Mortality associated with primary hyperparathyroidism.

561 patients with primary hyperparathyroidism were followed between 1961 and 1994. Relative survival was compared to that of the Australian population studied during the same time interval. Mortality was significantly greater in the hyperparathyroid population (P<0.001). Mortality was not greater in the patients with serum calcium levels >3.00 mmol/L compared to those with a serum calcium levels <3.00 mmol/L. 113 patients did not have parathyroid surgery. Their relative survival was not significantly different from those who had surgery but their mean serum calcium and parathyroid hormone (PTH) levels were significantly lower than those who had surgery. A re-analysis of the 453 patients followed between 1972 and 2011 was carried out and a 20-year survival analysis made of those diagnosed between 1972 and 1981 and those diagnosed between 1982 and 1991. The latter group had significantly worse relative mortality than the former group (P<0.001) but was significantly older at the time of diagnosis (56.94 ± 14.83 vs 52.01 ± 13.58, P<0.001). The serum calcium and serum PTH levels were not significantly different between these two groups.

Intravenous pamidronate in the treatment and prevention of osteoporosis.

BACKGROUND: Potent oral bisphosphonates are the mainstay of therapy for osteoporosis. However, there are patients who cannot have oral bisphosphonates (e.g. because of gastrointestinal side-effects). Therefore, we wanted to examine the effects of intermittent i.v. pamidronate (APD) on bone mineral density (BMD) in patients who needed bisphosphonate therapy but could not have oral bisphosphonates. AIM: To assess BMD before and after intermittent i.v. APD in patients requiring a bisphosphonate either for the prevention of osteoporosis on concurrent steroid therapy or for the treatment of osteoporosis. METHODS: This was a retrospective audit of 84 consecutive patients at risk of fractures commencing APD between October 1997 and May 2000. Patients were treated with intermittent i.v. APD. BMD as measured by dual-energy X-ray absorptiometry before and after APD was the main outcome. RESULTS: The mean length of treatment and mean total APD dose were 16.8 +/- 7.0 months and 186.1 +/- 79.5 mg respectively. The reasons for using APD were failure to qualify for oral bisphosphonates on the pharmaceutical benefits scheme due to lack of documented minimal trauma fractures (58%), symptomatic gastro--oesophageal disease (20%), intolerance of oral bisphosphonates (18%) and lack of efficacy of calcitriol (4%). Mean baseline T-score at lumbar (L) 2-4 spine and femoral neck were -1.54 +/- 1.22 and - 2.87 +/- 1.19, respectively. From baseline to after APD treatment, there was a significant increase in L2-4 BMD (0.883 +/- 0.175 vs 0.912 +/- 0.176 g/cm(2), P < 0.001, mean increase +3.5%), in femoral neck BMD (0.667 +/- 0.137 vs 0.680 +/- 0.134 g/cm(2), P= 0.001, mean increase +2.1%) and in trochanteric BMD (0.549 +/- 0.129 vs 0.566 +/- 0.132 g/cm(2), P < 0.001, mean increase +3.1%). One-third of the patients were on oral glucocorticoids at the time of the present study and they had a similar increase in BMD compared to patients not on gluco-corticoids. Mild side-effects occurred in seven patients, none of whom discontinued treatment. CONCLUSION: Intermittent APD increases BMD and may be a suitable alternative for patients who cannot have oral bisphosphonates.

A case of mistaken identity. A rare presentation of gonadal dysgenesis.

BACKGROUND: The incidence of gonadal dysgenesis (hermaphroditism) is recognised to be low. Rarer still is an initial late presentation in the general practice setting. OBJECTIVE: To present a case study of a 35 year old man diagnosed as a hermaphrodite after routine investigations in general practice for lower abdominal pain. He has normal male external genitalia, a fully formed uterus and vagina, with no identifiable gonads. DISCUSSION: This incidental finding in general practice is supported by a 46,X,i(Yp)/45,X karyotype and mosaicism for an isochromosome of the short arm of the Y. It is not unusual that with normal male genitalia, such patients are likely to survive undiagnosed or incorrectly diagnosed into adulthood.

The effect of o,p'-DDD on adrenal steroid replacement therapy requirements.

Two patients with adrenal carcinoma treated with 2,2-bis (2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane (o,p'-DDD) as adjuvant therapy were studied. Both patients developed hypoadrenalism while on o,p'-DDD and apparently adequate dexamethasone replacement therapy. The hypoadrenalism was overcome by increasing steroid replacement therapy. Dexamethasone levels were measured in the serum by radioimmunoassay and shown to be lowered by o,p'-DDD therapy. A study of the absorption and disappearance of dexamethasone from the circulation in response to a (1 mg oral dose indicated that the steroid was absorbed normally but was cleared more rapidly from the circulation of these two patients than from normal controls. This may be due to a change in the type of metabolites excreted. It is suggested that many of the reported side-effects of o,p'-DDD may be due to hypoadrenalism and may be controlled by greatly increasing the steroid replacement dose. The adequacy of corticosteroid replacement therapy may best be assessed by monitoring the levels of ACTH.

The measurement of antithyroglobulin autoantibodies in the presence of thyroglobulin.

An homogeneous phase radioassay (HRA) for antithyroglobulin autoantibodies (TgAb) in serum was investigated. In this method TgAb is allowed to react with 125I-Tg in solution and the immune complexes formed are separated by precipitation with sheep anti-human gammaglobulin. HRA proved to be suitable for the screening of sera prior to thyroglobulin (Tg) radioimmunoassay; being both sensitive, and unaffected by high endogenous levels of Tg. HRA was more sensitive than either of two commercial TgAb kits; a hemagglutination assay (Wellcome Australia Ltd.) and a solid phase radioassay (CIS France). Positive responses were obtained with 4 out of 42 normal subjects (titers up to 1/10), 24 out of 31 with untreated Graves' disease (titers up to 1/10,000) and all out of 18 with Hashimoto's thyroiditis (titers up to 1/10,000). Binding of 125I-Tg was displaceable with added unlabelled Tg, but in no case could it be abolished with less than 1,000 micrograms/l. Some sera exhibited more than one class of binding site and variation in both affinity and capacity for Tg was observed. It was concluded that the use of an assay standard for the reporting of results in units of concentration is invalid, although units of TgAb activity may be used as long as the analytical method is specified. Serum levels of TgAb may also be reported in semi-quantitative terms, such as in this report where a binding titer is used, or alternatively, antigen binding capacity may be reported.

Venous ACTH sampling in Cushing's syndrome.

A case of Cushing's syndrome in a 36-year-old woman, in whom the corticosteroid levels remained elevated in peripheral blood despite high doses of dexamethasone (8 mg/day), is reported. Although, on her skull X-ray film, the pituitary fossa was seen to be asymmetrically enlarged and had signs of possible erosion and depression of the floor on the left, the question whether this was an anatomical variant was raised. The correct diagnosis was made after measuring ACTH levels in venous blood samples taken from multiple sites, including the left petrosal sinus, in which a significant elevation of ACTH level, compared with the level in peripheral blood, was found.

Acromegaly and the heart--echocardiographic and nuclear imaging studies.

Left ventricular mass (LV mass) and function were assessed in 16 acromegalic patients by echocardiography, and rest and exercise gated blood pool scanning (GBPS) respectively. At the time of study, five patients had active acromegaly, five were hypertensive and three had coexisting coronary artery disease. Increased LV mass was found in six (38%) patients, of whom four were hypertensive and two others had active acromegaly of long duration. One normotensive patient, who did not have coronary disease, had increased LV mass associated with persistently elevated growth hormone (GH) levels for the previous 11 years. Abnormal LV function, as detected by GBPS, occurred only in the three patients with coronary disease. Thus, acromegaly is associated with increased LV mass in hypertensive patients and normotensive patients who have prolonged elevation of GH levels prior to adequate treatment. We found no detectable impairment of LV function, at rest or exercise unless other cardiac disease was present.

The value of ultrasound, gonadotropin, and estradiol measurements for precise ovulation prediction.

The exact prediction of ovulation is becoming more important in the management of infertile women. Graafian follicle diameter, measured by ultrasound and plasma follicle-stimulating hormone, luteinizing hormone, and estradiol levels were compared retrospectively as predictors of ovulation in 14 normal women in whom ovulation was dated by conventional ultrasound techniques. Follicle diameter was found to be a better predictor of the anticipated time of ovulation than endocrine estimations for short-term as well as long-term predictions in normal women. The relationship between follicle diameter and plasma estradiol for each day before ovulation was linear but contained a great amount of scatter, suggesting that the assessment of normality of follicular development in infertile women may not be possible with the use of these parameters.

Hypokalaemia occurring during insulin-induced hypoglycaemia.

Insulin-induced hypoglycaemia was used to test pituitary function in six patients with suspected pituitary deficiency. In each, a fall in serum potassium concentration of from 0-63 to 1-48 mEq/litre (mean fall 1-10 mEq/litre +/- 0-30 SEM) was observed during the two hour period following administration of 1-15 units of insulin per kilogram body weight. In several patients the resulting hypokalaemia was at a level which has been associated with cardiac complications.