- Email: [email protected]
ACID-BASE STATUS, pH, AND Pco2
1015
terminating a pregnancy, and that the doctors who suggested him could hardly be unaware of his views. Probably the referring doctors believed that they were acting in this patient’s best interests-but was their conduct exist for
RESULTS
OF MEASUREMENTS IN 5 CLINICAL STATES EXPRESSED CONVENTIONAL UNITS AND IN HYDROGEN-ION UNITS
IN
honest and ethical ? PETER DARBY.
London, S.W.11.
FAMILY SPENDING AND THE FAMILY DOCTOR SIR,-The Ministry of Labour’s report1 shows that the average number of persons per household is 3-06. The amount, known to be an underestimate, spent on alcoholic drinks and tobacco every week per household is El18s. 4d. On the other hand, the family doctor receives, for his 24-hour responsibility, about ls. 6d. (minus 38% for expenses) per week from the average household of 3 persons. These are strange values. 1. H. MILNER. I. London, N.7. ACID-BASE STATUS, pH, AND Pco2 his colleagues (Oct. 2) SIR The article by Dr. emphasises that, despite considerable advances in the laboratory techniques used for the assessment of acid-base status, many clinicians still find the interpretation of results difficult. The ingenious diagram suggested by Dr. Owen and his colleagues has much to commend it, but the attempt at clarification has not gone far enough and the fundamental difficulty still remains. In my experience the difficulty arises from the units used. Present teaching emphasises that in considering the acid-base status of a patient we must consider the hydrogen ion. The accepted Bronsted terminology defines acids and bases in terms of the hydrogen ion. If the investigation of acid-base state is to be clinically useful, mere assessment of the hydrogen-ion concentration is not enough. It is necessary to know the state of the mechanisms involving hydrogen-ion homoeostasis, and these can be conveniently characterised as respiratory and nonrespiratory. The confusion arises from the units used-surely the most heterogeneous to be found in clinical chemistry. The hydrogen-ion concentration is expressed as the negative logarithm of an activity (pH), the respiratory measurement (Pc02) as a pressure in mm. Hg, and the non-respiratory measurement as the concentration of an anion (bicarbonate) in
Owen and
1.
Ministry of Labour. Family Expenditure Survey for 1964. H.M.
Stationery Office,
1965.
per litre. To attempt to balance and collate measurein such units inevitably produces difficulty. Dr. Owen and his colleagues have expressed the hydrogen ion as a concentration in nEq. per litre and not as a pH, but they have retained the Pco2 and the bicarbonate. In the following
mEq.
ments
alternative system, all the measurements are expressed as alterations in hydrogen-ion concentration in nEq. per litre.! The hydrogen ions present in blood are controlled by respiratory mechanisms, and by other mechanisms which can be conveniently grouped together and called non-respiratory.
Thus, - [H+] respiratory + [H+] non-respiratory (1) convenient to express this relation as alterations in hydrogen-ion concentration from the normal values, as follows:
[H+]total in blood It is &Dgr;
........
more
(H+] respiratory + - [H+] non-respiratory - - (2) The most convenient points of reference from which to express the changes.in the hydrogen-ion concentration are the mean normal total [H+] of 40 nEq. per litre (pH 7-40) and the [H+] of the blood at a PC02 of 40 mm. Hg. Equation (2) can then be expressed, [H+] total -,40 ([H+] total - [H+] Pco2 40) +([H+] Pco2 40 40).(3) All these values may be read from a normal Astrup diagram which is in common use in the investigation of blood acid-base state. [H-] total is the actual pH of the blood converted to [H+] in nEq. per litre. The graph in the accompanying figure is useful for this purpose. [H+] Pco2 40 is similarly obtained from the Astrup diagram: it is the pH of the blood at a Pco2 of 40 mm. Hg with the hxmoglobin fully saturated. This pH value is converted to [H+] using the graph. The various values in equation (3) may be simplified to: &Dgr; H = R + NR (4) where &Dgr; H = [H ]] total - 40 (alteration in total hydrogen-ion concentration), R --- [he] total [H+] Pco, 40 (alteration in respiratory hydrogen-ion concentration), and NR = [H+] Pea, 40 40 (alteration in non-respiratory hydrogen-ion concentration). &Dgr; H, R, and NR are in nEq. per litre, and they all have a normal range of ±4 nEq. per litre. The relation between &Dgr; H, R, and NR is simple. The accompanying table shows results from different clinical states, expressed in conventional units as pH, Pco2, and standard bicarbonate, and in the suggested hydrogen-ion units. A positive sign means an increase in hydrogen-ion concentration, and a negative sign a decrease; the combined alterations in R and NR must always equal &Dgr; H, and the primary and compensatory changes of R or NR may be easily identified. If the change of R and NR are both in the same direction, the [H+] total in blood
= &Dgr;
=
-
..........
-
-
Graph An
activity
for conversion of pH to [H‘] in nEq. coefficient of 1 is assumed.
per litre.
1.
Whitehead,
T. P.
Ph.D.
thesis, University of Birmingham, 1964.
1016
alterations due to each measurement can be ascertained by mere examination of the numerical values. Department of Biochemistry, Queen Elizabeth Hospital, T. P. WHITEHEAD. Birmingham, 15.
Acid-base definitions and terminology are discussed in special article on p. 1010 and in an annotation on p. 1003.ED. L. a
DRUG SAMPLES SIR,—Iwas interested in Dr. Weinstein’s appeal (Oct. 9) for a scheme " to send unwanted [drug] samples to underdeveloped countries ". The Save the Children Fund works in 26 countries; and if it is possible for us to benefit by some of these samples, particularly the ones which our doctors overseas could use for children, we should be very grateful. We spend a great deal of our funds on medical supplies. J. K. BARDALL 29, Queen Anne’s Gate,
Supplies Secretary,
London, S.W.1.
Save the Children Fund.
FOLATE METABOLISM AND IRON DEFICIENCY SIR,-Dr. Gross and his colleagues (Oct. 9) cite 4 cases1 of abnormal urinary excretion of formiminoglutamic acid (FIGLU) among 28 infants with " unequivocal nutritional iron de" ficiency in support of the suggestion by Chanarin et al. and Dr. Vitale and his colleagues that iron deficiency may, itself, lead to folic-acid deficiency. Dr. Vitale and his colleagues demonstrated impairment of folate function in iron-deficient rats through diminution of hepatic formimino-transferase. Their inferences regarding a parallel abnormality in man were based on a study on iron deficiency in pregnancy by Chanarin et al. who, however, found " no obvious difference " between the iron-deficient and the iron-supplemented groups in urinary excretion of FiGLU. The conclusion of Chanarin et awl. that iron deficiency played an important part in producing folic-acid deficiency cannot be accepted in critical examination of their data. Thus: (a) the higher incidence of megaloblastic erythropoiesis in the irondeficient group could have been due to the fact that only selected patients were examined 3 4; (b) Chanarin and his co-workers themselves question 24 the reliability of hypersegmented neutrophils as an index of folic-acid deficiency; and (c) differences in the mean Lactobacillus casei levels between the folic-acid-supplemented group (i.e., iron plus folic acid) and the controls " did not prove to be statistically significant ". There are conflicting publications regarding urinary excretion of FiGLU in iron deficiency, both normal 5-8 and abnormal9 10 results having been recorded. The xtiology of iron deficiency in these cases has not always been stated, and the possibility remains that the abnormal results may have been due to the primary disorder. I have jointly observed 11 normal FiGLU and urocanic-acid excretion after histidine loading 12 13 in 12 patients with uncomplicated iron deficiency. The observation of Dr. Vitale and his colleagues in the rat is an important one which should be pursued in man, but any conclusions in this complex field should be based on unequivocal data. Department of Materia Medica and Therapeutics, S. D. MOHAMED. University of Aberdeen. A. 1. Gross, S., Keefer, V., Newman, J. Pediatrics, Springfield, 1964, 33, 315.
Chanarin, I., Rothman, D., Berry, V. Br. med. J. 1965, i, 480. Lowenstein, L., Brunton, L., Milad, A., Cooper, B. Proceedings of the Ninth Congress of the European Society of Hæmatology. Lisbon, 1963. 4. Chanarin, I., Rothman, D., Ardeman, S., Berry, V. Br. J. Hæmat. 1965, 11, 557. 5. Knowles, J. P., Prankerd, T. A. J., Westhall, R. G. Lancet, 1960, ii, 2. 3.
347. 6. 7.
8. 9. 10. 11. 12. 13.
Kohn, J., Mollin, D. L., Rosenbach, L. M. J. clin. Path. 1961, 14, 345. Mollin, D. L., Waters, S. A. H., Harris, E. B. in Vitamin B12 and Intrinsic Factor (edited by H. C. Heinreich); p. 737. Stuttgart, 1962. Kershaw, P. W., Girdwood, R. H. Scott. med. J. 1964, 9, 201. Knowles, J. P. Gut, 1962, 3, 42. Chanarin, I., Bennett, M. C., Berry, V. J. clin. Path. 1962, 15, 269. Mohamed, S. D., Roberts, M. Unpublished. Roberts, M., Mohamed, S. D. J. clin. Path. 1965, 18, 214. Mohamed, S. D., Roberts, M. ibid. (in the press).
MEASURING GLOMERULAR-FILTRATION RATE SIR,-I have read with interest the article by Dr. Breckenridge and Dr. Metcalfe-Gibson (Aug. 7), but I was surprised that they do not mention what seems the most important potential advantage of y-emitting radioactive tracers, such as 58Co-labelled vitamin B12, for the measurement of glomerularfiltration rate (G.F.R.). In fact y-emission offers the possibility of measuring the amount of tracer substance eliminated with the urine by external scintillation-counting over the bladder, thus avoiding vesical catheterisation.1 In this way determination of G.F.R. becomes simpler and more accurate: it is not disturbing to the patients, and it avoids errors due to incomplete collection of the urine-these are quite frequent, particularly at low urine flow-rates. A suitable technique for scintillation-counting over the bladder has been used with a different radioactive tracer, 131I-labelled sodium diatriozate (’Hypaque’), which is eliminated by the kidneys by glomerular filtration only, without being either excreted or reabsorbed by the tubules, and the renal clearance of which has been shown to equal that of inulin and hyposulphite in both normal and abnormal conditions. 131I-labelled sodium diatriozate may have additional advantages over 58Co-labelled vitamin B12, since it does not require any previous administration of non-labelled products, while the shorter half-life of radioiodine in comparison with radiocobalt reduces the radiation dose to the subjects. General Medical Clinic, University of Pisa, Italy.
C. BIANCHI.
SULPHONYLUREA HYPOTHYROIDISM IN DIABETICS SIR,—The statistically higher incidence of hypothyroidism in diabetics treated with tolbutamide and chloropropamide reported by Dr. Hunton and his co-workers (Sept. 4) is of great interest. I have had under observation three elderly female diabetics with hypothyroidism who have been treated with 1-2-5 g. of tolbutamide per day for 8 to 10 years. One of them had two episodes of transient secondary hypothyroidism while taking the sulphonylurea. She is aged 78 years with late-onset mild diabetes mellitus. 2 g. of tolbutamide had been taken daily for about 8 years. She had had three normal deliveries and had undergone a subtotal hysterectomy in the past. After the sudden onset of mild abdominal pains, vomiting, fever, and headaches in 1962 she was admitted to hospital. Pertinent physical findings included a temperature of 103°F, slight facial and periorbital lethargy, " puffiness," and delayed deep tendon reflexes. The thyroid
gland
enlarged. Complete blood-count, urinalysis, nitrogen and blood-cholesterol, total serum-protein, serum-electrolytes, and skull and chest X-rays were normal. Blood-glucose was 242 mg. per 100 ml. Lumbar puncture revealed changes compatible with a viral or aseptic meningitis. The serum-protein-bound-iodine (P.B.I.) was 2-8 µg. per 100 ml. and the 24-hour 1311 uptake was 7%. These values rose to 7-0 µg. per 100 ml. and 50%, respectively, 24 hours after intramuscular administration of 10 units of lyophilised beef thyrotropin.3 4The lethargy, somnolence, and periorbital oedema subsided, and the reflexes became brisk during the next few days. Repeat lumbar puncture revealed resolution of the previously abnormal spina-fluid changes. The tolbutamide was discontinued during the acute phase of the patient’s illness. She was asymptomatic when discharged and was instructed to resume her daily dosage of 2 g. of tolbutamide. Serum-P.B.I. and thyroidal radioactive uptakes were normal at subsequent visits. Waterloading, 17-hydroxycorticoid and 17-ketosteroid excretions, metyrapone tests,5 adrenocortical stimulations with was not
blood-urea
1. 2. 3. 4. 5.
Bianchi, C., Toni, P. Experientia, 1964, 20, 148. Bianchi, C., Toni, P. Excerpta med. Int. Congr. Ser. 1964, 78, 517. Querido, A., Stanbury, J. B. J. clin. Endocr. Metab. 1950, 10, 1192. Jeffries, W. McK., Levy, R. P., Palmer, W. G., Storaasl, J. P., Kelley, L. W., Jr. New Engl. J. Med. 1953, 249, 876. Liddle, G. W., Estep, H. H., Kendall, J. W., Jr., Williams, W. C., Jr., Townes, A. W. J. clin. Endocr. Metab. 1959, 19, 875.
terminating a pregnancy, and that the doctors who suggested him could hardly be unaware of his views. Probably the referring doctors believed that they were acting in this patient’s best interests-but was their conduct exist for
RESULTS
OF MEASUREMENTS IN 5 CLINICAL STATES EXPRESSED CONVENTIONAL UNITS AND IN HYDROGEN-ION UNITS
IN
honest and ethical ? PETER DARBY.
London, S.W.11.
FAMILY SPENDING AND THE FAMILY DOCTOR SIR,-The Ministry of Labour’s report1 shows that the average number of persons per household is 3-06. The amount, known to be an underestimate, spent on alcoholic drinks and tobacco every week per household is El18s. 4d. On the other hand, the family doctor receives, for his 24-hour responsibility, about ls. 6d. (minus 38% for expenses) per week from the average household of 3 persons. These are strange values. 1. H. MILNER. I. London, N.7. ACID-BASE STATUS, pH, AND Pco2 his colleagues (Oct. 2) SIR The article by Dr. emphasises that, despite considerable advances in the laboratory techniques used for the assessment of acid-base status, many clinicians still find the interpretation of results difficult. The ingenious diagram suggested by Dr. Owen and his colleagues has much to commend it, but the attempt at clarification has not gone far enough and the fundamental difficulty still remains. In my experience the difficulty arises from the units used. Present teaching emphasises that in considering the acid-base status of a patient we must consider the hydrogen ion. The accepted Bronsted terminology defines acids and bases in terms of the hydrogen ion. If the investigation of acid-base state is to be clinically useful, mere assessment of the hydrogen-ion concentration is not enough. It is necessary to know the state of the mechanisms involving hydrogen-ion homoeostasis, and these can be conveniently characterised as respiratory and nonrespiratory. The confusion arises from the units used-surely the most heterogeneous to be found in clinical chemistry. The hydrogen-ion concentration is expressed as the negative logarithm of an activity (pH), the respiratory measurement (Pc02) as a pressure in mm. Hg, and the non-respiratory measurement as the concentration of an anion (bicarbonate) in
Owen and
1.
Ministry of Labour. Family Expenditure Survey for 1964. H.M.
Stationery Office,
1965.
per litre. To attempt to balance and collate measurein such units inevitably produces difficulty. Dr. Owen and his colleagues have expressed the hydrogen ion as a concentration in nEq. per litre and not as a pH, but they have retained the Pco2 and the bicarbonate. In the following
mEq.
ments
alternative system, all the measurements are expressed as alterations in hydrogen-ion concentration in nEq. per litre.! The hydrogen ions present in blood are controlled by respiratory mechanisms, and by other mechanisms which can be conveniently grouped together and called non-respiratory.
Thus, - [H+] respiratory + [H+] non-respiratory (1) convenient to express this relation as alterations in hydrogen-ion concentration from the normal values, as follows:
[H+]total in blood It is &Dgr;
........
more
(H+] respiratory + - [H+] non-respiratory - - (2) The most convenient points of reference from which to express the changes.in the hydrogen-ion concentration are the mean normal total [H+] of 40 nEq. per litre (pH 7-40) and the [H+] of the blood at a PC02 of 40 mm. Hg. Equation (2) can then be expressed, [H+] total -,40 ([H+] total - [H+] Pco2 40) +([H+] Pco2 40 40).(3) All these values may be read from a normal Astrup diagram which is in common use in the investigation of blood acid-base state. [H-] total is the actual pH of the blood converted to [H+] in nEq. per litre. The graph in the accompanying figure is useful for this purpose. [H+] Pco2 40 is similarly obtained from the Astrup diagram: it is the pH of the blood at a Pco2 of 40 mm. Hg with the hxmoglobin fully saturated. This pH value is converted to [H+] using the graph. The various values in equation (3) may be simplified to: &Dgr; H = R + NR (4) where &Dgr; H = [H ]] total - 40 (alteration in total hydrogen-ion concentration), R --- [he] total [H+] Pco, 40 (alteration in respiratory hydrogen-ion concentration), and NR = [H+] Pea, 40 40 (alteration in non-respiratory hydrogen-ion concentration). &Dgr; H, R, and NR are in nEq. per litre, and they all have a normal range of ±4 nEq. per litre. The relation between &Dgr; H, R, and NR is simple. The accompanying table shows results from different clinical states, expressed in conventional units as pH, Pco2, and standard bicarbonate, and in the suggested hydrogen-ion units. A positive sign means an increase in hydrogen-ion concentration, and a negative sign a decrease; the combined alterations in R and NR must always equal &Dgr; H, and the primary and compensatory changes of R or NR may be easily identified. If the change of R and NR are both in the same direction, the [H+] total in blood
= &Dgr;
=
-
..........
-
-
Graph An
activity
for conversion of pH to [H‘] in nEq. coefficient of 1 is assumed.
per litre.
1.
Whitehead,
T. P.
Ph.D.
thesis, University of Birmingham, 1964.
1016
alterations due to each measurement can be ascertained by mere examination of the numerical values. Department of Biochemistry, Queen Elizabeth Hospital, T. P. WHITEHEAD. Birmingham, 15.
Acid-base definitions and terminology are discussed in special article on p. 1010 and in an annotation on p. 1003.ED. L. a
DRUG SAMPLES SIR,—Iwas interested in Dr. Weinstein’s appeal (Oct. 9) for a scheme " to send unwanted [drug] samples to underdeveloped countries ". The Save the Children Fund works in 26 countries; and if it is possible for us to benefit by some of these samples, particularly the ones which our doctors overseas could use for children, we should be very grateful. We spend a great deal of our funds on medical supplies. J. K. BARDALL 29, Queen Anne’s Gate,
Supplies Secretary,
London, S.W.1.
Save the Children Fund.
FOLATE METABOLISM AND IRON DEFICIENCY SIR,-Dr. Gross and his colleagues (Oct. 9) cite 4 cases1 of abnormal urinary excretion of formiminoglutamic acid (FIGLU) among 28 infants with " unequivocal nutritional iron de" ficiency in support of the suggestion by Chanarin et al. and Dr. Vitale and his colleagues that iron deficiency may, itself, lead to folic-acid deficiency. Dr. Vitale and his colleagues demonstrated impairment of folate function in iron-deficient rats through diminution of hepatic formimino-transferase. Their inferences regarding a parallel abnormality in man were based on a study on iron deficiency in pregnancy by Chanarin et al. who, however, found " no obvious difference " between the iron-deficient and the iron-supplemented groups in urinary excretion of FiGLU. The conclusion of Chanarin et awl. that iron deficiency played an important part in producing folic-acid deficiency cannot be accepted in critical examination of their data. Thus: (a) the higher incidence of megaloblastic erythropoiesis in the irondeficient group could have been due to the fact that only selected patients were examined 3 4; (b) Chanarin and his co-workers themselves question 24 the reliability of hypersegmented neutrophils as an index of folic-acid deficiency; and (c) differences in the mean Lactobacillus casei levels between the folic-acid-supplemented group (i.e., iron plus folic acid) and the controls " did not prove to be statistically significant ". There are conflicting publications regarding urinary excretion of FiGLU in iron deficiency, both normal 5-8 and abnormal9 10 results having been recorded. The xtiology of iron deficiency in these cases has not always been stated, and the possibility remains that the abnormal results may have been due to the primary disorder. I have jointly observed 11 normal FiGLU and urocanic-acid excretion after histidine loading 12 13 in 12 patients with uncomplicated iron deficiency. The observation of Dr. Vitale and his colleagues in the rat is an important one which should be pursued in man, but any conclusions in this complex field should be based on unequivocal data. Department of Materia Medica and Therapeutics, S. D. MOHAMED. University of Aberdeen. A. 1. Gross, S., Keefer, V., Newman, J. Pediatrics, Springfield, 1964, 33, 315.
Chanarin, I., Rothman, D., Berry, V. Br. med. J. 1965, i, 480. Lowenstein, L., Brunton, L., Milad, A., Cooper, B. Proceedings of the Ninth Congress of the European Society of Hæmatology. Lisbon, 1963. 4. Chanarin, I., Rothman, D., Ardeman, S., Berry, V. Br. J. Hæmat. 1965, 11, 557. 5. Knowles, J. P., Prankerd, T. A. J., Westhall, R. G. Lancet, 1960, ii, 2. 3.
347. 6. 7.
8. 9. 10. 11. 12. 13.
Kohn, J., Mollin, D. L., Rosenbach, L. M. J. clin. Path. 1961, 14, 345. Mollin, D. L., Waters, S. A. H., Harris, E. B. in Vitamin B12 and Intrinsic Factor (edited by H. C. Heinreich); p. 737. Stuttgart, 1962. Kershaw, P. W., Girdwood, R. H. Scott. med. J. 1964, 9, 201. Knowles, J. P. Gut, 1962, 3, 42. Chanarin, I., Bennett, M. C., Berry, V. J. clin. Path. 1962, 15, 269. Mohamed, S. D., Roberts, M. Unpublished. Roberts, M., Mohamed, S. D. J. clin. Path. 1965, 18, 214. Mohamed, S. D., Roberts, M. ibid. (in the press).
MEASURING GLOMERULAR-FILTRATION RATE SIR,-I have read with interest the article by Dr. Breckenridge and Dr. Metcalfe-Gibson (Aug. 7), but I was surprised that they do not mention what seems the most important potential advantage of y-emitting radioactive tracers, such as 58Co-labelled vitamin B12, for the measurement of glomerularfiltration rate (G.F.R.). In fact y-emission offers the possibility of measuring the amount of tracer substance eliminated with the urine by external scintillation-counting over the bladder, thus avoiding vesical catheterisation.1 In this way determination of G.F.R. becomes simpler and more accurate: it is not disturbing to the patients, and it avoids errors due to incomplete collection of the urine-these are quite frequent, particularly at low urine flow-rates. A suitable technique for scintillation-counting over the bladder has been used with a different radioactive tracer, 131I-labelled sodium diatriozate (’Hypaque’), which is eliminated by the kidneys by glomerular filtration only, without being either excreted or reabsorbed by the tubules, and the renal clearance of which has been shown to equal that of inulin and hyposulphite in both normal and abnormal conditions. 131I-labelled sodium diatriozate may have additional advantages over 58Co-labelled vitamin B12, since it does not require any previous administration of non-labelled products, while the shorter half-life of radioiodine in comparison with radiocobalt reduces the radiation dose to the subjects. General Medical Clinic, University of Pisa, Italy.
C. BIANCHI.
SULPHONYLUREA HYPOTHYROIDISM IN DIABETICS SIR,—The statistically higher incidence of hypothyroidism in diabetics treated with tolbutamide and chloropropamide reported by Dr. Hunton and his co-workers (Sept. 4) is of great interest. I have had under observation three elderly female diabetics with hypothyroidism who have been treated with 1-2-5 g. of tolbutamide per day for 8 to 10 years. One of them had two episodes of transient secondary hypothyroidism while taking the sulphonylurea. She is aged 78 years with late-onset mild diabetes mellitus. 2 g. of tolbutamide had been taken daily for about 8 years. She had had three normal deliveries and had undergone a subtotal hysterectomy in the past. After the sudden onset of mild abdominal pains, vomiting, fever, and headaches in 1962 she was admitted to hospital. Pertinent physical findings included a temperature of 103°F, slight facial and periorbital lethargy, " puffiness," and delayed deep tendon reflexes. The thyroid
gland
enlarged. Complete blood-count, urinalysis, nitrogen and blood-cholesterol, total serum-protein, serum-electrolytes, and skull and chest X-rays were normal. Blood-glucose was 242 mg. per 100 ml. Lumbar puncture revealed changes compatible with a viral or aseptic meningitis. The serum-protein-bound-iodine (P.B.I.) was 2-8 µg. per 100 ml. and the 24-hour 1311 uptake was 7%. These values rose to 7-0 µg. per 100 ml. and 50%, respectively, 24 hours after intramuscular administration of 10 units of lyophilised beef thyrotropin.3 4The lethargy, somnolence, and periorbital oedema subsided, and the reflexes became brisk during the next few days. Repeat lumbar puncture revealed resolution of the previously abnormal spina-fluid changes. The tolbutamide was discontinued during the acute phase of the patient’s illness. She was asymptomatic when discharged and was instructed to resume her daily dosage of 2 g. of tolbutamide. Serum-P.B.I. and thyroidal radioactive uptakes were normal at subsequent visits. Waterloading, 17-hydroxycorticoid and 17-ketosteroid excretions, metyrapone tests,5 adrenocortical stimulations with was not
blood-urea
1. 2. 3. 4. 5.
Bianchi, C., Toni, P. Experientia, 1964, 20, 148. Bianchi, C., Toni, P. Excerpta med. Int. Congr. Ser. 1964, 78, 517. Querido, A., Stanbury, J. B. J. clin. Endocr. Metab. 1950, 10, 1192. Jeffries, W. McK., Levy, R. P., Palmer, W. G., Storaasl, J. P., Kelley, L. W., Jr. New Engl. J. Med. 1953, 249, 876. Liddle, G. W., Estep, H. H., Kendall, J. W., Jr., Williams, W. C., Jr., Townes, A. W. J. clin. Endocr. Metab. 1959, 19, 875.