No abstract

To investigate the adrenostatic potential of a nonhypnotic low dose etomidate infusion, we administered 0.03 mg/kg etomidate in a bolus injection, followed by constant infusion of 0.3 mg/kg.h for 24 h to 6 patients with severe Cushing's syndrome. The dose-response relationship also was determined in 15 normal subjects. Three groups of 5 received, respectively, doses of 0.03, 0.1, and 0.3 mg/kg.h etomidate for 5 h after an initial bolus dose of 0.03 mg/kg. The response to exogenously administered ACTH [0.25 mg ACTH-(1-24)], injected after the etomidate or control infusion, was determined in all normal subjects. In the six hypercortisolemic patients, serum cortisol concentrations decreased from 1374 +/- 436 nmol/L (mean +/- SEM) to 188 +/- 91 nmol/L after 11 h of etomidate infusion and remained low until the end of the infusion. Cortisol levels returned to pretreatment concentrations by 24 h. Excretion of urinary free cortisol decreased from 1180 +/- 196 to 185 +/- 66 nmol/day. In the normal subjects, administration of etomidate led to a dose-dependent decrease in serum cortisol from about 550 to 83 nmol/L, while 11-deoxycortisol rose from low or undetectable levels up to 346 nmol/L. In response to ACTH, cortisol levels rose in inverse proportion to the etomidate dose. It was, however, significantly reduced compared to normal saline infusion even after the lowest dose. Changes in aldosterone and corticosterone concentrations were similar to those in cortisol, and 11-deoxycorticosterone changed in a pattern similar to that of 11-deoxycortisol. Two of five normal subjects reported tiredness during the highest etomidate infusion. No other side-effects were noted. We conclude that iv administered etomidate in a low nonhypnotic dose reduces serum cortisol concentrations in a dose-dependent manner in both hyper- and eucortisolemic subjects. This study suggests that etomidate at a dose of 0.1 mg/kg.h or lower may be an effective strategy for the control of severe hypercortisolemia.

Addison’s disease – the traditional term for primary adrenal insufficiency (PAI) – is defined as the clinical manifestation of chronic glucocorticoid- and/or mineralocorticoid deficiency due to failure of the adrenal cortex which may result in an adrenal crisis with potentially life-threatening consequences. Even though efficient and safe pharmaceutical preparations for the substitution of endogenous gluco- and mineralocorticoids are established in therapy, the mortality in patients with PAI is still increased and the health-related quality of life (HRQoL) is often reduced.PAI is a rare disease but recent data report an increasing prevalence. In addition to the common “classical” causes of PAI like autoimmune, infectious, neoplastic and genetic disorders, other iatrogenic conditions – mostly pharmacological side effects (e. g., adrenal haemorrhage associated with anticoagulants, drugs affecting glucocorticoid synthesis, action or metabolism and some of the novel anti-cancer checkpoint inhibitors) are contributing factors to this phenomenon.Due to the rarity of the disease and often non-specific symptoms at least in the early stages, PAI is frequently not considered resulting in a delayed diagnosis. Successful therapy is mainly based on adequate patient education as a cornerstone in the prevention and management of adrenal crisis. A focus of current research is in the development of pharmacokinetically optimized glucocorticoid preparations as well as regenerative therapies.

SummaryThe effects of oral bromocriptine in acromegaly have been studied. A dose of 5 mg six-hourly suppressed circulating growth hormone (GH) levels in nine out of 11 patients treated for seven to 11 weeks. This was associated with considerable clinical improvement in all patients, with abolition of excessive sweating, reduction in softtissue thickening, loosening of rings, decrease in shoe size, improvement in facial features, and loosening of dentures. Metabolic changes included improvement in glucose tolerance and reduction in hydroxyproline excretion. Unlike the actions of growth hormone release inhibiting hormone the suppression of GH was not accompanied by a reduction in insulin or glucagon secretion, though prolactin levels were suppressed. Side effects other than mild constipation were not seen when the full dose regimen was reached by slowly increasing the dose from 2-5 mg once daily. Bromocriptine holds promise as a safe and orally effective medical treatment to augment surgical or radiotherapeutic measures

The frequency, predisposing factors and course of agranulocytosis (granulocytes < 250/microliter) secondary to antithyroid drugs were studied in a cohort of 1256 continuously treated outpatients with hyperthyroidism during the 15 year period from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was 0.18% (95%-confidence intervals, 0.0-0.44%). This prevalence appears to be lower than reported in previous studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thionamide dose and to the body mass index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug- induced agranulocytosis were studied, and the following results obtained: Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3 +/- 19.7 vs 34.3 +/- 29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23-55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5-31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose.(ABSTRACT TRUNCATED AT 250 WORDS)