with a reasonably large bulla and moderate impairment of pulmonary function. Resection of a giant bulla seems neither to increase the size of other bullae nor to promote the formation of new ones.' 12 Patients with bullae who develop symptoms have almost invariably been smokers.'6 If they continue to smoke after the operation surgery has little to offer.'2 17
The possibility of unearthing a bulla meriting resection is one of several reasons why a discrepancy in clinical signs between the two sides of the chest in a patient with chronic airflow obstruction should prompt referral for a plain chest radiograph. WILLIAM J M KINNEAR Senior Registrar ANNE E TATrERSFIELD Professor of Respiratory Medicine Respiratory Medicine Unit, City Hospital, Nottingham NG5 1PB 1 Morgan MDI., Strickland B. Computed tomography in the asscssmcnt of bullous lung discase. Br]Dis Chest 1984;78:1(0-25.
2 '['ing ER, Klopstock R, Lyons RA. Mechanical properties ot' pulmonary cysts and bullac. Anm Rez RespirDis 1963;87:538-44. 3 Morgan MDL, Denison DM, Strickland B. The value of computed tomography for selecting patients with bullous lung disease for surgery. T'horax 1986;41:855-62. 4 Pride NB, Barter CE, Htugh-Jones P. '['he ventilation of bullae and the effect of their removal on thoracic gas volumes and tests of overall pulmonary function. Am Revz RespirDis 1973;107:83-98. 5 Reid L. The pathology ofJemphysema. Chicago: Year Book Medical Publishers, 1967. 6 Head JR, Avery EE. Intercavitary suction (Monaldi) in the treatment of emphysematous bullae and blebs. 7 Thorac Surg 1949;18:761-7. 7 Morgan MDL, Edwards CW, Morris J, Matthews HR. Origin and behaviour of emphysematous bullac. Thorax 1989;44:533-8. 8 Fitzgcrald MX, Keclan PJ, Cugell DW, Gaenslcr EA. Long term results of' surgery for bullous emphysema. .7 Thorac CardlovascSurg 1974;68:566-87. 9 Gelb AF, Gold WMINI, Nadel JA. Mtechanisms limiting airflow in bullous lung disease. Am Rez' Respir Dis 1973;107:571-8. 10 Shamji FM, Sachs HJ, Perkins DG. Cystic disease of the lung. Surg Clin North .Am 1988;68: 581-620. 1 1 Woo-Ming M, Capel LH, Belcber HR. The results of surgical treatment of large air cysts of the lung. Brj Dis Chest 1963;57:79-85. 12 Pearson MG, Ogilvie C. Surgical treatment of emphvsematous bullae: late outcome. Thorax 1983;38: 134-7. 13 Gunstenson J, McCormack RJM. The surgical management of emphysema. J Thorac Cardiovasc Surg 1973;65:920-5. 14 Potgeiter PD, Benator SR, Hewitson RP, Ferguson AD. Surgical treatment of bullous lung discase. T'horax 1981;36:885-90. 15 Davies GM, Simon G, Reid L. Pre and post-operative assessment of emphysematous bullac. Brj Dis Chest 1966;60:120-8. 16 Anonymous. Surgery for pulmonary emphysema [Editorial]. Lancei 1983;i: 1369. 17 Hughes JA, Macarthur AM, Hutchison DCS, Hugh-Jones P. Long term changes in lung function after surgical treatment of bullous emphysema in smokers and non-smokers. Thorax 1984;39: 140-2.
Small cell lung cancer Surgery offers good survival, but most patients do not have operable tumours Chemotherapy has undoubtedly increased short term survival in patients with small cell lung cancer, but few patients survive five years after treatment with chemotherapy alone. As Leonard pointed out in a recent review, "The aim of curing a majority of patients with this disease using systemic therapy seemed at the start of this decade to be a realistic goal but has at the end of it proved to be something of a diagnostic mirage. "' Now a group of surgeons in Edinburgh has reported impressive survival rates among patients with stage I and stage II disease who were treated by resection.2 They argue that many patients may have been denied surgical treatment because of "the current view of most physicians -hat small cell lung cancer is not a surgical disease." Should these results make physicians reassess their approach? What role does surgery have in the management of small cell lung cancer? About 60% of patients with limited disease3 and perhaps about 30% of those with extensive disease' will show a worthwhile clinical response to chemotherapy. Nevertheless, only 15-20% of those with limited disease survive for two years, and the prognosis for those with extensive disease is even worse.45 Chemotherapeutic regimens more intensive than those tried in the past decade are unlikely to have much impact on prognosis, nor are the analogues of drugs already assessed in established regimens. Studies with different durations of inductions and late intensification of treatment will continue, however, in the hope that more basic research, such as the identification of tumour cell markers, will help the clinician to predict the response to chemotherapy more accurately. Response may now be correlated with performance status, age, and stage of disease, but the discovery that patients who respond best to chemotherapy are those who are fit and young and have limited disease is less than surprising. The results of conventional surgical resection of operable small lung cancers are difficult to assess as the published five year survival figures range from zero to 35%.6-S The Edinburgh group's cumulative five year survival rate of 35% for patients with stage I disease and 23% for those with stage II disease represents 10 years' experience, during which 27 BMJ
VOLUME 300
27 JANUARY 1990
patients with stage I and 29 with stage II cancer were treated by surgical resection. These results are superior to those of a retrospective study of 71 patients with small cell lung cancer with similar disease stages in which only 12% had survived five years after surgery.8 Nevertheless, on the basis of this five year survival Sorensen et al concluded that selected patients with small cell lung cancer should be treated by surgery alone-that is, without adjuvant chemotherapy. The Edinburgh surgeons would agree and suggest that surgery offers "the prospect of long term survival" for patients with stage I and stage II small cell lung cancer. The surgeons used data collected by the Edinburgh lung cancer group to imply that many patients were denied potentially curative surgery and perhaps instead received chemotherapy. These data show that over the 10 years some 1800 patients with small cell lung cancer presented in Edinburgh, of whom only 127 were referred to surgeons.9 Yet surgeons must be aware that the vast majority of patients with small cell lung cancer present with inoperable disease. In the Edinburgh surgical series almost one third of patients did not have a preoperative diagnosis. The likely explanation for this is the continuing practice of most clinicians of referring to surgeons patients with peripheral pulmonary lesions who are fit enough for surgical resection and in whom malignant disease is probable even if not proved. If the surgical management of patients with small cell lung cancer has fallen into disrepute, as the Edinburgh surgeons suggest, their paper should be used as a timely reminder that most long term survivors of small cell lung cancer are the fortunate few who present with operable disease. All patients with proved small cell lung cancer (and who are otherwise fit) should have the benefit of a surgical opinion if they have stage I or stage II disease. Yet most patients cannot be treated surgically. Their disease is too extensive for such treatment and instead they receive polychemotherapy or radiotherapy, or both, or no specific treatment. Perhaps their awful prognosis might be improved by primary surgery with postoperative chemo209
therapy or neoadjuvant chemotherapy followed by surgery with or without thoracic irradiation. Certainly the results of cancer treatment policies are depressingly poor. GRAHAM CROMPTON Consultant Physician, Respiratorv Unit, Northern General Hospital, Edinburgh EH5 2DQ Lconard RCF. Small ccll lung canccr.
Brj Cancer 1989;59:487-90.
2 1'rasad US, Navlor AR, Walker \WS, Lamb 1), Cameron EX!J, \W'albanim P'R. Long term snirvival after pulmonary resection for small cell carcinoma o(t' thc lttig. Ttorax 1989;44:784-7. 3 Sm\ith JF, Fowlic SM, Gregor A. ct a/. Thc impact of clicinothcrapy ot[ small ccl carciinomna o f'thc bronchus. QJ,Med 1986;61:969-76. 4 Setlter EJ, Ihde DC. Therapy of small ccll lting cancer. A perspective on tso decadcs of clinical research. Sernin O)icol 1988;15:278-99. 5 Holove PY, Kalbfleisch J. 'I'he infltuence of myelossupprcssion on the response to chemotherapy in small ccll bronchogenic carcinoma. Ca(ncer 1984;54:41 1-5. 6 Fox W, Scadding JC. Medical Research Council comparativc trial of surgerv aild radiotherapy ftor primary treatment of small-celled or oat-celled carcinoma of' bronchus. Ian(ct 1973;ii.63-5. 7 Mountain CF. Clinical biology of small cell carcinoma: relationship to surgical therapv S ?imti ( tol 1978;5:272-9. 8 Sorensci HR, Lund C. Alstrup 1. Sursival in small ccll lumig carcimioma after suirgery TItorux 1986;41:479-82. 9 Edinburgh Lung Cancer Group. Patients presenting with lung cancer in south east Scotland. JI'horx 19X7;42:853-7.
Intact parathyroid hormone assays Interpretation must take account of biological variation Since their first development in 1963 parathyroid hormone immunoassays have been invaluable in assessing patients with disorders of calcium metabolism. ' The interpretation of the results of these immunoassays has, however, been complicated by the molecular heterogeneity of circulating parathyroid hormone. As a result of the proteolytic metabolism of parathyroid hormone, both within the parathyroid gland and elsewhere in the body, the circulation contains amine and carboxy terminal fragments of parathyroid hormone in addition to the intact parathyroid hormone (1-84) peptide.2 In an attempt to improve clinical discrimination immunoassays were developed with specificities for amino terminal and mid-terminal or carboxy terminal parathyroid hormone. In general these assays either lacked the required sensitivity or showed overlap between values in normal people and in groups of patients. The recently developed two site immunometric assays for parathyroid hormone allow the intact parathyroid hormone (1-84) peptide to be measured without interference from fragments.3' The sensitivities of these assays are in the low picomolar range-sufficient to measure the hormone in normal people. The main application of parathyroid hormone assays is in the differential diagnosis of hypercalcaemia. Initial evaluations of the new assays for intact parathyroid hormone showed improved clinical discrimination between patients with hyperparathyroidism and hypercalcaemia of malignancy.`~The distinction was not, however, complete; though the concentrations of intact parathyroid hormone in these groups are well separated, 3-5% of patients with hyperparathyroidism have values at the upper end of the reference range for normal people and 20-30% of patients with hypercalcaemia of malignancy have low but detectable concentrations of intact parathyroid hormone. Secondary hyperparathyroidism is a consistent feature of advanced renal failure. In the past the measurement of parathyroid hormone in patients with renal failure has been compromised by the presence of an excess of biologically inactive carboxy terminal fragments. Because the new assays are not affected by parathyroid hormone fragments they should overcome this problem. In patients with renal failure they should be sufficiently specific to follow either the clearance of intact parathyroid hormone after parathyroidectomy6 or the suppression of intact parathyroid hormone after treatment with calcium.7 This may not be the case for all
assays.'
Since the new assays are sensitive enough to measure intact parathyroid hormone concentrations in normal people and 210
follow changes within the reference range they have been used to study the physiology and control of its secretion.9 This work has defined the circadian rhythm of intact parathyroid hormone secretion in normal men. It was shown to rise in a broad peak outside the reference range from 0200 to 0600. This was accompanied by a parallel rise in concentrations of nephrogenous cyclic AMP, indicating that the intact parathyroid hormone released was biologically active. There was considerable variation in the return to baseline concentrations among normal people, with the period between 0600 and 1000 characterised by great variability among individuals. The assessment of the intact parathyroid hormone concentrations in an individual must take this variability into account. Early morning samples, such as those typically collected from patients in hospital, may have spuriously raised concentrations. Further studies have shown the absence of a synchronised circadian rhythm in patients with primary hyperparathyroidism.' Comparison of 24 hour profiles indicates that the best discrimination between normal people and patients with hyperparathyroidism is achieved when samples are taken between 1100 and 1400. Most patients screened for hypercalcaemia of malignancy have undetectable concentrations of intact parathyroid hormone. Finding detectable intact parathyroid hormone in such patients has been ascribed to a change in the calcium set point of the parathyroid glands." In patients with hypercalcaemia of malignancy with undetectable intact parathyroid hormone concentrations studies of the effects of treatment to lower calcium have confirmed that an increase in intact parathyroid hormone concentration occurs as the calcium decreases but while the patient remains hypercalcaemic.'2 When assessing these patients, therefore, intact parathyroid hormone concentrations should be measured before giving any treatment to lower calcium. Although intact parathyroid hormone seems more stable than previously suspected,3"' there is some variability. Short delays in separation and freezing of samples would not normally be expected to have substantial adverse effects on the clinical value of the assays, but such delays might lead to the misclassification of patients with only borderline increases in circulating intact parathyroid hormone concentration.' The development of assays of intact parathyroid hormone is an important advance in the laboratory assessment of calcium disorders. The improved sensitivity and specificity of the new assays make it possible to achieve better discrimination between clinical groups. But the use of these assays has also highlighted the extent of biological variation in intact parathyroid hormone and its rapid response to treatment. The BMJ VOLUME 300
27 JANUARY 1990
The possibility of unearthing a bulla meriting resection is one of several reasons why a discrepancy in clinical signs between the two sides of the chest in a patient with chronic airflow obstruction should prompt referral for a plain chest radiograph. WILLIAM J M KINNEAR Senior Registrar ANNE E TATrERSFIELD Professor of Respiratory Medicine Respiratory Medicine Unit, City Hospital, Nottingham NG5 1PB 1 Morgan MDI., Strickland B. Computed tomography in the asscssmcnt of bullous lung discase. Br]Dis Chest 1984;78:1(0-25.
2 '['ing ER, Klopstock R, Lyons RA. Mechanical properties ot' pulmonary cysts and bullac. Anm Rez RespirDis 1963;87:538-44. 3 Morgan MDL, Denison DM, Strickland B. The value of computed tomography for selecting patients with bullous lung disease for surgery. T'horax 1986;41:855-62. 4 Pride NB, Barter CE, Htugh-Jones P. '['he ventilation of bullae and the effect of their removal on thoracic gas volumes and tests of overall pulmonary function. Am Revz RespirDis 1973;107:83-98. 5 Reid L. The pathology ofJemphysema. Chicago: Year Book Medical Publishers, 1967. 6 Head JR, Avery EE. Intercavitary suction (Monaldi) in the treatment of emphysematous bullae and blebs. 7 Thorac Surg 1949;18:761-7. 7 Morgan MDL, Edwards CW, Morris J, Matthews HR. Origin and behaviour of emphysematous bullac. Thorax 1989;44:533-8. 8 Fitzgcrald MX, Keclan PJ, Cugell DW, Gaenslcr EA. Long term results of' surgery for bullous emphysema. .7 Thorac CardlovascSurg 1974;68:566-87. 9 Gelb AF, Gold WMINI, Nadel JA. Mtechanisms limiting airflow in bullous lung disease. Am Rez' Respir Dis 1973;107:571-8. 10 Shamji FM, Sachs HJ, Perkins DG. Cystic disease of the lung. Surg Clin North .Am 1988;68: 581-620. 1 1 Woo-Ming M, Capel LH, Belcber HR. The results of surgical treatment of large air cysts of the lung. Brj Dis Chest 1963;57:79-85. 12 Pearson MG, Ogilvie C. Surgical treatment of emphvsematous bullae: late outcome. Thorax 1983;38: 134-7. 13 Gunstenson J, McCormack RJM. The surgical management of emphysema. J Thorac Cardiovasc Surg 1973;65:920-5. 14 Potgeiter PD, Benator SR, Hewitson RP, Ferguson AD. Surgical treatment of bullous lung discase. T'horax 1981;36:885-90. 15 Davies GM, Simon G, Reid L. Pre and post-operative assessment of emphysematous bullac. Brj Dis Chest 1966;60:120-8. 16 Anonymous. Surgery for pulmonary emphysema [Editorial]. Lancei 1983;i: 1369. 17 Hughes JA, Macarthur AM, Hutchison DCS, Hugh-Jones P. Long term changes in lung function after surgical treatment of bullous emphysema in smokers and non-smokers. Thorax 1984;39: 140-2.
Small cell lung cancer Surgery offers good survival, but most patients do not have operable tumours Chemotherapy has undoubtedly increased short term survival in patients with small cell lung cancer, but few patients survive five years after treatment with chemotherapy alone. As Leonard pointed out in a recent review, "The aim of curing a majority of patients with this disease using systemic therapy seemed at the start of this decade to be a realistic goal but has at the end of it proved to be something of a diagnostic mirage. "' Now a group of surgeons in Edinburgh has reported impressive survival rates among patients with stage I and stage II disease who were treated by resection.2 They argue that many patients may have been denied surgical treatment because of "the current view of most physicians -hat small cell lung cancer is not a surgical disease." Should these results make physicians reassess their approach? What role does surgery have in the management of small cell lung cancer? About 60% of patients with limited disease3 and perhaps about 30% of those with extensive disease' will show a worthwhile clinical response to chemotherapy. Nevertheless, only 15-20% of those with limited disease survive for two years, and the prognosis for those with extensive disease is even worse.45 Chemotherapeutic regimens more intensive than those tried in the past decade are unlikely to have much impact on prognosis, nor are the analogues of drugs already assessed in established regimens. Studies with different durations of inductions and late intensification of treatment will continue, however, in the hope that more basic research, such as the identification of tumour cell markers, will help the clinician to predict the response to chemotherapy more accurately. Response may now be correlated with performance status, age, and stage of disease, but the discovery that patients who respond best to chemotherapy are those who are fit and young and have limited disease is less than surprising. The results of conventional surgical resection of operable small lung cancers are difficult to assess as the published five year survival figures range from zero to 35%.6-S The Edinburgh group's cumulative five year survival rate of 35% for patients with stage I disease and 23% for those with stage II disease represents 10 years' experience, during which 27 BMJ
VOLUME 300
27 JANUARY 1990
patients with stage I and 29 with stage II cancer were treated by surgical resection. These results are superior to those of a retrospective study of 71 patients with small cell lung cancer with similar disease stages in which only 12% had survived five years after surgery.8 Nevertheless, on the basis of this five year survival Sorensen et al concluded that selected patients with small cell lung cancer should be treated by surgery alone-that is, without adjuvant chemotherapy. The Edinburgh surgeons would agree and suggest that surgery offers "the prospect of long term survival" for patients with stage I and stage II small cell lung cancer. The surgeons used data collected by the Edinburgh lung cancer group to imply that many patients were denied potentially curative surgery and perhaps instead received chemotherapy. These data show that over the 10 years some 1800 patients with small cell lung cancer presented in Edinburgh, of whom only 127 were referred to surgeons.9 Yet surgeons must be aware that the vast majority of patients with small cell lung cancer present with inoperable disease. In the Edinburgh surgical series almost one third of patients did not have a preoperative diagnosis. The likely explanation for this is the continuing practice of most clinicians of referring to surgeons patients with peripheral pulmonary lesions who are fit enough for surgical resection and in whom malignant disease is probable even if not proved. If the surgical management of patients with small cell lung cancer has fallen into disrepute, as the Edinburgh surgeons suggest, their paper should be used as a timely reminder that most long term survivors of small cell lung cancer are the fortunate few who present with operable disease. All patients with proved small cell lung cancer (and who are otherwise fit) should have the benefit of a surgical opinion if they have stage I or stage II disease. Yet most patients cannot be treated surgically. Their disease is too extensive for such treatment and instead they receive polychemotherapy or radiotherapy, or both, or no specific treatment. Perhaps their awful prognosis might be improved by primary surgery with postoperative chemo209
therapy or neoadjuvant chemotherapy followed by surgery with or without thoracic irradiation. Certainly the results of cancer treatment policies are depressingly poor. GRAHAM CROMPTON Consultant Physician, Respiratorv Unit, Northern General Hospital, Edinburgh EH5 2DQ Lconard RCF. Small ccll lung canccr.
Brj Cancer 1989;59:487-90.
2 1'rasad US, Navlor AR, Walker \WS, Lamb 1), Cameron EX!J, \W'albanim P'R. Long term snirvival after pulmonary resection for small cell carcinoma o(t' thc lttig. Ttorax 1989;44:784-7. 3 Sm\ith JF, Fowlic SM, Gregor A. ct a/. Thc impact of clicinothcrapy ot[ small ccl carciinomna o f'thc bronchus. QJ,Med 1986;61:969-76. 4 Setlter EJ, Ihde DC. Therapy of small ccll lting cancer. A perspective on tso decadcs of clinical research. Sernin O)icol 1988;15:278-99. 5 Holove PY, Kalbfleisch J. 'I'he infltuence of myelossupprcssion on the response to chemotherapy in small ccll bronchogenic carcinoma. Ca(ncer 1984;54:41 1-5. 6 Fox W, Scadding JC. Medical Research Council comparativc trial of surgerv aild radiotherapy ftor primary treatment of small-celled or oat-celled carcinoma of' bronchus. Ian(ct 1973;ii.63-5. 7 Mountain CF. Clinical biology of small cell carcinoma: relationship to surgical therapv S ?imti ( tol 1978;5:272-9. 8 Sorensci HR, Lund C. Alstrup 1. Sursival in small ccll lumig carcimioma after suirgery TItorux 1986;41:479-82. 9 Edinburgh Lung Cancer Group. Patients presenting with lung cancer in south east Scotland. JI'horx 19X7;42:853-7.
Intact parathyroid hormone assays Interpretation must take account of biological variation Since their first development in 1963 parathyroid hormone immunoassays have been invaluable in assessing patients with disorders of calcium metabolism. ' The interpretation of the results of these immunoassays has, however, been complicated by the molecular heterogeneity of circulating parathyroid hormone. As a result of the proteolytic metabolism of parathyroid hormone, both within the parathyroid gland and elsewhere in the body, the circulation contains amine and carboxy terminal fragments of parathyroid hormone in addition to the intact parathyroid hormone (1-84) peptide.2 In an attempt to improve clinical discrimination immunoassays were developed with specificities for amino terminal and mid-terminal or carboxy terminal parathyroid hormone. In general these assays either lacked the required sensitivity or showed overlap between values in normal people and in groups of patients. The recently developed two site immunometric assays for parathyroid hormone allow the intact parathyroid hormone (1-84) peptide to be measured without interference from fragments.3' The sensitivities of these assays are in the low picomolar range-sufficient to measure the hormone in normal people. The main application of parathyroid hormone assays is in the differential diagnosis of hypercalcaemia. Initial evaluations of the new assays for intact parathyroid hormone showed improved clinical discrimination between patients with hyperparathyroidism and hypercalcaemia of malignancy.`~The distinction was not, however, complete; though the concentrations of intact parathyroid hormone in these groups are well separated, 3-5% of patients with hyperparathyroidism have values at the upper end of the reference range for normal people and 20-30% of patients with hypercalcaemia of malignancy have low but detectable concentrations of intact parathyroid hormone. Secondary hyperparathyroidism is a consistent feature of advanced renal failure. In the past the measurement of parathyroid hormone in patients with renal failure has been compromised by the presence of an excess of biologically inactive carboxy terminal fragments. Because the new assays are not affected by parathyroid hormone fragments they should overcome this problem. In patients with renal failure they should be sufficiently specific to follow either the clearance of intact parathyroid hormone after parathyroidectomy6 or the suppression of intact parathyroid hormone after treatment with calcium.7 This may not be the case for all
assays.'
Since the new assays are sensitive enough to measure intact parathyroid hormone concentrations in normal people and 210
follow changes within the reference range they have been used to study the physiology and control of its secretion.9 This work has defined the circadian rhythm of intact parathyroid hormone secretion in normal men. It was shown to rise in a broad peak outside the reference range from 0200 to 0600. This was accompanied by a parallel rise in concentrations of nephrogenous cyclic AMP, indicating that the intact parathyroid hormone released was biologically active. There was considerable variation in the return to baseline concentrations among normal people, with the period between 0600 and 1000 characterised by great variability among individuals. The assessment of the intact parathyroid hormone concentrations in an individual must take this variability into account. Early morning samples, such as those typically collected from patients in hospital, may have spuriously raised concentrations. Further studies have shown the absence of a synchronised circadian rhythm in patients with primary hyperparathyroidism.' Comparison of 24 hour profiles indicates that the best discrimination between normal people and patients with hyperparathyroidism is achieved when samples are taken between 1100 and 1400. Most patients screened for hypercalcaemia of malignancy have undetectable concentrations of intact parathyroid hormone. Finding detectable intact parathyroid hormone in such patients has been ascribed to a change in the calcium set point of the parathyroid glands." In patients with hypercalcaemia of malignancy with undetectable intact parathyroid hormone concentrations studies of the effects of treatment to lower calcium have confirmed that an increase in intact parathyroid hormone concentration occurs as the calcium decreases but while the patient remains hypercalcaemic.'2 When assessing these patients, therefore, intact parathyroid hormone concentrations should be measured before giving any treatment to lower calcium. Although intact parathyroid hormone seems more stable than previously suspected,3"' there is some variability. Short delays in separation and freezing of samples would not normally be expected to have substantial adverse effects on the clinical value of the assays, but such delays might lead to the misclassification of patients with only borderline increases in circulating intact parathyroid hormone concentration.' The development of assays of intact parathyroid hormone is an important advance in the laboratory assessment of calcium disorders. The improved sensitivity and specificity of the new assays make it possible to achieve better discrimination between clinical groups. But the use of these assays has also highlighted the extent of biological variation in intact parathyroid hormone and its rapid response to treatment. The BMJ VOLUME 300
27 JANUARY 1990
