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Biomedical subjects

J W Findling

Publications and source records attributed to J W Findling.

At least 55 records · Page 3Linked to original sources
PubMed1988

Fast cortisol-induced inhibition of the adrenocorticotropin response to surgery in humans.

Glucocorticoid negative feedback is exerted in at least two time domains: fast feedback (within minutes of the feedback signal) and delayed feedback (within hours of the feedback signal). Although delayed feedback is known to inhibit ACTH responses to a variety of stimuli in humans, whether there is fast feedback inhibition of the ACTH responses to such stimuli is not known. The purpose of this study was to evaluate the efficacy of a pharmacological injection of cortisol sodium succinate (CORT) as a rapid inhibitor of the ACTH response to surgery in patients undergoing thoracotomy for myocardial revascularization. Thirty patients were premedicated with diazepam and induced with thiopental sodium. They were assigned to one of four groups: group I, general anesthesia was maintained with enflurane (n = 8); group II, patients were anesthetized as in group I, but received a bolus injection of 500 mg CORT within 5 s of the start of surgery (n = 7); group III, anesthesia was maintained with 50-100 mg fentanyl (FENT; n = 8); and group IV, patients were anesthetized as in group III and given CORT as in group II (n = 7). Surgery induced a large increase in plasma ACTH in group I (no CORT, no FENT); the mean plasma ACTH level was 57 +/- 14 (+/- SE) pmol/L 10 min after the start of surgery, and it peaked at 92 +/- 18 pmol/L 50 min after the start of surgery. Administration of CORT at time zero (group II) resulted in a significant but attenuated ACTH response to surgery both 10 min (36.5 +/- 9.7 pmol/L) and 50 min (42.5 +/- 7.3 pmol/L) after the start of surgery. FENT per se (group III) significantly attenuated the ACTH response to surgery (e.g. plasma ACTH was 13 +/- 5 pmol/L 10 min and 21 +/- 7 pmol/L 50 min after the start of surgery). The combination of CORT and FENT (group IV) eliminated the ACTH response to surgery at all time points. In fact, plasma ACTH levels became undetectable (less than 4.4 pmol/L) from 30-50 min after the start of surgery. We conclude that a pharmacological dose of CORT administered at the time of stimulus introduction significantly attenuated the ACTH response to the stimulus (surgery). FENT not only inhibited the ACTH response to surgery per se, but amplified the effect of CORT, such that ACTH actually declined even during a large surgical stimulus. CORT clearly attenuates the ACTH response to surgery in humans in the fast feedback time domain.

Adrenocorticotropic Hormone↗
PubMed1987

The dissociation of renin and aldosterone during critical illness.

A syndrome of elevated PRA accompanied by inappropriately low plasma aldosterone (ALDO) levels has been identified in some critically ill patients. To determine whether this phenomenon is due to a disturbance in factors that stimulate ALDO, we measured PRA, angiotensin II (AII), potassium (K+), and ACTH levels in 83 patients admitted to an intensive care unit. In 59 patients, PRA was greater than 2.0 ng/ml X h. Of these, 24 had an ALDO to PRA ratio (ALDO/PRA) below 2 (group I), and 35 had an ALDO/PRA ratio of 2 or more (group II). An ALDO/PRA ratio below 2 was deemed inappropriately low. Despite markedly elevated PRA [34 +/- 12 (+/- SE) ng/ml X h], the group I patients had inappropriately low ALDO levels (19 +/- 5 ng/dL). Patients in group II had significantly higher ALDO levels (48 +/- 6 ng/dL) despite lower PRA (9 +/- 1 ng/ml X h). AII levels were appropriately elevated in group I (39 +/- 26 pg/mL) and significantly greater (P less than 0.5) than those in group II. PRA correlated well with AII in both groups. There were no differences in plasma ACTH or K+ in these 2 groups, and plasma cortisol levels were similarly elevated in both groups of patients. Of 66 consecutively studied patients, 14 (21%) had inappropriate ALDO (group I). Mortality was significantly greater in group I (75%) than in group II (46%; P less than 0.001). In summary, a significant subset (21%) of seriously ill patients have inappropriately low ALDO levels despite elevated PRA. This dissociation is not due to an impairment of AII production or changes in plasma ACTH or K+. This phenomenon is associated with a higher mortality during critical illness. In light of evidence of decreased adrenal androgen secretion during severe illness, this dissociation of renin and aldosterone may represent an additional adrenal adaptation designed to promote cortisol production in critically ill patients.

Adrenocorticotropic Hormone↗
PubMed1987

Inhibition of the adrenocorticotropin response to surgery in humans: interaction between dexamethasone and fentanyl.

We examined the plasma ACTH and cortisol responses to surgery in 25 patients with atherosclerotic heart disease undergoing myocardial revascularization. The patients were all premedicated with diazepam, and general anesthesia was induced with thiopental. They were randomly assigned to one of four groups: I) no dexamethasone (DEX), enflurane anesthesia, II) 40 mg DEX, iv, 45-60 min before sternotomy, enflurane anesthesia, III) no DEX, fentanyl [N-(1-phenethyl-4-piperidyl)propionanilide] anesthesia (50-100 micrograms/kg), and IV) DEX, fentanyl anesthesia. Isokalemic hemodilution of significant magnitude occurred during cardiopulmonary bypass. All groups had significant increases in plasma ACTH during surgery, which returned to control levels 22 h after the bypass. Group I (no DEX, no fentanyl) and group III (no DEX, fentanyl) patients had large similar increases in plasma ACTH, which peaked 2-4 h postbypass [400 +/- 83 (+/- SEM) pg/mL; 88 +/- 18 pmol/L]. The group II (DEX, no fentanyl) patients also had large increases in ACTH which were similar to those in groups I and III, except 2-4 h postbypass (183 +/- 91 pg/mL; 40 +/- 20 pmol/L). The group IV (DEX, fentanyl) patients had a significantly attenuated ACTH response to surgery; the mean plasma ACTH level 2-4 h postbypass was only 54 +/- 21 pg/mL (12 +/- 5 pmol/L). Therefore, although DEX or fentanyl alone had a minimal effect on the ACTH response to surgery, a significant attenuation occurred when DEX and fentanyl were used in combination. We conclude that glucocorticoids and morphine agonists exert interactive inhibitory effects on ACTH release in humans, probably by virtue of their suppression of CRH release from the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1987

Cushing's disease.

Cushing's disease is a form of Cushing's syndrome, persistent inappropriate hypercortisolism, that results from pituitary ACTH hypersecretion. It currently accounts for 70 per cent of adult cases of Cushing's syndrome and affects mainly women of childbearing age. The pathology, cause, and clinical and laboratory features of the disease are discussed. The initial step in diagnosis is documentation of endogenous hypercortisolism, which is followed by identification of the cause. Selective transsphenoidal resection of ACTH-producing pituitary adenomas is the initial treatment of choice. The roles of radiotherapy and medical therapy are discussed.

Adrenalectomy↗
PubMed1986

An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing's syndrome.

We have developed a high-dose dexamethasone suppression test that can be administered overnight with a single 8-mg dose and used the new procedure in the differential diagnosis of 83 patients with Cushing's syndrome. In 76 patients with surgically or pathologically proven cause--60 with Cushing's disease, 7 with the ectopic adrenocorticotrophic hormone syndrome, and 9 with adrenal tumors--suppression of plasma cortisol levels to less than 50% of baseline indicated a diagnosis of Cushing's disease. The test had a sensitivity of 92%, a specificity of 100%, and a diagnostic accuracy of 93%. These values equal or exceed those of the standard 2-day test whether based on suppression of urinary 17-hydroxycorticosteroids or plasma cortisol. We conclude that this overnight, high-dose dexamethasone suppression test is practical and reliable in the differential diagnosis of Cushing's syndrome.

17-Hydroxycorticosteroids↗
PubMed1986

Occult ectopic secretion of corticotropin.

The clinical, biochemical, radiographic, and morphologic features of ectopic corticotropin (ACTH)-dependent Cushing's syndrome are often indistinguishable from those of Cushing's disease (pituitary-dependent Cushing's syndrome). We encountered ten patients whose ectopic ACTH-secreting neoplasms were not clinically apparent for two months to 12 years after the diagnosis of hypercortisolism or in whom the site remains unknown. Five of these patients underwent unnecessary pituitary microsurgery, and a sixth was referred for surgery. The occult ectopic ACTH syndrome occurs with equal frequency in men and women and hypokalemia is present in 60%, in contrast to the female predominance and rarity of hypokalemia in Cushing's disease. We emphasize the importance of selective venous sampling for ACTH to establish the correct diagnosis. Thirty-nine similar cases from the literature help characterize this syndrome further.

ACTH Syndrome, Ectopic↗
PubMed1983

Cushing's disease in a patient with a 'nonfunctioning' pituitary tumor. Spontaneous development and remission.

A 40-year-old woman had visual loss and a large nonfunctioning pituitary tumor. After partial surgical resection and radiation treatment, clinical and biochemical evidence of Cushing's disease developed. The pituitary source of her adrenocorticotropic hormone hypersecretion was documented on selective venous sampling. After 18 months of medical therapy with metyrapone and aminoglutethimide, the patient experienced a spontaneous remission of her hypercortisolism. A "nonfunctioning" pituitary tumor has a hypersecretory potential.

Adenoma, Chromophobe↗
PubMed1982

Cushing's syndrome: problems in management.

CS comprises a group of disorders characterized by hypercortisolism. The variety of causes--pituitary-dependent CS (CD), adrenal tumor, and the ectopic ACTH syndrome--necessitates a variety of therapies--surgical, radiotherapeutic, and medical. Once a specific diagnosis is made, specific therapy can be instituted. Although some controversy persists regarding treatment, particularly that of CD, for most patients it is straightforward. However, in our experience with more than 60 patients, therapeutic dilemmas can arise in a number of circumstances, e.g. the patient with the radiologically normal sella or recurrent CD after adrenalectomy. In addition, the treatment of such conditions as the large ACTH-producing pituitary tumor, Nelson's syndrome, the malignant ectopic ACTH syndrome, and adrenal carcinoma is not entirely satisfactory. Our approach to these problems is illustrated by seven cases, and we emphasize that the proper management of CS requires both correct diagnosis and the logical application of all available therapies.

ACTH Syndrome, Ectopic↗
PubMed1982

Vitamin D metabolites and parathyroid hormone in Cushing's syndrome: relationship to calcium and phosphorus homeostasis.

We studied the effects of glucocorticoid excess on calcium and phosphorus homeostasis in relation to vitamin D metabolites and parathyroid hormone (PTH) in seven patients with spontaneous ACTH-dependent Cushing's syndrome. Remission of hypercortisolism resulted in a significant increase in tubular reabsorption of phosphate [from 76 +/- 4% to 89 +/- 2% (mean +/- SEM); P less than 0.01] and serum phosphorus (from 3.1 +/- 0.1 to 4.2 +/- 0.2 mg/dl; P less than 0.005). Serum calcium did not change, although there was a reduction in daily urinary calcium excretion from 0.23 +/- 0.02 to 0.107 +/- 0.02 mg calcium/mg creatinine. Serum immunoreactive PTH (iPTH) levels were normal during Cushing's syndrome (34 +/- 5 microleq/ml), but fell significantly after remission to 22 +/- 2 microleq/ml (P less than 0.05). This small decrease in iPTH did not correlate with the improvement of phosphate homeostasis. Plasma 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH2)D] concentrations in Cushing's syndrome did not differ from measurements in 97 normal subjects. After treatment, 25OHD did not change, but 1,25-(OH)2D fell in each patient from a mean of 44 to 22 pg/ml (P less than 0.02). 1,25-(OH)2D was inversely correlated with serum phosphorus (r = 0.59; P less than 0.01), but did not correlate with iPTH. The known impairment of intestinal calcium absorption in Cushing's syndrome cannot be attributed to a decrease in the circulating levels of 1,25-(OH)2D. Endogenous hypercortisolism decreases tubular phosphate reabsorption and serum phosphorus, increase tubular phosphate reabsorption and serum phosphorus, increases iPTH, and results in an increase in 1,25-(OH)2D. These events may contribute to the severe loss of bone mass in such patients and may account for the calciuria and phosphaturia of Cushing's syndrome.

25-Hydroxyvitamin D 2↗
PubMed1981

Pituitary ACTH dependency of nodular adrenal hyperplasia in Cushing's syndrome. Report of two cases and review of the literature.

Cushing's syndrome due to nodular adrenal hyperplasia comprises a clinically and biochemically heterogeneous group of disorders whose pathogenesis is unclear. We describe two patients with atypical steroid dynamics and large unilateral adrenal nodules who had pituitary ACTH-dependent disease. In the differential diagnosis of Cushing's syndrome, we recommend repeated ACTH measurement and selective venous sampling-particularly in those patients with impaired dexamethasone suppressibility and abnormal findings on computerized tomography.

Adrenal Gland Neoplasms↗
PubMed1981

Cushing's syndrome: problems in diagnosis.

Cushing's syndrome, an unusual group of disorders characterized by hypercortisolism, must be considered in the differential diagnosis of such common clinical problems as hirsutism, menstrual irregularity, hypertension, diabetes mellitus, and obesity. Its distinct forms--pituitary-dependent Cushing's syndrome (Cushing's disease), adrenal tumor and ectopic ACTH syndrome--must be identified correctly so that specific therapy can be administered. In the majority of cases, use of a relatively simple diagnostic sequence will provide accurate and rapid diagnosis. However, in our experience with more than 60 patients, diagnostic difficulties may arise from a variety of conditions (e.g., drug interference, alcohol ingestion, and depression). In addition, unusual circumstances, such as unexpected responses to dexamethasone, may complicate the diagnosis. Our approach to these problems is illustrated through a report of seven cases, and we emphasize that the proper management of Cushing's syndrome mandates a thorough marshalling of all the available data.

ACTH Syndrome, Ectopic↗
PubMed1981

Silent pituitary apoplexy: subclinical infarction of an adrenocorticotropin-producing pituitary adenoma.

A young woman developed intermittent headaches and progressive hyperpigmentation after bilateral adrenalectomy for Cushing's disease. Results of sellar polytomography were abnormal. Her plasma ACTH levels increased to 4750-7340 pg/ml and did not rise with insulin-induced hypoglycemia. Although she experienced no clinical features associated with spontaneous infarction of a pituitary tumor, plasma ACTH levels fell to 474-575 pg/ml, and hemorrhagic necrosis was found in a 5-mm chromophobe adenoma at transsphenoidal surgery. Postoperatively, ACTH levels returned to normal (51-88 pg/ml), with the rest of her anterior pituitary function remaining intact 4 yr later. Spontaneous infarction of pituitary microadenomas may be subclinical, resulting in improvement of pituitary hormone hypersecretion without impairment of other anterior pituitary hormone secretion.

Adenoma, Chromophobe↗
PubMed1981

Selective venous sampling for ACTH in Cushing's syndrome: differentiation between Cushing disease and the ectopic ACTH syndrome.

We performed selective venous catheterization and sampling for ACTH in six patients with ACTH-secreting pituitary adenomas (Cushing's disease) and four patients with occult ectopic ACTH-secreting neoplasms. In five patients with Cushing's disease in whom the inferior petrosal sinus could be catheterized, ACTH levels were unequivocally higher than simultaneous peripheral values: The ratio was greater than 2.0, with a range of 2.2 to 16.7. In contrast, the inferior petrosal sinus-to-peripheral ACTH ratio in three patients with ectopic ACTH secretion was less than 1.5. In the fourth patient, an arteriovenous gradient of 6.8 was shown 2 years before a bronchial carcinoid tumor was clinically apparent. Central-to-peripheral ACTH ratios at the level of the jugular bulb and jugular vein were not diagnostic. We conclude that selective venous ACTH sampling from the inferior petrosal sinus is a reliable and useful aid in the differential diagnosis of Cushing's syndrome when standard clinical and biochemical studies are inconclusive.

ACTH Syndrome, Ectopic↗