Effects of treatments by calcium and sex hormones on vertebral fracturing in osteoporosis.

Lateral radiographs of the thoracic and lumbar spine were taken periodically in 49 patients with osteoporosis. Thirty patients were postmenopausal, and 19 nonmenopausal with osteoporosis due to steroids, male hypogonadism, alcoholism, thyrotoxicosis or unknown cause. Patients were studied before, during and after treatment with high calcium alone, or with combined calcium and sex steroids. Calcium was given as effervescent calcium lactate gluconate, and sex hormones as oestradiol valerate, testosterone oenanthate, or methenolone oenanthate. A total of 964 films covering 409 patient-years were available for measurement. On each vertebra, deformity due to loss of anterior height was measured and assigned to one of four grades. For the time interval between each consecutive pair of films, a patient's vertebral fracture rate score was calculated and expressed per thousand patient-years. In comparison with the corresponding pretreatment fracture rate score, both the postmenopausal and the nonmenopausal groups who had not received sex hormones previously, failed to show significant changes (p = 0.144; p = 0.017) on high calcium alone during mean periods of 4.3 and 2.8 years respectively. If the first 2 years on high calcium were excluded for the postmenopausal group, they still failed to show a reduction in fracture rate score (observed for a mean period of 5.0 years; p = 0.04). When treated with combined calcium and sex hormones, both postmenopausal and nonmenopausal groups showed a lower fracture rate score of 20 and 207 respectively when compared with the pretreatment levels of 1500 and 1697 (in mean treatment periods of 3.2 and 4.4 years; p less than 0.001 in each case). When given high-dose calcium alone, but after treatment with sex hormones as well, the postmenopausal group showed no change in fracture rate score from pretreatment (in a mean of 3.1 years; p = 0.069); however the nonmenopausal group still showed a significant reduction in fracture rate score from 1697 to 42 over a mean period of 2.3 years (p = 0.001). The postmenopausal group, after stopping all treatment, showed a higher fracture rate score of 1286 (in a mean of 2.6 years) than did those on combined calcium and sex hormones, in whom the fracture rate score was 20 (in a mean of 3.2 years; p = 0.008). A subgroup of 11 patients with osteoporosis of both the menopausal and nonmenopausal types, had data both before (in a mean of 5.5 years) and during (for a mean of 2.5 years) treatment with calcium alone; the fracture rate scores were 1473 and 918 (p = 0.247).(ABSTRACT TRUNCATED AT 400 WORDS)

Childhood acromegaly successfully treated with interstitial irradiation using yttrium-90.

A child with a growth hormone producing tumour presented at the age of 4 1/2 years. The onset of the disease was at 18 months of age. Treatment was given with three doses of interstitial irradiation using yttrium-90 implants. There were no local complications from the procedures. Now, 11 years after diagnosis, she is asymptomatic, of normal appearance, and her height and the size of the pituitary fossa are normal. Growth hormone levels are almost normal, thyroid function is intact, and she is maintained on prednisone and sex hormones.

Long-term measurement of skeletal and lean body mass in Paget's disease of bone treated with synthetic human calcitonin.

Total body calcium (an index of skeletal mass), ulnar bone density, and total body potassium (lean body mass) were followed for up to 5 years in 38 patients with Paget's disease during treatment with synthetic human calcitonin. Calcium was measured by neutron activation, ulnar density by X-ray photodensitometry, and potassium by counting its natural 40K radioactivity. There was a significant rise in total skeletal mass in a group of 8 patients in the 12 months following the start of therapy, but overall, total bone mass and ulnar density remained constant during treatment. Small mean losses of body potassium were observed (approximately 4%) after several years elapsed on treatment. Over an average period of 12 months after discontinuation of therapy in 21 patients there was no significant mean change in calcium or potassium. The means of the ratios of total body calcium divided by predicted normal calcium (over the whole period of measurement) were 1.08 (males) and 0.99 (females) and were not significantly different. Comparison of the ulnar densities of patients and normal subjects gave similar results. The average ratio of measured to predicted normal potassium was 1.13 (both males and females). Thus there was no indication of depletion in skeletal mass below normal either in the untreated disease or resulting from treatment.

Successful treatment of Cushing's disease using yttrium-90 rods.

Interstitial irradiation using yttrium-90 (90Y) rods implanted by needle into the pituitary gland was used as primary treatment in 16 patients with pituitary dependent Cushing's disease. Clinical and biochemical remission was observed within three or six months in 13 and in the remaining three after a supplementary implant. There was no perioperative morbidity. Follow-up from the time of definitive operation ranged from six to 123 months (mean 39). No recurrence has been observed. The return of a normal diurnal cortisol rhythm has been observed in 10/12 patients studied after remission. Some form of long-term pituitary hormone replacement therapy was required in only the six patients who had received the largest irradiation dose. Implantation of 90Y is safe and effective treatment for patients with Cushing's disease, comparing favourably with selective trans-sphenoidal pituitary surgery.

Nuclear magnetic resonance imaging of the liver: initial experience.

Nuclear magnetic resonance (NMR) scans of the liver were obtained in 12 normal volunteers and 32 patients using a whole-body machine developed by Thorn-EMI Ltd., and the results were compared with x-ray computed tomography (CT). Two types of NMR scan, saturation-recovery and inversion-recovery, were performed in order to obtain values for the spin-lattice relaxation time, T1. Although the saturation-recovery scans show little soft-tissue detail, the inversion-recovery scans demonstrated the interlobar fissure, hepatic veins, portal veins, bile ducts, and gallbladder. In comparison with CT (Siemens Somatom 2), both types of NMR scan showed some blurring due to respiratory movement but much less linear artifact across the liver from the air-fluid interface in the stomach. Focal disease within the liver was demonstrated by both CT and NMR, although an area of focal atrophy and another of hepatic infarction were only recognized with NMR. In diffuse disease the pattern varied. In steatosis CT was virtually diagnostic, while NMR showed no specific features. In hemochromatosis, hepatitis, eight cases of cirrhosis, and one of Wilson disease, both techniques showed abnormalities of varying specificity. In two cases of cirrhosis and one of primary biliary cirrhosis, only the NMR scan was abnormal. Nuclear magnetic resonance images are now sufficiently anatomically detailed to permit serious comparisons with technically advanced computed tomography. The information revealed is fundamentally different and can be expected to have some diagnostic utility.

The acromegaly syndrome. Relation between clinical features, growth hormone values and radiological characteristics of the pituitary tumours.

One hundred and fifty-five acromegalics, 76 males (mean age 44 +/- 1.3 years) and 79 females (45 +/- 1.4 years) were studied. The frequency of clinical features were: acral enlargement 100 per cent, hyperhidrosis 65 per cent, headache 55 per cent, paraesthesiae 49 per cent, cardiac problems 34 per cent, hypertension 32 per cent, diabetes mellitus (clinical and chemical) 27 per cent, and visual field defects 6 per cent. Signs and symptoms, and particularly headache, did not show any relation with the size or shape of pituitary tumours, nor with growth hormone (GH) values, age, sex or weight. Mean of GH values at 60, 90 and 120 minutes during a GTT averaged 135 mIU/l, range 8-1833. Diabetes mellitus was more frequent and severe in patients with higher GH values, occurring in 32 per cent of patients with mean GH values greater than or equal to 50 mIU/l and only in 16 per cent of the rest (p less than 0.05). GH values correlated positively with size of tumours. Forty-nine per cent of patients presented with entirely intrasellar tumours, 27 per cent with suprasellar extensions and 23 per cent with partially empty sellae. The mean GH (238 mIU/l) of patients with suprasellar extensions was significantly higher (p less than 0.004) than those of the others. Younger acromegalics showed a tendency to larger tumours. Early treatment of acromegaly, particularly in young patients and those presenting with high GH values, is recommended.

Enhancement of relaxation rate with paramagnetic contrast agents in NMR imaging.

Enhancement of spin-lattice relaxation using oral ferric chloride and using inhaled oxygen is illustrated. A 0.06% solution of ferric chloride reduced the spin-lattice relaxation time in the fundus of the stomach from 730 ms to 285 ms. Ferric chloride may be useful as a bowel-labeling agent. In 5 volunteers inhalation of 100% oxygen decreased the mean observed spin-lattice relaxation time of blood within the left ventricular cavity. Although the change was small, it may have important uses in monitoring metabolic processes.

Magnetic resonance properties of hydrogen: imaging the posterior fossa.

Posterior fossa scans were performed on five healthy volunteers using a nuclear magnetic resonance (NMR) machine constructed by Thorn-EMI Ltd. Three different NMR scanning sequences were used. In the first, a type of saturation-recovery technique was used to produce images strongly dependent on the density of hydrogen nuclei, but with some dependence on the spin-lattice relaxation time (T1). In the second, an inversion-recovery technique was used to produce images with a stronger dependence on the spin-lattice relaxation time. In the third, a spin-echo technique was used to obtain images with a dependence on the spin-spin relaxation time (T2). All three types of NMR image were unaffected by bone artifact. Visualization of brain adjacent to the skull base was obtained without loss of detail due to partial-volume effect from bone. The saturation-recovery images highlighted arteries and veins that were clearly visible without the use of contrast agents. The inversion-recovery images showed remarkable gray-white matter differentiation enabling internal structure to be seen within the brainstem and cerebellum. The trigeminal nerve and ganglion were also seen outside the brain. Experience with the spin-echo technique is limited, but the images at the base of the brain show considerable soft-tissue detail. The NMR images of the posterior fossa in this study were comparable in quality to those obtained from a new rotate-rotate x-ray computed tomography machine and were superior in several respects.

Imaging of the brain by nuclear magnetic resonance.

A nuclear magnetic resonance (NMR) machine constructed by Thorn-EMI Ltd was used to produce tomographic images of the brain in eight volunteers and fourteen patients. The use of an inversion recovery technique designed to emphasise variations in the spin-lattice time constant (T1) resulted in remarkable differentiation between grey and white matter in all subjects examined. White matter was seen both centrally and peripherally to subcortical level and the basal ganglia were clearly demarcated by the surrounding white matter and ventricular system. The posterior fossa was visualised with substantially less artefact than with X-ray computed tomography (CT) and both the brainstem and middle cerebellar peduncle were clearly shown. Pathological appearances in patients with glioblastoma multiforme, cerebral infarction, and cerebral aneurysm were demonstrated and compared with those seen with CT. The technique will require thorough clinical evaluation but appears to have considerable potential in the diagnosis of neurological disease.

Medical nuclear magnetic resonance imaging: I. Physical principles.

For over 30 years, nuclear magnetic resonance (NMR) spectroscopy has been used for chemical analysis and for studying molecular behavior, but NMR imaging is a recent addition to the methods available to radiologists for investigating the interior of the body. It uses radiofrequency radiation in the presence of a magnetic field to produce anatomical cross sections. The images may be simple maps of the concentration of the hydrogen nucleus, or they may depend on tissue relaxation times, which describe how rapidly hydrogen nuclei exchange energy with their surroundings. In this article, the basic concepts and physical principles of conventional NMR spectroscopy are introduced. In subsequent articles, the various approaches to producing NMR images will be outlined, and the types of information obtainable from NMR scanners will be discussed.

Interstitial pituitary irradiation with 90Y for the treatment of acromegaly. A reappraisal.

The management of 54 acromegalics referred to us between 1974 and 1978 has been analysed. Twenty-two patients were treated with pituitary implants of yttrium-90 (90Y). Eleven are in complete remission (mean growth hormone (GH) less than 11 mIU/l), 8 had improved (mean GH 11-20 mIU/l or 50% less than preoperatively) and 3 were poor responders. Two patients had temporary 6th nerve paresis. Seven patients are on replacement therapy. Thirty-one patients were not implanted for the following reasons with a number of patients having more than one: extension of the tumour into the sphenoid sinus 10, or above the sella 3, partially empty sella 9, internal carotids too close to midline 2, invisible landmarks 1, mild acromegaly 6, poor general health 3, declined investigations or operation 6. It is concluded that pituitary implant of yttrium is an effective and safe form of treatment in carefully selected patients.

Radiologic observations on bone resorption in Paget's disease.

The diagnosis of Paget's disease of bone at its earliest osteolytic phase is difficult and requires radiographs of the highest quality. Calcitonin controls the bone resorption of uncomplicated Paget's disease but does not prevent disuse osteoporosis in normal and pagetic bones. Cessation of treatment leads to a recurrence of the osteolytic phase of the disease in some patients. Retreatment with human calcitonin arrests the bone resorption and permits bony consolidation of resorption clefts.

Treatment of Cushing's disease in juveniles with interstitial pituitary irradiation.

Nine juvenile patients (five boys and four girls aged 10--18 with Cushing's disease were treated with pituitary implantation of 198Au and/or 90Y. No patient had any surgical complication from the procedure. At the latest assessment, 3 months to 17 years after operation, Cushing's disease was in remission in all the patients; the response time following operation was a few days to 3 months. Radiology of the pituitary fossa at time of pituitary implantation was normal in all patients and remains so. The final height in six patients is 149--172 cm (59--67.5 inches) and three patients who continue to grow have increased by 13, 6 and 3 cm since implantation. Only one patient required full pituitary hormone replacement therapy, and he had been previously treated by external irradiation, and one other patient failed to complete puberty. In all the other seven sexual maturation is normal and one has fathered two children. We conclude that pituitary implantation with interstitial irradiation is a satisfactory form of treatment for Cushing's disease in juveniles.

Pregnancies in women with hyperprolactinaemia: clinical course and obstetric complications of 41 pregnancies in 27 women.

Observations are reported on 41 pregnancies in 27 patients who initially had infertility and raised serum prolactin concentrations. Associated symptoms were secondary amenorrhoea (81 per cent) and galactorrhoea (81 per cent). All patients were at risk of pituitary expansion during pregnancy, especially these 19 (70 per cent) with radiological evidence of pituitary tumours. Fifteen patients had 21 pregnancies after pituitary implantation with 90yttrium; 14 patients had 20 pregnancies without prior pituitary implantation or any other attempt to prevent tumour expansion. During pregnancies, tumour enlargement as shown by diminished visual acuity, visual field defects, severe headaches, diabetes insipidus and radiological changes occurred only in 3 of the 14 patients who had not had implants. Two patients who became pregnant both before and after pituitary implantation suffered tumour expansion in their pregnancies before implantation, but not when pregnant after the operation. The induction and Cesarean section rates were about 30 per cent in 32 term pregnancies in 25 patients. Details of how pregnancy was achieved and the associated obstetric problems are given.

Treatment of prolactin-secreting pituitary tumours in young women by needle implantation of radioactive yttrium.

Twenty-one young female patients are described who presented with amenorrhoea, galactorrhoea or infertility, and were treated by 90Y pituitary implantation of 20,000 rads. There was no morbidity. In all patients serum prolactin values were elevated and radiographs of the pituitary fossa were abnormal. Observations are available for 1--76 months (mean 27) after implantation. The median fall in prolactin values was 60 per cent while there was no deterioration in pituitary function if normal pre-operatively. Luteinizing hormone values, both basally and following gonadotrophin-releasing hormone, rose to normal after operation; several instances of sellar remodelling were observed radiologically, and no instance of relapse was found radiologically, biochemically or clinically. Thirteen patients desiring fertility have been observed since implantation; so far nine have become pregnant, in three instances without any additional therapy; since four patients became pregnant twice, a total of 13 pregnancies have occurred. No case of tumour expansion was observed during pregnancy. 90Y implantation can be considered as a therapeutic procedure in young female patients requiring fertility which is competitive with surgical methods, and together with a short course of bromocriptine if needed, could prove to be the treatment of choice.

A comparison of radiography and radioisotope scanning in the detection of Paget's disease and in the assessment of response to human calcitonin.

In eight patients with symptomatic Paget's disease, radiographs and radioisotope bone scans have been compared before treatment by high dose synthetic human calcitonin (CIBA 47175-Ba) and three months and 12 months later. In six patients quantitative radioisotope scans allowed calculation of relative radioactivity in normal bone, Paget's disease and bone adjacent to osteoarthritic joints. Comparison of radiographs and scans showed 69 sites diagnosed as Paget's disease on both examinations; nine sites showed radiographic changes of Paget's disease but had negative radioisotope scans and two sites were abnormal on the scan but radiologically normal. One of these two reverted towards normal during treatment with calcitonin. Comparison of analogue scans done at three months and 12 months with initial scans showed diminished uptake in Paget's disease compared with normal bone, and quantitation showed this was due to decreased absolute uptake in Paget's disease and a slight increase in normal bone. Osteoarthritic bone showed no significant response to calcitonin.

The pituitary fossa in Cushing's syndrome. A retrospective analysis of 93 patients.

A retrospective analysis of the pituitary fossa in 93 patients with Cushing's syndrome is presented. Radiological evidence of a pituitary tumour was found in 20 of 86 patients with pituitary-dependent disease (23%). In 11 of the 20 patients, the diagnosis depended on analysis of lateral tomograms. None of the seven patients with disease which was not pituitary-dependent had evidence of an abnormal sella. One of 20 controls without known endocrine disease had an abnormal sella.