Assessing quality of life in Australian patients with Graves' ophthalmopathy.

AIMS: To determine quality of life and adequacy of education and counselling in Australian patients with Graves' ophthalmopathy during the course of their illness. METHODS: A cross sectional study was conducted at the orbital and endocrinology clinics of Royal Brisbane Hospital on 162 consecutive patients with Graves' ophthalmopathy who were managed between the 1992 and 2000. The Graves' ophthalmopathy quality of life (GO-QOL) survey modified for Australian conditions was distributed to study participants. Of the 19 questions asked, nine questions related to visual functioning, eight questions were about the psychosocial consequences of changed appearance, and two questions referred to education and counselling. Additionally, clinical data on the severity of illness were collected retrospectively from the medical notes of these patients. RESULTS: Completed questionnaires were received from 128 patients. The majority of patients reported limitations in daily activities such as hobbies, driving, watching television and reading, as well as impaired self confidence. The mean GO-QOL scores in this study were (100 representing maximum QOL): visual functioning 59.0 (SD 28.0), psychosocial consequences of changed appearance 54.5 (28.4), and education and counselling 59.1 (38.8). Only about a quarter of patients indicated that education and counselling were adequate and helpful. CONCLUSION: Graves' ophthalmopathy profoundly affects QOL and adequate education and counselling are essential for helping patients to cope with their illness. The GO-QOL survey is a simple, practical tool that can be used easily in a clinic to determine the QOL issues in subjects with Graves' ophthalmopathy.

Long-term bone loss after renal transplantation: comparison of immunosuppressive regimens.

Serial measurements of serum and urine markers of bone metabolism and of forearm bone density (BMD) by dual photon absorptiometry were performed in 22 patients undergoing renal transplantation in 1986. Patients were randomised to immunosuppression with (1) cyclosporin alone (CsA group, n = 10), (2) cyclosporin for 3 months followed by azathioprine-prednisone (CsA/AzP group, n = 3) or (3) long-term azathioprine-prednisone (LT AzP group, n = 9). As no reduction in bone mineral density (BMD) was noted in the first 6 months, groups 2 and 3 were considered together (AzP group, n = 12). Mean +/- SEM BMD fell by 19 +/- 2% at 36 months (n = 19, p < 0.01), with similar reductions seen in the CsA and AzP groups. At 60 months, BMD of the AzP group was 25 +/- 3% below baseline (p < 0.01), while the CsA group were only 5 +/- 4% below baseline (p = NS vs baseline, p < 0.05 vs AzP group). The degree of reduction in BMD over 5 years correlated with total glucocorticoid dose (r = 0.63, p < 0.05), but not with biochemical markers of bone turnover. Serum alkaline phosphatase fell post-transplant in patients treated with AzP, but not in the CsA group. These results demonstrate significant loss of forearm bone mineral with long-term follow-up after renal transplantation, but suggest that patients treated with cyclosporin monotherapy may be at lower risk of this complication.

Blunted parathyroid response to correction of hypercalcemia in subjects with squamous cell carcinoma.

In malignancy-associated hypercalcemia (MAH) elevated plasma calcium levels are believed to inhibit parathyroid secretion independently of the underlying tumor. This predicts that correction of hypercalcemia should disinhibit circulating parathyroid hormone (PTH) levels, irrespective of the underlying disease. We have tested this hypothesis in subjects with multiple myeloma (MM) and squamous cell carcinoma (SCC) treated with pamidronate. In the MM group, PTH levels returned to normal as hypercalcemia was corrected. In contrast, PTH levels remained low in the SCC group despite a similar fall in plasma calcium. Calcitriol levels were significantly higher and magnesium levels slightly lower in the SCC group than those in the MM group. We conclude that the parathyroid response to the correction of hypercalcemia is blunted in subjects with SCC but not MM. In addition to hypercalcemia, other factors, perhaps related to tumor secretion of PTH-related protein, may therefore contribute to suppressing PTH secretion in MAH due to SCC.

Single-dose intravenous pamidronate is effective alternative therapy for Paget's disease refractory to calcitonin.

We have conducted an open, prospective study to investigate the efficacy of a single 60 mg infusion of pamidronate as alternative therapy in 15 subjects with severe Paget's bone disease refractory to calcitonin. Disease activity was assessed with a visual-analogue score of symptom severity, plasma alkaline phosphatase and quantitative estimation of 99mTc-methylene biphosphonate uptake on bone scan. All indices of disease activity fell after pamidronate, reaching a nadir at 3 months. Although disease activity increased thereafter, only 3 subjects required retreatment within 12 months. Plasma calcium fell after 3 days and remained below baseline levels for 6 months associated with evidence of secondary hyperparathyroidism. Pamidronate was well tolerated; femoral neck fractures occurred in 2 subjects with severe local Paget's disease but were unlikely to be due to the drug. We conclude that pamidronate is an effective and promising alternative for treatment of patients with severe Paget's disease no longer adequately controlled by calcitonin. Calcium supplementation may be prudent to prevent secondary hyperparathyroidism associated with the use of this agent.

Graves' disease in pregnancy: TSH receptor binding inhibiting immunoglobulins and maternal and neonatal thyroid function.

We studied interrelationships between maternal and neonatal thyroid function, TSH receptor binding inhibiting immunoglobulins (TBII), and dose of thionamide antithyroid drugs in 44 women with active Graves' disease presenting during 46 pregnancies, and their 48 infants. The women were treated with propylthiouracil (PTU) or carbimazole (CBZ). In 30 pregnancies (30 infants) treatment was withdrawn from 3 to 18 weeks before delivery (Group A). Drug treatment (PTU, n = 10, dose 50-400 mg/day or CBZ, n = 6, dose 5-45 mg/day) was continued throughout pregnancy and delivery in 16 pregnancies producing 18 infants (Group B). The maternal TBII at delivery was well correlated with maternal free thyroxine index (FTI) averaged over the third trimester (r = 0.603, P less than 0.001) and umbilical venous serum TBII (r = 0.940, P less than 0.001). Neonatal FTI was independently related to umbilical vein TBII (t = 2.29, P = 0.03) and maternal dose of antithyroid drug (t = -2.21, P = 0.03). Neonatal thyrotoxicosis was seen in all four infants (8% of births) of women whose TBII levels at delivery exceeded 70%. No child was born with a subnormal FTI but 7/18 infants in group B had raised TSH at birth. This was more likely to occur (P = 0.05) if maternal TBII was less than 30% (6/10) than if maternal TBII was greater than 30% (1/8). Four Group B women with FTI in the lower half of the reference range delivered infants with raised TSH compared with 3/14 (21%) women whose FTI was in the upper half of the reference range or above (P = 0.05). In pregnant women with active Graves' disease TBII levels reflect stimulatory TSH receptor antibody activity. TBII measurements are of use in the prediction of neonatal thyrotoxicosis and impaired neonatal thyroid function in infants of women treated with antithyroid drugs.

Role of 131I-metaiodobenzylguanidine in the localization of suspected phaeochromocytomas.

Iodine-131-metaiodobenzylguanidine is a recently-developed radiopharmaceutical agent for adrenal medullary scintigraphy. Twenty-one scans with 131I-metaiodobenzylguanidine were performed in 20 adults with suspected phaeochromocytomas over a four-year period. All patients previously had undergone computed tomographic scans of the abdomen and pelvis. The computed-tomographic scans were abnormal in 14 patients (16 tumours), eight (nine tumours) of whose 131I-metaiodobenzylguanidine scans gave positive results. Both types of scan gave negative results in the remaining six patients. Among 12 patients who underwent surgery or postmortem examination, the 131I-metaiodobenzylguanidine scan correctly showed eight phaeochromocytomas; six tumours that were found on computed-tomographic scans but not on 131I-metaiodobenzylguanidine scans proved not to be phaeochromocytoma. The 131I-metaiodobenzylguanidine scan probably gave a true-positive result in an additional case (surgical confirmation was not available). None of the remaining seven patients in whom the 131I-metaiodobenzylguanidine scan gave negative results has been shown to harbour a phaeochromocytoma on extended follow-up (2.5 to four years). Iodine-131-metaiodobenzylguanidine is a highly sensitive and specific agent for the localization of phaeochromocytomas. In patients with suspected phaeochromocytomas and abnormal computed-tomographic findings, 131I-metaiodobenzylguanidine permits a non-invasive, functional evaluation of the morphological abnormalities to be made. The importance of making a biochemical diagnosis of a phaeochromocytoma before attempting localization studies is emphasized.

The effect of long-term diphenylhydantoin therapy on glucose tolerance and insulin secretion: a controlled trial.

The influence of long-term administration of diphenylhydantoin (DPH) on glucose tolerance and insulin secretion was studied in a random controlled trial in non-epileptic patients receiving the drug for 2 years following recovery from myocardial infarction. While receiving DPH, insulin response to glucose was less than that in the control group, both in absolute terms and when related to the blood glucose level. Despite this, glucose tolerance did not differ from the control group. One month after cessation of DPH, the plasma insulin response had returned to the levels found in the control group, and glucose tolerance had improved to be significantly better than that found in the control group. Thus, the tendency of DPH to impair the insulin response to glucose has been confirmed in this controlled study. However, this does not result in significantly impaired glucose tolerance; it is suggested that the decreased insulin secretion is accompanied by improved insulin sensitivity.

Glucagon and diabetes. I. The failure of hyperglucagonaemia to influence the response of established diabetic ketoacidosis to therapy.

Clinical and biochemical variables were examined during two standardized, low-dose insulin regimens in seven subjects with diabetic ketoacidosis and one with hyperosmolar coma, in order to determine whether glucagon levels can be suppressed in ketoacidosis and whether hyperglucagonaemia influences the clinical and biochemical responses to treatment. Glucagon concentrations were significantly elevated (36.6-697.0 pmol/l) at presentation in all subjects. After institution of insulin treatment (4-8 u/h), glucose and glucagon levels decreased rapidly, and in five of the eight subjects glucagon levels reached undetectable concentrations (less than 3.0 pmol/l) during the initial treatment period. Further, neither plasma glucagon concentrations at presentation, nor the rate of glucagon decline during insulin treatment, appeared to influence the rapidity of the glucose decline or the persistence of the ketoacidosis. Thus, low-dose exogenous insulin suppresses glucagon secretion in diabetic ketoacidosis, and the changes in glucagon concentrations during treatment are unrelated to the clinical response.

Pregnancy following bromocryptine therapy for the amenorrhoea-galactorrhoea syndrome due to a pituitary tumour.

A woman developed amenorrhoea and galactorrhoea after partial removal of a pituitary tumor during pregnancy. Hyperprolactinaemia was supressed by therapy with bromocryptine (CB 154, Sandoz) resulting in cessation of galactorrhoea in two months, spontaneous menstruation after eight months, and pregnancy after twelve months.

Hypothalamic hypopituitarism following external radiotherapy for tumours distant from the adenohypophysis.

Three cases of panhypopituitarism and five of isolated growth hormone deficiency which occurred following previous external irradiation of tumours distant from the adenohypophysis are described. The hypothalamic pituitary region received between 2800 and 12 000 rads in each case, 1-9 years before endocrine deficiency was recognized. Evidence is presented that the site of damage is in the region of the hypothalamus rather than the pituitary gland itself. Individuals treated with X-ray therapy in whom the hypothalamic-pituitary region is exposed to irradiation would appear to be at risk of developing some degree of delayed hypothalamic-pituitary dysfunction.