Cyclical edema and hypokalemia due to occult episodic hypercorticism.

Yearly episodes of edema, hypokalemia, anxiety, and depression were found to be due to cortisol and deoxycorticosterone surges secondary to a pituitary adenoma in a woman without any of the usual clinical features of Cushing's syndrome. During the long clinical remissions, she had no recognizable laboratory abnormality. She had two episodes in the year following incomplete transphenoidal pituitary tumor resection, but has had none in 2 yr since receiving radiotherapy. The episodes were caused by mineralocorticoid actions of large ACTH-induced increases in cortisol and deoxycorticosterone secretion. A history of episodic edema and hypokalemia, often attributed in women to surreptitious diuretic abuse, requires a careful search for hypercorticism even in the absence of clinical Cushing's syndrome.

Tixocortol pivalate, a corticosteroid with no systemic glucocorticoid effect after oral, intrarectal, and intranasal application.

Tixocortol pivalate is a corticosteroid with topical anti-inflammatory activity equal to that of hydrocortisone. It was evaluated in a group of 18 normal subjects to determine whether it exerted any systemic glucocorticoid activity after single oral or intrarectal doses and after short-term dosing by the intranasal route. Effects of tixocortol pivalate were compared to those of oral dexamethasone and intrarectal betamethasone 21-phosphate. By the three routes, tixocortol pivalate does not induce any changes in plasma cortisol, leukocyte counts (neutrophils, lymphocytes, monocytes, eosinophils), blood glucose, or 24-hr urinary excretion of sodium and potassium, whereas there were changes after dexamethasone and betamethasone. Tixocortol pivalate, however, increased urinary free cortisol-like substances. It is concluded that tixocortol pivalate given for short periods by nonparenteral routes does not induce a measurable systemic glucocorticoid effect.

Early experience with laparoscopic approach for adrenalectomy.

BACKGROUND: Adrenalectomy performed by a posterior or transabdominal approach causes substantial postoperative pain. The purpose of this study was to evaluate laparoscopy as a potential approach for adrenalectomy. METHODS: We performed 25 consecutive laparoscopic adrenalectomies on 22 patients from April 1, 1992, to March 30, 1993. Laparoscopic surgery was performed by using a lateral decubitus flank approach with four 11 mm trocars. RESULTS: Twelve right and 13 left adrenal glands were removed in a mean time of 2.3 hours. Three patients underwent bilateral adrenalectomies in a mean time of 5.3 hours. The 15 women and 7 men range in age from 31 to 60 years (mean, 42 years). The adrenal gland diseases were nonfunctional adenoma (seven), pheochromocytoma (five), Cushing's disease (four), Cushing's adenoma (four), primary aldosteronism (two), dehydroepiandrostenedione sulfate hypersecretion (one), angiomyolipoma (one), and medullary cyst (one). Average tumor size was 4.1 cm (range, 1 to 15 cm). Laparoscopic adrenalectomy was successful in 96% of patients, with one patient requiring a laparotomy because of inadequate exposure. The median postoperative stay was 4 days (range, 2 to 19), with a mean of five narcotic injections. There were no deaths, and morbidity was minor. CONCLUSIONS: Laparoscopy can be used successfully for adrenalectomy. It produces less postoperative pain and rapid return to normal activity. It may be the preferred method for removing most adrenal gland lesions that require operation.

Short-term benefit from oral vancomycin treatment of regressive-onset autism.

In most cases symptoms of autism begin in early infancy. However, a subset of children appears to develop normally until a clear deterioration is observed. Many parents of children with "regressive"-onset autism have noted antecedent antibiotic exposure followed by chronic diarrhea. We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology. To help test this hypothesis, 11 children with regressive-onset autism were recruited for an intervention trial using a minimally absorbed oral antibiotic. Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features. Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at follow-up. Although the protocol used is not suggested as useful therapy, these results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with autism.

Autism and Clostridium tetani.

Autism is a severe developmental disability believed to have multiple etiologies. This paper outlines the possibility of a subacute, chronic tetanus infection of the intestinal tract as the underlying cause for symptoms of autism observed in some individuals. A significant percentage of individuals with autism have a history of extensive antibiotic use. Oral antibiotics significantly disrupt protective intestinal microbiota, creating a favorable environment for colonization by opportunistic pathogens. Clostridium tetani is an ubiquitous anaerobic bacillus that produces a potent neurotoxin. Intestinal colonization by C. tetani, and subsequent neurotoxin release, have been demonstrated in laboratory animals which were fed vegetative cells. The vagus nerve is capable of transporting tetanus neurotoxin (TeNT) and provides a route of ascent from the intestinal tract to the CNS. This route bypasses TeNT's normal preferential binding sites in the spinal cord, and therefore the symptoms of a typical tetanus infection are not evident. Once in the brain, TeNT disrupts the release of neurotransmitters by the proteolytic cleavage of synaptobrevin, a synaptic vesicle membrane protein. This inhibition of neurotransmitter release would explain a wide variety of behavioral deficits apparent in autism. Lab animals injected in the brain with TeNT have exhibited many of these behaviors. Some children with autism have also shown a significant reduction in stereotyped behaviors when treated with antimicrobials effective against intestinal clostridia. When viewed as sequelae to a subacute, chronic tetanus infection, many of the puzzling abnormalities of autism have a logical basis. A review of atypical tetanus cases, and strategies to test the validity of this paper's hypothesis, are included.

Cimetidine and glucose tolerance (oral and intravenous).

In the intravenous glucose tolerance test (seven subjects) plasma glucose was not modified, but the insulin levels were lower 2 min after cimetidine was given. Cimetidine modified the oral glucose tolerance test in 13 subjects by increasing the glucose values after 60 min. Insulin levels at that time were also significantly higher. These findings support the hypothesis that cimetidine, an H2 antagonist, could alter glucose handling through its effect on histaminic fibers of the islets of Langerhans.

Suprasellar disturbance in the syndrome of fertile eunuchoidism: case report.

A case of fertile eunuchoidism is presented. The diagnosis was established on the basis of low androgen secretion in the presence of active spermatogenesis, increase in testosterone output after gonadotrophin stimulation, and adequate peripheral response to exogenous testosterone. Resistance to clomiphene stimulation but normal pituitary response to LH-RH was elicited indicating a suprasellar disturbance as the cause of the disorder.

Laparoscopic adrenalectomy. The importance of a flank approach in the lateral decubitus position.

Adrenalectomy is usually performed via transabdominal or posterior approaches. Unfortunately, both approaches are associated with painful postoperative syndromes. Recently, laparoscopic surgery was applied to organ removal. During a period of 12 months, we performed a series of successful laparoscopic adrenalectomies (10 of the right and 11 of the left gland). The pathologies were medullary cyst (1), angiomyolipoma (1), DHEAS hyperplasia (1), primary aldosteronism (2), Cushing's adenoma (3), pheochromocytoma (4), Cushing's syndrome (4), and nonfunctional adenoma (5). A flank approach was taken with four 11-mm trocars. Electrocautery and blunt forceps were used for dissection. The vessels were secured with medium-large titanium clips, and the adrenal was removed in a sterile plastic bag. The average operating time was 2.3 h, and median postoperative stay was 4 days. Two patients required blood transfusion of 2 units postoperatively. We believe this technique is adequate for the surgical removal of adrenal tissue, resulting in less postoperative pain and in rapid recovery. It may also change the surgical management of asymptomatic adrenal lesions.

Carpenter's syndrome with empty sella and abnormal LRH and TRH response.

Two sisters with Carpenter's syndrome and empty sella have been evaluated for pituitary function. The TRH injection brought a normal response of TSH and prolactin. There were no change in FSH and LH, but a paradoxical increase of growth hormone and cortisol. The injection of LRH brought a normal response of FSH and LH, no change in TSH and cortisol values and a paradoxical increase in prolactin and growth hormone.

Fenfluramine in the treatment of non-insulin-dependent diabetics: hypoglycemic versus anorectic effect.

A few studies have suggested that the anorectic drug fenfluramine has a hypoglycemic effect. The major problem in interpreting those studies, however, is the difficulty in dissociating the effect of weight loss on blood glucose from the direct effect of fenfluramine. In a double-blind study of 28 diabetic females treated with oral hypoglycemic agents, a significant decrease in fasting blood glucose (from 195 +/- 17 mg/dl to 152 +/- 15 mg/dl after four weeks, and to 155 +/- 14 mg/dl after eight weeks) was observed in fenfluramine-treated patients (n = 14). Corresponding values in the placebo group were 185 +/- 12 mg/dl and 201 +/- 16 mg/dl respectively. Glucose tolerance after a standard meal was also improved after fenfluramine treatment. Weight loss was minimal and not significantly different for the two groups. From these observations, it can be concluded that fenfluramine has a lowering effect on blood glucose which is independent of its effect on weight.

Cushing syndrome with food-dependent periodic hormonogenesis.

Periodic hormonogenesis has been described in patients with ACTH-dependent hypercorticism, and fluctuations of cortisol secretion have also been observed in patients with adrenal tumors. In this report, we studied a 41-year-old white male who presented with hypertension, central obesity, and muscle weakness of 2-years duration. His plasma cortisol was low (4.5 micrograms) in the morning and high in the evening (29.3 micrograms). Urinary free cortisol was 750 micrograms/day. A 24-hour cycle demonstrated highest values at noon and in late afternoon. This pattern was not suppressed by dexamethasone. When the patient was kept fasting, plasma cortisol remained low all day, and became elevated immediately after meal administration overnight. A left-sided adrenal mass was demonstrated and removed. In vitro, the adenylate cyclase activity of tumor tissue demonstrated more significant response to vasopressin than to ACTH; other tested peptides were inactive. We propose that a humoral factor induced by eating was responsible for the periodic hormonogenesis, directly stimulating the adrenal secretion of cortisol.

Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing's syndrome.

BACKGROUND: Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known. METHODS: We studied a 48-year-old woman with Cushing's syndrome, nodular adrenal hyperplasia, and undetectable plasma corticotropin concentrations in whom food stimulated cortisol secretion. RESULTS: Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone. The cortisol concentrations increased in response to oral glucose (4-fold increase) and a lipid-rich meal (4.8-fold increase) or a protein-rich meal (2.6-fold increase), but not intravenous glucose. The infusion of somatostatin blunted the plasma cortisol response to oral glucose. Intravenous infusion of gastric inhibitory polypeptide (GIP) for one hour increased the plasma cortisol concentration in the patient but not in four normal subjects. Fasting plasma GIP concentrations in the patient were similar to those in the normal subjects; feeding the patient test meals induced increases in plasma GIP concentrations that paralleled those in plasma cortisol concentrations. Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin. In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producting or aldosterone-producing adenomas responded to corticotropin but not to GIP. CONCLUSIONS: Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder.