甲状旁腺激素测定对原发性甲状旁腺功能亢进症的诊断意义(附9例临床病理报告)

对经手术和病理证实的9例原发性甲状旁腺功能亢进症(PHPT)患者,进行血钙和甲状旁腺激素(PTH)等测定,血钙为2.17～3.6mmol/L(正常值为2～2.6mmol/L),PTH为165.5～1266.7mmol/L(正常值为20～90ng/L)。血钙间歇性升高4例,持续性升高5例,PTH各为<500ng/L和>500ng/L。病程<2年和>2年者,PTH各为<300ng/L和>300ng/L。瘤重<2g者,PTH均<500ng/L,而>2g者大多>500ng/L。提示PTH与血钙、病程和瘤重有关。如将PTH和血钙结合分析,可提高PHPT的诊断率。     

SECRETION OF PARATHYROID HORMONE IN PRIMARY HYPERPARATHYROIDISM

Circulating parathyroid hormone was assayed in sixty-nine patients with primary hyperparathyroidism. The patients were divided into two groups, those with radiological evidence of osteitis fibrosa (twenty patients) and those without such evidence. In this latter group the mean concentration of circulating parathyroid hormone was higher than the mean in a group of normal subjects, but there was great overlap with the normal range, limiting the diagnostic value of the assay in such cases. Much higher concentrations were found in the patients with osteitis fibrosa: all nine patients with concentrations of parathyroid hormone above 3 ng/ml had osteitis fibrosa.     

THE LOSS OF CIRCADIAN RHYTHM FOR INTACT PARATHYROID HORMONE AND NEPHROGENOUS CYCLIC AMP IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM

The measurement of serum intact parathyroid hormone (PTH) (1-84) over a 24-h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N-cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1-84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1-84) secretion.     

CONTROL OF SECRETION OF PARATHYROID HORMONE IN SECONDARY HYPERPARATHYROIDISM

The response of the parathyroids to an infusion of calcium has been studied in patients with secondary hyperparathyroidism due to either vitamin D deficiency or to chronic renal failure. Two specific homologous immunoradiometric assays for human parathyroid hormone (PTH) have been used to assess the response, one specific for the amino-terminus (N-PTH), the other specific for the carboxy-terminus (C-PTH) of the molecule.
In both the vitamin D deficient and the uraemic patients, in response to a 4 mg/kg/h infusion of calcium generally for 4 h, suppression of N-PTH was similar, falling to around 20–30% of the initial value. In the uraemic subjects, the degree of suppression was inversely related to the initial plasma calcium ( r = 0·9, P < 0·001). Measured with the C-PTH assay, the response was generally less, particularly in the uraemic subjects in whom it was often preceded by an initial rise in C-PTH.
In both groups of subjects, suppression of N-PTH began as soon as the plasma calcium began to rise and before hypercalcaemia was produced. At the end of the infusion the concentration of N-PTH rose quickly, although the plasma calcium was still high. In four uraemic subjects the rate of infusion of calcium was reduced after 1–1·5 h to limit the rise in plasma calcium. As the calcium approached a plateau, the concentration of N-PTH was found to rise again.
These results indicate the importance of using PTH assays of well defined specificity to evaluate autonomy, and show that the degree of suppression achieved is dependent both on renal function and basal plasma calcium. In addition, these observations suggest that the direction and rate of change of plasma calcium are important in the control of secretion of parathyroid hormone.     

NON-AUTONOMY OF HORMONE SECRETION IN PRIMARY HYPERPARATHYROIDISM

Parathyroid hormone (PTH) was measured by radioimmunoassay in the plasma of twenty patients with surgically proven primary hyperparathyroidism during intravenous infusions of calcium and/or EDTA. All patients studied showed significant increases in plasma PTH during induced hypocalcaemia and significant decreases in plasma PTH during induced hypercalcaemia. The secretion of para thyroid hormone was not autonomous in these patients with primary hyperparathyroidism, regardless of histological type, but varied with induced changes in serum calcium concentration. The presence of immunoreactive hormonal sub-fragments in plasma seems the most likely explanation for the sharp contrast between our data and earlier studies. In spite of the difficulties presented by this complex pattern of hormonal metabolism, the radioimmunoassay for parathyroid hormone is clinically quite useful, particularly in the differential diagnosis of hypercalcaemia.     

甲状旁腺腺瘤的CT诊断

本文介绍了甲状旁腺腺瘤的CT检查方法,并报告了15例手术和病理证实的甲状旁腺腺瘤的CT表现。其中12例(占80％)术前CT检查作出准确定位诊断。文中还分析了腺瘤的强化曲线特征并与血管强化曲线进行了比较。     

CHANGES OF URINARY CYCLIC AMP EXCRETION AND PLASMA PARATHYROID HORMONE LEVELS BEFORE AND AFTER PARATHYROIDECTOMY IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM

Urinary cyclic AMP excretion and plasma parathyroid hormone(PTH) levels were examined in three patients with primary hyperparathyroidism before and after parathyroidectomy. Plasma PTH and urinary cyclic AMP in the individual patients decreased in parallel following parathyroidectomy. During surgery there was a statistically significant correlation between PTH levels and cyclic AMP excretion in individual patients. These findings support the claim that the rate of urinary cyclic AMP excretion reflects endogenous PTH activity in patients with primary hyperparathyroidism.     

OSTEOID MINERALIZATION DEFECT IN PRIMARY HYPERPARATHYROIDISM

Using a quantitative histological technique, four unselected patients with primary hyperparathyroidism were investigated and all were found to have a delayed or defective mineralization of osteoid, although their diet contained an adequate amount of vitamin D. This abnormality was most marked in the one patient with radiological bone disease. Mineralization of osteoid occurred during subsequent vitamin D administration, together with an improvement in ⁴⁵Ca absorption by the gut; osteoclast numbers and serum acid phosphatase levels also increased. We suggest that (1) endogenous vitamin D deficiency and hyperparathyroidism frequently co-exist, (2) vitamin D metabolism is abnormal in hyperparathyroidism, and (3) radiological loss of bone density and erosions in hyperparathyroidism are due to impairment of the process of bone repair, i.e. there is defective mineralization of the osteoid which is laid down by osteoblasts to fill the resorption lacunae.     

A COMPARISON OF NEPHROGENOUS CYCLIC AMP, TOTAL URINARY CYCLIC AMP AND THE RENAL TUBULAR MAXIMUM REABSORPTIVE CAPACITY FOR PHOSPHATE IN THE DIAGNOSIS OF PRIMARY HYPERPARATHYROIDISM

A determination was made of total urinary adenosine 3′-5′cyclic monophosphate (UcAMP), nephrogenous cyclic AMP (NcAMP) excretion and also of the renal tubular maximum reabsorptive capacity for phosphate T_mPO₄/GFR (all expressed as a function of the glomerular filtrate) in fourteen patients with primary hypercalcaemic hyperparathyroidism and twelve control normal subjects. The hyperparathyroid patients gave a mean excretion of UcAMP (7·0 ± 45·68 nmol/100 ml GF; mean ± SEM), NcAMP (6·19 ± 0·64 nmol/100 ml GF) which were significantly greater (P < 0·001) than those of normal controls, (2′45 ± 0·15nmol/100 ml GF and 1·25 ± 0·12nmol/100 ml GF) respectively. The difference between the patients and controls for the maximum renal tubular reabsorptive capacity for phosphate (T_mPO₄/GFR) (patients 0·55 ± 0·04, controls 1·05 ± 0·05 mmol/l GFR) was also highly significant (P<0·001). Statistical evaluation of the results obtained from the patients with primary hyperparathyroidism revealed that there was a positive correlation between the level of plasma calcium and immunoreactive parathyroid hormone (PTH) (r=+0·46), NcAMP(r=+0·337), UcAMP (r=+0·36), and an inverse correlation with the T_mPO₄/GFR (r=?0·62). There was also a positive correlation between plasma immunoreactive PTH and NcAMP(r=+0·31), and UcAMP(r=+0·35), and an inverse correlation with the T_mPO₄/GFR (r=?0–39). Successful removal of a single parathyroid adenoma in six patients was associated with a highly significant fall in the excretion of UcAMP, NcAMP, and a rise in the T_mPO₄/GFR (P<0·005). The combination of a low T_mPO₄/GFR and a high excretion of UcAMP or NcAMP in the presence of hypercalcaemia is highly suggestive of primary hyperparathyroidism in the absence of clinical evidence of malignant disease.     

FASTING CALCIUM EXCRETION AND PARATHYROID HORMONE TOGETHER DISTINGUISH FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA FROM PRIMARY HYPERPARATHYROIDISM

Routine estimation of plasma calcium has made the finding of asymptomatic hypercalcaemia a frequent occurrence. A high index of suspicion for familial hypocalciuric hypercalcaemia (FHH) will lead to accurate diagnosis and avoidance of unnecessary parathyroid surgery. Four FHH kindreds with 16 hypercalcaemic members were found in an unselected referral population over 3 years. Differentiation from primary hyperparathyroidism (42 patients in the same period) was facilitated by analysis of fasting blood and urine for renal handling of calcium, phosphate and cyclic AMP. We found that a plot of serum PTH against fasting calcium excretion separated all cases of each disorder. The discriminatory power of these two variables was confirmed by multivariate discriminant function analysis. An elevated plasma chloride was found to be common to both diseases and of no value in differentiation.     

原发性干燥综合征眼科诊断试验的评价

目的:在我国患者中重新评价原发性干燥综合征(PSS)眼科诊断试验的临床价值。方法:用Schirmer试验、BUT试验和角膜荧光素活体染色试验。在112例PSS患者和185例对照者中,评估上述试验的敏感度和特异度及其主要影响因素。结果:Schirmer、角膜荧光素活体染色和BUT试验的特异度分别为43.8％、93.5％和31.4％,敏感度分别为91.7％、50.0％和87.5％。统计分析显示Schirmer试验和BUT试验的特异度与年龄呈负相关(P<0.001),而敏感度与年龄呈正相关(P<0.05)。在55岁以上的患者,除角膜荧光素活体染色试验外各项试验的诊断价值有限。按目前我国诊断KCS的标准,上述三项试验中两项或两项以上异常,诊断的敏感度和特异度分别为84.8％和49.7％。结论:有持续性眼干患者并Schirmer试验(<5mm/5min)和(或)角膜荧光素活体染色试验阳性可明显提高临床诊断的敏感度(79.5％)和特异度(97.8％)(P<0.001)。     

PARATHYROID SUPPRESSIBILITY IN HYPERPARATHYROIDISM DUE TO CHRONIC RENAL FAILURE: STUDIES WITH AUTOTRANSPLANTED PARATHYROID TISSUE

Suppressibility of parathyroid hormone (PTH) secretion by calcium was evaluated in six patients with chronic renal failure and parathyroid tissue autotransplanted into the forearm. One patient was reinvestigated after renal transplantation. Plasma PTH levels were measured in the venous effluent of transplanted parathyroid tissue (VE) and in peripheral blood (PB) with two radioimmunoassays (RIA). One of these detected predominantly the intact human parathyroid hormone-(1–84) [PTH-(1–84)] (N-assay) and another in addition carboxyl (COOH)-terminal fragments (C-assay). At 5 min after the start of 12-min calcium infusions, resulting in a mean increase of plasma calcium levels of 0±6 mmol/l (P < 0±01), PTH was lowered to 44±10% (mean ± SE) (P < 0±01) of preinfusion levels in the VE and to 88±4% (P < 0±05) in PB, when measured in the N-assay; subsequently the plasma calcium level remained raised and PTH level lowered. When estimated in the C-assay, PTH was significantly lowered to 82± 6% (P < 0–05) in the VE at 120 min, and to between 91 ± 2% and 96 ± 2% (P < 0±01- < 0±05) in the PB at 20 to 120 min after the start of the calcium infusions. The results were extended with gel permeation chromatography of representative plasma samples. After renal transplantation and restoration of renal function gel filtration analysis indicated that the levels of intact PTH-(1–84) were 49±6 and of its COOH-terminal fragments 3±5 higher in the VE than in PB. In response to i.v. calcium administration intact PTH and its COOH-terminal fragments were lowered to 25% and 62% in the VE, and to 29% and 86% in PB, respectively. These findings demonstrate that the secretion of intact PTH-(1–84) is suppressed within minutes in response to i.v. calcium administration; a slower fall of the secretion of COOH-terminal PTH fragments was demonstrated only after restoration of near-normal renal function.     

TREATMENT WITH ŒSTROGENS OF PRIMARY HYPERPARATHYROIDISM IN POST-MENOPAUSAL WOMEN

Ethinylœstradiol was administered to 10 post-menopausal hyperparathyroid patients. There was a gradual fall in the fasting plasma-calcium and urine-calcium and in the 24-hour- urine calcium and hydroxyproline, which was maintained up to one year in the patients who continued therapy. Œstrogen treatment of hyperparathyroidism in post-menopausal women might be expected to prevent bone disease by inhibiting bone resorption, and stone disease by reducing urine-calcium.     

原发性甲状旁腺功能亢进症64例外科治疗的经验

自1956～1989年外科治疗原发性甲状旁腺功能亢进症64例,手术成功62例(96.9％)。甲状旁腺腺瘤以右下好发(占41.4％),其次为左下(占25.9％)、左上(占13.8％)及右上(占10.3％)。异位旁腺腺瘤(占8.6％)。手术成功的关键是诊断可靠、术前定位明确、熟悉甲状旁腺的解剖及病变、系统而有步骤地探查。     

REGULATION OF CALCIUM-PARATHYROID HORMONE FEEDBACK IN PRIMARY HYPERPARATHYROIDISM: EFFECTS OF BISPHOSPHONATE TREATMENT

Dichloromethylene bisphosphonate (C12MBP), a powerful inhibitor of bone resorption, was administered to 27 patients with primary hyperparathyroidism. It was given by either intravenous infusion (six patients, 500-100 mg day), or by intramuscular injection (six patients, 100-200 mg/day) or by mouth (15 patients, 1600-2400 mg/day) for 20-180 days. Sustained suppression of bone resorption was observed in all patients, as judged by a fall in the urinary hydroxyproline excretion. In contrast, the hypocalcaemic effect was inconsistent and short-lived, particularly in the patients without overt bone disease. The fall in serum calcium seemed largely to be due to a transient dissociation between bone resorption and bone formation and was associated with increases in circulating parathyroid hormone (PTH). In ten patients given the bisphosphonate orally for 6 months, serum calcium was unchanged but serum PTH was significantly raised. These results suggest that C12MBP may be of use for short-term correction of severe hypercalcaemia due to hyperparathyroidism, particularly in the patients with overt bone disease. However, its long-term use should not be recommended because of increased PTH secretion.     

CHANGES IN CYCLIC AMP AND ELECTROLYTES AFTER PARATHYROIDECTOMY IN PRIMARY HYPERPARATHYROIDISM

Changes in the excretion of urinary cyclic AMP, calcium and phosphate, and serum calcium, ionized calcium, and magnesium were studied after parathyroidectomy for primary hyperparathyroidism. Urinary cyclic AMP decreased rapidly and 8 of 11 patients had a significant reduction 1 h postoperatively, but changes in serum calcium and ionized calcium were delayed. Serum calcium concentrations closely parallelled those of serum ionized calcium and phosphate excretion returned to normal almost 7 h later than that of cyclic AMP. Excretion of urinary calcium rose rapidly at 4 h after surgery because calcium clearance improved after the reduction in circulating parathyroid hormone. The fall in urinary calcium at about 24 h was due to the subsequent reduction in serum calcium.     

SCREENING FOR MULTIPLE ENDOCRINE NEOPLASIA SYNDROME (TYPE 1) IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM

In 63 consecutive patients with primary hyperparathyroidism (HPT) a prospective screening study was undertaken for coexistent multiple endocrine neoplasma-(MEN)-syndrome type 1. The screening consisted of a clinical examination, a radiological examination of the sella turcica with skeletal tomography (and in equivocal cases computed tomography), visual field examination by perimetry and a hormonal evaluation including measurements of the serum levels of prolactin, gastrin, pancreatic polypeptide (PP) and subunits of human chorionic gonadotrophin (HCG-alpha and -beta). Clinical examination did not reveal any signs of endocrine disease suggestive of a MEN-1 syndrome. In only one case there was a radiological abnormality of the sella turcica; this patient had an empty sella syndrome and a raised serum prolactin value. All other prolactin values were within the normal range. In 41% of the patients raised serum gastrin levels were found; these tended to normalize after parathyroidectomy. As a group, patients with raised gastrin values were older than the others and generally they had hypo- or achlorhydria. The serum PP levels were raised in 28% of the patients but there was no clinical evidence of a pancreatic tumour in any of these cases, and the serum HCG-alpha and -beta levels were within the normal range in all patients but two. We conclude that the incidence of MEN-1 syndrome in unselected patients with primary HPT must be low, and that investigations for this syndrome are justified only in HPT patients with specific symptoms or with a positive family history.