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A patient presented with mild hyperthyroidism, elevated serum T4 and T3, and an inappropriately raised serum thyrotrophin (TSH). There was no evidence of pituitary tumour (alpha-subunit secretion and CT scan of the pituitary were normal). The TSH response to TRH was greater than normal. The elevated TSH was suppressed by oral triiodothyronine (100 micrograms daily for 10 d). The normal diurnal variation of TSH was preserved. Intravenous injection of the dopamine receptor blocking agent domperidone led to a greater than normal elevation in TSH (maximum increments 18-20 mU/l). This increased dopaminergic tone was similar in studies carried out in the morning and late evening. The dopamine agonist bromocriptine (2.5 mg twice daily) failed to suppress serum TSH either acutely or over 6 weeks. The circadian rhythm was unaltered by this treatment. Basal serum prolactin levels were normal, and responded appropriately to TRH, domperidone and bromocriptine. These observations indicate that dopamine does not control the diurnal variation of TSH in nontumoral TSH-mediated hyperthyroidism. The increased dopaminergic tone demonstrated may be secondary to the primary failure of pituitary-thyroid feedback in the condition.

The case is reported of a young woman with severe hypertension, unilateral renal artery stenosis, variously normal or marginally high plasma concentrations of active renin, angiotensin II, aldosterone, sodium, and potassium; and normal total exchangeable and total body sodium and potassium. Arteriograms and ureter catheterization showed the stenosis to be severe, but the unstimulated renal vein renin and angiotensin II differential to be modest. Captopril caused an initial fall in angiotensin II and arterial pressure. During prolonged captopril treatment, plasma angiotensin II and aldosterone remained depressed; exchangeable and total body sodium and potassium were unaltered. Blood pressure fell further to normal levels during prolonged captopril treatment, while subsequent surgical correction of the renal artery stenosis was curative; absolute values of blood pressure and plasma angiotensin II were similar in both situations. The findings support, without proving, the concept that chronic modest elevation of angiotensin II may be responsible for sustained hypertension in unilateral renal artery stenosis. Patients of this type contrast sharply with those, also with severe renal artery stenosis or occlusion, who have gross elevation of renin, angiotensin II, and aldosterone, with sodium and potassium deficiency. Captopril or surgery are effective in both syndromes, but the manner of response to treatment differs markedly.

We report five patients with phaeochromocytoma associated with pregnancy and review the 42 other cases reported in the literature from 1980 to 1987. The overall maternal mortality was 17% and the fetal loss 26%; antenatal diagnosis of phaeochromocytoma reduced the maternal mortality to zero and the fetal loss to 15%, but was made in only 53% of the patients. Although phaeochromocytoma is rare, a high index of clinical suspicion must be maintained and all those at risk investigated if earlier diagnosis and improved outcome are to be achieved. Once the diagnosis is confirmed, alpha-blockade is essential and beta-blockade may be required. CT scan or magnetic resonance imaging may be used to localize the tumour during the antenatal period. In the first and second trimesters, tumour resection has a good fetal outcome; in later pregnancy, delivery by elective caesarean section followed by tumour resection is recommended.

A controversy still exists in regard to hypothalamic pituitary function long-term after cure of hypercortisolism due to Cushing's disease. In an attempt to resolve this controversy, we have studied 15 patients, treated at least 6 years previously, by bilateral adrenalectomy. None of these patients had had pituitary-directed therapy. The maximum increment response of serum TSH in response to TRH was greater than 5 mU/l in 13 of the 15. Serum PRL response to TRH, GH response to insulin-induced hypoglycaemia, gonadotrophin responses to LHRH and nocturnal PRL secretion were normal in all patients studied. When nocturnal GH secretion was corrected for age, body mass index and menopausal status it was definitely abnormal in only two patients. The mean nocturnal GH secretion did not differ from that measured in a control group of Addisonian patients. The series of patients also did not differ significantly from the Addisonian patients in relation to the pattern of changes in plasma ACTH, over 24 h after an 0800 h oral dose of hydrocortisone. There was a significant rise in plasma ACTH between 2200 h and 0600 h in both groups of patients. The plasma ACTH concentrations were significantly higher in post-adrenalectomy patients. Hypothalamic pituitary function is normal in the long-term in the majority of patients treated by bilateral adrenalectomy for Cushing's disease.

We have studied 46 members of a large kindred with familial hypocalciuric hypercalcaemia (FHH) after a neck exploration failed to cure hypercalcaemia in an asymptomatic patient. Serum calcium, serum phosphate, plasma parathormone and vitamin D metabolites do not distinguish affected members from patients with hyperparathyroidism. Because of the continuing debate as to whether or not FHH is a variant of, or distinct from, hyperparathyroidism, we have carried out a review of surgical experience with subtotal parathyroidectomy in hyperparathyroidism secondary to parathyroid hyperplasia and in FHH. Whereas the procedure is successful in 90 per cent of the former cases only one case of FHH has been cured by it. This provides evidence for the two conditions being aetiologically distinct. Before patients with asymptomatic hypercalcaemia are referred for parathyroid surgery the calcium:creatinine clearance ratio should be measured using a 2 h urine sample collected after an overnight fast and a fasting blood sample. If this ratio is less than 0.01 then screening of first degree relations should be undertaken before any parathyroid surgery is performed. Unnecessary surgery can therefore be avoided.

Spironolactone alone in full dosage failed to correct hypertension in a patient with Conn's syndrome and renal impairment, although the previously increased total exchangeable sodium fell to normal and the previously suppressed plasma angiotensin II did not rise above the normal range. Addition of the converting enzyme inhibitor captopril reduced plasma angiotensin II to very low levels, with a slight further fall in exchangeable sodium. Blood pressure was well controlled. Because hypertension in Conn's syndrome resistant to spironolactone usually also responds poorly to removal of the adenoma, and is difficult to treat with conventional hypotensive agents, the combination of a converting enzyme inhibitor with a potassium conserving diuretic is worthy of trial in such cases.

This case report records the rare presentation of accelerated hypertension secondary to long-standing renal tuberculosis and the subsequent beneficial response to surgery predicted by lateralisation of renin levels within the renal veins. The patient's hypertension proved difficult to control medically and he was therefore assessed for possible surgical management. Renin sampling revealed clear lateralisation within the renal veins indicating possible benefits from surgery. Nephro-ureterectomy was performed and, post-operatively, the patient's hypertension, while not completely resolved, was easily controlled with monotherapy. Patients with unilateral renal tuberculosis and hypertension which prove difficult to control should have measurement bilaterally of renal venous renin which may indicate potential benefits from surgery.

Fifteen patients with hypertension and unilateral renal artery disease were treated with captopril alone; 10 came to operation and were later assessed postoperatively with no drug treatment. Captopril caused both immediate and sustained decreases in plasma angiotensin II and aldosterone, with increases in plasma active renin and blood angiotensin I concentrations. Decrements in systolic and diastolic pressure 2 hours after the first dose of captopril were closely correlated with the initial decreases in plasma angiotensin II. Blood pressure was decreased by long-term captopril therapy irrespective of whether plasma angiotensin II was abnormally high before treatment. The long-term response of both systolic and diastolic pressure correlated well with the response to surgery. By contrast, the blood pressure decrease 2 hours after the initial dose of captopril variously underestimated and overestimated the decrease during prolonged use of the drug and did not relate to surgical outcome. In patients who, before treatment, had secondary aldosteronism, hyponatremia, hypokalemia and sodium and potassium deficiency, captopril corrected these abnormalities. In the remaining patients, long-term captopril therapy did not alter exchangeable sodium, plasma sodium or total body potassium, although plasma potassium levels increased.

The relationships between plasma atrial natriuretic factor (ANF), blood pressure (BP) and age have not been clearly defined. We measured plasma ANF levels and BP in 128 normal subjects (65 male; 63 female; mean age 48 years, range 20-87 years) on no medication. In subjects of 75 years or less (n = 120) plasma ANF was 5.7 +/- 0.3 pmol/l (mean +/- SEM). Plasma ANF did not differ between sexes (males 5.6 +/- 0.4 pmol/l, females 5.9 +/- 0.4 pmol/l). There was a positive correlation between plasma ANF and age, correlation coefficient (r) = 0.46, systolic BP (r = 0.44), diastolic BP (r = 0.22) and mean BP (r = 0.37) (all P less than 0.01), but after multiple linear regression analysis plasma ANF only related significantly (P less than 0.01) to age and systolic BP once other factors had been excluded. We also measured plasma ANF after erect and supine posture and during a 21IV normal saline infusion given over 4 hrs (n = 24; age range 21-62 years) after an overnight fast. Mean plasma ANF was 5.9 +/- 1.1 pmol/l erect, 7.4 +/- 1.6 pmol/l supine and rose to 10.1 +/- 1.4 pmol/l after saline (both P less than 0.05 vs basal). Response to saline was assessed as the area under the curve of hourly measurements. Neither this nor peak ANF during saline infusion correlated with age. We conclude that basal plasma ANF is influenced by age and systolic BP but plasma ANF response to acute saline stimulation is not.

A patient developed papilloedema and hepatic dysfunction while being treated with perhexiline maleate. These later regressed when the drug was withdrawn. Patients should be monitored for these potentially serious side-effects while on this drug.

It has been suggested that the first-phase feedback of steroid feedback on ACTH secretion is abnormal in Cushing's disease patients studied after adrenalectomies. We have performed hydrocortisone infusions (100 mg over 2 h) in 15 patients who had previously undergone bilateral adrenalectomy for Cushing's disease. None had had any pituitary-directed therapy and none had a pituitary macroadenoma. Their responses were compared with a group of seven hypoadrenal patients. A significant rise in serum cortisol was observed between 5 and 10 min in both groups. The first significant fall in ACTH occurred between 30 and 45 min in both groups. There was no abnormality of first-phase feedback in the Cushing's group and our results do not therefore support previous speculation that such an abnormality provides evidence for a higher central nervous system (CNS) aetiology of Cushing's disease.

A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger-Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively.

Forty four subjects (23 obese controls, 11 patients with possible Cushing's syndrome, and 10 patients with definite Cushing's syndrome) underwent low dose (0 X 5 mg every six hours for two days) dexamethasone suppression tests during which serum cortisol concentration at 0800 and excretion of urinary free cortisol over 24 hours were measured. Serum cortisol concentration fell to below 60 nmol/1 (2 X 2 micrograms/100 ml) in 31 subjects and remained above 250 nmol/1 (9 X 1 micrograms/100 ml) in the 13 others. Excretion of urinary free cortisol showed a similar response, falling to below 110 nmol (40 micrograms)/24 h in 31 and remaining above 180 nmol (65 micrograms)/24 h in the 13 others. There was complete concordance between the two variables in terms of the pattern of response. Serum cortisol concentration fell to below 60 nmol/1 (2 X 2 micrograms/100 ml) in at least 97% (31 of a possible 32) of subjects without Cushing's syndrome. On the other hand, a serum cortisol concentration of above 250 nmol/1 (9 X 1 micrograms/100 ml) after low dose dexamethasone gave a false positive diagnosis of Cushing's syndrome in at most only one of 13 patients (7 X 7%). Measurement of serum cortisol concentration during the low dose dexamethasone test is simpler than, and as accurate and reliable as, measurements of urinary steroids.

Sixteen patients with clinically active acromegaly were investigated; four of these had insulin-independent diabetes mellitus. Those acromegalic subjects who were not diabetic exhibited excessive insulin responses to glucose and arginine stimulation. By contrast, plasma glucagon concentrations in these patients did not differ significantly from those in control subjects. Acromegalic patients who also had insulin-independent diabetes had a markedly reduced insulin response to glucose stimulation, while arginine-induced insulin secretion was relatively well preserved. Although there was a tendency for plasma glucagon concentrations to be higher in the diabetic than in the nondiabetic group of acromegalic subjects, this difference did not achieve statistical significance either in the basal state or during the glucose amd arginine infusion tests.

Reported cases of cyclical Cushing's syndrome are rare. Of 14 successive patients with Cushing's syndrome nine collected sequential urine samples for the estimation of cortisol:creatinine ratio. Five had cyclical Cushing's syndrome while two had considerable variation in urinary cortisol excretion without a cyclical pattern being established. Two of the five patients with a cyclical syndrome had paradoxical responses to dexamethasone. In only one patient with a cyclical pattern did the cortisol:creatinine ratio fall after treatment with bromocriptine or cyproheptadine, or both. The high incidence of the cyclical form of Cushing's syndrome has important clinical implications. A high index of suspicion of the syndrome is required in patients with symptoms or signs of Cushing's syndrome but with normal cortisol values, in patients with fluctuating cortisol values, and in patients with anomalous responses to dexamethasone. Because of possible variations in steroidogenesis the results of drug studies in Cushing's syndrome must be interpreted cautiously.

A 37 year old male with a strong family history of autoimmune disease presented with typical symptoms of hyperthyroidism. He had exophthalmos but no goitre. Hyperthyroidism was confirmed by failure of 131I neck uptake to suppress after 7 days treatment with triiodothyronine. Six years previously a diagnosis of primary hypothyroidism has been made. At diagnosis of hyperthyroidism, thyroglobulin antibodies, thyroidal microsomal antibodies and thyroid stimulating immunoglobulins were detected. The absence of thyroid growth stimulating immunoglobulins and presence of immunoglobulins blocking TSH-induced growth may account for the absence of goitre throughout. HLA -B8, -B, -DR3 and -DR4 genotypes, low C4 complement concentrations and islet cell autoantibodies were detected at the time of diagnosis and 1 year later diabetes mellitus developed.

Islet B-cell function and insulin sensitivity were estimated with the aid of a mathematical model from repeated fasting plasma glucose and insulin measurements over a 6 year period in 131 patients with type 2 diabetes mellitus who could be managed satisfactorily on dietary therapy alone. They presented between the ages of 40 and 69 years, and were studied before and after one year of treatment, and then at regular intervals from 12 until 72 months later. A method of averaging the individual trends by means of a linear model regression technique was used to assess the progression of their diabetes. Dietary management over the first 12 months resulted in weight loss from 118% to 106% average body weight, and improved insulin sensitivity from 26% to 40% of normal (p less than 0.001). From 12 to 72 months, the fasting plasma glucose rose at a mean rate of 0.23 mmol/l per year (p less than 0.001) despite a rate of weight loss of 0.2% average body weight per year (p less than 0.01). The estimated islet B-cell function, expressed as a percentage of normal, decreased significantly (p less than 0.05) at a rate of 1.5% per year, with no statistically significant change in insulin sensitivity. Extrapolation suggests the reduction in B-cell function predated the departure of fasting plasma glucose from the normal range.

Four out of twenty-three acromegalic patients selected for treatment with external megavoltage pituitary irradiation between 1961 and 1975 developed progressive visual failure. They had received megavoltage external irradiation through multiple portals from a cobalt-60 unit over a period of 3 weeks. Visual deterioration began 2 months to 6 years after irradiation. In two patients the optic nerves were explored. In both, post-mortem later confirmed radiation damage to the optic nerves and hypothalamus. In one case there was also necrosis of the right frontal lobe with necrosis and inflammation of the bone surrounding the pituitary fossa. In the two other patients, extensive clinical and neuroradiological investigation excluded the presence of a suprasellar mass as a cause for this visual failure and a clinical diagnosis of radiation necrosis was made.

To establish a rapid test for Cushing's syndrome we measured serum cortisol during and following iv dexamethasone infusion (5 micrograms.kg-1.h-1 for 5 h from 10.00 h) in simple obesity (N = 19) and in Cushing's syndrome (N = 12). We had first established that 5 micrograms.kg-1.h-1 was the lowest dose which consistently lowered serum cortisol in simple obesity. In obesity, serum cortisols ranged from undetectable (less than 30) to 48 nmol/l at 17.00, less than 30 to 37 at 19.00 and less than 30 to 38 at 08.00 h the following day. Serum cortisol at these three times did not show any overlap between simple obesity and Cushing's syndrome. Having established these findings we proceeded to study a group of patients with polycystic ovarian disease. These patients behaved differently. Their values at 17.00 and 19.00 h did not overlap those of Cushing's syndrome. However, at 08.00 h, 5 of the 7 had values within the range seen in Cushing's syndrome with a mean of 290 +/- 99 nmol/l. In conclusion, 17.00 and 19.00 h serum cortisol levels distinguish between Cushing's syndrome and both simple obesity and polycystic ovarian disease. However, in the latter, cortisol suppression is less prolonged than in simple obesity. This finding may be important for our understanding of the pathogenesis of the disease.

A young male patient demonstrated unusual features of Cushing's syndrome, atrial myxomas and freckled skin pigmentation. At 4.5 years of age he presented with intermittent swelling of his face and abdomen associated with weight gain and mild hypertension. A left atrial myxoma, suspected from routine physical examination, was surgically removed at 6.1 years of age. The initial mild symptoms clinically thought to be due to Cushing's syndrome, persisted intermittently without any consistent biochemical abnormality. At 10 years of age height velocity decreased and at 12 years early osteoporosis was observed radiologically. Repeated dexamethasone tests revealed a paradoxical increase in cortisol and corticotrophin from normal basal levels. Further investigation showed a cyclical pattern of hypercortisolism. The removal of a pituitary microadenoma failed to correct the features of Cushing's syndrome or prevent intermittent hypercortisolism. At 15.3 years a second left atrial myxoma was removed. This was followed by bilateral adrenalectomy. Histologically the features were consistent with primary pigmented nodular adrenocortical disease. This is the first patient described with cyclical Cushing's syndrome as part of this unusual complex of disorders.

We assessed serum growth hormone (GH) levels in ten patients with acromegaly during a 24-hour profile and a 75-g oral glucose tolerance test (GTT). Serum GH levels were measured after five weeks of bromocriptine mesylate therapy, 20 mg daily (P1), after five weeks without bromocriptine mesylate therapy (P2), and again five weeks following restarting treatment with bromocriptine, 20 mg daily (P3). During the 24-hour profile, the following occurred: (1) mean serum GH level of the group was lower during P1 (20.5 mU/L) and P3 (20.8 mU/L) than P2 (49.6 mU/L); (2) in six individual patients during P1 and P3, there was a significant reduction in the mean serum GH value; and (3) a marked circadian variation in the serum GH value was present both with and without the drug therapy in five patients. During the GTT, the mean serum GH value was lower during P1 (18.4 mU/L) and P3 (16.7 mU/L) than P2 (43.3 mU/L), and in seven individual patients during P1 and P3, there was a significant reduction in the mean serum GH value. Overall, a clear reduction in serum GH values due to bromocriptine was demonstrated. In individual patients, serum GH values during a 24-hour profile and GTT gave similar indications of response.

Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight of our patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. We conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop in the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism.

1. Arterial pressure and exchangeable sodium (NaE) were measured in patients with Conn's syndrome, essential hypertension, renal artery stenosis and chronic renal failure. Comparison was made with a control group. Urine sodium excretion was measured separately from the two kidneys in patients with renal artery stenosis. 2. Compared with control, mean NaE was significantly increased in Conn's syndrome, and was normal in essential hypertension, renal artery stenosis and chronic renal failure. 3. The correlation of arterial pressure with NaE was positive and significant in Conn's syndrome, essential hypertension and chronic renal failure. 4. In contrast the correlation was significantly negative in unilateral renal artery stenosis. Patients with lowest NaE had hyponatraemia, hypokalaemia and secondary hyperaldosteronism. 5. Urinary sodium excretion from the unaffected kidney in unilateral renal artery stenosis correlated positively with arterial pressure, possibly reflecting the phenomenon of pressure-natriuresis. Patients subsequently responding least well to surgery excreted least sodium from the untouched kidney for a given arterial pressure. 6. The findings suggest important roles for arterial pressure in the regulation of sodium balance (predominant in renal artery stenosis), and for sodium balance in the regulation of arterial pressure (predominant in Conn's syndrome). The observations in essential hypertension are compatible either with an exact balance between these mechanisms or with the existence of some other mechanism raising blood pressure.

The prevalence of secondary forms of hypertension in diabetes is unknown. One hundred and five of 465 patients randomly selected from a diabetic clinic population were found to be hypertensive. Hypertensive patients aged less than 70 years were screened for renal artery stenosis using intravenous digital subtraction angiography. Two angiograms were technically unsatisfactory. All 18 insulin-dependent patients successfully screened had normal renal arteriograms. Five of 24 non-insulin-dependent patients had unilateral renal artery stenosis but functional tests did not clearly suggest that renal artery stenosis was causing the hypertension in these cases. No patient was referred for surgery or angioplasty. We conclude that renal artery stenosis is common in hypertensive non-insulin-dependent diabetics but may not, in many cases, be the cause of the hypertension. The criteria for investigating diabetic hypertensives for renal artery stenosis should be no different from those used in the general hypertensive population.

Malignant hypertension with severe hyponatraemia, hypokalaemia, depletion of sodium and potassium, and elevated blood levels of renin, angiotensin I, angiotensin II, aldosterone, and arginine vasopressin developed in a woman with renal-artery occlusion. Plasma angiotensin II was disproportionately high in relation to exchangeable sodium. Captopril, by inhibiting conversion of angiotensin I to angiotensin II, further elevated the blood levels of renin and angiotensin I but corrected all other abnormalities. Unilateral nephrectomy was subsequently curative.

An 11-year-old male presented with a 2-year history of headache and lethargy. Serum PRL was elevated at 14,000 mU/l and computerized tomography showed a pituitary macroadenoma. Visual fields and fundi were normal and the testes showed early pubertal changes. There was normal responsiveness of serum cortisol but absence of GH response to hypoglycaemia. After bromocriptine therapy for 4 months serum PRL had fallen to 90 mU/l and the tumour was not visible on repeat computerized tomography. After 7 months treatment, repeat pituitary function testing showed restoration of GH response to hypoglycaemia. Treatment with bromocriptine was continued and there was spontaneous progression of normal puberty; the serum testosterone continued to rise, and height maintained the 50th centile. Bromocriptine therapy should be considered as initial therapy in the management of prolactinomas in prepubertal patients.

The effect of the converting enzyme inhibitor captopril on arterial pressure, the components of the renin-angiotensin-aldosterone system, and body sodium and potassium content was studied in eight hypertensive patients with renal artery stenosis and, in conjunction with diuretics, in seven patients with hypertension unresponsive to previous treatment. Two hours after the first dose, captopril caused significant falls in systolic and diastolic pressures, plasma angiotensin II, and aldosterone, with converse increases in angiotensin I and both active and total renin; the initial fall in diastolic pressure was significantly related to the drop in plasma angiotensin II. The biochemical changes were sustained during prolonged treatment, even when diuretics were added. One untreated patient with renal artery occlusion had severe secondary aldosterone excess, was sodium and potassium depleted, and severely hyponatraemic and hypokalaemic; captopril restored blood pressure, plasma electrolyte concentrations, and exchangeable sodium and total body potassium to normal. In one man with renal artery stenosis and overall renal impairment captopril led to sodium retention, and blood pressure did not fall until a diuretic was added. In the remaining patients with renal artery stenosis, pretreatment renin, angio tensin II, and aldosterone concentrations were either normal or only modestly raised, and plasma electrolyte concentrations and body content of sodium and potassium were normal. Captopril alone controlled arterial pressure in all, three cases showing a gradual fall of pressure over the first six weeks of treatment; no significant changes in exchangeable sodium or total body potassium were seen. The group of patients with previously intractable hypertension were all controlled with a combination of captopril and diuretic.

The development of proteinuria, and more rarely nephrotic syndrome, has been seen with the use of the first orally active converting-enzyme inhibitor captopril. Both of these side effects appear to occur more frequently when the drug is used at higher dose, particularly in the presence of renal impairment. We have used enalapril, a new orally active converting-enzyme inhibitor in the treatment of a patient with drug-resistant hypertension and renal impairment who previously developed nephrotic syndrome with captopril. Recurrence of the nephrotic syndrome was not seen in this patient during a period of 20 months on enalapril. On the contrary, urinary protein excretion over the same period was reduced to around 1 g in 24 hours. Our experience would suggest that enalapril may usefully be substituted for captopril in the treatment of hypertensive patients in whom the latter has caused proteinuria or nephrotic syndrome.