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.     

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.     

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.     

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.     

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.     

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.     

EFFECTS OF CHANGE IN BODY POSTURE ON PLASMA AND SERUM ELECTROLYTES IN NORMAL SUBJECTS AND IN PRIMARY ALDOSTERONISM

We observed that change in body posture from the supine to the erect position in normal volunteers was associated with a rise in circulating potassium and a fall in sodium concentrations, irrespective of whether the electrolytes were measured in serum or plasma, or whether head-up tilt or ambulation was used. In patients with primary aldosteronism, the fall in serum sodium and rise in serum potassium with ambulation tended to obscure the characteristic electrolyte abnormalities of that syndrome. These changes in potassium and sodium could contribute to the rise in aldosterone secretion on orthostasis. The body posture of patients should be considered in the interpretation of plasma and serum electrolyte levels.     

TERTIARY HYPERPARATHYROIDISM AFTER LONG-TERM PHOSPHATE SUPPLEMENTATION IN ADULT-ONSET HYPOPHOSPHATAEMIC OSTEOMALACIA

We report the development of tertiary hyperparathyroidism ina patient with a sporadic form of adult-onset hypophosphataemicosteomalacia who had been treated with vitamin D or calcitrioland large doses of phosphate. This observation suggests thateven with concomitant vitamin D or calcitriol therapy, long-termoral phosphate supplementation may lead to the development ofhypercaicaemic hyperparathyroidism. Caution is recommended whenrelatively large doses of phosphate are used to treat hypophosphataemicosteomalacia of diverse causes. KEY WORDS: Hypophosphataemic osteomalacia, Long-term phosphate therapy, Tertiary hyperparathyroidism     

COMPARISON OF INTESTINAL CALCIUM ABSORPTION AND CIRCULATING 1,25-DIHYDROXYVITAMIN D LEVELS IN MALIGNANCY-ASSOCIATED HYPERCALCAEMIA AND PRIMARY HYPERPARATHYROIDISM

The relation between circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) levels and intestinal calcium absorption--as determined by an oral calcium load test--was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid-like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid-like features. It is postulated that in the former, the 'inappropriately' detectable or raised 1,25(OH)2D levels may have been due to enhanced renal 1 alpha-hydroxylase activity stimulated by the parathyroid hormone (PTH)-like effect of a non-PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non-humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is 'end organ' resistance to the effects of 1,25(OH)2D due to a generalized malabsorptive process.     

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。     

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.     

DYNAMIC TESTS OF PARATHYROID FUNCTION FOR DIAGNOSIS OF PRIMARY HYPERPARATHYROIDISM IN MALIGNANCY

Hypercalcaemia can be caused by malignant diseases as well as by primary hyperparathyroidism (HPT). The two disorders may occur together and an accurate discrimination between them is sometimes not possible from basal measurements of calcium and parathyroid hormone (PTH) concentrations. In primary HPT the regulation of PTH secretion is maintained, albeit the set-point is shifted to a hypercalcaemic value. Therefore, when serum calcium is lowered by ethylene diamine tetra-acetic acid (EDTA) infusions or calcitonin injections, patients with primary HPT display enhanced secretion of PTH already within the hypercalcaemic range, whereas parathyroid function remains suppressed in malignancy-associated hypercalcaemia. Tests based on this principle enable a specific identification of HPT. The present report describes eight hypercalcaemic patients with disseminated malignancy where HPT could be diagnosed by the use of such stimulatory tests.     

腹主动脉狭窄后心肌重量和血液流变学的改变

大鼠腹主动脉狭窄３个月后，全心重／体重、左心室重／体重和左心室湿重／干重等比值增加；红细胞变形能力减弱，聚集性增强，电泳率减慢，血浆纤维蛋白原浓度升高，全血和血浆粘度增加；并且全心重／体重、左心室重／体重和左心室湿重／干重等比值与血液粘度、红细胞刚性指数和聚集指数等血液流变学指标显著正相关。血液粘度升高，可能使心肌负荷增加，并引起心肌缺血，刺激心肌蛋白质合成，进而诱发并促进心肌肥厚的发生和发展。     

心脏瓣膜替换术后氧的供需关系变化

本文观察了４２例风湿性心脏病瓣膜替换术患者，术后早期氧耗（ＶＯ２Ｉ）的动态变化以及氧供（ＤＯ２Ｉ）、氧摄取率（Ｏ２ＥＲ）和心脏指数（ＣＩ）的变化对它的影响。麻醉诱导后经颈内静脉置入ＳｗａｎＧａｎｚ漂浮导管至肺动脉，用于血液动力学的监测。根据热稀释法原理测定心输出量；在测定前，同时抽取动脉及混合静脉血标本作血气分析。ＶＯ２Ｉ、ＤＯ２Ｉ、Ｏ２ＥＲ均根据Ｆｉｃｋ氏公式计算而得。结果显示：①瓣膜替换术后早期ＶＯ２Ｉ明显增加，机体处于高代谢状态；②其增加主要是通过Ｏ２ＥＲ的升高得以实现，与ＤＯ２Ｉ呈非依赖性关系；③术后２４小时后，ＣＩ明显增加，ＤＯ２Ｉ相应增加；而ＶＯ２Ｉ无显著增加，Ｏ２ＥＲ亦回落至正常范围并维持一平台，提示ＤＯ２Ｉ和ＶＯ２Ｉ在术后２４小时后已趋于平衡。本文还就ＶＯ２Ｉ升高的原因及Ｏ２ＥＲ增高的机制进行讨论。     

心脏直视手术中输自体血前后脑电图和颈动脉血流变化的观察

采用输自体血，可减少术后库血的用量，减少了因输库血引起的并发症，有明显的社会意义和经济效益。为观察输自体血前后对脑电图的变化，我们进行一系列的观察，结果显示：在体外循环开始前脑电波波率、波幅两组无明显差异（Ｐ＞０．０５）。放血后颈动脉平均流速、流量较放血前明显加快，这与同时输入液体，血液稀释有关。在手术结束时各项指标表明输自体血对患者脑电图无影响。     

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.     

EVIDENCE FOR A ROLE OF CYCLIC AMP IN NEUROMUSCULAR TRANSMISSION

Experiments were undertaken to determine if the effects of epinephrine in promoting neuromuscular transmission were mediated by adenosine 3':5'-cyclic phosphate (cyclic AMP). Dibutyryl cyclic AMP and the methyl xanthines, theophylline and caffeine (which inhibit cyclic AMP hydrolysis), were found to increase the amplitude of the end plate potential in the isolated rat diaphragm. Like epinephrine (which is known to promote cyclic AMP synthesis), these agents appear to facilitate the release of acetylcholine from the motor neuron. This interpretation is supported by the observation that theophylline and dibutyryl cyclic AMP markedly increased the frequency but not the amplitude of the spontaneous miniature end plate potentials. In addition, these drugs increased the number of transmitter packets released in response to nerve stimulation. These results are consistent with the view that cyclic AMP plays a role in the release of acetylcholine and in the "defatiguing effect" of epinephrine.