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Biomedical subjects

H L Fehm

Publications and source records attributed to H L Fehm.

At least 217 records · Page 12Linked to original sources
PubMed1982

[Fatal complication of intravenous administration of synthetic adrenocorticotrophin].

Synthetic 1-24adrenocorticotrophin (tetracosactid, Synacthen) is used in clinical medicine for diagnostic and therapeutic purposes. Side effects may occur due to unphysiological stimulation of endogenous adrenocortical hormone production. Allergic reactions to tetracosactid are rare. Anaphylactic shock leading to death was observed after intravenous injection of tetracosactid in a 14-year-old girl with bronchial asthma. Adrenocorticotrophin antibodies could be demonstrated after death in serum and ascitic fluid using the double antibody method.

Adolescent↗
PubMed1982

Multiple cellular forms of corticotrophs in surgically removed pituitary adenomas and periadenomatous tissue in Cushing's disease.

Transsphenoidally removed samples of pituitary adenomas from 14 patients with Cushing's disease and 5 patients with Nelson's syndrome always contained groups of uniform small ACTH-cells. Antibodies against the pro-opiocortin precursor fragments beta-endorphin, ACTH, and 16k-peptide recognized material in typical adenoma cells. A subpopulation of these cells, varying in number from sample to sample, specifically exhibited alpha-melanotropin immunoreactivity. Most periadenomatous samples showed signs of severe degeneration. Typical Crooke cells only occurred in samples from patients with Cushing's syndrome, but, with this exception, no clear differences between pituitaries of patients with Cushing's and Nelson's syndromes could be discerned. Two other forms of ACTH-immunoreactive cells were observed: rare, single, highly immunoreactive cells, with characteristics of both normal and Crooke cells, and numerous syncytial groups of cells in an advanced state of disintegration, presumably the remnants of hyperplastic follicles. The four different corticotrophs are characterized according to their fine structure and immunoreactivity in this study.

Adenoma↗
PubMed1979

Differential and integral corticosteroid feedback effects on ACTH secretion in hypoadrenocorticism.

Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began congruent with30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism). The dose-sensitive feedback effects of dexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg.

Adrenal Cortex Hormones↗
PubMed1979

Positive rate-sensitive corticosteroid feedback mechanism of ACTH secretion in Cushing's disease.

To define the nature of the disturbance of the corticosteroid feedback mechanism in Cushing's disease, the dynamic aspects of the ACTH response to corticosteroid administration have been studied in patients with Cushing's disease after total adrenalectomy (C.d. post adx.). The results were compared with those obtained in patients with Addison's disease (control group). Different experimental designs for administration of cortisol were chosen to provide extreme variations in the input signal. The response of the system was evaluated by measuring plasma ACTH concentrations (radioimmunoassay) at short time intervals. Infusion of cortisol at constant rate (50 mg/h for 2 h) resulted in a transient, paradoxical rise in ACTH levels with a maximum at 15 min. (315+/-65%, mean+/-SEM). In contrast, in the control group there was an immediate and rapid decrease in ACTH levels with a significant inhibition after 15 min (80+/-6%, mean+/-SEM). Infusion of 50 mg cortisol for 5 and 15 min, respectively, produced an increase in ACTH levels, which was confined to the time when cortisol levels were rising (maximum: 137+/-30% and 139+/-10% at 5 and 15 min, respectively, mean+/-SEM). This increase corresponded in time to the first decrease in ACTH levels in the Addisonian patients. With bolus injections of 25 mg cortisol, ACTH levels remained unchanged during the first 15 min. The time-course in the patients with C.d. post adx. was essentially the same as in the Addisonian patients. From these results it is concluded that in the patients with C.d. post adx. the rapid, rate-sensitive feedback mechanism was converted into a positive one, whereas the delayed, dose-sensitive mechanism was completely undisturbed. The capacity of dexamethasone to activate rate-sensitive feedback elements was markedly diminished. Accordingly, there were only minor positive feedback effects upon ACTH secretion in the patients with C.d. post adx.

Addison Disease↗
PubMed1979

Pathophysiology of Cushing's disease.

The term Cushing's disease is applied to those cases of Cushing's syndrome in which hypercortisolism is secondary to inappropriate secretion of ACTH by the pituitary. Studies on control of ACTH secretion in these patients reveal: (a) that the episodic secretion of ACTH is similar to the normal; however, frequency and amplitude of the secretory episodes lack the normal circadian rhythm; (b) that ACTH release can be stimulated by vasopressin and metyrapone in a normal or above-normal manner; and (c) that it can be suppressed by large doses of corticosteroids. When the dynamic aspects of the ACTH response to corticosteroid administration are studied, it appears that the normally negative differential feedback mechanism is converted into a positive one, whereas the delayed, integral mechanism is undisturbed. Patients with Cushing's disease in the presence of obvious pituitary tumors cannot be distinguished from those without pituitary tumors by studying only the pituitary function. All these and other well-known facts would favor the concept that ACTH secretion in Cushing's disease is under hypothalamic control whether or not a pituitary tumor is present. Moreover, there are observations that suggest that brain centers superior to the hypophysiotropic area of the hypothalamus are involved in the pathophysiology of Cushing's disease. This concept has led to the discovery of neurotropic drugs that are able to induce complete remission of Cushing's syndrome in a cerain percentage of patients. In some patients with severe psychiatric diseases, neuroendocrine abnormalities are present that resemble closely those characteristic for Cushing's disease. With the most refined neuroradiological methods, pituitary microadenomas are demonstrable in approximately 70% of patients with Cushing's disease, and this number compares well with those of earlier autopsy findings (70 to 80%). In a small number of patients (4 to 10%), these tumors are large and can easily be detected by standard roentgenograms of the head. Recent studies on the frequency of these large tumors do not support the hypothesis that adrenalectomy accelerates the progression of these tumors. In this case the term "Nelson's syndrome" would be uncessary. It is established that complete cure of Cushing's disease can be obtained in most patients with selective removal of a microadenoma from the pituitary gland. The current experience with this microsurgical procedure caused a renewed interest in Cushing's original suggestion that the disease is primarily a pituitary disorder. However, there are already a number of enigmatic observations. Possibly, the recent ultrastructural studies using immunocytochemical methods will resolve some of these problems. At this moment it is impossible to decide whether Cushing's disease is primarily a CNS or a pituitary disorder, when all arguments for one or the other hypothesis are taken into account...

Adrenal Cortex Hormones↗
PubMed1978

The effect of cyproterone acetate on adrenal cortical function in children with precocious puberty.

8 children with precocious puberty were treated with cyproterone acetate (CPA). During treatment there were no definite clinical signs of depressed adrenocortical function. The plasma cortisol concentrations were grossly depressed and the diurnal cortisol rhythm was abolished. Two months after discontinuation of CPA treatment the adrenocortical function had greatly improved. The lysin-vasopressin stimulation test revealed in one child a normal, in another child an exaggerated ACTH response during CPA therapy. Fasting plasma ACTH concentrations were elevated compared with normal controls, but they were very low compared with patients with Addison's disease. The results suggest that CPA has a twofold effect leading to adrenocortical insufficiency: i.e., inhibition of cortisol secretion by the adrenals themselves and inhibition of ACTH secretion at the hypothalamopitiuitary level.

Adolescent↗
PubMed1978

Prolonged infusions of Ile5-angiotensin-II in sodium replete and deplete man: effects on aldosterone, ACTH, cortisol, blood pressure, and electrolyte balance.

Angiotensin II (Ile5) was infused for 72 h into 4 sodium replete (3 ng/kg/min) and 8 sodium deplete (3 or 6 ng/kg/min) healthy young men after appropriate control periods, and the effects on aldosterone secretion, plasma cortisol, ACTH, renin activity, plasma and urinary electrolytes, and blood pressure were assessed. Sustained contrived elevation of plasma angiotensin II levels in sodium replete subjects to the range of moderate sodium depletion led to a sustained increase in plasma and urinary aldosterone levels, which further and significantly increased between the 1st and 2nd days of angiotensin II infusion, when gross sodium retention during infusion was prevented. This additional increase may be explained as the expression of a "trophic" effect of angiotension II on the zona glomerulosa. In the sodium deplete state, the absolute increment of aldosterone secretion for a given elevation of angiotensin II levels diring infusion was larger than in sodium replete subjects. This confirms the conclusions from previous short-term angiotensin II infusion experiments that sodium deficiency sensitizes the zona glomerulosa against angiotensin II. The "trophic" effect of angiotensin II on the adrenal gland seems to be one mechanism by which the sensitization is brought about, but insufficient for its full explanation. Since plasma ACTH and cortisol, plasma sodium and potassium concentrations, and potassium blance did not change significantly across sodium depletion or angiotensin II infusion, the mechanism of sensitization awaits its full elucidation. The effect of angiotensin II on blood pressure was blunted by soidum depletion. The opposite shifts in sensitivity against angiotensin II of the zona glomerulosa and of resistance blood vessels with changes in the sodium state seem to be an effective and important means in the regulation of body sodium.

Adrenocorticotropic Hormone↗
PubMed1977

Paradoxical ACTH response to glucocorticoids in Cushing's disease.

To define further the defect in the steroid feedback mechanism in Cushing's disease, we studied the acute effects of intravenous administration of glucorticoids on plasma ACTH levels in seven patients with this disease after total adrenalectomy. In seven other patients with hypoadrenocorticism ACTH was readily suppressed; a significant decrease (72.5+/-5 per cent, mean +/- S.E.M., P less than 0.002) occurred within 15 minutes of the start of an infusion of 50 mg per hour of cortisol. In contrast, in the seven adrenalectomized patients with Cushing's disease, cortisol induced a transient paradoxical rise in ACTH levels, with a maximum at 15 minutes (347+/-99 per cent,, P less than 0.05). A similar ACTH response was observed with dexamethasone. Cushing's disease is characterized by a paradoxical transient rise in ACTH after glucocorticoid administration. This effect was more pronounced in adrenalectomized than in nonadrenalectomized patients.

Adolescent↗