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Skeletal disease in primary hyperparathyroidism.

Most patients with primary hyperparathyroidism in the 1980s do not have evidence of bone disease when they are evaluated by conventional radiography. We sought to determine whether skeletal involvement can be appreciated when more sensitive techniques, such as bone densitometry and bone biopsy, are utilized. We investigated 52 patients with primary hyperparathyroidism. They had mild hypercalcemia, 2.8 +/- 0.03 mmol/liter (11.1 +/- 0.1 mg/dl), low normal phosphorus, 0.9 +/- 0.03 mmol/liter (2.8 +/- 0.1 mg/dl), and no symptoms or specific radiological signs of skeletal involvement. The greatest reduction in bone mineral density was found at the site of predominantly cortical bone, the radius (0.54 +/- 0.1 g/cm; 79 +/- 2% of expected), whereas the site of predominantly cancellous bone, the lumbar spine (1.07 +/- 0.03 g/cm2), was normal (95 +/- 3% of expected). The site of mixed composition, the femoral neck (0.78 +/- 0.14 g/cm2), gave an intermediate value (89 +/- 2% of expected). Preferential involvement of cortical bone with apparent preservation of cancellous bone in primary hyperparathyroidism was confirmed by percutaneous bone biopsy. Over 80% of patients had a mean cortical width below the expected mean, whereas cancellous bone volume in over 80% of patients was above the expected mean. The results indicate that the majority of patients with asymptomatic primary hyperparathyroidism have evidence by bone densitometry and bone biopsy for cortical bone disease. The results also indicate that the mild hyperparathyroid state may be protective of cancellous bone. The therapeutic implications of these observations await further longitudinal experience with this study population.

Biopsy↗

Primary hyperparathyroidism during pregnancy.

Historically, primary hyperparathyroidism during pregnancy was associated with significant risk of maternal morbidity and fetal death. Maternal hypercalcemia results in fetal hypercalcemia, leading to suppression of fetal parathyroid gland function. Neonatal hypocalcemia with tetany is a common occurrence after birth when maternal calcium flow is interrupted. From 1930 to 1990, 109 cases of women with primary hyperparathyroidism associated with pregnancy have been reported, 39 of whom were treated surgically before delivery. Although fetal mortality rates for medically treated women have improved, fetal morbidity continues to remain higher than in women who undergo surgical treatment of parathyroid disease during pregnancy. Of 850 patients treated surgically for primary hyperparathyroidism since 1960, 12 were pregnant. Four of the patients were treated medically during pregnancy and underwent surgery after delivery; all four infants had neonatal hypocalcemia and tetany. The remaining eight patients were treated surgically during pregnancy: six in the second trimester and two (one with associated pancreatitis and one with hypercalcemic crisis) during the first trimester. There was no fetal or maternal morbidity or death in the surgical group. Parathyroid adenomas were present in 10 of the patients, hyperplasia in one, and parathyroid carcinoma in one. The management of maternal primary hyperparathyroidism diagnosed during pregnancy should be based on the patient's symptoms and severity of disease. Hyperparathyroidism characterized by progressive symptoms should be treated surgically, preferably during the second trimester. Symptom-free patients and those with mild hypercalcemia diagnosed in the third trimester may be managed medically, postponing operation until after delivery.

Female↗

Cardiovascular disease, hypertension and renal function in primary hyperparathyroidism.

OBJECTIVES: Patients with primary hyperparathyroidism run an increased risk of death in cardiovascular disease. Long ago, hypertension was found to frequently occur in these patients. The aim of this study was to compare the death risk after surgery for hyperparathyroidism of hypertensive patients with that of normotensive ones, and to investigate relations between variables of cardiovascular disease and variables of hyperparathyroidism and renal function. METHODS: A series of 845 patients with primary hyperparathyroidism and serum creatinine <or=160 micromol L-1 was followed-up mean 10.2 (SD 5.7) years after surgery. Survival and correlation tests were performed. Death risk was estimated using a hazard function according to Poisson. RESULTS: The death risk of hypertensive hyperparathyroid patients was 50% higher compared with that of the normotensive patients, but the yearly death risk decrease after surgery for the hypertensive patients was almost doubled as compared with the decrease of the normotensive patients. Cardiovascular disease was directly related to serum calcium level, adenoma weight, osteitis fibrosa, and serum creatinine, and inversely related to glomerular filtration rate and urine osmolality, but unrelated to the symptom variables. A negative relation was found between cardiovascular disease and renal stone disease. CONCLUSIONS: It can be concluded that cardiovascular disease is more a part of primary hyperparathyroidism than just associated with it, being related to both serum calcium and adenoma weight. There was also a relationship between cardiovascular disease and decreased renal function. Death risk decrease after surgery was rather more pronounced for the hypertensive patients compared with the normotensive ones.

Age Distribution↗

Nephrolithiasis during pregnancy secondary to primary hyperparathyroidism.

Nephrolithiasis secondary to primary hyperparathyroidism infrequently complicates pregnancy. It can cause severe maternal and fetal complications. We present a case of a pregnant woman with nephrolithiasis and primary hyperparathyroidism. We reviewed the management of nephrolithiasis due to primary hyperparathyroidism during pregnancy. We believe that early recognition and timely intervention can significantly reduce the incidence of complications.

Adult↗

[Two cases of primary hyperparathyroidism].

Two cases of primary hyperparathyroidism with urolithiasis are reported. These cases were preoperatively localized by CT-scan and 201T1-chloride scintiscan. Primary hyperparathyroidism is one of the most significant pathogenesis of urolithiasis and determination of serum Ca level is valuable in screening for primary hyperparathyroidism. CT-scan, ultrasonogram and scintiscan with 201T1-chloride are useful and are non-invasive studies to detect preoperative localization of parathyroid tumors.

Adenoma↗

Immunological aberration in primary hyperparathyroidism.

Altered immunological reactivity in primary hyperparathyroidism is suggested by the strong association between this disorder and malignancy. The present study was carried out to determine whether altered lymphocyte proliferation in response to common mitogens (PHA, Con-A, PWM) exists in primary hyperparathyroidism, and, if so, whether the abnormality resides in the lymphocytes or in humoral factors present in the plasma of patients with hyperparathyroidism. Ficoll-Hypaque purified lymphocytes from 6 patients with primary hyperparathyroidism and 4 normal volunteers were stimulated with PHA, Con-A and PWM in the presence of plasma from patients with primary hyperparathyroidism and normal AB+ plasma. The incorporation of [3H]thymidine in unstimulated (control) and stimulated cultures was determined. The results demonstrate that lymphocyte proliferation was significantly higher when both patients' and normal lymphocytes were stimulated with mitogens in the presence of patients' plasma. These findings suggest that plasma from patients with primary hyperparathyroidism contains a potentiator of lymphocyte mitogenesis, or, alternatively lacks an inhibitor of lymphocyte activation that is present in normal plasma.

Adult↗

[Methylene blue in surgery of primary hyperparathyroidism].

Is surgery for primary hyperparathyroidism easier when methylene blue (MB) is given preoperatively? This retrospective study compares the durations of interventions for primary hyperparathyroidism carried out after i.v. MB administration to those when no MB was given. Over a period of 20 years (June 1976 to December 1996), 175 consecutive patients (56 men and 119 women, with ages ranging from 16 to 92, mean 59.6) were operated upon for primary hyperparathyrodism; 55 were operated before February 1986--the period when BM was introduced routinely, and 120 after. Thirty-two other patients were excluded from the study: 14 had had a previous cervicotomy and 18 another procedure in addition to the parathyroidectomy (usually on the thyroid gland), two conditions which prolonged the time devoted to parathyroid identification and excision. Preoperative calcemia averaged 2.97 mmol/L (2.34 to 4.59) and mean preoperative PTH was equal to 2.6 times the upper normal limit (0.5 to 24.1). Both groups were similar for as age, sex, preoperative calcium and PTH, and histologies. Methylene blue was administered intravenously (5 mg/kg diluted in 500 cc of 5% glucose) over a period of time of one hour starting two hours prior to surgery. All 175 procedures were performed by two surgeons and duration of surgery was recorded from the anesthesiologist's notes. There were 149 adenomas (85%), 24 hyperplasias (14%), a combination of both in two, and unspecified in two others. Except for a case of acute lower back pain synchronous to the injection of the dye (which was immediately stopped), MB was well tolerated. Mean duration for the 55 interventions performed without MB was 68 minutes (35 to 140, median 60), compared to 49 minutes for the 120 procedures carried out after MB had been given (20 to 155, median 45). Differences in operative, times were highly significant (p < 10(-6) and represented a gain of time of 27%. Surgery for primary hyperparathyroidism was significantly shorter when it was preceded by the administration of MB, a dye which facilitates the identification of pathologic parathyroid gland(s).

Adenoma↗

Usefulness of diagnostic imaging in primary hyperparathyroidism.

BACKGROUND: In patients with primary hyperparathyroidism, prevention of urinary stone recurrence can be achieved by surgical removal of the enlarged parathyroid gland. To ensure the efficacy of surgery for primary hyperparathyroidism, preoperative localization of the enlarged gland is important. In the present study, usefulness of diagnostic imaging for localization of the enlarged gland was investigated in primary hyperparathyroidism. METHODS: We retrospectively examined the findings of imaging studies and clinical records in 79 patients (97 glands) who underwent surgical treatment for primary hyperparathyroidism at Chiba University Hospital between 1976 and 2000. The detection rates of accurate localization were investigated for imaging techniques, such as ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), thallium-201 and technetium-99m pertechnetate (Tl-Tc) subtraction scintigraphy and 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy, and analysed in relation to the size and weight of the gland and pathological diagnosis. RESULTS: The detection rates by US, CT, MRI, Tl-Tc subtraction scintigraphy and MIBI scintigraphy were 70%, 67%, 73%, 38% and 78%, respectively. The overall detection rate changed from 50% to 88% before and after 1987. The detection rate of MIBI scintigraphy was superior to Tl-Tc subtraction scintigraphy. CONCLUSION: In primary hyperparathyroidism, improvement of accurate localization of an enlarged parathyroid gland was demonstrated along with recent advances in imaging techniques including MIBI scintigraphy.

Adenoma↗

[Borderline primary hyperparathyroidism].

The clinical presentation of primary hyperparathyroidism has changed considerably after the application of biochemical autoanalysers. The condition was previously found with characteristic symptoms in bone, kidneys and the gastrointestinal tract; less than 1% of patients were assumed to be asymptomatic. Today, most patients have mild and uncharacteristic symptoms. Primary hyperparathyroidism has been detected with increasing frequency in the western world, but there are large variations within demographically otherwise comparable areas. There are also regional differences regarding the incidence of surgical treatment of the disease. Demographic studies have shown increased morbidity and mortality primarily from cardiovascular and possibly malign diseases related to hypercalcemia. Follow-up studies based on surgical series have shown increased mortality related to preoperative serum calcium level. In view of the altered clinical picture of primary hyperparathyroidism, treatment of moderate and possibly "benign" primary hyperparathyroidism has been actualised. At an international consensus conference in 1990, this patient group was defined by an arbitrary serum calcium limit of 3.0 mmol/l, but this limit has been found to be unacceptably high. Regardless of where the upper limit is set, there are so far well accepted indications for surgery, but only one in two patients fulfil these criteria. A working group of endocrinologists and endocrine surgeons from nine university clinics in Scandinavia have recently initiated a prospective, randomised study evaluating surgical treatment and a systematic follow-up of patients with borderline primary hyperparathyroidism.

Bone Density↗

Primary hyperparathyroidism.

The incidence of primary hyperparathyroidism amongst the elderly has increased during the last decade. Recent studies show that the incidence has risen to 277 per million population after the introduction of automated techniques for measuring the serum calcium. The diagnosis of primary hyperparathyroidism in patients over 60 has increased fivefold in men and more than sixfold in women. Coincidentally there has been a diversity of clinical presentation and an increasing interest in the manifestation. We report three patients who presented with entirely different clinical pictures but who were proved to have primary hyperparathyroidism.

Aged↗

Primary hyperparathyroidism: presentation and management.

164 hypercalcemic patients were examined to determine the co-relation, frequency and mode of presentation of primary hyperparathyroidism. Primary hyperparathyroidism was diagnosed in 11 patients (6.7%). All of them presented late with renal and bony complications. The incidence of primary hyperparathyroidism appears to be lower than that of the western countries, and the introduction of routine serum calcium estimates can be expected to yield more cases of primary hyperparathyroidism especially asymptomatic cases.

Adult↗

Association between myotonic dystrophy and primary hyperparathyroidism.

A case of primary hyperparathyroidism in a patient with myotonic dystrophy is reported. A 56-year old female with myotonic dystrophy, admitted to hospital with a urinary tract infection, had widespread muscle atrophy and myotonia with bilateral cataracts. Biochemical findings of normal renal function but raised blood calcium, depressed blood phosphate and increased parathyroid hormone, were consistent with a diagnosis of primary hyperparathyroidism. Thallium scanning of the parathyroids showed an area of discordant thallium suggesting a parathyroid adenoma. When the left lower parathyroid was later excised, histology was consistent with the diagnosis of parathyroid adenoma. As far as the authors are aware this is the first report of myotonic dystrophy and primary hyperparathyroidism in the same patient.

Adenoma↗

Are concomitant surgical procedures acceptable in patients undergoing cervical exploration for primary hyperparathyroidism?

Cervical exploration for primary hyperparathyroidism is an extremely safe procedure with essentially no operative mortality or morbidity and with success rates approaching 98%. These results have encouraged experienced surgeons to perform other surgical procedures concomitantly with cervical exploration with use of the same general anesthetic agent. This retrospective study was performed to assess the safety and efficacy of this practice. At our institution, 117 patients underwent cervical exploration for primary hyperparathyroidism in combination with an additional surgical procedure, including breast (25), biliary (21), gynecologic (19), intra-abdominal (18), and cardiothoracic (6) operations. The mean operative time was 155 minutes, and the mean duration of hospitalization was 7.6 days. Postoperatively, 115 patients (98%) were normocalcemic. Nine complications (mostly minor), which occurred in eight patients, related primarily to the concomitant surgical procedure. No operative mortality occurred. If performed by experienced surgeons in carefully selected patients, cervical exploration for primary hyperparathyroidism in combination with another elective operation is safe and cost-effective.

Adult↗

Vertebral osteopenia: a new indication for surgery in primary hyperparathyroidism.

Most patients with primary hyperparathyroidism have reduced radial and preserved vertebral bone density. We have identified a subset of patients with low lumbar spine bone density at diagnosis. This study assessed the effect of parathyroidectomy (undertaken based upon accepted surgical guidelines) or nonintervention on bone mineral density (BMD) in these patients. Twenty-two of 143 (15%) patients with mild primary hyperparathyroidism had lumbar spine BMD more than 1.5 SD below the mean for an age- and sex-matched population (z-score). Fourteen underwent parathyroidectomy, whereas 8 were followed with no intervention. All had annual BMD measurements for 4 yr after enrollment or after surgery. After parathyroidectomy, there was a brisk sustained rise in lumbar spine BMD [yr 1, 15 +/- 3% (P < 0.005); yr 4, 21 +/- 4% (P < 0.01)]. In those followed without surgery, BMD did not change significantly at any site. Postmenopausal women showed the same pattern as the cohort as a whole, i.e. increased BMD after surgery [yr 1, 13 +/- 3% (P < 0.01); yr 4, 16 +/- 5% (P < 0.01)], but no worsening was found with nonintervention despite the passage of years in the menopause. We conclude that parathyroidectomy markedly improves lumbar spine BMD in patients with vertebral osteopenia. It is proposed that reduced cancellous bone density should become a new indication for surgery in primary hyperparathyroidism.

Bone Density↗

Clinical utility of an immunoradiometric assay for parathyroid hormone (1-84) in primary hyperparathyroidism.

The reliable diagnosis of primary hyperparathyroidism depends on the measurement of PTH. The PTH assays in widespread use measure not only the hormone but also hormone fragments, thus limiting the clinical utility of the assays. A new immunoradiometric assay (IRMA) using an antigenic determinant at the extreme amino-terminal of the PTH molecule detects only full-length PTH (1-84). We compared three PTH assays and determined the presence of PTH (1-84) and PTH fragments in serum and parathyroid adenomas of patients with primary hyperparathyroidism. We studied 56 patients with primary hyperparathyroidism. PTH levels were increased in 63% using the midmolecule RIA; in 73% in the "intact" IRMA; and in 96% in the PTH (1-84)-IRMA. The PTH (1-84)-IRMA correlated with the other assays (midmolecule RIA R = +0.736; P < 0.0001; "intact"-IRMA R = +0.951; P < 0.0001) and indices of disease activity (serum calcium R = +0.511, P < 0.0001; alkaline phosphatase R = +0.489, P = 0.001; and radius bone density R = -0.366, P < 0.01). In 21 consecutive patients undergoing parathyroidectomy, 18 had parathyroid adenomas. Intact PTH was higher than PTH (1-84)-IRMA in both serum and glandular homogenates from these patients. Similar proportions of PTH (1-84) and hormone fragments were found in both adenomas [66 +/- 3% of "intact" PTH-reflected PTH (1-84) and sera (73 +/- 2% of "intact" PTH reflected PTH (1-84)]. We conclude that the PTH (1-84)-IRMA offers improved diagnostic sensitivity in patients with primary hyperparathyroidism than other currently available assays. This study also provides evidence that both PTH (1-84) and PTH fragments are produced in parathyroid adenomas and that peripheral metabolism of hormone and fragment does not alter the proportion of bioactive hormone.

Adenoma↗

[Primary hyperparathyroidism treated surgically].

Primary hyperparathyroidism is a systemic disease, more and more frequently recognized-concerning 1 to 3% of the population. Statistically appears in 1 of 1000 adults, with significant advantage of women. In Poland every year about 30 new cases are noticed and incidence increases with an age. In spite of significant advance of the knowledge, it still makes a lot of diagnostic troubles. It appears to be non-specific illness, characterised by just one symptom, mainly urolithiasis, sometimes chronic ulcer disease, chronic pancreatitis, arterial hypertension, disorders of the movement or psychic disorders. Parathyroid adenoma which is the main reason of the disease is usually single and small, multiple and bigger ones are found exceptionally. In about 2% of cases they are localized in mediastinum. In the article the basic symptoms, diagnostic and therapeutic problems were shown, especially concerning surgical treatment which is safe, radical and efficacious method when performed by experienced surgical team and the conduct from choice on primary and secondary hyperparathyroidism.

Adult↗