phosphorus chemistry. These symptoms, however, also occur in normocaicemic PPH. This similarity of characteristics seems to indicate a genetic factor in addition to the obvious metabolic relationship. Findings of biopsies of the parathyroid gland in patients with these characteristics were normal or hyperplastic despite what seemed to be a hypoparathyroid dysfunction. Neither biopsy, nor determination of renal tubular reabsorption of phosphorus, nor Ellsworth-Howard* testing is reliable in the diagnosis of PH, PPH, or idiopathic hypoparathyroidism. (Regardless of the defect, there have been no subjects that have not responded to treatment with vitamin D and calcium gluconate.) Report o f case The classic clinical and laboratory observations reported, including the Pickwickian facies and
stature, shortened arms and legs, brachymetacarpalia and brachymetatarsalia, mental retardation, and an interesting corroborating dental history, were made of this patient. The subject has been studied from birth, and his entire clinical-bio chemical history is known. History The subject was a full-term spontaneous delivery. His weight, at birth, was 14 pounds. He had a peculiarly shaped head with prominent frontal areas. At the age of 3 weeks, thete was an abnormal increase in weight, and thyroid in sufficiency was the presumptive diagnosis. Large quantities of thyroid extract were prescribed, but there was no appreciable gain in weight or height. The first tooth, a lower incisor, erupted at the age of 6 months, but subsequent eruption was re tarded. The subject did not walk until the age of 18 months, nor did he talk until he was 3 years old. When the subject was 5 years old, he received radiation treatments for the abdomen; however, reasons for this treatment are obscure. At the age of 7, the subject was tall for his age and noticeably overweight. Since then, however, his height has not changed significantly, and weight increases have been minimal. Although the sub ject started school when he was 7, he soon was placed in an institution for retarded children be cause he could not comprehend a normal firstgrade curriculum. The subject received a thorough examination at the age of 15, which revealed him to be awk ward and of stocky and subnormal stature. Other characteristics found were as follows: an enlarged head, particularly in the frontal areas; opacities of both lenses; thickness of the calvarium; large frontal sinuses; calcification in the intercranial regions, above and bilateral to the sella turcica, and multiple, poorly calcified, unerupted teeth in both anterior and posterior regions. A positive Chvostek’s test confirmed a diagnosis of tetany. Two clinical tests that confirm a diagno sis of tetany are Chvostek’s and Trousseau’s signs. Chvostek’s sign is considered positive when spasm of the facial musculature is elicited by tapping on the preauricular region at the exit of the facial nerve. Trousseau’s sign is present when there is pedal or carpal spasm after a pressure cuff, at 5 mm. Hg above systolic, is applied to the leg or arm for 3 minutes.
Chemistry studies indicated calcium, 7.2 mg./ 100 ml.; phosphorous, 6.4 mg./lOO ml., and al kaline phosphatase, 25.4 King-Armstrong units. Diagnosis was intracranial neoplasm with second ary hypoparathyroidism. When the subject was 19 years old, he com plained of stiffness and paresthesia of fingers and toes. There was a pronounced loss of scalp hair, and findings described at the age of 15 were con firmed, except that the alkaline phosphatase level was now normal. Diagnosis at the age of 19 was pseudohypoparathyroidism. A regimen of vitamin D and orally administered calcium was instituted. Gradually, symptoms abated, and serum calcium and phosphorus values returned to normal. Daily doses of 80,000 units of vitamin D were main tained. Psychometry, at the age of 22, showed the subject to have an I.Q. of 56, which placed him in the lowest 1 percent of the general population. The next year, after having been taken off vita min D for 8 months, the subject’s serum calcium and phosphorus levels remained normal, and there were no clinical signs of tetany. Examination When the subject was 38 years old, he was re ferred to us by his dentist because of severe, lancinating pain of the left side of the mandible that radiated to the lower lip on that side. During examination, we learned that the subject received excellent care at home. Although he could not read, he played the piano by ear with proficiency. He was placid and cooperative, but he was aware of his problems and deficiencies. The subject resented being treated like a boy (he ap peared much younger than 38, had a childish voice and hairless face, and had immature reason ing ability and attitudes). The subject was pre occupied with his physical appearance (he wore a baseball cap at all times because of alopecia). Also, since his father’s death from coronary dis ease, he had been worried about heart trouble. The subject had never used tobacco or alco holic beverages. Over the years, he had re ceived medication of phenobarbital, meproba mate, multivitamins, salicylates, and laxatives. The family had no history of diabetes, tuber culosis, or other disease. The subject’s two sisters were both of normal stature and intelligence. The elder sister, however, had suffered from some form of malignant neoplasm. Cranin-Katz: PSEUDOHYPOPARATHYROIDISM ■ 743
■ Physical examination: Physical examination revealed a pulse of 82, blood pressure 110/70 mm. Hg, and 20 respirations per minute. The subject was moderately obese and short-statured
with pronounced dolichocephaly and alopecia (Fig. 1). The scalp was covered with many abrasions and lacerations, which were said to be factitious. He had narrow shoulders, broad hips and moderate scoliosis. The subject’s voluntary movements were poorly coordinated and his physical responses were slow. Body hair was scant, pubic hair and axillary hair were practically nonexistent, and genitalia were small and underdeveloped. Vision of the left eye was extremely poor, and both lenses had peripheral opacities. The neck was extremely short and was limited in move ment. There was a smooth liver edge two fingerbreadths below the costal margin, and a 3-mm.diameter sinus 2 cm. posterior to the anus. Fingers and arms were quite short, as were the fourth toes. Neurologically, the Chvostek and the Trous seau signs were negative. ■ Oral examination: The lips were heavy, flaccid, and poorly developed. The saliva was ropy and profuse. The palatal vault was high and narrow, with a compressed maxilla. The tongue was well papillated, extended in midline, and had good mobility and color. Other membranes were pink, moist, and firm; there were no masses, discolorations, or areas of bleeding or inflamma tion. The dentition, which was in adequate re pair, consisted of the 6 maxillary and mandibular anterior teeth (Fig. 2). Digital pressure of the buccal alveolar ridge of the left side of the mandible caused the subject much pain. The region of the mental foramen was particularly sensitive. The neck was free of glandular en largement. ■ Radiographic examination: General radio graphs revealed a thickening of the calvarium
Fig. 1 ■ Full-face view (top) and profile (bottom) of subject at age 38
744 ■ JADA, Vol. 74, March 1967
Fig. 2 ■ Subjects's dentition consisting of 6 maxillary and mandibular anterior teeth
Fig. 3 ■ Radiographs of 6 anterior teeth of upper and lower jaws
tables with widening of the diploid spaces and radial striations; massive frontal sinuses; numer ous small calcifications in the region of the basal ganglions; biconcave upper dorsal vertebrae and fifth lumbar vertebra; coxa valga deformity of the femur with widening of the distal portions of the femora and cortical thinning. In the radiographs, the anterior teeth of both jaws were present and, though the roots appeared short, the anatomy and the bony architecture was essentially normal. In all four posterior quad rants, poorly formed, hypocalcified teeth lay in random positions. In the left side of the mandible, 2 such teeth, probably rudimentary unerupted premolars, were close to the mental foramen (Fig. 3, 4). ■ Laboratory findings: Laboratory results revealed calcium level of 9.4 m g./100 ml., phos phorus level of 3.6 m g./100 ml., and alkaline phosphotase, 11.7 King-Armstrong units. The parathormone test (Elsworth-Howard) was made with 200 units of parathormone taken intravenous ly. There was no significant change in serum phos phorus or an increase in urinary phosphorus output. ■ Diagnosis: Diagnosis from clinical findings was pseudopseudohypoparathyroidism. Distin guishing characteristics are as follows: mental deficiency; deformities of skeleton, including dolichocephaly, high-arched palate, stubby digits, in creased carrying angle of arms, and dwarfism with radiographic evidence of osteodysgenesis; oligodontia with malformed and unerupted pre molars and molars; testicular hypogonadism; bi lateral cortical cataracts; left internal strabismus; congenital hypertropia; pilonidal sinus, and hyper keratosis follicularis.
Treatment and course With the patient under intravenous, synergistic basal narcosedation and regional block anesthesia, a classic left mandibular crestal mucoperiosteal incision was made, and the flap was reflected buccally. The underlying bone appeared normal morphologically and responded to bur and oste otome as expected. Three hyporcalcified, poorly developed teeth (Fig. 5) were dissected free. Care was exercised while operating in the mental foramen region. The wound was dusted with sulfanilimide crystals and primary closure was effected by use of no. 3-0 silk sutures. Wound healing was slow, but eventually a nor mal ridge with a healthy mucous membrane cov ering was achieved. There was no postoperative paresthesia. The lancinating pain was immediate ly relieved in the operative region and has not recurred (Fig. 6).
Fig. 4 ■ Radiograph shovys 3 unerupted premolars on left side of mandible. Two teeth are close to region of mental foramen
Cranin-Katz: PSEUDOHYPOPARATHYROIDISM ■ 745
resting phase. The etiology is unknown. It is only speculated that there is a genetic relation ship between PH and PPH. Additional basic re search is needed to determine the cause and pos sible prevention of this condition.
Fig. 5 ■ Three hypocalcified, poorly developed teeth dissected free
Fig. 6 ■ Postoperative radiographs of operative region from which 3 unerupted teeth were dissected
Pathological diagnosis Pathological diagnosis of specimens was trabeculated bone with regions of acellular, osteoid mar row and malformed tooth with secondary dentin and pulpal calcifications.
Sum m ary A discussion of hypoparathyroidism, pseudohypo parathyroidism, and pseudopseudohypoparathy roidism is presented. The distinction between PH and PPH is not clear. It appears, however, that patients mature out of PH and into PPH, the
746 ■ JADA, Vol. 74, March 1967
Doctor Cranin is director of dental services, Brookdale Hospital Center, Brooklyn, and associate attending dental and oral surgeon, Mount Sinai Hospital, 100th Street and Fifth Avenue, New York, 10029. Doctor Katz is assistant attending dentist, Brookdale Hospital Center, Brooklyn, and assistant attending dentist, and chief of the department of oral diagnosis, Mount Sinai Hospital. *A n evaluation made after the injection of 200 units of parathormone given intravenously. Serum and urinary phosphorus levels are evaluated. It has been found that, in normal patients, phosphorus values are not changed after this procedure. Therefore, use of the test in dif ferentiating PH from hypoparathyroidism is questionable. 1. Kleiner, I. S., and Orten, J. M. Biochemistry, ed. 6. St. Louis, C. V . Mosby Co., 1962. 2. M cLean, F. C. Bone. Sci Amer 192:84 Feb., 1955. 3. Harrison, T. R., and others. Principles of internal medicine, ed. 4. New York, McGraw-Hill Book Co., 1962. 4. Albright, F., and others. Pseudo-hypoparathyroidism— an example of "Seabright-Bantam syndrome": re port of 3 cases. Endocrinology 30:922 June, 1942. 5. Boorstein, S. Asymmetrical congenital malformation of the extremities with a case report of two cases. Ann Surg 63:192 Feb., 1916. 6. Boorstein, S. Symmetrical congenital brachydactylia; report of five cases. Surg Cynec Obstet 4 3 :654 Nov., 1926. 7. Albright, F.; Forbes, A. P., and Henneman, P. H. Pseudo-pseudohypoparathyroidism. Trans Assn Am er Phy sicians 65:337, 1952. 8. Cohen, M . L., and Donnell, G. N. Pseudohypopara thyroidism with hypoparathyroidism. A case report and review of literature. J Pediat 56:369 March, 1960. 9. Cruz, C. E., and Barnett, N. Mental retardation in pseudopseudohypoparathyroidism: case reports of siblings and review of literature. Amer J Ment Defic 67:381 Nov., 1962. 10. M ann, J. B.; Alterman, S., and Hills, A. G. A l bright's hereditary osteodystrophy comprising pseudohy poparathyroidism and pseudo-pseudohypoparathyroidism. W ith a report of two cases representing the complete syndrome occurring in successive generations. Ann Intern M ed 56:315 Feb., 1962. 1 1. Papadatos, C., and Alivisatos, J, G. Pseudo-pseu dohypoparathyroidism. A disputable syndrome. J Pediat 57:436 Sept., 1960. 12. Papaioannou, A. C., and Matsas, B. E. Albright's hereditary osteodystrophy (without hypocalcem ia). (Brachym etacarpal dwarfism without tetany, or pseudo pseudohypoparathyroidism). Report of a case and review of the literature. Pediatrics 31 :599 April, 1963.
More research is needed to determine the dis tinction between pseudohypoparathyroidism and pseudopseudohypoparathyroidism. Both conditions, however, present orocranial prob lems pertinent to the dental profession. The patient discussed in this report demonstrates most of the classic clinical and laboratory findings.
Pseudohypoparathyroidism (PH) and pseudo pseudohypoparathyroidism (PPH) are formidable terms. The conditions are rare. Data, however, are accumulating in sufficient amounts to warrant alerting the dental profession to orocranial problems. This report includes a discussion of parathyroid function, a survey of the literature, and a report of a case.
Parathormone is a protein with a molecular weight of about 7,000. The protein is a chain of 83 amino acid residues of 17 amino acids.1 If the normal calcium levels are thought of as 100 percent, about 70 percent of the level is main tained by a simple solubility mechanism. The re maining 30 percent is controlled by a feedback mechanism of the parathormone. Parathormone is involved with the regulation of serum calcium levels and serum phosphorus levels, elimination of both into the urine, in creased activity of serum phosphatase, and migration of calcium from the bony depots if there is insufficient calcium in the diet. Parathormone release raises the blood calcium and lowers the blood phosphorus. It acts, primarily, in two regions. In bone, parathormone promotes the release of calcium from more sol uble intercrystalline substance and from the hydroxyapatite crystals.2 In the kidneys, para thormone increases urinary elimination of phos phates by inhibiting tubular reabsorption. Pure 741
hyperfunction could cause osteitis fibrosa cys tica.3 Parathormone secretion is governed by the calcium ion level in the blood. Normal levels vary from 9.5 to 11 mg./100 ml. Below this level, parathormone secretion is increased. Higher levels are, in part, balanced by the kidneys, which have a renal threshold of about 9 mg./100 ml. Serum calcium levels affect neuromuscular ir ritability. Levels below 5 to 7 mg./100 ml. cause tetany. Thus, pure hypofunction would result in pedocarpal spasm. Excretion of calcium is partly through the kidneys; but most calcium excretion is through the small intestinal mucosae. Vitamin D has a major role in preventing excessive loss of calcium through the intestinal wall. Review o f lite ra tu re In 1942, Albright4 reported on a group of pa tients who suffered the clinical and laboratory manifestations of hypoparathyroidism but who failed to respond to parathormone. Most of the patients were mentally retarded, short and stocky, with rounded faces, shortened metacarpals or metatarsals or both, subcutaneous calcinosis, and calcification of the basal ganglions. Although Boorstein5'8 reported bilaterally sym metrical brachymetacarpalia and brachymetatarsalia as early as 1916, the term “pseudohypopara thyroidism,” was not used until Albright’s report4 in 1942. The term, “pseudopseudohypoparathy roidism,” was used 10 years later in a paper by Albright, Forbes, and Henneman.7 In that report, the diséase of a 29-year-old patient was described. The subject had all the characteristics of PH but no corroborating laboratory evidence of hy pocalcemia. Since that time, 42 cases with vary ing additional characteristics have been added to the medical literature.8'10 Additional clinical findings reported are epi physeal dysplasia, osteochondromas, defective or delayed dentition and dental eruption, thick ened calvarium, osteoporosis, corneal or lentic ular opacities, blue scleras, mental retardation, and abnormal electrocardiograph tracings. Some of these characteristics have been observed in other independent congenital or hereditary syn dromes, such as brachydâctylia, or in other meta bolic disorders. Consistencies appear as more cases are report ed. Twice as many females as males are affected 742 ■ JADA, Vol. 74, March 1967
by the disease, and classic clinical and radiographic features have appeared. The term pseudopseudohypoparathyroidism has been criticized11 because it does not défine the syndrome it identifies. For example, there appears to be no dysfunction of the parathyroid glands. Changing the names of pseudohypopara thyroidism and pseudopseudohypoparathyroidism to Albright’s hereditary osteodystrophy has been discussed. As a more definitive term, we suggest hereditary osteopleiotropy. Chemically, PH may show hypocalcemia, whereas PPH does not. In three cases, early-age hypocalcemia spontaneously changed to normocalcemia as the subjects matured. This change seems to indicate a change from PH to PPH. Therefore, it has been suggested that PH and PPH are two forms of the same syndrome be cause of the similarities of symptoms and find ings, and because both diseases were reported in members of the same family, suggesting genetic relationships. The most recent review by Papaioannou and Matsas12 introduced evidence that hypocalcemia and hyperphosphatemia should not be consid ered pathognomonic features to distinguish PH from PPH. Papaioannou and Matsas suggest that PH is the extreme form of the less severe. Some of the reported characteristics, such as méritai re tardation, disturbed dental development, and ectopic calcinosis, which are common in idio pathic hypoparathyroidism, suggest metabolic dis turbance of calcium and phosphorus chemistry. These symptoms, however, also occur in normocaicemic PPH. This similarity of characteristics seems to indicate a genetic factor in addition to the obvious metabolic relationship. Findings of biopsies of the parathyroid gland in patients with these characteristics were normal or hyperplastic despite what seemed to be a hypoparathyroid dysfunction. Neither biopsy, nor determination of renal tubular reabsorption of phosphorus, nor Ellsworth-Howard* testing is reliable in the diagnosis of PH, PPH, or idiopathic hypoparathyroidism. (Regardless of the defect, there have been no subjects that have not responded to treatment with vitamin D and calcium gluconate.) Report o f case The classic clinical and laboratory observations reported, including the Pickwickian facies and
stature, shortened arms and legs, brachymetacarpalia and brachymetatarsalia, mental retardation, and an interesting corroborating dental history, were made of this patient. The subject has been studied from birth, and his entire clinical-bio chemical history is known. History The subject was a full-term spontaneous delivery. His weight, at birth, was 14 pounds. He had a peculiarly shaped head with prominent frontal areas. At the age of 3 weeks, thete was an abnormal increase in weight, and thyroid in sufficiency was the presumptive diagnosis. Large quantities of thyroid extract were prescribed, but there was no appreciable gain in weight or height. The first tooth, a lower incisor, erupted at the age of 6 months, but subsequent eruption was re tarded. The subject did not walk until the age of 18 months, nor did he talk until he was 3 years old. When the subject was 5 years old, he received radiation treatments for the abdomen; however, reasons for this treatment are obscure. At the age of 7, the subject was tall for his age and noticeably overweight. Since then, however, his height has not changed significantly, and weight increases have been minimal. Although the sub ject started school when he was 7, he soon was placed in an institution for retarded children be cause he could not comprehend a normal firstgrade curriculum. The subject received a thorough examination at the age of 15, which revealed him to be awk ward and of stocky and subnormal stature. Other characteristics found were as follows: an enlarged head, particularly in the frontal areas; opacities of both lenses; thickness of the calvarium; large frontal sinuses; calcification in the intercranial regions, above and bilateral to the sella turcica, and multiple, poorly calcified, unerupted teeth in both anterior and posterior regions. A positive Chvostek’s test confirmed a diagnosis of tetany. Two clinical tests that confirm a diagno sis of tetany are Chvostek’s and Trousseau’s signs. Chvostek’s sign is considered positive when spasm of the facial musculature is elicited by tapping on the preauricular region at the exit of the facial nerve. Trousseau’s sign is present when there is pedal or carpal spasm after a pressure cuff, at 5 mm. Hg above systolic, is applied to the leg or arm for 3 minutes.
Chemistry studies indicated calcium, 7.2 mg./ 100 ml.; phosphorous, 6.4 mg./lOO ml., and al kaline phosphatase, 25.4 King-Armstrong units. Diagnosis was intracranial neoplasm with second ary hypoparathyroidism. When the subject was 19 years old, he com plained of stiffness and paresthesia of fingers and toes. There was a pronounced loss of scalp hair, and findings described at the age of 15 were con firmed, except that the alkaline phosphatase level was now normal. Diagnosis at the age of 19 was pseudohypoparathyroidism. A regimen of vitamin D and orally administered calcium was instituted. Gradually, symptoms abated, and serum calcium and phosphorus values returned to normal. Daily doses of 80,000 units of vitamin D were main tained. Psychometry, at the age of 22, showed the subject to have an I.Q. of 56, which placed him in the lowest 1 percent of the general population. The next year, after having been taken off vita min D for 8 months, the subject’s serum calcium and phosphorus levels remained normal, and there were no clinical signs of tetany. Examination When the subject was 38 years old, he was re ferred to us by his dentist because of severe, lancinating pain of the left side of the mandible that radiated to the lower lip on that side. During examination, we learned that the subject received excellent care at home. Although he could not read, he played the piano by ear with proficiency. He was placid and cooperative, but he was aware of his problems and deficiencies. The subject resented being treated like a boy (he ap peared much younger than 38, had a childish voice and hairless face, and had immature reason ing ability and attitudes). The subject was pre occupied with his physical appearance (he wore a baseball cap at all times because of alopecia). Also, since his father’s death from coronary dis ease, he had been worried about heart trouble. The subject had never used tobacco or alco holic beverages. Over the years, he had re ceived medication of phenobarbital, meproba mate, multivitamins, salicylates, and laxatives. The family had no history of diabetes, tuber culosis, or other disease. The subject’s two sisters were both of normal stature and intelligence. The elder sister, however, had suffered from some form of malignant neoplasm. Cranin-Katz: PSEUDOHYPOPARATHYROIDISM ■ 743
■ Physical examination: Physical examination revealed a pulse of 82, blood pressure 110/70 mm. Hg, and 20 respirations per minute. The subject was moderately obese and short-statured
with pronounced dolichocephaly and alopecia (Fig. 1). The scalp was covered with many abrasions and lacerations, which were said to be factitious. He had narrow shoulders, broad hips and moderate scoliosis. The subject’s voluntary movements were poorly coordinated and his physical responses were slow. Body hair was scant, pubic hair and axillary hair were practically nonexistent, and genitalia were small and underdeveloped. Vision of the left eye was extremely poor, and both lenses had peripheral opacities. The neck was extremely short and was limited in move ment. There was a smooth liver edge two fingerbreadths below the costal margin, and a 3-mm.diameter sinus 2 cm. posterior to the anus. Fingers and arms were quite short, as were the fourth toes. Neurologically, the Chvostek and the Trous seau signs were negative. ■ Oral examination: The lips were heavy, flaccid, and poorly developed. The saliva was ropy and profuse. The palatal vault was high and narrow, with a compressed maxilla. The tongue was well papillated, extended in midline, and had good mobility and color. Other membranes were pink, moist, and firm; there were no masses, discolorations, or areas of bleeding or inflamma tion. The dentition, which was in adequate re pair, consisted of the 6 maxillary and mandibular anterior teeth (Fig. 2). Digital pressure of the buccal alveolar ridge of the left side of the mandible caused the subject much pain. The region of the mental foramen was particularly sensitive. The neck was free of glandular en largement. ■ Radiographic examination: General radio graphs revealed a thickening of the calvarium
Fig. 1 ■ Full-face view (top) and profile (bottom) of subject at age 38
744 ■ JADA, Vol. 74, March 1967
Fig. 2 ■ Subjects's dentition consisting of 6 maxillary and mandibular anterior teeth
Fig. 3 ■ Radiographs of 6 anterior teeth of upper and lower jaws
tables with widening of the diploid spaces and radial striations; massive frontal sinuses; numer ous small calcifications in the region of the basal ganglions; biconcave upper dorsal vertebrae and fifth lumbar vertebra; coxa valga deformity of the femur with widening of the distal portions of the femora and cortical thinning. In the radiographs, the anterior teeth of both jaws were present and, though the roots appeared short, the anatomy and the bony architecture was essentially normal. In all four posterior quad rants, poorly formed, hypocalcified teeth lay in random positions. In the left side of the mandible, 2 such teeth, probably rudimentary unerupted premolars, were close to the mental foramen (Fig. 3, 4). ■ Laboratory findings: Laboratory results revealed calcium level of 9.4 m g./100 ml., phos phorus level of 3.6 m g./100 ml., and alkaline phosphotase, 11.7 King-Armstrong units. The parathormone test (Elsworth-Howard) was made with 200 units of parathormone taken intravenous ly. There was no significant change in serum phos phorus or an increase in urinary phosphorus output. ■ Diagnosis: Diagnosis from clinical findings was pseudopseudohypoparathyroidism. Distin guishing characteristics are as follows: mental deficiency; deformities of skeleton, including dolichocephaly, high-arched palate, stubby digits, in creased carrying angle of arms, and dwarfism with radiographic evidence of osteodysgenesis; oligodontia with malformed and unerupted pre molars and molars; testicular hypogonadism; bi lateral cortical cataracts; left internal strabismus; congenital hypertropia; pilonidal sinus, and hyper keratosis follicularis.
Treatment and course With the patient under intravenous, synergistic basal narcosedation and regional block anesthesia, a classic left mandibular crestal mucoperiosteal incision was made, and the flap was reflected buccally. The underlying bone appeared normal morphologically and responded to bur and oste otome as expected. Three hyporcalcified, poorly developed teeth (Fig. 5) were dissected free. Care was exercised while operating in the mental foramen region. The wound was dusted with sulfanilimide crystals and primary closure was effected by use of no. 3-0 silk sutures. Wound healing was slow, but eventually a nor mal ridge with a healthy mucous membrane cov ering was achieved. There was no postoperative paresthesia. The lancinating pain was immediate ly relieved in the operative region and has not recurred (Fig. 6).
Fig. 4 ■ Radiograph shovys 3 unerupted premolars on left side of mandible. Two teeth are close to region of mental foramen
Cranin-Katz: PSEUDOHYPOPARATHYROIDISM ■ 745
resting phase. The etiology is unknown. It is only speculated that there is a genetic relation ship between PH and PPH. Additional basic re search is needed to determine the cause and pos sible prevention of this condition.
Fig. 5 ■ Three hypocalcified, poorly developed teeth dissected free
Fig. 6 ■ Postoperative radiographs of operative region from which 3 unerupted teeth were dissected
Pathological diagnosis Pathological diagnosis of specimens was trabeculated bone with regions of acellular, osteoid mar row and malformed tooth with secondary dentin and pulpal calcifications.
Sum m ary A discussion of hypoparathyroidism, pseudohypo parathyroidism, and pseudopseudohypoparathy roidism is presented. The distinction between PH and PPH is not clear. It appears, however, that patients mature out of PH and into PPH, the
746 ■ JADA, Vol. 74, March 1967
Doctor Cranin is director of dental services, Brookdale Hospital Center, Brooklyn, and associate attending dental and oral surgeon, Mount Sinai Hospital, 100th Street and Fifth Avenue, New York, 10029. Doctor Katz is assistant attending dentist, Brookdale Hospital Center, Brooklyn, and assistant attending dentist, and chief of the department of oral diagnosis, Mount Sinai Hospital. *A n evaluation made after the injection of 200 units of parathormone given intravenously. Serum and urinary phosphorus levels are evaluated. It has been found that, in normal patients, phosphorus values are not changed after this procedure. Therefore, use of the test in dif ferentiating PH from hypoparathyroidism is questionable. 1. Kleiner, I. S., and Orten, J. M. Biochemistry, ed. 6. St. Louis, C. V . Mosby Co., 1962. 2. M cLean, F. C. Bone. Sci Amer 192:84 Feb., 1955. 3. Harrison, T. R., and others. Principles of internal medicine, ed. 4. New York, McGraw-Hill Book Co., 1962. 4. Albright, F., and others. Pseudo-hypoparathyroidism— an example of "Seabright-Bantam syndrome": re port of 3 cases. Endocrinology 30:922 June, 1942. 5. Boorstein, S. Asymmetrical congenital malformation of the extremities with a case report of two cases. Ann Surg 63:192 Feb., 1916. 6. Boorstein, S. Symmetrical congenital brachydactylia; report of five cases. Surg Cynec Obstet 4 3 :654 Nov., 1926. 7. Albright, F.; Forbes, A. P., and Henneman, P. H. Pseudo-pseudohypoparathyroidism. Trans Assn Am er Phy sicians 65:337, 1952. 8. Cohen, M . L., and Donnell, G. N. Pseudohypopara thyroidism with hypoparathyroidism. A case report and review of literature. J Pediat 56:369 March, 1960. 9. Cruz, C. E., and Barnett, N. Mental retardation in pseudopseudohypoparathyroidism: case reports of siblings and review of literature. Amer J Ment Defic 67:381 Nov., 1962. 10. M ann, J. B.; Alterman, S., and Hills, A. G. A l bright's hereditary osteodystrophy comprising pseudohy poparathyroidism and pseudo-pseudohypoparathyroidism. W ith a report of two cases representing the complete syndrome occurring in successive generations. Ann Intern M ed 56:315 Feb., 1962. 1 1. Papadatos, C., and Alivisatos, J, G. Pseudo-pseu dohypoparathyroidism. A disputable syndrome. J Pediat 57:436 Sept., 1960. 12. Papaioannou, A. C., and Matsas, B. E. Albright's hereditary osteodystrophy (without hypocalcem ia). (Brachym etacarpal dwarfism without tetany, or pseudo pseudohypoparathyroidism). Report of a case and review of the literature. Pediatrics 31 :599 April, 1963.