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[Primary hyperparathyroidism. An analysis of 152 patients with special references to acute life threatening complications (acute hyperparathyroidism)].

Tthe findings of 150 patients with proven primary hyperparathyroidism are reported. The purpose of the analysis was to find differences between the various clinical manifestations of the disease. Furthermore the occurrence of acute hyperparathyroid crisis in our series as well as in the literature are described. 65.8% of the patients were females, 34.2% were males. The leading symptom in 98 patients (group I) were kidney stones and in 23 patients (group II) cystic bone disease. Both manifestations of the disease occurred in only 7 patients (group III) and no symptoms related to the kidneys or to the bones occurred in 24 patients (group IV). Because of the difference of the clinical manifestations the additional data were analyzed for each group separately and compared with each other. There was no difference in the mean serum calcium levels for all four groups, however, patients of group I were on the average younger, the duration of the disease was longer and the weight of the parathyroid adenoma was lower compared to the other three groups. Data are presented regarding calcium excretion, phosphate clearance and tubular reabsorption of phosphate for each group. At operation single or multiple adenoma formation was present in 133 patients, whereas diffuse hyperplasia was found in 17 and carcinoma in 2 other patients. 46 of the adenomas were found in atypical anatomical localisation. This observation is responsible for the many unsuccessful or second explorations of the neck. The weight of the adenomas varied between 0.1 and 23.5 g. The most difficult diagnosis was that of diffuse hyperplasia. The success of the surgical intervention was usually established in over 80% of the cases within 24 to 48 hours after the operation with a significant fall of serum calcium. There is still no definite explanation for the variability of the clinical manifestations of primary hyperparathyroidism. Parathyroid hormone determinations on larger numbers of patients are not yet published. The assumption, that different hormones or peptide fragments are responsible for the different action on bone and kidney is discussed. In our series of 152 patients acute hyperparathyroid crisis occurred eight times. Our findings are compared to the other well documented cases in the literature. Main symptoms were nausea, vomiting abdominal pain and different states of cerebral dysfunction. Most of the patients had calcium levels over 16 mg/100 ml. Partial renal insufficiency with elevated blood urea and phosphate retention was found in ov er 50% of the cases. Overall mortality of all cases with acute parathyroid crisis is 52.5%. The pathogenesis of acute hyperparathyroidism and the implications of high calcium levels are discussed. According to our own experience hypercalcemia can be controlled with an intensive therapeutic program and emergency operation for acute parathyroid crisis is no longer necessary.

Acute Disease

Back pain and vertebral crush fractures: an unemphasized mode of presentation for primary hyperparathyroidism.

During a 3-year period, 14 of 319 patients (4.4%) with surgically proved primary hyperparathyroidism had spinal rarefaction with vertebral crush fractures but no unequivocal roentgenographic evidence of osteitis fibrosa generalisata. All complained of back pain, and this was the presenting complaint in 9 of the 14 patients. This incidence was significantly higher (P less than 0.001 for women; P less than than 0.01 for men) than the incidence of similar roentgenographic findings among patients of the same age undergoing operation for protruded intervertebral disks during this same time period. Although tradition equates roentgenographically evident bone disease in primary hyperparathyroidism with the classis findings of osteitis fibrosa generalisata, our observations emphasize that patients with primary hyperparathyroidism occasionally may present in a manner that is indistinguishable symptomatically and roentgenographically from that of postmenopausal or senile osteoporosis.

Age Factors

1alpha-hydroxyvitamin D3 in primary hyperparathyroidism.

The surgical management of primary hyperparathyroidism with severe bone disease (and tertiary hyperparathyroidism) has frequently been complicated by severe and prolonged post-operative hypocalcaemia. In seven such cases a short-pre-operative course of 1alpha-hydroxyvitamin D3 has been found to abolish these adverse features virtually completely and even to diminish pre-operative symptoms where present. Exacerbation of hypercalcaemia has not occurred and this regimen is thus recommended as a routine measure.

Adult

Effect of verapamil on insulin response to alcohol hypoglycemia in patients with primary hyperparathyroidism.

In hypercalcemic patients with primary hyperparathyroidism who were fasted over a prolonged period, alcohol ingestion induced a significant fall in glucose whereas insulin remained unchanged. The hypercalcemic patients thereby differed from normocalcemic subjects, who showed a significant decline in both glucose and insulin when alcohol was ingested after a prolonged period of fasting. An increased uptake of calcium into the beta-cells appears to have been a prerequisite for the occurrence of an unchanged insulin secretion during alcohol hypoglycemia in hypercalcemic patients, since a calcium-blocking agent, verapamil, infused intravenously during and after alcohol ingestion, brought about a normalization of the insulin response to alcohol hypoglycemia in such patients.

Adolescent

Tetracycline fluorescence in uremic and primary hyperparathyroid bone.

Twenty-five patients with end-stage renal disease, nine of whom were receiving pharmacologic doses of vitamin D, and seventeen patients with primary hyperparathyroidism underwent bone biopsy following a three-day course of tetracycline administration. The mean width of the fluorescent tetracycline bands were significantly greater in the bones of patients with uremia than in those with primary hyperparathyroidism. This difference was due to wide labels present in the patients with uremia who had not been treated with vitamin D, as no differences existed in mean label widths of patients with uremia who had received this compound and the patients with primary hyperparathyroidism. Comparison of the maximum label widths distinguished not only primary hyperparathyroid patients from those with uremia, but uremic patients who had recieved vitamin D from those who had not been so treated. Quantitative microscopy of standard, nonfluorescent histologic features failed to make this latter distinction. These data are consistent with the presence of a wide zone of instantaneously fluorescing material in uremic bone following tetracycline administration, which does not relate to bone apposition occurring during antibiotic administration. This phenomenon probably represents a delay in mineral maturation which is normalized by vitamin D. Furthermore, it is apparent that the use of a continuously administered (single) tetracycline label will result in an overestimation of bone formation rates, particularly in osteomalacic states.

Adult

Calcitonin activity of the thyroid gland in primary hyperparathyroidism.

The thyroidal content of calcitonin was investigated in patients with euthyroid goitre, patients undergoing laryngectomies or neck operations and finally patients with primary hyperparathyroidism using method of biological titration. Patients with primary hyperparathyroidism had markedly decreased content of calcitonin in the thyroid gland when compared with the content of calcitonin of both groups of patients without calcium metabolism disturbance. Decreased content of calcitonin in patients with primary hyperparathyroidism can be explained by long lasting hypercalcaemia during which the rate of biosynthesis of calcitonin in the C cells does not keep up with the rate of release of calcitonin into the circulation.

Adult

Primary hyperparathyroidism and breast cancer.

Three cases demonstrating the coexistence of primary hyperparathyroidism and breast carcinoma with the disappearance of hypercalcemia following removal of parathyroid adenomas are presented. In these cases, the patients had the typical diagnostic findings of primary hyperparathyroidism. Reluctance to perform neck explorations in such patients does not appear warranted.

Adenoma

Approach to the Patient With Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disorder in which patients develop multiple endocrine tumors simultaneously. Among these, primary hyperparathyroidism is the most common and often the earliest manifestation. All patients with MEN1 and hypercalcemia should have surgery, with most patients requiring surgical treatment before the age of 50 years. The timing of parathyroid surgery mainly depends on hypercalcemia and the presence of renal or skeletal complications. The goals of treatment are to correct hypercalcemia, prevent target organ damage, and minimize the risk of postoperative hypoparathyroidism as much as possible. Currently, the most widely recommended surgical approach is subtotal parathyroidectomy via the cervical approach (removal of 3 or 3.5 glands). With advances in imaging technology, patients with clearly localized lesions-particularly younger patients-may be candidates for individualized unilateral resection (ie, removal of both glands on the affected side). In addition, recurrent hypercalcemia after surgery is relatively common in patients with MEN1. The management of the remaining glands remains challenging, such patients usually need reoperation, calcimimetic therapy, or clinical observation. For patients requiring repeated parathyroid surgeries, in addition to searching for multifocal lesions, the possibility of ectopic parathyroid glands should also be taken into account. Ectopic parathyroid adenoma, caused by abnormal embryonic migration, complicates surgery in both sporadic and MEN1-related primary hyperparathyroidism. However, in MEN1, their higher frequency and multiglandular distribution make localization even more challenging, often leading to incomplete resection and recurrence.

Humans

Hyporegenerative anemia in primary hyperparathyroidism.

A series of patients with primary hyperparathyroidism showed a high incidence of anemia. Red cell morphology and indices, iron, folate and B12 were generally normal and reticulocyte counts inappropriately low. Focal fibrosis of the marrow space was observed in marrow biopsies from two patients, but no patient showed overt signs of a myelophthisic process. Anemia tended to occur in those with more severe hyperparathyroidism (higher serum calcium level or radiographic osteitis fibrosa cystica). Since severe hyperparathyroidism frequently compromises renal function, it is not always clear whether the anemia should be attributed to renal failure or to the metabolic disease. In nine of the 24 anemic patients, however, renal function was normal. Hyperparathyroidism may cause a hyporegenerative anemia, the mechanisms for which have not been elucidated.

Anemia

Delayed fracture healing in primary hyperparathyroidism.

The incidence of fractures in primary hyperparathyroidism is highly variable. The possibility that there might be an increased susceptibility to fracture is discussed. Healing in most is without delay. Three cases of delayed or nonunion following fracture are presented. In all three, healing accelerated dramatically after excision of a parathyroid adenoma. A pathological fracture secondary to the hyperparathyroidism of parathyroid carcinoma healed after excision of the tumor allowed regression of the osseous lesions. The endocrinologic mechanisms which cause nonunion in a small percentage of cases have not been clearly elucidated.

Female

Influence of 1,25-dihydroxycholecalciferol on parathyroid activity in patients with primary hyperparathyroidism.

Parathyroid morphology and blood chemistry were studied in five patients with primary hyperparathyroidism treated with 1,25-dihydroxycholecalciferol (1,25-DHCC) for 2 to 11 days before planned operation. Before the institution of treatment all patients were hypercalcemic, whereas the serum immunoreactive parathyroid hormone (iPTH) concentration either was elevated or normal. During the treatment the urinary phosphate excretion was significantly increased, whereas the calcium excretion and the serum concentrations of calcium and phosphate were unaffected or only slightly changed. Serum iPTH decreased during the first days of treatment, but returned then to increased levels close to the pretreatment ones. The treatment was tolerated well by the patients. Light and electron microscopy of the removed parathyroid glands disclosed one adenoma in each of the five patients, the other glands exhibiting either a slight hyperplasia or a normal appearance. Both the adenomatous and the non-adenomatous parathyroid tissue showed a predominance of dark chief cells and three of the adenomas exhibited a varying number of atrophic and oxyphil cells. The non-adenomatous glands were composed of atrophic and dark chief cells. Signs of low functional activity were ultrastructurally observed in the parathyroid parenchymal cells. It is suggested that 1,25-DHCC treatment of patients with primary hyperparathyroidism inhibits parathyroid hormone secretion.

Adult

Twenty-five year experience with primary hyperparathyroidism at Columbia Presbyterian Medical Center.

A retrospective review of 500 patients with primary hyperparathyroidism seen from 1951 to 1975 was conducted; the effect of routine screening of calcium and phosphate levels (initiated in 1968) on the incidence and spectrum of the disease was analyzed. The majority of the patients (77%) were diagnosed in the eight-year period after routine biochemical screening was instituted. Comparing the group of patients diagnosed before the advent of biochemical screening and those diagnosed since screening was instituted, we found: (1) a small but significant increase in the number of asymptomatic patients diagnosed (from 2% to 12%); (2) no change in the incidence of related medical disorders, i.e., nephrocalcinosis and hypertension; (3) no change in the incidence of primary hyperplasia and adenoma; and (4) no change in the mean serum calcium level, the mean age at diagnosis, or the number or location of the involved parathyroid glands. Although routine calcium screening has identified significantly more cases of primary hyperparathyroidism, screening apparently does not enable diagnosis at an earlier stage.

Adenocarcinoma

Primary hyperparathyroidism in paraneoplastic hypercalcaemia.

Hypercalcaemia is often associated with malignant disease. Causes of elevated serum-calcium levels in the absence of bony metastases include parathyroid-hormone production by the tumour, osteolytic factors made by the tumour, and coexistent primary hyperparathyroidism. By measuring nephrogenous cyclic-A.M.P. excretion to assess parathyroid-hormone function, we have determined the mechanism of such hypercalcaemia in 15 patients. Nephrogenous cyclic A.M.P. ranges from 0.05 to 2.40 mumol/g of creatinine in normal subjects, from 2.27 to 8.45 mumol/g in patients with primary hyperparathyroidism, and from 0.50 to 1.30 mumol/g in patients with proven non-hyperparathyroid hypercalcaemia without malignancy. 9 patients (60%) with hypercalcaemia and malignancy had normal levels of nephrogenous cyclic A.M.P. (range 0.35-2.07 mumol/g creatinine). The other 6 (40%) had elevated nephrogenous cyclic A.M.P. (range 2.70-5.55 mumol/g) consistent with increased parathyroid-hormone secretion. Surgical exploration of the neck in these patients showed that the increased parathyroid-hormone secretion was secondary to primary hyperparathyroidism, not ectopic hyperparathyroidism. Thus, the data indicate that coexistent hyperparathyroidism may be common in patients with hypercalcaemia and malignancy and that the measurement of nephrogenous cyclic A.M.P. is very useful in identifying patients at risk for hyperparathyroidism.

Adenocarcinoma

[Sacroiliac changes, HLA-B27 negative, in primary hyperparathyroidism and osteomalacia].

Radiological sacroiliac (SI) changes were found in 3 patients, 2 with primary hyperparathyroidism (1 also with associated chondrocalcinosis) and 1 with osteomalacia. Osteomalacia was due to celiac disease. None of the 3 patients, all females, had a history of psoriasis, urethritis, iritis or chronic colitis. There was no renal function impairment. Peripheral joints were affected in the patient with associated condrocalcinosis. HLA B 27 was negative in all cases. Low back pain and vertebral stiffness were present in the patient with osteomalacia. A dramatic improvement in pain and stiffness ensued after vitamin D injections. These SI lesions, which may simulate ankylosing spondylitis, were attributable to subchondral bone changes related to the metabolic bone diseases. In the case of osteomalacia the SI lesions were predominantly on the right side, where there was a Looser's zone on the ischial ramus suggesting that pseudofractures could be a cause of SI changes. Metabolic osseous diseases such as osteomalacia or primary hyperparathyroidism should be investigated in cases of HLA B 27 negative radiological "sacroiliitis".

Aged

Primary hyperparathyroidism in a New Zealand community: a review of 40 cases.

Forty cases of primary hyperparathyroidism presenting over a 15 year period, have been reviewed. The disease was equally prevalent in both sexes with highest incidence in the sixth decade. Most patients presented with renal colic or calculi (73 percent) and skeletal disease was found in only 13 percent. A single parathyroid adenoma was found in 32 cases and hyperplasia was diagnosed in only two cases. Follow-up questionnaires were sent to 32 patients, and in 27 of these a full clinical and laboratory assessment was undertaken. Of 26 patients with renal colic preoperatively only six continued to experience colic one year after parathyroid surgery. Thirty percent of all patients were hypertensive preoperatively, and in only two patients did blood pressure normalise after surgery. Fourteen of 27 patients followed-up were found to be hypertensive. A highly significant fall was noted in serum calcium, chloride, alkaline phosphatase and urine calcium excretion postoperatively. Recurrence of the disease was low and less than 8 percent in this series. The low incidence (1 per 10 000 population per year) suggests that primary hyperparathyroidism is under diagnosed in the Christchurch community.

Adolescent

The surgical treatment of primary hyperparathyroidism: a 20 year experience.

Analysis of a series of 200 surgically treated cases of primary hyperparathyroidism was carried out in an effort to identify not only the changing clinical patterns and improved diagnostic methods but also to assess the long term results of our conventional operative methods in light of recent reports of a high incidence of diffuse hyperplasia and a high recurrence rate when surgery is restricted to removal of the adenoma. As reported by others the "chemical diagnosis" of primary hyperparathyroidism, the clinical setting in which unsuspected hypercalcemia is demonstrated on routine blood analysis, accounts for the majority of diagnoses today. Impending or actual "parathyroid crisis" has been observed with alarming frequency. The use of the thiazide challenge test provides a useful diagnostic aid in many instances. The incidence of diffuse hyperplasia was 6% in this series while an adenoma was present in 88%. No instance of recurrence was observed in either the cases of adenomas or diffuse hyperplasia.

Adenoma

Blood pressure in subjects with hypercalcaemia and primary hyperparathyroidism detected in a health screening programme.

Primary hyperparathyroidism was the most likely diagnosis in sixty-eight non-thiazide treated patients with hypercalcaemia detected in a health screening. The group included fifty-five females and thirteen males with a mean +/- SEM age of 55.0 +/- 0.7 years. On a pair basis, these patients were compared with a series of sixty-eight age- and sex-matched normocalcaemic subjects selected from the health screening register. Five subjects in each group were receiving medication for hypertension. Systolic and diastolic blood pressures were significantly higher in the hypercalcaemic subjects in the remaining fifty-eight pairs (P less than 0.001). This difference was unrelated to impaired renal filtration and many other factors associated with hypertension. It is concluded that hypercalcaemia and/or other effects of deranged parathyroid function per se may result in a blood pressure elevation on which need not necessarily attain the level of hypertension.

Adult

[The electrocardiogram and arterial hypertension in primary hyperparathyroidism].

Cardiovascular conditions of 27 patients with primary hyperparathyroidism have been examinated. Hypertension has been found to be the only alteration significantly present (33,33% of patients), while heart disease are uncommon. Hypertension is often present without concomitant disease of the kidney. Blood pressure became normal in only one case over nine (11,11%) after parathyroidectomy.

Adult