T. J. McKenna

THE OVERNIGHT DEXAMETHASONE TEST IS A WORTHWHILE SCREENING PROCEDURE

The overnight low‐dose dexamethasone test is a convenient screening procedure for Cushings syndrome. Claims that the test is associated with a high incidence of ‘false positives’, rendering it of little value particularly in obese and hospital in‐patients, have been investigated in the present study. The data from 100 consecutive subjects undergoing overnight low‐dose dexamethasone tests to examine for the possibility of Cushings syndrome, were reviewed. Cushings syndrome was identified in four patients, normal suppression of cortisol values occurred in 84 patients and 12 patients exhibited false positive results. Differences in body weights, body mass indices or in‐patient status did not distinguish between those subjects with normal suppression of plasma cortisol and those subjects who yielded false positive results. These data indicate that the simple overnight dexamethasone test substituted for the more cumbersome traditional 48‐h dexamethasone test in 84 of 96 patients who did not have Cushings syndrome. Thus the overnight test provides a useful screening procedure but a small percentage of patients, approximately 12.5%, will require additional procedures to exclude Cushings syndrome.

Silent ischaemia in diabetic men with autonomic neuropathy.

Autonomic neuropathy is associated with an increased incidence of silent myocardial infarction and sudden death. The purpose of this study was to investigate the prevalence of silent myocardial ischaemia in diabetic patients with autonomic neuropathy and without. Five standard autonomic function tests were performed on 41 men with diabetes: postural change in blood pressure, postural change in heart rate, heart rate response to deep breathing, heart rate response to Valsalvas manoeuvre, and blood pressure response to sustained handgrip. There were 17 patients with autonomic neuropathy (group A) and 24 with normal autonomic function (group B). All patients underwent 24 hour ambulatory electrocardiographic monitoring to detect silent ischaemia. There was no significant difference in risk factors for coronary artery disease or history of angina pectoris between these groups. The prevalence of silent ischaemia was 64.7% in group A (95% confidence interval (95% CI) 38.33 to 85.79%) and 4.1% in group B (95% CI 0.11 to 21.12%). This represents a relative risk of 42.2 (95% CI 4.5 to 39.4, p less than 0.001). These results are consistent with the concept that autonomic neuropathy may prevent the development of anginal pain and thus obscure the presence of ischaemic heart disease. Twenty four hour ambulatory electrocardiographic monitoring may identify a subgroup of diabetic patients with autonomic neuropathy who have myocardial ischaemia and to whom treatment may be offered.

Dissociation of adrenal androgen and cortisol secretion in Cushing's syndrome

OBJECTIVES While ACTH may modulate adrenal androgen production, there is evidence that other factors are required. Cushings disease and ectopic ACTH secretion provide a little utilized opportunity to examine adrenal androgen levels in conditions of ACTH excess. We have compared plasma cortisol values with plasma levels of androstenedione, dehydroeplandrosterone (DHEA), DHEA‐sulphate (DHEAS), testosterone and an Index of free testosterone, the testosterone/sex hormone binding globulin ratio, prior to treatment in patients with Cushings syndrome.

Polyostotic fibrous dysplasia with contrasting responses to calcitonin and mithramycin : aetiological and therapeutic implications

SummaryTREATMENT of a patient with symptomatic progressive fibrous dysplasia offered an opportunity to examine the effectiveness of agents known to influence bone turnover, in modifying the activity of the disorder. In response to calcitonin markedly elevated urinary hydroxyproline excretion was unaltered although serum alkaline phosphatase tended to fall. However, the urinary calcium excretion more than doubled. In contrast, the introduction of intravenous mithramycin, brought about a reduction in serum alkaline phosphatase, urinary hydroxyproline excretion and urinary calcium. However, nausea, abnormal liver function and poor patient compliance resulted in abandoning mithramycin. The diphosphonate etidronate did not make any definite impact. Only mithramycin held promise for the effective treatment of fibrous dysplasia in this patient, but its potential toxicity and the need for intravenous administration limit its applicability. Calcitonin-resistant osteocolast activity is possibly involved in the aetiology of fibrous dysplasia.

Mineralocorticoid and glucocorticoid status in idiopathic haemochromatosis

OBJECTIVE A number of studies have suggested that both primary (Addisons disease) and secondary adrenal failure may be caused by idiopathic haemochromatosis. There is little information on mineralocorticoid secretion. We have assessed the mineralocorticoid and glucocorticoid status of patients with idiopathic haemochromatosis. DESIGN Cross‐sectional study.

The relationship of blood glucose and haemoglobin A1 levels in diabetic subjects

Recommendations exist that fasting plasma glucose (FPG) levels can be substituted for glycosylated haemoglobin A, (HbA,) in Type II diabetic subjects (DM II), which have potential important financial implications. The present study was designed to expand this examination and to include Type I DM (DMI) patients and random blood glucose (RBG) values. Data were obtained from 234 DM II and 104 DM I patients, over 3 years. Correlation of HbA1 with FPG levels in DM II yielded an r value of 0.61. Correlation of HbA, with RBG and 2 h post prandial glucose measurements yielded r values of 0.59 and 0.51 respectively, p<0.001. In DM I, similar correlations gave r values ranging between 0.27 and 0.38, p<0.01-0.001.Thus while significant correlations exist between HbA1 and FPG and RBG measurements in both DM I and DM II, clinically applicable information on long-term diabetic control can only be achieved from glucose measurements in DM II but the correlation is not sufficiently tight to recommend substitution of plasma glucose for HbA1 determinations, despite the cost advantages.

Plasma pro-opiomelanocortin fragments and adrenal steroids following administration of metyrapone to normal and hirsute women

The present study was undertaken to characterize further the adrenal abnormalities in the polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH). We have previously reported the close association of elevated estrone levels with amenorrhea in hyperandrogenemic patients. In addition we have suggested that high estrone levels in PCOS occur as a consequence of the provision of excess substrate, androstenedione, for conversion to estrone. In the present study plasma estrone levels rose following endogenous adrenal stimulation induced using metyrapone; the highest plasma estrone levels achieved were seen in patients with PCOS and occurred later than peak androstenedione levels. These findings are consistent with the hypothesis that elevated estrone levels occurring in PCOS may arise as a consequence of increased adrenal androgen secretion. In addition, we have examined ACTH and other pro-opiomelanocortin (POMC) fragments in an attempt to identify a factor responsible for the excessive adrenal androgen secretion occurring in hirsute patients. Plasma levels of ACTH, and of immunoreactive β-endorphin and h-lipotropin were not elevated when androgen levels were raised prior to therapy, although these POMC fragments, and also the 16K fragment, rose in response to metyrapone treatment as did androgen levels. Following treatment with dexamethasone there was more profound suppression of the 16K, β-endorphin and h-lipotropin responses to metyrapone stimulation, than of the ACTH response, as indicated by decreased POMC-fragment/ACTH ratios; this parallels the dissociation of Cortisol from androgens in hirsute patients under similar conditions. However, we have not identified a POMC fragment which consistently parallels changes in androgen levels in patients with idiopathic hirsutism or PCOS.

Suprasellar Germinoma - Occult Presentation with Hypothalamic Failure 18 Months Before Diagnosis

SummaryHormonal evidence of widespread hypothalamic failure, including diabetes insipidus, hyper-prolactinaemia, growth failure, hypothyroidism, and adrenal failure, was present in a boy of 14 years. Investigation with computerised axial tomography (CT) and metrizamide encephalography failed to identify any anatomical abnormality at the time of presentation. However, 18 months later papilloedema was noted at which time a suprasellar mass and gross dilatation of the ventricular system were readily identified using CT and a germinoma was subsequently diagnosed and treated. In the light of this experience we recommend that when “idiopathic” hypothalamic failure is diagnosed, imaging procedures, including CT or nuclear magnetic resonance examinations, should be repeated on at least one occasion, after an interval of approximately 6 months.

TSH as an index of L-Thyroxine replacement and suppression therapy

SummaryWhen hypothalamic-pituitary function is normal, serum TSH levels measured by ultrasensitive assay yield bioassays of endogenous thyroid action and thus provide an ideal index of thyroid secretion and its relationship to fluctuating endogenous thyroid levels. It is theoretically possible that patients receiving exogenous L-thyroxine for primary hypothyroidism should have suppressed TSH levels if physiological needs are constantly met. To examine this possibility free thyroxine, FT4 and TSH were measured in 90 clinically euthyroid patients receiving treatment with L-thyroxine for primary hypothyroidism. TSH levels were normal in 44, suppressed in 16 and elevated in 30 patients. FT4 levels were normal in 68, elevated in 13 and suppressed in 9 patients. Normal TSH levels were associated with normal FT4 levels in 79.5% of patients, elevated FT4 levels in 13.6% and low FT4 in 6.8%. Suppressed TSH levels were associaed with elevated FT4 levels in 37.5% of patients and normal FT4 levels in 62.5%. When FT4 levels were normal, however, TSH levels were normal in only 51.5% and abnormal in 48.5%. We also examined the possibility that FT4 levels may remain within normal range when TSH is suppressed during L-thyroxine treatment for goitre or cancer. FT4 and TSH were measured in 45 patients on L-thyroxine as TSH suppression treatment. TSH was suppressed in 23 patients (51.1%), normal in 20 (44.4%) and elevated in 2 (4.5%). When TSH was suppressed, FT4 was elevated in 30.4% but normal in 69.6% of patients. In summary, these observations do not support the hypothesis that a suppressed TSH level indicates optimal replacement in patients with primary hypothyroidism, rather that TSH levels should be normal. Where TSH suppression is required this can be achieved in approximately 70% of patients without elevating the Free T4 level.

Nelson's syndrome following partial pituitary microadenomectomy and pregnancy

We report for the first time the development of Nelsons syndrome in a patient who had previously undergone unsuccessful pituitary microadenomectomy and subsequently bilateral adrenalectomy. The removal of a 3‐mm portion of a microadenoma did not protect against the development of Nelsons syndrome within 3 years which was closely related to pregnancy, a previously noted association. This report suggests that the development of Nelsons syndrome depends not on the size of the initial pituitary tumour but rather on its individual potential for proliferating once free of the inhibitory effects of glucocorticold excess