The rapid low-dose (1 microgram) cosyntropin test in the immediate postoperative period: results in elderly subjects after major abdominal surgery.

BACKGROUND: Recently the rapid low-dose (1 microgram) cosyntropin test has been found to be superior to the standard (250 micrograms) rapid cosyntropin test for evaluating the hypothalamic-pituitary-adrenal axis. Because the 1-microgram test has not been studied in postoperative patients, we evaluated the test after major abdominal surgery. METHODS: We performed rapid 1-microgram cosyntropin tests in 20 patients aged 65 years or older immediately and 24 hours after uncomplicated elective abdominal surgery (group A) and in 10 patients who were suspected of having adrenal insufficiency after abdominal surgery (group B). Subsequently, 250 micrograms of cosyntropin was infused over 8 hours on 2 successive days in group B patients. RESULTS: Ninety-five percent of group A patients had normal rapid 1-microgram cosyntropin test results immediately after surgery and 90% had normal test results 24 hours postoperatively. Six group B patients had abnormal rapid 1-microgram cosyntropin test results. Additional testing indicated primary adrenal insufficiency in 2 patients and central adrenal insufficiency in 1 patient; another patient probably had primary adrenal insufficiency and 2 patients appeared to be euadrenal. Four group B patients had normal rapid 1-microgram cosyntropin test results. After additional testing, 3 of these patients appeared to have normal adrenal function; 1 probably had primary adrenal insufficiency. CONCLUSION: The rapid 1-microgram cosyntropin test accurately evaluated adrenal gland function in selected patients after uncomplicated surgery. The test, however, was difficult to interpret in unselected seriously ill postoperative patients. Therefore we recommend that postoperative patients with unexplained hypotension or other features suggestive of adrenal insufficiency who have random plasma cortisol levels less than 20 micrograms/dL be treated with glucocorticoids and the hypothalamic-pituitary-adrenal axis be studied by standard tests after recovery.

Serum parathyroid hormone-related protein levels during lactation.

We measured parathyroid hormone-related protein (PTHrP) in the serum of 15 healthy women within three days of beginning breast-feeding and within one hour of completing nursing. A sensitive immunoradiometric assay that measures N-terminal PTHrP containing at least the first 74 amino acids was used. We found normal PTHrP values in all patients. Values one day before and two days after delivery in a hypoparathyroid woman who chose not to breast-feed were also normal. Since N-terminal PTHrP fragments of 1-36 amino acids or more are biologically active, we believe additional studies using sensitive PTHrP assays that measure smaller fragments and investigations performed under other conditions of breast-feeding are necessary before concluding that PTHrP does not have a role in calcium homeostasis in nursing mothers. Furthermore, additional studies in hypoparathyroid nursing mothers should be performed.

Postoperative acute adrenal failure caused by transient corticotropin deficiency.

BACKGROUND: Acute adrenal insufficiency after a surgical procedure or trauma is rarely reported. In recent years, however, we have treated seven patients with acute primary adrenal insufficiency and three patients with secondary adrenal insufficiency who presented with shock after a surgical procedure or trauma. The standard cosyntropin test was misleading for the diagnosis of corticotropin deficiency. METHODS: In this study we measured serum cortisol in patients older than 65 years who had unexplained hypotension after an abdominal surgical procedure. If the serum cortisol was less than 15 micrograms/dl, we performed 1 microgram and standard (250 micrograms) cosyntropin tests and measured thyroxine, thyrotropin, leutinizing hormone in all patients, and free testosterone in men. RESULTS: We identified five (5%) of 105 patients after an operation who displayed evidence of corticotropin deficiency (i.e., serum cortisol < 15 micrograms/dl during hypotension, prompt hemodynamic improvement with glucocorticoid therapy, and normal response to standard dose cosyntropin). In these patients 1 microgram cosyntropin produced abnormal peak cortisol levels. These patients also had thyrotropin or leutinizing hormone deficiency. After recovery the low hormone levels improved or became normal. CONCLUSIONS: Postoperative adrenal insufficiency, particularly that caused by transient corticotropin deficiency, is more common in patients than currently recognized. The 1 microgram cosyntropin test may be more sensitive than the standard test for identifying secondary adrenal insufficiency.

Subclinical hormone secretion by incidentally discovered adrenal masses.

OBJECTIVE: To determine the frequency of subclinical hormone secretion in incidentally discovered adrenal masses. DESIGN: We reviewed the radiologic reports of 1779 consecutive computed tomographic scans of the chest, abdomen, and pelvis. SETTING: Regional referral medical center. PATIENTS: Eighty-nine patients with abnormalities of one or both adrenal glands were identified. Patients with nonadrenal gland malignant neoplasms, primary aldosteronism, adrenal hemorrhage, and death or severe illness were not investigated. The final study group consisted of 26 patients with incidentally discovered adrenal masses. MAIN OUTCOME MEASURES: Aldosterone secretion was assessed by measuring plasma renin activity and the plasma aldosterone concentration in patients with unexplained hypokalemia. We evaluated cortisol secretion by performing a 1-mg overnight dexamethasone suppression test and by measuring the corticotropin concentration at 8 AM by a sensitive method. In patients with low corticotropin values, we also measured the 24-hour urinary excretion of free cortisol and 17-ketosteroids and assessed diurnal variation by measuring plasma cortisol concentrations at 8 AM and 4 PM. Adrenal medullary function was studied by measuring urinary free catecholamines. RESULTS: One patient had unrecognized primary aldosteronism, two patients had elevated free catecholamine excretion, and three patients (12%) had subclinical Cushing's syndrome. CONCLUSION: Based on our observations and a review of the literature, we conclude that subclinical hormone secretion, especially cortisol secretion, is more common in patients with incidentally discovered adrenal masses than previously appreciated. Surgeons and anesthesiologists must be alert to the possibility that adrenal insufficiency or a hypertensive crisis may develop in the perioperative period in patients with incidentally discovered adrenal masses.

Reduced calcitriol requirements for treating hypoparathyroidism during lactation. A case report.

We reduced the dose of calcitriol from 0.75 to 0.25 microgram/d to maintain low normal serum calcium levels in a hypoparathyroid woman during lactation. Calcitriol requirements quickly returned to 0.75 microgram/d when she discontinued breast-feeding. In her previous pregnancy, failure to reduce the dose of calcitriol resulted in serious hypercalcemia 11 days after she began breast-feeding. The changing requirement for calcitriol in our patient related directly to the falling level of estradiol. Although the cause or causes of diminished calcitriol requirements in hypoparathyroid women during lactation remains unclear, increased bone resorption promoted by low plasma estrogen levels may be an important mechanism. We conclude that the dose of calcitriol should be reduced during lactation and that both the hypoparathyroid mother and her infant should be carefully monitored to detect abnormal serum calcium levels.

Transient corticotropin deficiency in critical illness.

We describe three critically ill patients who displayed indirect evidence of transient corticotropin deficiency. All these patients were elderly, were poorly nourished, and had unexplained hypotension intraoperatively or immediately postoperatively. During the hypotensive episodes, they had inappropriately low plasma cortisol levels (10, 12, and 6 micrograms/dl) and responded dramatically to the administration of glucocorticoids. A normal response to infusion of synthetic corticotropin excluded primary adrenal insufficiency. Two patients tested had low thyroxine levels without increased thyrotropin concentrations and depressed levels of gonadotropins. In all three patients, the dose of glucocorticoids was successfully tapered and then discontinued. After recovery, serum thyroxine levels increased, gonadotropins reverted to normal concentrations, and the administration of metyrapone to two patients demonstrated normal hypothalamic-pituitary-adrenal function. Cortisol levels of less than 15 micrograms/dl in critically ill patients suggest the presence of adrenal insufficiency. The infusion of synthetic corticotropin may not exclude adrenal insufficiency attributable to corticotropin deficiency. If direct tests of corticotropin reserve are impractical, treatment with glucocorticoids is warranted.

Spurious elevation of plasma immunoreactive adrenocorticotropic hormone in cyclic Cushing's syndrome.

We studied a 40-year-old woman with cyclic Cushing's syndrome who demonstrated abnormal high-dose dexamethasone suppression and metyrapone stimulation tests. These results, associated with persistent elevations of plasma adrenocorticotropic hormone (ACTH) levels, suggested ectopic secretion of ACTH. Surprisingly, an adrenal adenoma with atrophy of the contralateral adrenal gland was found at exploratory laparotomy. Subsequent ACTH determinations that extract ACTH from the plasma before assay suggested that the apparent increase in ACTH concentration in our routine assay was due to the presence of an interfering substance(s). We conclude that the diagnosis of Cushing's syndrome continues to depend on a battery of adrenal function tests and radiographic procedures and recommend that measurements of ACTH be performed only after extraction of ACTH from specimens.

Thyroid gland size in pregnancy. An ultrasound and clinical study.

We estimated the size of the thyroid gland by palpation and measured thyroid gland volume with ultrasound in the immediate postpartum period and six months after delivery in 16 women. The 13% reduction in the mean thyroid gland volume detected six months after delivery implied that the thyroid gland enlarges slightly during pregnancy. Physical examination, however, did not detect any goiters during the immediate postpartum period and did not identify a change in thyroid gland size six months after delivery. The thyroid gland enlargement that occurs during pregnancy is not large enough to be detected by physical examination. We urge physicians to discard the commonly held notion that goiter frequently develops during pregnancy.

Rapid loss of lactate dehydrogenase isoenzyme activity in serum by cold-induced formation of immunoglobulin G-lactate dehydrogenase complex.

Lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum from a patient recovering from a myocardial infarction was extremely unstable when stored at 0 degree C. The activity of each LD isoenzyme except LD-1 decreased by at least 40% when serum was stored at 0 degree C for 4 h. The patient's erythrocyte LD activity had normal stability at lower temperatures, but LD from other sources, when added to the patient's serum, rapidly lost activity at 0 degree C. The patient's serum contained an immunoglobulin G that combined--at 0 degree C but not at 21 degrees C--primarily with LD isoenzymes containing one or more M subunits. Because this immunoglobulin-LD complex has no enzyme activity, we used 125I-labeled purified LD to study formation of the complex. NAD+ blocked the formation of immunoglobulin-LD complex but could not dissociate the complex and restore the LD activity.

Peripheral resistance to thyroid hormone in a family: heterogeneity of clinical presentation.

We describe a family with thyroid hormone resistance. Juvenile Graves disease was diagnosed in the propositus, an 8-month-old boy. He was initially given propylthiouracil, and at 22 months of age underwent subtotal thyroidectomy. A diagnosis of hyperthyroidism was made in a younger sister at 3 months of age. Because of the unusual occurrence of juvenile Graves disease in two siblings, we evaluated the parents. The mother was euthyroid on physical examination and by thyroid hormone measurements. The father, although clinically euthyroid, had markedly elevated thyroid hormone values. In the three affected members, serum thyrotropin concentrations and results of thyrotropin-releasing hormone infusion tests were inappropriate for the elevated serum thyroid hormone levels. The father was given increasing doses of triiodothyronine. Complete suppression of TRH-induced TSH release did not occur until a daily dose of 300 micrograms triiodothyronine was administered. Furthermore, this large dose of T3 did not produce clinical evidence of hyperthyroidism or result in changes in his systolic ejection time intervals. This family therefore had the unusual feature of clinical heterogeneity. The two children had mainly pituitary resistance to thyroid hormone and were hyperthyroid; the euthyroid father, on the other hand, had generalized tissue resistance to thyroid hormone.

Interference in a chromogenic alpha-amylase assay caused by dye-labeled oligosaccharide-induced precipitation of lipoprotein.

We examined the mechanism by which hypertriglyceridemia interferes with the Roche Diagnostics "Amylochrome" procedure for measurement of amylase in lactescent samples with normal and above-normal amylase activity. The serum blank recommended in the Amylochrome protocol to compensate for lactescence remains inappropriately turbid, compared with the test, and is partly responsible for the underestimation of amylase activity. Other major interference is seen when lipoprotein in hyperlipemic samples with above-normal amylase activity reacts with the soluble oligosaccharide-triazinyl dye product of the Amylochrome assay to form a flocculent blue precipitate. The formation of this precipitate in the test, and its removal, diminish lactescence due to lipemia, an effect that cannot be matched by any manipulation of a serum blank procedure. Oligosaccharide-dye product is removed as a component of the precipitate.