[Comparison of osteodensitometric and quantitative bone ultrasound parameters among patients with pseudopseudohypoparathyroidism, pseudohypoparathyroidism type Ia and primary hyperparathyroidism]


NOVEMBER 20, 2004

Ca&Bone - 2004;7(04)

[INTRODUCTION - Parathyroid hormone (PTH) excretion is increased both in primary hyperparathyroidism (pHPT) and in pseudohypoparathyroidism type Ia (PHP Ia). Pseudo-pseudohypoparathyroidism (P-PHP) is considered to be the normocalcemic form of pseudohypoparathyroidism type Ia. Our aim was to assess bone mineral content and bone quality as well as to determine whether these parameters are related to PTH levels in the above mentioned disorders. PATIENTS AND METHOD - 10 patients with pseudopseudohypoparathyroidism (P-PHP, age: 41.6 ±5.4 ys) were compared to 10 patients with primary hyperparathyroidism (pHPT) and to 10 healthy subjects, matched for age and gender. Moreover, nine patients with pseudohypoparathyroidism type Ia (PHP, age: 34.2 ±5.43 ys) were compared to nine age- and gender-matched patients with primary hyperparathyroidism and to nine healthy controls, respectively.The occurrence of previous bone fractures was recorded and bone mass was measured (by dual photon absorptiometry on the axial bones and by single photon absorptiometry on the forearm). Quantitative ultrasound (QUS) examination was performed both on the calcaneus by broadband ultrasound attenuation (BUA, dB/MHz) and speed of sound (SOS, m/s) measurements and on the proximal phalanges by amplitude-dependent speed of sound (AdSOS, m/s) measurements. In addition, some laboratory parameters of calcium metabolism were tested. RESULTS - No difference was found between PHP Ia and pHPT in bone mass.The lowest value was observed at the radius. Among the QUS parameters, pathologically low AdSOS was found at the phalanges in PHP Ia and it was lower than in pHPT patients, whereas at the calcaneus BUA showed a similar tendency. Bone mass did not significantly differ between P-PHP and healthy controls, it was decreased, however, at the forearm in the patients. Pathological AdSOS was found in P-PHP, which was lower than in pHPT. SOS at the calcaneus was lower in P-PHP than in pHPT, though it was not considered pathological. Laboratory results were typical for the diseases and the radiological examinations confirmed the diagnosis. Bone fractures occurred in three and two patients with PHP Ia and P-PHP, respectively, while no fractures were recorded in the pHPT and healthy groups. CONCLUSION - Bone loss among patients with PHP Ia is considered to be the impact of PTH excess on bone tissue.The deterioration of bone quality and architecture may play a role in the development of bone fractures.]



Further articles in this publication


[Biochemical processes of the bone in patients treated with clodronate for metastatic prostate cancer]


[INTRODUCTION - The bone remodelling process of 81 patients with metastatic prostate cancer was analyzed and correlated to PSA levels. PATIENTS AND METHODS - The patients were recruited from 9 collaborating urology departments. Levels of β-CrossLaps, BALP, urine calcium and urine phosphate were measured. All patients were treated identically (TUR plus an LH-RH analogue or MAB), according to GCP guidelines. After the appearance of metastasis, the patients also received a bisphosphonate compound (clodronate). RESULTS - Bone degradation and formation showed a correlation both in living and deceased patients, indicating that the two processes are not independent. A progressive decrease in the PSA level was associated with a decrease in the β-CrossLaps level. CONCLUSION - In addition to PSA, β-CrossLaps and BALP, two markers of bone metabolism, might prove good predictors of metastasis formation and of response to therapy. Evaluation of the markers relative to agedependent osteoporosis can further improve their predictive value.]


[A de novo heterozygous R551K point mutation and an A986S polymorphism in a patient with neonatal severe primary hyperparathyroidism]

CSÁKVÁRY Violetta, TÓTH Miklós, PATÓCS Attila, VARGA Ibolya, OROSZLÁN György, RÁCZ Károly

[INTRODUCTION - Familial hypocalciuric hypercalcemia and neonatal severe primary hyperparathyroidism are caused by inactivating mutations of the calcium-sensing receptor (CaSR) gene. We report the case of a now 9.5 years old boy who presented with the clinical syndrome of neonatal severe hyperparathyroidism. PATIENT AND METHODS - At the age of 2 days the patient developed respiratory distress. Clinical studies revealed increased serum calcium (3.1 mmol/l), non-suppressed serum parathyroid hormone level (48.3 pg/ml) and severe undermineralization of bones, as well as periosteal calcification in the distal part of both femurs suggesting fractures during the intrauterine life. Parathyreoidectomy was not performed.At the age of 6 years normal mental and physical development, persisting hypercalcemia without clinical symptoms, normal skeletal morphology, absence of new bone fractures, and absence of renal stones or nephrocalcinosis were documented, and the patient has remained completely symptom-free until his present age of 9.5 years. Sequence analysis of the entire coding region (exons 2-7) of the CaSR gene in peripheral leukocyte DNA revealed a heterozygous mutation at codon 551 (AGG→AAG) predicting a change of arginine to lysine (R551K). In addition, a known heterozygous polymorphism at codon 986 (GCC→TCC) was found in the proband and in his father. CONCLUSION - Our patient seems to represent the fourth reported case of neonatal severe primary hyperparathyroidism with a heterozygous de novo mutation of the CaSR gene. In addition, this case provides new evidence that with time the disease of neonatal severe hyperparathyroidism may spontaneously turn into a symptomless, benign condition resembling familial hypocalciuric hypercalcemia.]


[The pathophysiological role of the cell surface calcium-sensing receptor New clinical entities and drugs, potential therapeutic targets]

TÓTH Miklós

[The extracellular calcium-sensing receptor (CaSR) was recognized and cloned a decade ago. It is a G-proteincoupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. Diseases known as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism and autosomal dominant hypocalcemia are the consequences of naturally occurring mutations of the CaSR. However, the spectrum of the CaSR diseases became more complex with the recognition of both hypo- and hypercalcemic states caused by anti-CaSR autoantibodies. Activating anti-CaSR autoantibodies have been implicated in the pathogenesis of isolated idiopathic hypoparathyroidism and of hypoparathyroidism associated with autoimmune polyglandular syndromes. Inactivating CaSR autoantibodies may cause fluctuating hypercalcemic disorder that resembles primary hyperparathyroidism. The CaSR recently became one of the most intensively investigated target of potential new drugs. Cinacalcet has been approved for the treatment of secondary hyperparathyroidism associated with chronic renal insufficiency and for the management of inoperable or metastatic parathyroid carcinoma.The CaSR may be one of the main molecular target of strontium ranelate, wich is a new antiosteoporotic compound.]

All articles in the issue

Related contents


[The effect of sex hormone replacement on radial bone mineral content in boys with panhypopituitarism]


[INTRODUCTION - Children with pituitary insufficiency normally receive growth hormone and thyroid hormone substitution, but glucocorticoid treatment is rarely necessary. Sex hormone replacement is introduced in puberty, which, at the same time, promotes growth and bone maturation. In this study the effect of testosterone replacement on bone mineral content was examined. PATIENTS AND METHODS - Nine boys (16.3±1.3 years) with hypopituitarism were involved in the study who had been receiving growth hormone and thyroid hormone replacement for several years by the beginning of the study.Androgen was substituted by the intramuscular administration of 50 mg testosterone biweekly.The children's height,weight, the rate of pubescence, and bone age were checked, and bone mineral density was measured by single photon absorptiometry every six month. During the substitution treatment serum thyroxin and testosterone levels remained in the normal ranges. RESULTS - A significant increase in bone mineral density was observed during the testosterone treatment, with Z-scores -1.80, -0.91 and +0.14 at baseline, 12 and 24 months, respectively (p<0,001). Z-scores adjusted for bone age remained in the normal range throughout the study (-0.904 at baseline and -0.946 at one year). CONCLUSION - The increase rate of bone mineral density (0.16 g/cm/year) was significantly higher compared both to the normal reference in this age group (0.07 g/cm/yr, p=0.0015) and to the normal reference relative to their bone age (p<0.0006). The increase in bone mineral density suggests that testosterone replacement has an important role both in the quantitative and qualitative development of bones.]


[Renal stone formation after parathyroidectomy in patients with primary hyperparathyroidism]

BERCZI Csaba, BALÁZS György, LUKÁCS Géza, TÓTH Csaba

[INTRODUCTION - The incidence of renal stone formation was studied in patients with primary hyperparathyroidism after parathyroidectomy. PATIENTS AND METHODS - Ninety-two patients operated on for hyperparathyroidism were included in the study. In Group 1 the patients (n=44) had kidney stones before parathyroidectomy. Patients with no history of nephrolithiasis (n=48) before the operation were assigned to Group 2. After the operation the occurrence of renal stones was assessed for both groups.The presence of any association between the recurrence of renal stones and various clinical parameters was analysed. RESULTS - The serum concentration of Ca and parathormone decreased to the normal range in both groups after the operation. Stone formation was observed in nine cases in five patients during follow-up. All five patients belonged to Group 1.Thirty-three % of these recurrent stones were diagnosed within the first year and 89% within 5 years. Statistical analysis did not reveal any significant association between recurrent stone formation and gender, age, preoperative serum levels of Ca and parathormone or the histology of parathyroid glands. CONCLUSION - The incidence of recurrent renal stones after successful parathyroidectomy significantly decreased in patients with primary hyperparathyroidism.]


[Disturbance of bone development in experimental hepatic cirrhosis in growing rats]

FERENCZ Viktória és munkatársai

[INTRODUCTION -The pathomechanism of hepatic osteopathy is not fully understood.We investigated how bone parameters change in growing rats with experimentally induced fatty liver, liver cirrhosis and hepatocellular carcinoma. METHODS - Liver disease was induced by administration of CCl4 and phenobarbital (PB) following a single injection of diethylnitrosamine (DEN) in 55 Fischer 344 rats.Animals were sacrificed and their femur removed at week 8 or 16. Bone mineral content (BMC), femoral length, cortical index (ratio of cortical thickness and total diameter at the diaphysis) and ultimate bending load (Fmax) of femora were determined. Results of animals treated with DEN+PB+CCl4 (group DPC, n=21) were compared to untreated animals (n=14) and to a second control group treated only with DEN+PB (group DP, n=20). RESULTS - Fatty liver and cirrhosis developed in each animal in the DPC group (n=21) at week 8 and in a subgroup of these animals (n=11) hepatocellular carcinoma also appeared by week 16. No changes in bone parameters were observed in this group at week 8, but lower BMD, femoral length, cortical index and Fmax values were found at week 16 compared to the untreated controls or to the DP group (p<0.05 for both). In the DP group no fatty liver or cirrhosis was observed at any time. Femoral length and Fmax values were higher in the DP group at week 8 compared to the untreated controls (p<0.05 for both).At week 16, however, no difference could be detected. CONCLUSION - Experimentally induced liver cirrhosis and hepatocellular carcinoma are associated with growth inhibition and reduced bone mineral content, cortical index and mechanical resistance in growing rats.]


[Is there any association between the location of the parathyroid adenoma and the presence of nephrolithiasis in primary hyperparathyroidism?]


[INTRODUCTION - The majority of patients with primary hyperparathyroidism recurrently produce kidney stones, while the rest have other clinical manifestations (metabolic bone disease, acute pancreatitis, depression, etc.).The aim of this study was to examine whether there is any association between the clinical symptoms and the location of adenoma. PATIENTS AND METHODS - The records of 91 patients (10 males, 81 females, mean age: 61.9 years, range: 20-70 ys) operated for primary hyperparathyroidism between 1995 and 2000 were retrospectively evaluated. One patient was excluded from the study because of parathyroid cancer. Nephrolithiasis was noted in 55 cases and other clinical symptoms in 35 cases. The diagnosis of pHPT was confirmed by the surgery, which also determined the precise location of the adenoma. RESULTs - In the kidney stone group, the adenoma was located in the left inferior parathyroid gland in 50 cases (91 %), (χ2=67.5, p<0,00001), in the left superior parathyroid gland in 2 patients, while in 3 patients multiple hyperplasia was found. In the group without nephrolithiasis the adenoma was located in the right inferior parathyroid gland in 24 patients (69 %), (χ2=43.9, p<0,0001), while in 3 patients each it was detected in the left and right superior parathyroid gland, respectively. Multiple hyperplasia was also observed in 3 patients and ectopic location in 2 patients. CONCLUSION - The results raise the possibility that the clinical manifestation of the pHPT, i.e., whether it is or is not accompanied with nephrolithiasis, may be influenced by the location of the adenoma.This suggests that either the biological effects of the parathyroid hormone or its biologically active hormone fragments are different according to in which of the four glands it is produced.Therefore, we recommend that in patients with kidney stones where the preoperative imaging fails to reveal the location of the adenoma, during surgery the search for the adenoma should be started at the left inferior parathyroid gland.]