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A woman with bone pain, fractures, and malabsorption
calliper method was 1-11 and for the manual method 3-38. With the degree of agreement’ method the limits of agreement for the posterior altanto-dens interval showed that the manual method may be 7-3 mm greater than or 6-4 mm less than with the calliper method-a difference of 25-30%. Both methods were reliable, and correlations were satisfactory. The coefficient of repeatability was better for the calliper (indicating precision) than the manual method, and although degree of agreement was good for both methods, the electronic calliper was nearly four times faster, with reduced tedium and increased accuracy. This calliper has previously been used in the manufacturing industries in which accurate measurements can be vital. We have extended its use to clinical research and adapted the software to allow data input directly to the patient data files. The PC-linked electronic calliper is useful in research-based radiological measurements and may prove as valuable in specialties in which metrology is important. G Solanki, A Tammam, *H A Crockard, J Stevens *Department of Surgical Neurology, National Hospital Neurosurgery, London WC1N 3BG, UK
for
Neurology and
1 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; i: 307-10.
stated, but rather tertiary hyperparathyroidism as originally established by Dent and his colleagues.2,3 40 years ago Dent described two patients with the association of coeliac disease and autonomous hyperparathyroidism. In his classic paper in details of 12 19682 he gave patients with to coeliac disease or chronic hyperparathyroidism secondary renal failure, in whom parathyroid overactivity eventually became autonomous and was associated with formation of a parathyroid adenoma or carcinoma, leading to the hypercalcaemia and osteitis fibrosa that are otherwise typical of primary hyperparathyroidism. Dent called this syndrome tertiary hyperparathyroidism, a term originally coined in 1963 by St Goar,4 in discussion of a patient with a parathyroid adenoma and parathyroid bone disease secondary to chronic renal failure. Since Dent’s day the syndrome has become very well recognised in renal replacement centres, at which successful renal transplant or dialysis of uraemic patients has often led to the unmasking of tertiary hyperparathyroidism, with the complications of hypercalcaemia and worsening bone disease. Fortunately the state here is usually transient, since the hyperplastic parathyroids slowly reduce their activity once they are no longer stimulated by the hypocalcaemia and calcitriol deficiency of chronic renal failure. Surely there is little that is new under the sun. Oliver
Wrong
Division of
A woman with bone
malabsorption
1
SIR-In the case report by Bertoli and colleagues (Feb 3, p 300)’ the calcium concentrations in the table are reported in mmolBL (6-6 and 8-8), being regarded by the authors as "within normal ranges". I suspect that they intended the units to be mg/dL since 6-6 mmol/L is extremely high. If this assumption is correct, then the patient had hypocalcaemia in 1982. This even finding suggests that the
2
hyperparathyroidism was more likely to have been tertiary than primary with the development of an adenoma in parathyroids, which had been appropriately hyperplastic to compensate for the calcium and vitamin D losses longstanding coeliac disease.
of
Neil R M Buist Paediatric Metabolic Laboratory, OR 97201, USA
Oregon
Health Sciences
University, Portland,
1 Bertoli A, Di Daniele N, Troisi A, Lauro R. A woman with bone fractures, and malabsorption. Lancet 1996; 347: 300.
pain,
Author’s reply SiR-Buist is right. There was a mistake in the table: calcium and phosphate values were in mg/dL; values in SI units are:
The 1982 calcium level (1-65 mmon/L) seems below the normal range, but if we take into account albumin and globulins and calculate the ionised calcium we obtain a value within normal concentrations (1 -08 mmol/L). Aldo Bertoli Università Degli Studi di Roma "Tor Vergata", Dipartimento di Medicina Interna, Cattedradi Medicina Interna, 00168 Rome, Italy
SiR-The described
Nephrology,
Middlesex
Hospital,
London W1N 8AA, UK
pain, fractures, and
patient with coeliac disease and bone disease by Bertoli and colleagues’ did not have concomitant (ie, coincidental) hyperparathyroidism as
3 4
Bertoli A, Di Daniele N, Troisi A, Lauro R. A woman with bone pain, fractures, and malabsorption. Lancet 1996; 347: 300. Davies DR, Dent CE, Wilcox A. Hyperparathyroidism and steatorrhoea. BMJ 1956; ii: 1133-37. Davies DR, Dent CE, Watson L. Tertiary hyperparathyroidism. BMJ 1968; ii: 295-99. St Goar WT. Case records of Massachusetts General Hospital.
N Engl J Med 1963;
268: 943-53.
SiR-As reported by Bertoli et al,’ severe manifestations of coeliac disease still occur if treatment is inadequate or diagnosis delayed. We report a similar case. A 29-year-old white woman was admitted to hospital for evaluation of bleeding after tooth extraction. Diarrhoea and growth retardation had started at age 4 years. The patient had her menarche at age 8. After receiving a "hormone injection", vaginal bleeding stopped. Menstrual periods recurred at age 18 and continued at regular intervals until age 27, when they stopped. The patient had consulted several alternative medicine practitioners and followed various dietary regimens without improvement of her diarrhoea. At admission the patient was malnourished (weight 43 kg, height 162 cm) and anaemic but had no bruises. Bleeding time was normal (2 min) but she had a severe coagulopathy (time 5% of normal, partial thromboplastin time: 58 s), hypochronic anaemia (haemoglobin 6-1 g/dL), iron deficiency, and hypocalcaemia with hyperparathyroidism. Sex hormones were with compatible secondary amenorrhoea. Stool analysis showed steatorrhea (stool weight 580 g/day, fat: 48 g/day). Biopsy specimens from the descending part of the duodenum showed subtotal villous atrophy. Gliadin antibodies were raised. She received gluten-free diet and oral calcium and intravenous vitamin K and iron. After 2 days, blood coagulation had greatly improved and vitamin K and iron were changed to oral preparations. She was discharged after 19 days on vitamin D supplements. The patient had a menstrual period 6 weeks after discharge. At 9-month follow-up she was 5 months pregnant and weighed 59 kg. The pregnancy resulted in a healthy child but the patient lost all her teeth during pregnancy. 829
This case illustrates the multitude of problems which may result from prolonged malabsorption in coeliac disease. It is likely that her premature osteoporosis will be irreversible. *Heinz F Hammer, Heimo Ramschak Department of Internal Medicine, University of Graz, 8036 Graz, Austria
surgery is no surgery. In future, the organisers of vascular congresses should open their exhibition booths to dog
breeders and golf equipment manufacturers, promoting safe, effective, and pleasant ways of exercise therapy.
Rudolph G Vanmaele Antwerp University Hospital and Medical School, B-2650 Edegem, Belgium
1
Bertoli A, Di Daniele N, Troisi A, Lauro R. A woman with bone fractures, and malabsorption. Lancet 1996; 347: 309.
pain, 1
2
Angioplasty for intermittent claudication 3
about the Ruckley (Feb 3, p 277)’ SIR-Bradbury danger in the proliferation of indications for percutaneous transluminal angioplasty (PCTA) in peripheral arterial occlusive disease without validation by randomised trials. I agree with every word. My major concern is the use of PCTA for mild claudication. Until the introduction of angioplasty everybody agreed that mild claudication required conservative management, including control of risk factors (smoking, hypertension, lipid and glucose metabolism disorders) and exercise (walking). The clinical benefit of vasoactive drugs has always been controversial. Recently many transluminal devices have been developed for the treatment of peripheral arterial occlusive disease. These devices are claimed to be safe, noninvasive, and to yield results equivalent to those of traditional surgery. They are indeed less invasive in a conventional sense but they are aggressive to the arterial wall (eg, puncture with heavy gauge catheters or balloon dilation). In experienced hands complications are infrequent and the immediate results are encouraging, even spectacular,z but PCTA is not a "harmless puncture" or a "minor operation". These new procedures should have their indications established carefully, as with any operation. In peripheral arterial occlusive disease treatment decisions must be made in the light of the patient’s general condition and the severity of symptoms. If an intervention is justified, the choice between traditional or transluminal surgery, will depend on the site and morphology of the lesions. Patients with mild symptoms need neither technique, only conservative treatment. Patients with mild or moderate claudication have little to gain when PCTA is successful but much to lose if it fails. Vascular procedures are often "oneshot" operations; failure calls for more extensive reconstructions and even, ultimately, amputation. For patients with limited symptoms this escalation is very hard to accept, especially since some studies report better results with conservative treatment.3 In vascular medicine most published work is about surgical procedures. There are few reports on conservative treatment and they usually focus on the controversial vasoactive drugs. Most of the exhibition stands at meetings in this specialty are taken by companies introducing devices that are all newer, less invasive, more sophisticated, betterand more expensive. No wonder that medical opinion is so biased in favour of intervention over conservative treatment. Who is going to promote conservative treatment, since there is nothing to sell? Trade exhibitors who not only present their newest equipment but also emphasise its limitations would greatly increase their credibility. The evaluation of conservative treatment should be encouraged and published. Surgery is like the army: it has to be there, it needs to be well trained and equipped, but every effort should be made to avoid bringing it into action. Just as soldiers are proud of their status, so I am proud to and
warn
member of the vascular surgical profession. Like the military, I am prepared for aggressive action if the patient needs it, but in all other cases I am convinced that the best
be
a
830
Bradbury AW, Ruckley CV. Angioplasty for lower-limb ischaemia: time for randomised controlled trials. Lancet 1996; 347: 277-78. Whyman M, Fowkes F, Kerracher E, et al. A randomised controlled trial of percutaneous balloon angioplasty (PTA) for intermittent claudication. Eur J Vasc Endovasc Surg (in press). Perkins J, Collin J, Morris P. Exercise training vs angioplasty for stable claudication: long and medium term results of a prospective randomised trial. Eur J Vasc Endovasc Surg (in press).
Hormonal
contraception for
men
SIR-In her science and medicine report, Bonn (Feb 3, p 316)’ does not do justice to recent advances in the search for effective, reversible contraceptive methods for men. The two WHO-sponsored clinical studies to which she refers have considerably advanced our knowledge by establishing the contraceptive efficacy of hormone-induced azoospermia and severe oligozoospermia (0-1-3-0 million/mL),2,3 and have provided indirect information on the characteristics and potential acceptability of such novel methods. These studies were specifically designed to test the principle that hormonal suppression of spermatogenesis can provide effective contraception. They did not set out to evaluate the practicality of the prototype hormonal regimen used (testosterone enanthate 200 mg intramuscular weekly). Bonn asks whether the nine men in the first study who stopped testosterone injections before the full year of contraceptive efficacy because of separation or divorce from their partner did so because of increased aggressiveness. No evidence for this was recorded in the study. Of the 271 men who started injections, 67 stopped their participation before the full period of the study for personal or medical reasons or difficulties with the injection schedule or method. The rate of discontinuations for separation or divorce was 4-1 (95% CI 1-9-7-8) per 100 person-years. It is difficult to judge whether this is higher or lower than expected among a cohort of couples volunteering for a prototype male contraceptive method from seven different countries (Australia, China, Finland, France, Sweden, UK, and USA) since no direct comparison group is practical or ethically possible. The rate of discontinuations for the same reasons was very similar in the second study of 399 volunteer couples from Australia, China, France, Hungary, Singapore, Sweden, Thailand, UK, and USA. Only a rough comparison with national figures can be made. The number of legal divorces granted for the years 1990-92 in Australia, Sweden, and UK are in the range 2-3-3-0 per 1000 population per year.4 About a third of the population in these countries are men aged 15-64 years, giving divorce rates in the range 7-9 per 1000 men per year. Rates of divorce in the age range similar to the volunteers in these studies (21-45 years) may be considerably higher. Conservatively doubling these estimates to include separations and dissolution of nonmarital relationships yields rates in the range 1-5-2 per 100 person-years, which are not much different from those noted in the WHO studies. The potential for supraphysiological concentrations of testosterone to induce behaviour or mood changes is a genuine concern and needs to be addressed appropriately.’ However, the frequency of behavioural side-effects of other hormonal regimens, particularly those based on androgenprogestogen combinations, may be very different from those seen with testosterone enanthate. Behavioural issues and
for
Neurology and
1 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; i: 307-10.
stated, but rather tertiary hyperparathyroidism as originally established by Dent and his colleagues.2,3 40 years ago Dent described two patients with the association of coeliac disease and autonomous hyperparathyroidism. In his classic paper in details of 12 19682 he gave patients with to coeliac disease or chronic hyperparathyroidism secondary renal failure, in whom parathyroid overactivity eventually became autonomous and was associated with formation of a parathyroid adenoma or carcinoma, leading to the hypercalcaemia and osteitis fibrosa that are otherwise typical of primary hyperparathyroidism. Dent called this syndrome tertiary hyperparathyroidism, a term originally coined in 1963 by St Goar,4 in discussion of a patient with a parathyroid adenoma and parathyroid bone disease secondary to chronic renal failure. Since Dent’s day the syndrome has become very well recognised in renal replacement centres, at which successful renal transplant or dialysis of uraemic patients has often led to the unmasking of tertiary hyperparathyroidism, with the complications of hypercalcaemia and worsening bone disease. Fortunately the state here is usually transient, since the hyperplastic parathyroids slowly reduce their activity once they are no longer stimulated by the hypocalcaemia and calcitriol deficiency of chronic renal failure. Surely there is little that is new under the sun. Oliver
Wrong
Division of
A woman with bone
malabsorption
1
SIR-In the case report by Bertoli and colleagues (Feb 3, p 300)’ the calcium concentrations in the table are reported in mmolBL (6-6 and 8-8), being regarded by the authors as "within normal ranges". I suspect that they intended the units to be mg/dL since 6-6 mmol/L is extremely high. If this assumption is correct, then the patient had hypocalcaemia in 1982. This even finding suggests that the
2
hyperparathyroidism was more likely to have been tertiary than primary with the development of an adenoma in parathyroids, which had been appropriately hyperplastic to compensate for the calcium and vitamin D losses longstanding coeliac disease.
of
Neil R M Buist Paediatric Metabolic Laboratory, OR 97201, USA
Oregon
Health Sciences
University, Portland,
1 Bertoli A, Di Daniele N, Troisi A, Lauro R. A woman with bone fractures, and malabsorption. Lancet 1996; 347: 300.
pain,
Author’s reply SiR-Buist is right. There was a mistake in the table: calcium and phosphate values were in mg/dL; values in SI units are:
The 1982 calcium level (1-65 mmon/L) seems below the normal range, but if we take into account albumin and globulins and calculate the ionised calcium we obtain a value within normal concentrations (1 -08 mmol/L). Aldo Bertoli Università Degli Studi di Roma "Tor Vergata", Dipartimento di Medicina Interna, Cattedradi Medicina Interna, 00168 Rome, Italy
SiR-The described
Nephrology,
Middlesex
Hospital,
London W1N 8AA, UK
pain, fractures, and
patient with coeliac disease and bone disease by Bertoli and colleagues’ did not have concomitant (ie, coincidental) hyperparathyroidism as
3 4
Bertoli A, Di Daniele N, Troisi A, Lauro R. A woman with bone pain, fractures, and malabsorption. Lancet 1996; 347: 300. Davies DR, Dent CE, Wilcox A. Hyperparathyroidism and steatorrhoea. BMJ 1956; ii: 1133-37. Davies DR, Dent CE, Watson L. Tertiary hyperparathyroidism. BMJ 1968; ii: 295-99. St Goar WT. Case records of Massachusetts General Hospital.
N Engl J Med 1963;
268: 943-53.
SiR-As reported by Bertoli et al,’ severe manifestations of coeliac disease still occur if treatment is inadequate or diagnosis delayed. We report a similar case. A 29-year-old white woman was admitted to hospital for evaluation of bleeding after tooth extraction. Diarrhoea and growth retardation had started at age 4 years. The patient had her menarche at age 8. After receiving a "hormone injection", vaginal bleeding stopped. Menstrual periods recurred at age 18 and continued at regular intervals until age 27, when they stopped. The patient had consulted several alternative medicine practitioners and followed various dietary regimens without improvement of her diarrhoea. At admission the patient was malnourished (weight 43 kg, height 162 cm) and anaemic but had no bruises. Bleeding time was normal (2 min) but she had a severe coagulopathy (time 5% of normal, partial thromboplastin time: 58 s), hypochronic anaemia (haemoglobin 6-1 g/dL), iron deficiency, and hypocalcaemia with hyperparathyroidism. Sex hormones were with compatible secondary amenorrhoea. Stool analysis showed steatorrhea (stool weight 580 g/day, fat: 48 g/day). Biopsy specimens from the descending part of the duodenum showed subtotal villous atrophy. Gliadin antibodies were raised. She received gluten-free diet and oral calcium and intravenous vitamin K and iron. After 2 days, blood coagulation had greatly improved and vitamin K and iron were changed to oral preparations. She was discharged after 19 days on vitamin D supplements. The patient had a menstrual period 6 weeks after discharge. At 9-month follow-up she was 5 months pregnant and weighed 59 kg. The pregnancy resulted in a healthy child but the patient lost all her teeth during pregnancy. 829
This case illustrates the multitude of problems which may result from prolonged malabsorption in coeliac disease. It is likely that her premature osteoporosis will be irreversible. *Heinz F Hammer, Heimo Ramschak Department of Internal Medicine, University of Graz, 8036 Graz, Austria
surgery is no surgery. In future, the organisers of vascular congresses should open their exhibition booths to dog
breeders and golf equipment manufacturers, promoting safe, effective, and pleasant ways of exercise therapy.
Rudolph G Vanmaele Antwerp University Hospital and Medical School, B-2650 Edegem, Belgium
1
Bertoli A, Di Daniele N, Troisi A, Lauro R. A woman with bone fractures, and malabsorption. Lancet 1996; 347: 309.
pain, 1
2
Angioplasty for intermittent claudication 3
about the Ruckley (Feb 3, p 277)’ SIR-Bradbury danger in the proliferation of indications for percutaneous transluminal angioplasty (PCTA) in peripheral arterial occlusive disease without validation by randomised trials. I agree with every word. My major concern is the use of PCTA for mild claudication. Until the introduction of angioplasty everybody agreed that mild claudication required conservative management, including control of risk factors (smoking, hypertension, lipid and glucose metabolism disorders) and exercise (walking). The clinical benefit of vasoactive drugs has always been controversial. Recently many transluminal devices have been developed for the treatment of peripheral arterial occlusive disease. These devices are claimed to be safe, noninvasive, and to yield results equivalent to those of traditional surgery. They are indeed less invasive in a conventional sense but they are aggressive to the arterial wall (eg, puncture with heavy gauge catheters or balloon dilation). In experienced hands complications are infrequent and the immediate results are encouraging, even spectacular,z but PCTA is not a "harmless puncture" or a "minor operation". These new procedures should have their indications established carefully, as with any operation. In peripheral arterial occlusive disease treatment decisions must be made in the light of the patient’s general condition and the severity of symptoms. If an intervention is justified, the choice between traditional or transluminal surgery, will depend on the site and morphology of the lesions. Patients with mild symptoms need neither technique, only conservative treatment. Patients with mild or moderate claudication have little to gain when PCTA is successful but much to lose if it fails. Vascular procedures are often "oneshot" operations; failure calls for more extensive reconstructions and even, ultimately, amputation. For patients with limited symptoms this escalation is very hard to accept, especially since some studies report better results with conservative treatment.3 In vascular medicine most published work is about surgical procedures. There are few reports on conservative treatment and they usually focus on the controversial vasoactive drugs. Most of the exhibition stands at meetings in this specialty are taken by companies introducing devices that are all newer, less invasive, more sophisticated, betterand more expensive. No wonder that medical opinion is so biased in favour of intervention over conservative treatment. Who is going to promote conservative treatment, since there is nothing to sell? Trade exhibitors who not only present their newest equipment but also emphasise its limitations would greatly increase their credibility. The evaluation of conservative treatment should be encouraged and published. Surgery is like the army: it has to be there, it needs to be well trained and equipped, but every effort should be made to avoid bringing it into action. Just as soldiers are proud of their status, so I am proud to and
warn
member of the vascular surgical profession. Like the military, I am prepared for aggressive action if the patient needs it, but in all other cases I am convinced that the best
be
a
830
Bradbury AW, Ruckley CV. Angioplasty for lower-limb ischaemia: time for randomised controlled trials. Lancet 1996; 347: 277-78. Whyman M, Fowkes F, Kerracher E, et al. A randomised controlled trial of percutaneous balloon angioplasty (PTA) for intermittent claudication. Eur J Vasc Endovasc Surg (in press). Perkins J, Collin J, Morris P. Exercise training vs angioplasty for stable claudication: long and medium term results of a prospective randomised trial. Eur J Vasc Endovasc Surg (in press).
Hormonal
contraception for
men
SIR-In her science and medicine report, Bonn (Feb 3, p 316)’ does not do justice to recent advances in the search for effective, reversible contraceptive methods for men. The two WHO-sponsored clinical studies to which she refers have considerably advanced our knowledge by establishing the contraceptive efficacy of hormone-induced azoospermia and severe oligozoospermia (0-1-3-0 million/mL),2,3 and have provided indirect information on the characteristics and potential acceptability of such novel methods. These studies were specifically designed to test the principle that hormonal suppression of spermatogenesis can provide effective contraception. They did not set out to evaluate the practicality of the prototype hormonal regimen used (testosterone enanthate 200 mg intramuscular weekly). Bonn asks whether the nine men in the first study who stopped testosterone injections before the full year of contraceptive efficacy because of separation or divorce from their partner did so because of increased aggressiveness. No evidence for this was recorded in the study. Of the 271 men who started injections, 67 stopped their participation before the full period of the study for personal or medical reasons or difficulties with the injection schedule or method. The rate of discontinuations for separation or divorce was 4-1 (95% CI 1-9-7-8) per 100 person-years. It is difficult to judge whether this is higher or lower than expected among a cohort of couples volunteering for a prototype male contraceptive method from seven different countries (Australia, China, Finland, France, Sweden, UK, and USA) since no direct comparison group is practical or ethically possible. The rate of discontinuations for the same reasons was very similar in the second study of 399 volunteer couples from Australia, China, France, Hungary, Singapore, Sweden, Thailand, UK, and USA. Only a rough comparison with national figures can be made. The number of legal divorces granted for the years 1990-92 in Australia, Sweden, and UK are in the range 2-3-3-0 per 1000 population per year.4 About a third of the population in these countries are men aged 15-64 years, giving divorce rates in the range 7-9 per 1000 men per year. Rates of divorce in the age range similar to the volunteers in these studies (21-45 years) may be considerably higher. Conservatively doubling these estimates to include separations and dissolution of nonmarital relationships yields rates in the range 1-5-2 per 100 person-years, which are not much different from those noted in the WHO studies. The potential for supraphysiological concentrations of testosterone to induce behaviour or mood changes is a genuine concern and needs to be addressed appropriately.’ However, the frequency of behavioural side-effects of other hormonal regimens, particularly those based on androgenprogestogen combinations, may be very different from those seen with testosterone enanthate. Behavioural issues and