Clues for early detection of autoimmune Addison's disease - myths and realities.

BACKGROUND: Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce. OBJECTIVE: Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD. MATERIAL AND METHODS: A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values. RESULTS: Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L-1 [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L-1 [2-442]) than in those without (81 nmol L-1 [1-668], P < 0.001). CONCLUSION: The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

Inter-observer variation in the results of the clinical andrological examination including estimation of testicular size.

Inter-observer variation in andrological examination by 10 clinical investigators from five Nordic and Baltic countries was investigated. In addition, information on intra-observer variation was obtained for six of the 10 investigators. Testicular size was measured using Prader's orchidometer and one of the investigators also performed an ultrasound estimate of testicular size. A highly significant difference (p < 0.001) between observers was found with an inter-observer error of 16% in estimating testicular size in 23 young men. The difference in the estimate tended to increase with increasing testicular size. There was no significant intra-observer difference in two measurements performed on consecutive days. Only differences in median testis size, which were greater than 31% between measurements by two investigators, were found to be significant at the 5% level. The ultrasound estimate of testicular size was significantly lower than the orchidometer estimate, with a mean difference of 3.6 mL for the left testis and 4.3 mL for the right testis. Tanner staging of genitalia and diagnosis of a varicocele was subject to great inter-observer variation, and for the diagnosis of varicocele only one-third of the investigators was able to reproduce their results on a second examination. In conclusion, it was found that the clinical andrological examination of young men is subject to great inter-observer variation. This should be kept in mind when results from different studies are compared as well as in daily clinical practice.

Effects of exercise on hypoglycaemic responses in insulin-dependent diabetes mellitus.

This study sought to determine whether moderate exercise influences hypoglycaemic responses in insulin-dependent diabetes mellitus (IDDM). Ten patients with IDDM and no history of hypoglycaemia unawareness or autonomic neuropathy were included. The patients were studied in random order on 4 occasions: twice during euglycaemia (once at rest and once on a treadmill) and twice during a gradual drop in blood glucose from 5 to 2 mmol/l (once at rest and once on a treadmill). Blood samples for hormones and glucose were drawn, and a symptom questionnaire was filled out every 5 min. Cognitive tests were performed at the start and end of each study. Glucose thresholds for hormones and symptoms are reported as the plasma glucose level at which responses were more than two standard deviations above basal level and continued to increase. The thresholds for adrenaline and noradrenaline release came at a significantly higher blood glucose level during exercise than at rest: 2.7 +/- 0.2 vs 2.1 +/- 0.2 mmol/l (p < 0.05) for adrenaline and 2.7 +/- 0.2 vs 2.0 +/- 0.1 mmol/l (p < 0.01) for noradrenaline. Thresholds for neuroglycopenic symptoms were also at a significantly higher blood glucose level during exercise: 2.6 +/- 0.2 vs 2.0 +/- 0.2 mmol/l (p < 0.05). During hypoglycaemia, patients showed a non-significant trend towards a lower score on cognitive tests during exercise than at rest. It is concluded that moderate exercise during a gradual drop in blood glucose does not mask hypoglycaemic responses in patients with IDDM.