Biomedical subjects
Publications and source records attributed to P C Carpenter.
The regulation of ACTH-cortisol production in the pathophysiology of the various forms of Cushing's syndrome is discussed. The diagnostic algorithms for the differential diagnosis of Cushing's syndrome are reviewed with emphasis on the precision of the evaluation, diagnostic pitfalls, and the influence of some of the more recently developed procedures on this diagnostic evaluation.
Although considerable advances have been made in the understanding of Cushing's syndrome in the recent past, many difficulties persist in the diagnosis and management of patients with hypercortisolism. Precision in the diagnosis of Cushing's syndrome and the differentiation of its various forms have gradually improved, but a substantial number of cases have laboratory or radiologic findings that can be misleading or at least difficult to interpret. Furthermore, other conditions may mimic Cushing's syndrome and add to the diagnostic difficulties. Surgical extirpation of primary adrenal lesions that cause the hypercortisolism or of the neoplasms responsible for the ectopic production of adrenocorticotropic hormone remains the treatment of choice for these problems. Currently, transsphenoidal surgical exploration is the treatment of choice for Cushing's disease.
In a 32-year-old woman, acquired, isolated corticotropin deficiency resulted from postpartum lymphocytic hypophysitis. The literature suggests that lymphocytic hypophysitis may cause acquired deficiencies of anterior, and possibly posterior, pituitary hormones. Immunologic evaluation of our patient failed to uncover anticorticotroph antibodies. Prompt recognition of this potentially fatal condition is important because of the availability of effective treatment.
A rare cause of Cushing's syndrome appearing to originate in the adrenal glands is primary pigmented nodular adrenocortical disease (PPNAD). It may be variably associated with a complex of other pathologic characteristics that include cardiac myxomas, cutaneous myxomas, and lentigines, mammary myxoid lesions, testicular tumors, pituitary adenomas, and neuroectodermal tumors. We have reviewed the clinical, biochemical, radiographic, operative, and pathologic details of seven patients with PPNAD who have been evaluated at Mayo Clinic. Biochemical testing supported autonomous adrenal hyperfunction. This was based on the failure of cortisol suppression by high-dose dexamethasone, failure of pituitary stimulation by metyrapone administration, either normal or suppressed basal adrenocorticotropic hormone (ACTH) levels, normal radiographic studies of the sella turcica, and normal abdominal and thoracic computerized tomography in search of an ectopic ACTH-producing tumor. Six patients underwent bilateral total adrenalectomy without postoperative complications. Nelson's syndrome has not occurred, but acute adrenocortical insufficiency may have contributed to the death of one patient. To recognize the possible diagnosis of PPNAD preoperatively is important to proceed directly with adrenalectomy, avoiding unnecessary pituitary surgery. Moreover, if PPNAD is part of the broader pathologic complex, the possible presence of cardiac myxomas that may be multiple, recurrent, in atypical locations, and familial must be borne in mind.
Twenty-five patients were identified with non-pituitary, nonadrenal ACTH-secreting tumors (bronchial carcinoid, bronchial small cell carcinoma, pancreatic islet cell carcinoma, medullary thyroid carcinoma, thymic carcinoids, metastatic adenocarcinoma, and pancreatic cystadenoma). Clinical features were weakness, hypertension, cushingoid appearance, peripheral edema, personality disorders, and hyperpigmentation. Biochemical features were a markedly increased urinary free cortisol level (all patients), hypokalemia (71 percent of patients), and an elevated ACTH level (72 percent of patients). Surgical therapy consisted of bilateral total adrenalectomy (56 percent of patients). Twelve percent underwent transsphenoidal hypophysectomy and 36 percent had excision of their tumor. No surgical therapy was undertaken in 28 percent. Bilateral total adrenalectomy in patients with a slow-growing malignancy or an unknown tumor secreting ACTH is beneficial in relieving symptoms and prolonging life. Excision of nonmalignant ACTH-producing tumors yields an excellent long-term prognosis.
Of 40 patients (16 males and 24 females), 29 had cardiac myxoma(s), 14 had skin pigmentation (lentigo and several types of nevi) which also commonly affected the lips, 6 had skin myxoma(s), and 12 had both pigmentation and myxoma(s); 18 had primary pigmented nodular adrenocortical disease (Cushing syndrome was present in 11); 10 had myxoid mammary fibroadenomas; 9 had testicular tumor(s) (large-cell calcifying Sertoli cell tumor, Leydig cell tumor, or adrenocortical rest tumor, or a combination); and 4 had pituitary adenoma with gigantism or acromegaly. The maximum number of conditions present together was five, occurring in two patients; each of the remaining patients had at least two of the conditions. The overlap, in this sizeable number of patients, of various combinations of the same rare or very rare conditions unlikely to occur together by chance with any degree of frequency is striking evidence for a unique syndrome. The patients were young (mean age at diagnosis of the first component, 18 years). Pathologic involvement tended to be multicentric (heart and skin) and bilateral in paired organs (adrenal, breast, and testis). Thirteen patients (32%) are alive and well. Twelve patients are alive but with complications of cardiac myxoma (in 8), testicular tumors (in 2), residual Cushing syndrome (in 1), or bilateral pulmonary nodules (in 1). Twelve patients are dead: 9 of cardiac myxoma, 1 of intracranial (nonpituitary) tumor, and 2 postoperatively. The status of three is unknown.
Rarely, acromegaly is produced by neuroendocrine neoplasms elaborating a substance similar to or identical with growth hormone-releasing factor. This report reviews the cases described to date and presents the clinicopathologic features of a patient with acromegaly, mild sellar enlargement, and elevated growth hormone levels associated with a large bronchial carcinoid tumor. Normalization of serum growth hormone levels and regression of acromegaly followed resection of the bronchial tumor, which was shown, by bioassay and immunocytochemistry, to contain a growth hormone-releasing factor.
Four patients (two males and two females, ages 12-21 years) had clinical features of the Cushing syndrome. Results of biochemical tests (in three patients tested) suggested the presence of an autonomously functioning adrenocortical neoplasm. However, radiologic examination of the adrenals did not show an adrenal tumor. The four patients underwent curative bilateral total adrenalectomy and did not manifest the Nelson syndrome postoperatively (follow-up, 2-22 years). The adrenal pathologic findings in these patients were similar. Gross findings included: 1) decreased, normal, or slightly increased total gland weight; 2) studding of the external and cut surfaces by small (less than 4 mm) black, brown, dark-green , red, or (rarely) yellow nodules; and 3) cortical atrophy and disorganization of the normal zonation between the nodules. Microscopically, the nodules were composed predominantly of enlarged, globular, cortical cells with granular eosinophilic cytoplasm that often contained lipofuscin. Twenty-four similar cases have been reported. Findings in these plus our four cases identify a special type of adrenocortical pathology associated with Cushing syndrome, for which we suggest the name "primary pigmented nodular adrenocortical disease."
Referral patterns from internists to departments of nuclear medicine or radiology are important determinants of whether adrenal glands are imaged by computed tomography (CT) or by radioisotope scintigraphy. To assist clinicians in making an informed choice, computed tomographic scans were compared with isotope scintigrams using 131I-19-iodocholesterol (19-IC) and 131I-6 beta-iodomethyl-19-norcholesterol (NP-59). In general, imaging techniques serve to localize diseases that are diagnosed on the basis of biochemical tests of adrenal function. Computed tomographic scanning and NP-59 scanning are of comparable diagnostic accuracy. Both are superior to 19-IC scanning in the diagnosis of Cushing's syndrome and primary aldosteronism. Computed tomographic scanning is faster and less expensive, and involves lower radiation doses to the patient than scintigraphy. Adrenocortical isotope scanning as a routine procedure has been superseded by computed tomographic scanning at the Mayo Clinic.
The records of 62 patients (36 female and 26 male) with pathologically confirmed adrenal cortical carcinoma who had operations between 1960 and 1980 were reviewed. The mean age was 48 years. There were 36 (58%) functioning tumors and 26 (42%) nonfunctioning tumors. Curative resection was performed in 31 patients, palliative resection in 14, and open biopsy alone in 17 with an overall operative mortality rate of 9.7% and a 5-year survival rate of 16%. There was no significant difference in survival rates between patients who had operations alone and those who had operations plus adjunctive therapy. Patients with stages I to III lesions or those who underwent curative resections had significantly longer survival than had those with stage IV disease or those who had palliative resections, respectively. Factors that failed to influence survival rates included palliative resection versus biopsy, tumor size, grade, function, and patient sex or age. We conclude that operative staging is prognostically valuable, aggressive surgical treatment is recommended in stages I to III lesions, and a prospective randomized study of adjuvant treatment for all stages of adrenal cortical carcinoma is indicated.
Explore the source record for details and available documents.
Two patients with overproduction of thyroid-stimulating hormone (TSH) are described. The first patient, a 25-year-old man with recurrent hyperthyroidism, had a pituitary adenoma and highly elevated levels of TSH. While the patient was receiving 0.3 mg of thyroid daily, and basal TSH level was 161 microM/ml. Despite an increase in the thyroid hormone therapy, serum TSH levels remained elevated. The administration of thyrotropin-releasing hormone (TRH) or dexamethasone resulted in no changes in TSH level. The second patient was an 18-year-old man who had inappropriately elevated levels of TSH 3 months after radioiodine therapy for hyperthyroidism. A gradual increase in thyroid hormone replacement therapy decreased the serum TSH levels from 250 to 14.8 microM/ml. The administration of TRH led to huge increases of TSH. Dexamethasone inhibited basal TSH but not TRH-stimulated TSH levels. The overproduction of TSH was attributed to autonomous, neoplastic secretion in the first case and to partial, selective pituitary thyrotroph resistance to thyroid hormone in the second.
To determine if the adrenal sensitivity to angiotensin II in patients with an aldosterone-producing adenoma differs from that in patients with idiopathic hyperaldosteronism, we infused graded doses of angiotensin II into 17 patients with primary aldosteronism and measured their plasma aldosterone concentrations after each dose. At a rate of 0.5 ng angiotensin II/kg.min, the mean increase in the plasma aldosterone concentration in the 8 patients from whom an aldosterone-producing adenoma was subsequently removed was 4 +/ 2.4 ng/dl (mean +/- SE), which was significantly less (P less than 0.01) than the mean increase (23 +/- 4.8 ng/dl) in the 9 patients with idiopathic hyperaldosteronism. The threshold dose of angiotensin II in the patients with aldosterone-producing adenoma was 1.0 +/- 0.24 ng/kg.min, significantly greater (P less than 0.05) than the threshold dose (0.3 +/- 0.07 ng/kg.min) in the patients with idiopathic hyperaldosteronism. We conclude that the sensitivity of aldosterone-producing adenomas to angiotensin II is significantly less than that of the hypersecreting adrenal tissue in patients with idiopathic hyperaldosteronism. This difference in adrenal sensitivity might in part explain the difference in the response of plasma aldosterone concentrations to upright posture in these two subsets of aldosteronism with low renin activity.
Explore the source record for details and available documents.
A corticotropin antiserum was obtained from rabbits immunized with synthetic 1--24 corticotropin conjugated with bovine serum albumin. The antiserum did not cross react with synthetic alpha-melanotropin or with synthetic beta-endorphin and had a cross reactivity of 0.23% with human beta-lipotropin. We developed a radioimmunoassay with the antiserum obtained, in which we used polyethylene glycol in conjunction with a second precipitating antibody for fast (15-min) separation of antibody-bound and free corticotropin. The assay had a sensitivity of 16 ng/L and was validated on patients with various pituitary and adrenal diseases. From 103 normal subjects, the median value for corticotropin in specimens collected during the morning was 34 ng/L of plasma; the upper 95% confidence limit of the normal range was 98 ng/L.
Adrenal imaging in the past has been limited in its clinical application by the long interval between administration of dose and visualization of adrenal glands. We review our experience with the use of a newer labeling agent, NP-59, in 29 patients with various adrenal disorders and in 4 normal subjects. With this agent, identification of adrenal lesions is possible with a high degree of accuracy, and diagnostic information is usually available within 48 hours. NP-59 is particularly useful in evaluating primary aldosteronism and selected cases of Cushing's syndrome.
Bilateral testicular Leydig cell tumors in a patient with Nelson's syndrome and a Leydig cell tumor of the ovary in a woman with a virilizing syndrome were successfully imaged with [6beta-131I]iodomethyl-19-norcholest-5(10)-en-3beta-ol (NP-59). Uptake by these tumors was comparable to uptake by adrenal glands in patients with funtioning adrenal tumors or bilateral hyperplasia. Scanning the gonads with NP-59 may be a helpful imaging procedure in localizing possible sites for exploratory surgery in certain cases of gonadal neoplasia.