Management of primary hyperparathyroidism in the elderly.

Of 166 surgical patients for whom the diagnosis of primary hyperparathyroidism was established over a 20-year period, about one-third were over 60 years of age. For an additional 9 patients, or operation was advised, usually because of other life-endangering disease and the presence of only a mild degree of hypercalcemia without complications. In recent years, nearly 50 per cent of the patients did not have renal calculi or osteitis fibrosa cystica; this was unrelated to age. Most of the patients with management problems were seen since 1965. Age alone was not a dominant factor in relation to serious complications from hypercalcemia, the presence of other critical disease increasing the risk of operation, or the development of major postoperative complications. The only death from primary hyperparathyroidism occurred in a 74-year old patient who refused re-operation and died from an acute hypercalcemic crisis. A liberal, but selective, policy of surgical treatment is justified for primary hyperparathyroidism in the elderly. Patients for whom the diagnosis of primary hyperparathyroidism is established may be separated into three groups: those for whom early operation is indicated, those for whom operation should be delayed to permit recovery from other life-endangering acute disease, and those for whom operation is unjustified because of minimal uncomplicated hypercalcemia and other serious disease greatly limiting life expectancy. These categories encompass all age groups and are not restricted to the elderly. All patients require periodic re-evaluation.     

Asymptomatic primary hyperparathyroidism

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. In adults with the disease, a single, benign adenoma is seen approximately 80 percent of the time, with multiple gland involvement comprising most of the remaining patients. Very rarely, a parathyroid cancer is responsible but it is seen in less than 0.5 percent of patients with primary hyperparathyroidism. In this article, we will review important clinical and diagnostic features of asymptomatic primary hyperparathyroidism as well as considerations for surgical or medical management of the disease.     

Acute primary hyperparathyroidism

Acute primary hyperparathyroidism is an unusual form of primary hyperparathyroidism characterized by life-threatening hypercalcemia. Forty-three cases reported in the literature since 1974 are reviewed, along with five new cases. The average age of the patients was 55 (27 to 82), with an even distribution between men and women. Marked hypercalcemia (17.5 +/- 2.1 mg/dl) was accompanied by parathyroid hormone levels 20 times normal. Virtually all patients had symptoms. Hyperparathyroid bone disease occurred in 53 percent of patients; even more (69 percent) had nephrolithiasis or nephrocalcinosis. Combined renal and skeletal involvement was seen in 50 percent. Only three deaths were recorded. The pathophysiology of the acute hyperparathyroid state is unknown but appears to consist of uncontrolled parathyroid hormone secretion followed by cycles of hypercalcemia, polyuria, dehydration, reduced renal function, and worsening hypercalcemia. These features of acute primary hyperparathyroidism are compared with the features reported in the literature antedating multichannel screening, and with the features of the common form of primary hyperparathyroidism. Clinical guidelines by which the diagnosis may be suspected are also reviewed.     

Treatment of primary hyperparathyroidism

We present four treatment categories for patients with primary hyperparathyroidism and describe the results of studies of patients in each category. These categories are primary surgical, secondary surgical, “biochemical” hyperparathyroidism and medical management with oral administration of neutral phosphate. The importance of the parathyroid surgeon as a diagnostician during parathyroid exploration is stressed from the point of view of the detection and aggressive surgical treatment of parathyroid chief cell hyperplasia. Short-term (1 to 2 weeks) and long-term (5 to 29 months) studies of the state of parathyroid function in relation to calcium homeostasis after successful resection of hyperfunctioning parathyroid tissue are described.Although incomplete, our 5 year prospective study of “biochemical” hyperparathyroidism shows that in approximately 20 per cent of these patients the disease progresses to where our criteria for surgical intervention are met and that no one criterion or combination of criteria has been identified as being of predictive value in determining which patients will ultimately require surgical intervention. In patients with persistent or recurrent hyperparathyroidism, chronic oral treatment with neutral phosphate was successful in decreasing serum calcium from more than 12.0 mg/dl to less than 11.0 mg/dl in four of seven patients, but significant increases in serum creatinine occurred in three of these seven patients. Significant decreases in serum calcium did not occur in patients with serum calcium values less than 11.0 mg/dl, and there were no changes in serum creatinine in this group. Nephrolithiasis was controlled in seven of eight patients, but the specific effectiveness of neutral phosphate treatment in all these patients could not be assessed because only two had metabolically active disease at the start of treatment.     

Verapamil in primary hyperparathyroidism

In a female patient with primary hyperparathyroidism and disturbances of cardiovascular function clinical, biochemical and electrocardiographic as well as bone scintigraphic parameters were analyzed before and during therapy with verapamil (Falicard) for 7 month. Verapamil therapy resulted in decrease of the frequency of the supraventricular tachycardia, and, in higher doses (4 X 120 mg), also reduction of blood pressure, however, with dose limiting bradycardia and prolongation of PQ-time. Both the normalization of serum phosphate level, diminution of hypercalcemia of the ionized calcium and the decrease of hypercalciuria and increase of scintigraphic index as an expression of the decrease of high activity of bone metabolism suggest alterations of the calcium homeostasis. Under oral calcium load the constantly increased PTH values markedly could be suppressed indicating an alteration of intracellular parathyroid calcium set point. Discussion is performed with respect to possible protective metabolic and cardiovascular effects of calcium antagonists in this endocrine functional disorder.     

Familial isolated primary hyperparathyroidism

Familial primary hyperparathyroidism (PHPT) Is usually encountered in the context of multiple endocrine neoplasia (MEN) syndromes. Few families have been reported in the literature where PHPT was the only abnormality. However, in these families no long-term follow-up data were reported and no genetic linkage studies were performed. OBJECTIVE We investigated a large family with a familial primary hyperparathyroidism for biochemical and genetic markers of multiple endocrine neoplasia syndromes. DESIGN A family screening study. PATIENTS Thirty-seven family members participated in this study including 7 patients who had been previously operated upon for PHPT. MEASUREMENTS Serum calcium (albumin adjusted), was measured in all family members. Hypercalcaemic subjects and patients who had been operated upon for PHPT were assessed for biochemical markers of MEN syndromes (serum gastrin, prolactin, calcitonin, fasting plasma glucose and 24-hours urinary excretion of adrenaline, noradrenaline and vanillylmandelic acid (VMA). Genetic linkage analysis was performed using DNA markers linked to chromosome 11q13, the presumed MEN type 1 (MEN-1) locus. RESULTS Four new patients with PHPT and two with probable PHPT were discovered. No clinical or biochemical evidence of MEN syndromes could be detected. DNA marker pMS5l(D11S97) was Informative, maximum two-point lodscore of 2·12 at a recombination fraction of 0·05 confirming linkage to chromosome 11q13. CONCLUSIONS Familial PHPT can exist as a separate clinical entity. Isolated familial PHPT is caused by mutation in a gene located in the MEN-1 region on chromosome 11q13, possibly the MEN-1 locus.     

妊娠并发原发性甲状旁腺功能亢进症

妊娠并发原发性甲状旁腺功能亢进症(primary hyperparathyroidism,PHPT)相关报道目前在我国较为罕见,常因其初期缺乏典型临床表现而容易出现漏诊、误诊,导致母儿并发症及死亡率增加,且目前尚无明确诊疗指南或共识。本文就妊娠并发PHPT的相关研究进行综述。     

The management of primary hyperparathyroidism

Recent improvements in parathyroid imaging have led to renewed interest in the criteria for, and the surgical approach to, parathyroidectomy. It therefore seemed appropriate to review current evidence relating to the evaluation and management of primary hyperparathyroidism for those working within a general endocrine service. The recommendations are based on an electronic search spanning the past decade using the search terms hyperparathyroidism, management and parathyroidectomy/surgery, but we have also included key publications outside this period. The findings have been graded systematically (Appendix), according to the quality of the information available, to indicate the level of evidence on which they are based.     

Musculoskeletal manifestations of primary hyperparathyroidism

Clinical Rheumatology - Primary hyperparathyroidism (PHPT) can be associated with a variety of musculoskeletal complaints, which occasionally can be the leading or presenting manifestation. In this...     

Renal manifestations of primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is associated with nephrolithiasis and nephrocalcinosis. Hypercalciuria is one of the multiple factors that is implicated in the complex pathophysiology of stone formation. The presence of a renal stone (symptomatic or asymptomatic) categorizes PHPT as symptomatic and is an indication for parathyroid adenomectomy. Progression of nephrocalcinosis is largely reversible after successful surgery, but the residual risk persists. PHPT is also associated with declining renal function. In case of asymptomatic mild PHPT, annual renal functional assessment is advised. Guidelines suggest that an estimated glomerular filtration rate (eGFR) < 60 ml / minute / 1.73 m(2) is an indication for parathyroid adenomectomy. This article discusses how to monitor and manage renal stones and other related renal parameters in case of PHPT.     

原发性甲状旁腺功能亢进症的分子发病机制

原发性甲状旁腺功能亢进症（甲旁亢）的分子机制在过去的10年间取得很多新进展。散发性原发性甲旁亢的主要机制如下：（1）原癌基因cyclinD1/PRAD1过度表达。（2）pRB对cyclinD1的增殖抑制作用失活。（3）抑癌基因MEN1突变失活。（4）MEN1基因产物menin功能失活导致转化生长因子-β信号转导通路受阻。遗传性原发性甲旁亢的主要机制为：（1）多内分泌腺瘤病1型：MEN1基因突变失活。（2）多内分泌腺瘤病2a型：RET基因突变。（3）家族性低尿钙高钙血症：钙敏感受体基因杂合突变。（4）新生儿严重的甲旁亢：钙敏感受体纯合突变。另外,HRPT2基因突变可引起家族性原发性甲旁亢、甲旁亢-颚肿瘤综合征、甲状旁腺腺瘤囊性变、甲状旁腺癌。