Effects of bromocriptine and cyproheptadine on basal and corticotropin-releasing factor (CRF)-induced ACTH release in a patient with Nelson's syndrome

The effects of bromocriptine, a dopamine agonist, and cyproheptadine, a serotonin antagonist, on basal and corticotropin-releasing factor (CRF)-stimulated ACTH release were investigated in a 40-year-old female patient with Nelson's syndrome. Oral administration of either bromocriptine (2.5 mg) or cyproheptadine (8 mg) caused a marked drop in plasma ACTH levels. Intravenous administration of synthetic ovine (o) CRF (50 micrograms) produced an exaggerated response of plasma ACTH. Short-term (3-week) treatment with either bromocriptine (7.5 mg/day) or cyproheptadine (12 mg/day) resulted in a marked suppression of basal ACTH release. Furthermore, a blunted response of plasma ACTH to oCRF was observed after short-treatment with either drug. However, after a longer period of treatment with cyproheptadine (18-week), plasma ACTH levels rose again and hyperresponsiveness to oCRF was restored to the pretreatment levels. These data indicate that synthetic oCRF is a potent secretagogue for ACTH release in a patient with Nelson's syndrome. It is suggested that bromocriptine and cyproheptadine are effective drugs in reducing basal and CRF-stimulated ACTH release, possibly acting at the pituitary level in this case. However, the apparent refractoriness after chronic treatment with cyproheptadine may limit its therapeutic use in the present case.     

Effect of an oral serotonin antagonist,ketanserin, on plasma ACTH concentrations in Nelson's syndrome.

A study was performed to see whether ketanserin, a serotonin antagonist, would reduce the raised concentrations of adrenocorticotrophic hormone (ACTH) in patients with Nelson''s syndrome. Six patients who had undergone bilateral adrenalectomy for Cushing''s disease and who had Nelson''s syndrome were given ketanserin 40 mg twice daily and placebo, for at least two months each, in a double blind crossover study. Ketanserin had no effect on ACTH concentrations. In healthy people serotonin seems to have a stimulatory role in the regulation of ACTH secretion, and the effect of ketanserin in reducing the ACTH response to hypoglycaemia suggested that it might prove useful in Nelson''s syndrome. These results show that it is not indicated in these patients.     

A correlative study between cortisol and ACTH in Cushing's disease following bilateral adrenalectomy and in Nelson's syndrome.

Correlation analysis was used to investigate the interrelation between plasma ACTH and serum cortisol concentrations determined at 8:00, 12:00, 16:00 and 22:00 h in 48 patients bilaterally adrenalectomized for Cushing's disease, including 23 patients with a pituitary adenoma (Nelson's syndrome). In the patients without evidence of a pituitary adenoma a significant inverse correlation was found at 8:00, 16:00, 22:00 h and additionally when all the pairs of estimations were analyzed. In a full-blown Nelson's syndrome an inverse correlation was not proved (p = 0.05). During remission in Nelson's syndrome an inverse correlation between cortisol and ACTH concentrations was stated at 8:00 h and after the evaluation of all the pairs of estimations. The results of our studies have shown that exogenous cortisol exerts a partial inhibitory action on ACTH secretion in patients bilaterally adrenalectomized for Cushing's disease. In active Nelson's syndrome this influence is questionable, it comes however into prominence during remission.     

In vivo and in vitro ACTH response to ovine corticotropin-releasing factor in a bronchial carcinoid from a patient with ectopic ACTH syndrome

ACTH response in vivo and in vitro to synthetic ovine corticotropin-releasing factor (o-CRF) was examined in a bronchial carcinoid from a patient with ectopic ACTH syndrome. o-CRF, 1 microgram/kg iv bolus, scarcely increased plasma ACTH or cortisol on one occasion, but they showed a low response on retesting. On the other hand, 10(-8) and 10(-7) M of o-CRF significantly stimulated ACTH release in cultured bronchial carcinoid cells.     

Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome.

The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sleep apnea (OSA) suggest dysfunction of specific neural sites that integrate afferent airway signals with autonomic and somatic outflow. We determined neural responses to the Valsalva maneuver by using functional magnetic resonance imaging. Images were collected during a baseline and three Valsalva maneuvers in 8 drug-free OSA patients and 15 controls. Multiple cortical, midbrain, pontine, and medullary regions in both groups showed intensity changes correlated to airway pressure. In OSA subjects, the left inferior parietal cortex, superior temporal gyrus, posterior insular cortex, cerebellar cortex, fastigial nucleus, and hippocampus showed attenuated signal changes compared with controls. Enhanced responses emerged in the left lateral precentral gyrus, left anterior cingulate, and superior frontal cortex of OSA patients. The anterior cingulate, cerebellar cortex, and posterior insula exhibited altered response timing patterns between control and OSA subjects. The response patterns in OSA subjects suggest deficits in particular neural pathways that normally mediate the Valsalva maneuver and compensatory actions in other structures.     

Androgen secretion in ectopic ACTH syndrome and in Cushing's disease: modifications before and after surgery.

The role of ACTH in the control of adrenal androgen secretion is known, although the possible existence of other regulatory factors has been also suggested. While some data concerning Cushing's disease have been reported, only few studies concerned androgen levels in ectopic ACTH secretion. The aim of this study was to evaluate serum DHEA-S, androstenedione (A) and testosterone (T) levels in 36 women with ACTH-dependent Cushing's syndrome (30 with Cushing's disease and 6 with ectopic ACTH secretion) before and after surgery. Two men with ectopic ACTH production were also studied. In 30 women with Cushing's disease serum DHEA-S (9.6 +/- 0.9 micromol/l), A (15.2 +/- 1.2 nmol/l) and T (4.1 +/- 0.5 nmol/l) were higher than in controls (p < 0.01): elevated DHEA-S, A and T values were found in 8, 18 and 17 cases, respectively. After adenomectomy in 15 apparently cured patients DHEA-S, A and T levels were low at 1 - 3 months and at 6 - 12 months after surgery. At 18 - 24 months, DHEA-S remained low in spite of cortisol normalisation. In ectopic Cushing's syndrome, A levels were significantly higher (23.1 +/- 4.9 nmol/l) than in Cushing's disease (p < 0.05), while no differences were found in DHEA-S and T levels. Two patients had elevated DHEA-S values, 3 women had high T levels and 7 of the 8 patients had very high A concentration that was lowered in 3 operated cases. In conclusion, the pattern of adrenal androgen secretion is rather different in patients with pituitary or with ectopic Cushing's syndrome. While the frequency of DHEA-S and T alterations is similar, androstenedione secretion is greatly increased in the latter condition. It is suggested that in ACTH-secreting non-pituitary tumours, the production of a POMC-derived peptide, although unidentified, may lead to preferentially stimulated androstenedione secretion, without affecting other enzymatic pathways.     

Alpha-delta sleep in a patient with nocturnal panic attacks

Sleep and Biological Rhythms - We report here on our finding of an alpha-delta sleep in a 40-year-old-female patient suffering from panic attacks, including nocturnal panic attacks, who complained...     

Impaired water diuresis in a patient with pseudo-Bartter syndrome.

A 32-year-old man was diagnosed as having pseudo-Bartter syndrome due to surreptitious habitual vomiting and to maldigestion related to decayed teeth. His chief complaints were muscle pain and weakness. In this case, metabolic alkalosis, hypokalemia, hypochloremia, increased plasma renin activity and aldosterone levels were noticed with marked decreases in urinary chloride excretion. Creatinine clearance (GFR) and renal plasma flow (RPF) were also decreased. Blood pressure was normal, but the pressor response to angiotensin II was attenuated. Before treatment with 0.9% saline infusion, plasma vasopressin (AVP) was not suppressed sufficiently by lowering the plasma osmolality (Posm) with an oral water load (WL), but it normally responded to a rise in Posm due to hypertonic saline infusion. Moreover, plasma AVP was normally suppressed by WL after the replenishment of saline. Plasma atrial natriuretic peptide (ANP) was low before WL, but increased normally in response to WL. However, inconsistent with the normal response in this case, decreases in plasma AVP failed to dilute urinary osmolality and to increase urine flow, irrespective of the levels of plasma ANP. These results indicate that chronic inanition due to surreptitious vomiting causes impaired renal diluting ability through decreases in GFR and RPF, irrespective of the levels of plasma AVP and ANP.     

Phase-shifted diurnal rhythm of cortisol secretion in a patient with Cushing's syndrome due to adrenocortical adenoma

A 21-year-old woman with Cushing's syndrome was found to have a marked diurnal variation in cortisol secretion. Serum cortisol concentrations and urinary excretion of 17-hydroxycorticosteroids were normal in the morning but clearly increased in the afternoon. The patient was cured by resection of an adrenocortical adenoma. ACTH and prostaglandin E1 stimulated cortisol release from incubated adenoma tissues in vitro. The cause of the abnormal diurnal rhythm of cortisol secretion is unknown.     

Simultaneous sleep study and nasoendoscopic investigation in a patient with obstructive sleep apnoea syndrome refractory to continuous positive airway pressure: a case report

Introduction

There seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.

Case presentation

A 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses.

Conclusion

This case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication.