Rapid measurement of corticotropin (ACTH) with a modified immunochemiluminescent assay.
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Biomedical subjects
Publications and source records attributed to J W Findling.
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We describe an elderly man who presented with hypercalcemia associated with suppressed intact parathyroid hormone (PTH) levels. Despite renal insufficiency the circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) was in the upper part of the normal range. Known causes of hypercalcemia were absent and mild hypercalcemia with suppression of intact PTH persisted until after bilateral hip replacement for severe arthritis (1 year after presentation). After hip replacement the ionized calcium normalized, intact PTH normalized, and 1,25(OH)2D decreased markedly. We believe the abnormalities in mineral homeostasis were related to production of 1,25(OH)2D by inflammatory mononuclear cells associated with arthritis.
Fine needle aspiration (FNA) biopsy in thyroid diagnosis has significantly reduced the need for diagnostic thyroidectomy. The relative proportion of therapeutic thyroid surgery is therefore increasing and, since a significant number of therapeutic procedures are indicated to alleviate tracheoesophageal complications, surgeons are likely to be confronted with an increasing percentage of potentially challenging cases in the face of declining thyroidectomy caseloads. All thyroidectomies done at the authors' institution from 1987 through 1990 were studied in order to assess the potential impact of FNA on thyroid surgery and to specifically analyze the management of those cases accompanied by tracheoesophageal complications. It is concluded that 18% of the 87 thyroidectomies in this series could possibly have been avoided had FNA been obtained routinely. The clinical manifestations and surgical management of those cases associated with tracheoesophageal complications are presented. General therapeutic strategies for such cases are also summarized.
Gastric exclusion has been introduced as a surgical treatment for morbid obesity. We describe two women who had undergone gastric bypass for obesity with metabolic bone disease and secondary hyperparathyroidism. In one patient transiliac bone biopsy after double tetracycline labelling demonstrated histologic evidence of hyperparathyroidism with osteitis fibrosa cystica. Six additional women who had undergone gastric exclusion were evaluated. Serum phosphorus, calcium, and creatinine were normal in all but one patient who had hypocalcemia. Serum immunoreactive parathyroid hormone was elevated in seven of eight patients and urinary calcium was less than or equal to 2 mmol/d (80 mg/24 h) in 6 patients. Lumbar spine bone mineral density was 86 +/- 7 (mean +/- SE) per cent of predicted and femoral neck bone mineral density was 89 +/- 6 per cent of predicted. Women who have had gastric exclusion for obesity may develop secondary hyperparathyroidism which could result in loss of bone mass.
The clinical, biochemical, and radiographic features of ectopic ACTH-dependent Cushing's syndrome are often indistinguishable from those of pituitary ACTH-dependent hypercortisolism (Cushing's disease). We prospectively evaluated 29 patients with ACTH-dependent hypercortisolism by means of bilateral inferior petrosal sinus ACTH sampling with ovine CRH (oCRH) stimulation. Patients with Cushing's disease (n = 20), had a maximal basal inferior petrosal sinus to peripheral ACTH ratio (IPS:P-ACTH) of 11.7 +/- 4.4 (+/- SE) from the dominant IPS, which increased to 50.8 +/- 18.3 after oCRH administration. Bilateral IPS sampling was necessary to correctly identify patients with Cushing's disease, since the maximal basal nondominant IPS:P-ACTH was less than 2.0 in over 50% of the patients and remained less than 2.0 after oCRH administration in one third. In contrast, patients with occult ectopic ACTH-secreting neoplasms (n = 9) had maximal basal IPS:P-ACTH of 1.2 +/- 0.1 that did not change after oCRH administration. Occult ectopic ACTH-secreting neoplasms were found in 7 of 9 patients from 0.4-14 yr after the recognition of Cushing's syndrome, and 4 of these patients had intermittent hypercortisolism with prolonged periods of remission. Selective endobronchial lavage for ACTH correctly localized a radiologically occult ACTH-secreting bronchial carcinoid in 1 patient, and magnetic resonance imaging identified a similar neoplasm in a patient with a normal chest computed tomographic scan. Basal ACTH and urinary free cortisol excretion were significantly higher in patients with ectopic ACTH than in those with Cushing's disease, but overlap existed between groups. High dose dexamethasone suppression testing inaccurately classified 24% of patients, and radiological imaging of the pituitary and adrenal glands was misleading. The occult ectopic ACTH syndrome is a common form of ACTH-dependent hypercortisolism that cannot be distinguished from Cushing's disease with routine clinical studies. The accurate differential diagnosis of ACTH-dependent Cushing's syndrome requires bilateral inferior petrosal sinus ACTH sampling with oCRH stimulation.
Adrenocorticotrophic hormone (ACTH)-producing bronchial carcinoid tumors tend to occur in the middle third of the lung adjacent to pulmonary vessels. Because they cause signs and symptoms when quite small (by virtue of their ACTH production), they may not be detected by CT. MR imaging was performed in 10 consecutive patients with surgically proved ACTH-producing bronchial carcinoid tumors in order to test the ability of MR to clarify equivocal or indeterminate findings on CT examinations. All bronchial carcinoid tumors had high signal intensity on T2-weighted and short-inversion-time inversion-recovery images, facilitating their distinction from pulmonary vasculature. In eight patients, the CT and MR images were equivalent in the detection of bronchial carcinoid tumors. In two patients, MR showed tumors in the middle third of the lung that were equivocal on CT. MR imaging may distinguish small bronchial carcinoid tumors from adjacent pulmonary vessels in the central third of the lung at a time when the CT study is nondiagnostic or equivocal.
Acute mitral obstruction may lead to an increase in atrial natriuretic peptide (ANP) due to increased atrial pressure and a large increase in arginine vasopressin (AVP) due to simultaneous arterial and ventricular baroreceptor unloading. We measured ANP and AVP concentration after transseptal puncture and during percutaneous retrograde mitral balloon valvuloplasty (PRMV) in 11 patients (mean age 57 +/- 12 years; nine women) with mitral stenosis and congestive heart failure. Atrial septal puncture per se resulted in a significant increase in ANP and AVP without a significant change in aortic pressure. Subsequent PRMV led to a further increase in ANP, a transient decrease in aortic pressure from 89 +/- 7 to 45 +/- 4 mm Hg, and a large (fivefold) increase in AVP. ANP and AVP were no longer different from baseline values 18 to 24 after the procedure. This study suggests that transseptal puncture and acute mitral obstruction are major stimuli to ANP release and that combined unloading of arterial and left ventricular mechanoreceptors is a very potent vasopressinergic stimulus.
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A subset of critically ill patients has been described with low plasma aldosterone (Aldo) despite elevated plasma renin activity (PRA). In order to investigate possible mechanisms for these findings, the present study evaluated the Aldo response to exogenous ACTH or metoclopramide (MCP) in normal subjects and in patients admitted to the medical ICU. In addition, measurements of clinical status (Acute Physiology and Chronic Health Evaluation [APACHE II]) and atrial natriuretic peptide (ANP) were correlated with adrenal status. Critically ill patients were subdivided into normal (greater than 2) and subnormal (less than 2) Aldo-to-PRA ratio (Aldo/PRA). Patients with basal Aldo less than 70 ng/dl exhibited subnormal Aldo responses to ACTH, regardless of basal Aldo/PRA. However, normal responses to MCP were noted regardless of basal Aldo/PRA. No correlation between Aldo/PRA and APACHE II score or ANP levels was found. We conclude that critically ill patients with dissociated Aldo and renin can generate a normal Aldo response to MCP. This suggests that this syndrome is due to functional and potentially reversible dysfunction of the zona glomerulosa of the adrenal cortex.
We report a postmenopausal woman with primary hyperparathyroidism (PHPT) and severe hypercalcemia while her total calcium intake was more than 2 g daily. Despite a markedly elevated intact PTH level, her serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] level was low (17 pmol/L; 7 pg/mL). With reduced calcium intake, her serum calcium normalized, and 1,25-(OH)2D increased to 122 pmol/L (51 pg/mL). At the same time, intact PTH decreased to 32% of the initial value. PHPT may be associated with low circulating 1,25-(OH)2D levels. Furthermore, low 1,25-(OH)2D levels in PHPT may be due to a direct effect of severe hypercalcemia and be reversible with correction of hypercalcemia.
Clinically significant hypoglycemia is an unusual complication of anorexia nervosa. We describe a 44-year-old woman with a 5-year history of anorexia nervosa who presented with hypoglycemic coma and eventually experienced sudden death. Biochemical studies showed suppressed levels of insulin, C peptide, and proinsulin during hypoglycemia; appropriate elevations of growth hormone and cortisol levels were observed, suggesting that the hypoglycemia was related to severe malnutrition. Nine previously reported cases of severe hypoglycemia in anorexia nervosa are reviewed (six of the patients involved also died). The presence of severe hypoglycemia in anorexia nervosa implies a grave prognosis and mandates aggressive medical and nutritional therapy to improve the chance of survival.
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The objective of this study was to determine the effects of transient aortic valve occlusion (balloon valvuloplasty) on vasoactive hormones in patients with heart failure. Plasma atrial natriuretic peptide, vasopressin, aldosterone, adrenocorticotropic hormone (ACTH), and plasma renin activity were measured before, immediately after, and 30 minutes and 18 to 24 hours following balloon inflation in 18 patients. Mean right atrial and pulmonary wedge pressures were 6 and 18 mm Hg before inflations, respectively, and were unchanged after balloon inflations (5 and 13 mm Hg, respectively). Systemic systolic/diastolic pressures were 139 +/- 8/65 +/- 4 mm Hg before occlusion, decreased to 47 +/- 5/34 +/- 3 mm Hg during occlusion, and returned to baseline after occlusions. Baseline atrial natriuretic peptide levels were 267 +/- 43 pg/ml and increased to 513 +/- 71 pg/ml after balloon inflations. Vasopressin levels before occlusion were 9.1 +/- 2.2 pg/ml and increased to 21.4 +/- 4.8 pg/ml after balloon inflations. Plasma renin activity was 5.4 +/- 1.4 ng/ml/hr before inflations and was not significantly changed after balloon inflations. No clinically significant changes in plasma sodium, potassium, creatinine, and osmolality were observed after the procedure. Aldosterone increased from 23 +/- 4 to 40 +/- 7 ng/dl 10 minutes after the last inflation. Plasma ACTH measured in seven patients with increased aldosterone was 28 +/- 8 pg/ml before and increased to 295 +/- 157 pg/ml 10 minutes after balloon inflations. The increases in natriuretic peptide and vasopressin were likely due to elevated intracardiac and decreased arterial pressures, respectively; they persisted in spite of no clinically significant changes in filling pressures 12 to 24 hours after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
A recent report measured a decrease in plasma ACTH concentration by immunoradiometric assay (IRMA) during infusion of ACTH-(1-24) in humans. It was concluded that this decrease in ACTH concentration was due to short loop ACTH autoregulation. The present study demonstrates that the decrease in ACTH concentration measured by IRMA was due to an artifact of the IRMA. We injected 250 micrograms ACTH-(1-24), iv, into five normal male volunteers after overnight 2.5-g metyrapone administration. The ACTH concentration measured by IRMA decreased from 59.6 +/- 9.7 pmol/L before to 4.8 +/- 2.0 pmol/L 1 min after ACTH-(1-24) injection. The ACTH concentration measured by IRMA increased thereafter in a mirror image of the decline in ACTH-(1-24) measured by RIA. Addition of ACTH-(1-24) to plasma in vitro resulted in a decrease in the ACTH concentration measured by IRMA which was of similar magnitude to that observed in vivo. ACTH-(1-24) infusion in vivo or addition to ACTH-(1-39)-containing plasma in vitro decreased ACTH-(1-39) measured by IRMA by binding to N- but not C-terminal antibody without forming a detectable sandwich complex. We conclude that although ACTH short loop feedback may exist, it cannot be detected after ACTH-(1-24) injection with the use of a two-site IRMA.
We evaluated a new, commercially available two-site immunoradiometric assay (IRMA) for corticotropin (ACTH) in human plasma. The precision and detection limit were an improvement over radioimmunoassay (RIA). Addition of ACTH 1-24 or ACTH 18-39 to plasma containing ACTH 1-39 resulted in a decrease in measured ACTH. Results by both IRMA and RIA are reported and compared for normal subjects, patients with Cushing's disease, and patients with ectopic ACTH. Effects of administering dexamethasone, metyrapone, ACTH 1-24, and corticoliberin were evaluated. The present assay is more sensitive, specific, and reproducible than RIA. The presence of fragments of ACTH or "big" ACTH that are reactive in RIA may lead to artifactually low ACTH concentrations by IRMA. Therefore, RIA may still be necessary for differential diagnosis of ectopic ACTH syndromes. However, the IRMA is an improvement for evaluating pituitary--adrenal function in patients with low concentrations of ACTH in plasma.
Fine needle aspiration of the thyroid has achieved increasing acceptance as a valuable diagnostic aid in the evaluation of nodular thyroid disease. It has been suggested, however, that this procedure should be performed only in major medical centers. We report our experience with thyroid needle aspiration in 400 consecutive patients seen in the ambulatory setting of a community hospital. Benign cytology was found in 80% of patients. Surgery was recommended in 51 patients (12.8%) with either suspicious or malignant cytology, and cancer was found in 31 (61%) of these patients. Non-diagnostic aspirates accounted for 7.2% of patients. Thyroid imaging failed to add anything to the diagnostic evaluation. Our results compare favorably to those from university centers and show that thyroid needle aspiration can be performed well in a community hospital setting. We believe that it should be the initial study in patients with nodular goiter.