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Biomedical subjects

J L Doppman

Publications and source records attributed to J L Doppman.

At least 73 records · Page 4Linked to original sources
PubMed1997

Selective excision of adenomas originating in or extending into the pituitary stalk with preservation of pituitary function.

When the surgeon identifies an adenoma within the gland and selectively excises it, endocrine-active pituitary tumors are usually cured and pituitary function is preserved. Occasionally ectopic adenomas arise primarily in the pituitary stalk or arise superiorly in the midportion of the anterior lobe and extend upward within the stalk. To determine if these tumors can be selectively excised with preservation of pituitary function, the authors examined the outcome of selective adenomectomy in 10 patients with Cushing's disease with an ectopic adenoma originating in, and confined to, the stalk (four microadenomas) or an adenoma extending superiorly through the diaphragma sella and into the stalk (five microadenomas and one macroadenoma) from an operative series of 516 patients with Cushing's disease. To reach the adenoma transsphenoidally in these patients, the diaphragma sella was incised anteroposteriorly in the midline to the anterior edge of the stalk, the suprasellar cistern was entered, and the adenoma was selectively excised using care to limit injury to the infundibulum. After selective adenomectomy, Cushing's disease remitted in all patients. All patients were hypocortisolemic immediately after surgery and required hydrocortisone for up to 21 months. Apart from the adrenal axis, pituitary function was normal in five patients in the immediate postoperative period, including two patients with tumors confined to the stalk and three patients with preoperative hypothyroidism (one patient) and/or hypogonadism (three patients). Three others with transient postoperative hypothyroidism (one patient) or diabetes insipidus (two patients) had normal pituitary function within 7 months of surgery. One patient with hypothyroidism and one with hypogonadism before surgery had panhypopituitarism postoperatively. A patient with a microadenoma located high in the stalk next to the optic chiasm had bitemporal hemianopsia postoperatively. These results demonstrate the feasibility of achieving curative transsphenoidal resection and preservation of pituitary function in cases of pituitary adenomas that are confined to the pituitary stalk or tumors that extend superiorly within the stalk from an intrasellar origin.

Adenoma↗
PubMed1996

Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study.

OBJECTIVE: To compare the sensitivity of somatostatin receptor scintigraphy done using [111In-DTPA-DPhe1]octreotide with that of other imaging methods in the localization of gastrinomas in patients with the Zollinger-Ellison syndrome. DESIGN: Prospective study. SETTING: Referral-based clinical research center. PATIENTS: 80 consecutive patients with the Zollinger-Ellison syndrome. INTERVENTIONS: Conventional tumor localization studies (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], selective angiography, and bone scanning) and somatostatin receptor scintigraphy done using [111In-DTPA-DPhe1]octreotide with single-photon emission CT imaging at 4 and 24 hours. Patients with possible liver metastases had biopsies done for confirmation, and 15 patients had exploratory laparotomies done to assess primary tumor localization. RESULTS: Extrahepatic gastrinomas or liver metastases were identified by ultrasonography in 19% of patients, by CT in 38% of patients, by MRI in 45% of patients, by angiography in 40% of patients, and by somatostatin receptor scintigraphy in 70% of patients. Somatostatin receptor scintigraphy was as sensitive as the other tests combined (59%), and when the results of all other tests were added to the somatostatin receptor scintigraphy results, tumors were localized in 75% of patients. Among patients with a possible primary tumor, the results of ultrasonography were positive in 9%, the results of CT were positive in 31%, the results of MRI were positive in 30%, the results of angiography were positive in 28%, and the results of somatostatin receptor scintigraphy were positive in 58%. Somatostatin receptor scintigraphy was as sensitive as all of the other imaging studies combined; when the results of scintigraphy were added to the results of the other studies, possible primary tumors were identified in 68% of patients. In 24 patients who had histologically proven metastatic liver disease, sensitivities for the detection of any metastatic liver lesions were 46% for ultrasonography, 42% for CT, 71% for MRI, 62% for angiography, and 92% for somatostatin receptor scintigraphy. Somatostatin receptor scintigraphy was significantly better than all of the conventional imaging methods in the identification of gastrinomas later found at surgery (P = 0.004), but it still missed 20% of gastrinomas. CONCLUSIONS: Somatostatin receptor scintigraphy is the single most sensitive method for imaging either primary or metastatic liver lesions in patients with the Zollinger-Ellison syndrome. Because of its sensitivity, simplicity, and cost-effectiveness, it should be the first imaging method used in these patients. For patients with negative results on somatostatin receptor scintigraphy, guidelines about the use of other imaging studies are proposed.

Adolescent↗
PubMed1996

Inferior petrosal sinus sampling in healthy subjects reveals a unilateral corticotropin-releasing hormone-induced arginine vasopressin release associated with ipsilateral adrenocorticotropin secretion.

Arginine vasopressin (AVP) acts synergistically with corticotropin-releasing hormone (CRH) to stimulate ACTH release from the anterior pituitary. In a previous study of bilateral simultaneous inferior petrosal sinus (IPS) sampling in healthy human subjects, we observed lateralized ACTH secretion, suggesting lateralized secretion of an ACTH-regulating hypothalamic factor. To investigate this possibility, we measured ACTH, CRH, AVP, and oxytocin (OT) levels in the IPS and the peripheral circulation in nine normal volunteers, before and after 1 microgram/kg i.v. bolus ovine CRH (oCRH). At baseline, ACTH, AVP, and OT exhibited a significant (P < 0.05) two to threefold intersinus gradient (ISG), indicating the existence of a dominant petrosal sinus. Endogenous CRH was undetectable in all samples. Despite similar exogenous oCRH levels in both petrosal sinuses, oCRH caused a significant increase (P < 0.001) in the ACTH ISG (15.8 +/- 5.6, mean +/- SEM), suggesting increased responsiveness of one dominant side of the anterior pituitary. This was associated with an ipsilateral CRH-induced AVP release and a significant increase (P < 0.01) in the AVP ISG (8.6 +/- 2.3), suggesting lateralized AVP secretion by the hypothalamus. Furthermore, the increased AVP ISG after oCRH correlated strongly with the ACTH ISG (r = 0.92, P < 0.01). oCRH administration did not affect OT. These findings suggest that there is a dominant petrosal sinus in healthy volunteers that appears to reflect a dominant side of the adenohypophysis, characterized by increased functional activity and/or responsiveness of the pituitary corticotrophs. This may reflect lateralized hypothalamic and/or suprahypothalamic function resulting in CRH-responsive lateralized secretion of AVP from parvocellular and/or magnocellular axons in the median eminence and the posterior pituitary. Although the functional and teleologic significance of these findings remains to be investigated, our data suggest a novel mechanism for CRH-mediated ACTH release, namely CRH-induced release of AVP which then enhances CRH action on the corticotrophs. Furthermore, our data represent the first direct evidence for the concept of brain lateralization with respect to neuroendocrine secretion.

Adrenocorticotropic Hormone↗
PubMed1996

Is reoperation for gastrinoma excision indicated in Zollinger-Ellison syndrome?

BACKGROUND: Surgical excision of gastrinomas in patients with Zollinger-Ellison syndrome (ZES) decreases the incidence of hepatic metastases, but long-term biochemical cures are achieved in fewer than 30% of cases. A growing number of patients have persistent or recurrent disease after initial operation. The effect of reoperation in these patients has not been previously reported. METHODS: From December 1982 to August 1995, 120 patients with ZES underwent operation for gastrinoma resection. Seventy-eight patients had recurrent or persistent ZES after operation; 17 patients underwent 18 reoperations. After initial operation all patients underwent yearly functional and imaging studies. If a tumor was unequivocally imaged, reexploration was done. RESULTS: Five patients, all with sporadic disease, were disease free after operation, with a median follow-up of 28 months. Tumor was found in all 18 reoperations and resected in 17. In patients with continuing disease-free intervals, locations of gastrinomas included pancreatic head lymph nodes (three), liver metastasis (one), and pancreatic tail lymph node (one). There were no deaths in the cured group; two patients in the group with persistent disease have died (median follow-up, 34 months). CONCLUSIONS: Reoperation for gastrinoma excision resulted in elimination of disease in 30% of patients and should be considered for patients with imageable disease.

Adult↗
PubMed1996

A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma.

OBJECTIVES: The authors evaluate the results of preoperative imaging protocols and surgical re-exploration in a series of patients with missed parathyroid adenomas after failed procedures for primary hyperparathyroidism. BACKGROUND: The success rate is lower and the complication rate is increased in patients undergoing reoperation for primary hyperparathyroidism compared with initial procedures. Scarring and distortion of tissue planes plus the potential for ectopic gland location leads to this worsened outcome. METHODS: Two hundred eighty-eight consecutive patients with persistent/recurrent hyperparathyroidism were treated at a single institution after a failed procedure or procedures at outside institutions. Two hundred twenty-two of these patients (77%) were believed to have a missed single adenoma, and these patients underwent 228 operations and 227 preoperative work-ups. Preoperative evaluation consisted of a combination of four noninvasive imaging studies--neck ultrasound, nuclear medicine scan, neck and mediastinal computed tomography scan, and neck and mediastinal magnetic resonance imaging. Based on the noninvasive testing alone, 27% patients underwent surgery whereas the other patients underwent invasive studies, including selective angiography (58%), selective venous sampling for parathyroid hormone (43%), or percutaneous aspiration of suspicious lesions (15%). RESULTS: Abnormal parathyroid adenomas were found in 209 of 222 initial procedures and 6 of 6 second procedures, with an overall success rate in terms of resolution of hypercalcemia in 97% (215/222) of patients. The single most common site of missed adenoma glands was in the tracheal-esophageal groove in the posterior superior mediastinum (27%). The most common ectopic sites for parathyroid adenomas are thymus (17%), intrathyroidal (10%), undescended glands (8.6%), carotid sheath (3.6%), and the retroesophageal space (3.2%). The most sensitive and specific noninvasive imaging test is the sestamibi subtraction scan, with 67% true-positive and no false-positive results. The rate of true-positive and false-positive results for ultrasound, computed tomography, magnetic resonance imaging, and technetium thallium scans were 48%/21%, 52%/16%, 48%/14% and 42%/8%, respectively. The incidence of injury to the recurrent laryngeal nerve was 1.3%. CONCLUSIONS: A single missed parathyroid adenoma is the most common cause for a failed initial parathyroid operation. Appropriate use of preoperative imaging tests and knowledge of the potential location or parathyroid adenomas can lead to very high cure rates with minimal morbidity.

Adenoma↗
PubMed1996

Metastatic gastrinomas: localization with selective arterial injection of secretin.

PURPOSE: To evaluate localization of hepatic metastases with the intraarterial secretin injection test in Zollinger-Ellison syndrome (ZES). MATERIALS AND METHODS: Results in 74 patients with ZES (aged 15-70 years) were retrospectively studied. All patients had undergone computed tomography (CT), magnetic resonance (MR) imaging, ultrasound, abdominal angiography, and an intraarterial secretin test, in which venous blood is sampled periodically after injection of secretin. RESULTS: Twenty-two patients had liver metastases. An increase in venous gastrin concentration of at least 25% at 20 seconds or 50% at 30 seconds after injection indicated a positive result. Results were positive in 41% of patients with and 2% without liver metastases (P < .0001). Sensitivity of the intraarterial secretin test was 41%; of CT and ultrasound, 64%; and of MR imaging and angiography, 77%. Intraarterial secretin test results assisted in clinical management in 22% of patients. CONCLUSION: With the criteria developed, the intraarterial secretin test had high specificity but low sensitivity. It should be used when imaging results are unclear.

Adolescent↗
PubMed1996

Parathyroid adenomas in the aortopulmonary window.

PURPOSE: To describe localization studies in nine patients with ectopic parathyroid adenomas in the aortopulmonary window. MATERIALS AND METHODS: Nine patients with ectopic parathyroid tissue (eight adenomas, one hyperplastic gland) in the aortopulmonary window were examined with ultrasound (US), computed tomography (CT), magnetic resonance (MR) imaging, and scintigraphy. Diagnostic arteriography (n = 4) and venous sampling (n = 3) were performed in the first four patients; arteriography for the purpose of staining was attempted in the last five patients. RESULTS: The results of CT and MR imaging studies were positive in eight of nine patients (89%) and five of eight patients (63%), respectively. The results of thallium/technetium scintigraphy were negative in three patients scanned (0%), but the results of a repeat study in one patient were positive (33%). Sestamibi scans were positive in six of six patients (100%). Single photon emission CT was performed in all six patients and enabled distinction between adenomas in the aortopulmonary window and those in the thymus. CONCLUSION: Ectopic parathyroid glands in the aortopulmonary window are usually detected at sestamibi scintigraphy, and SPECT is helpful in distinguishing these adenomas from more common adenomas in the anterior mediastinum. CT and MR imaging studies can also enable this distinction, but imaging must extend below the aortic arch.

Adenoma↗
PubMed1996

Factitious Cushing syndrome.

There have been few reports of factitious Cushing syndrome. To characterize the clinical and laboratory features leading to this unusual diagnosis, we describe 6 patients (5 women, 1 man), ages 31-44, identified retrospectively among 860 patients evaluated for hypercortisolism at the National Institutes of Health Clinical Center. All six patients had multiple surgeries unrelated to Cushing syndrome and a history of depression or anxiety. Four patients had close contact with the medical profession, three a history of drug abuse, and three had undergone previous treatment for Cushing syndrome. The physical features of Cushing syndrome were variable and not helpful in the differential diagnosis with endogenous Cushing syndrome. Four patients had striking variability in urine-free cortisol (UFC) and 17-hydroxysteroid (17-OHCS) values from low to high. Adrenal computed tomography, performed in two patients, showed small adrenal glands (n = 1) or a left-sided mass (n = 1), and adrenal magnetic resonance imaging, performed in one patient, showed atrophic glands. Pituitary magnetic resonance imaging, carried out in four patients, was either normal (n = 1) or exhibited questionable signs of microadenoma (n = 3). Determination of synthetic glucocorticoids by high pressure liquid chromatography (HPLC) was positive in the four patients in whom it was performed. Factitious Cushing syndrome is a difficult diagnosis. To conserve time and resources, high pressure liquid chromatography analysis of urine steroids, the most definitive test for the factitious disorder, should be performed whenever there is clinical suspicion of glucocorticoid abuse.

Adrenal Glands↗
PubMed1996

Inferior petrosal sinus arginine vasopressin concentrations in normal volunteers and patients with Cushing's disease.

In patients with Cushing's disease (CD), basal inferior petrosal sinus arginine vasopressin (AVP) concentrations are greater than peripheral levels and are further increased by the administration of CRH. AVP has an interpetrosal sinus gradient similar to that for ACTH, leading to the hypotheses that petrosal sinus AVP might either be derived from the corticotroph adenoma or be important for adenoma formation. To determine whether petrosal sinus AVP is truly increased in patients with CD, we compared inferior petrosal sinus and peripheral venous AVP and ACTH levels in 23 patients with CD and 9 healthy volunteers before and after iv ovine CRH. In both groups, AVP and ACTH showed interpetrosal lateralization, such that greater levels of both hormones were found at each time point in a single dominant petrosal sinus. When both hormones exhibited lateralization (an intersinus gradient > 1.5), ACTH and AVP always lateralized together. In patients with CD, the ACTH interpetrosal sinus lateralization correctly identified the side of the pituitary containing the tumor in 75% of evaluable patients, whereas the AVP interpetrosal sinus lateralization identified 63% (P = NS). Ovine CRH stimulated AVP in both the dominant and nondominant petrosal sinuses in patients with CD. Although basal AVP in the dominant petrosal sinus was not significantly different in patients with CD and normal volunteers (144 +/- 85 vs. 13.0 +/- 4.3 pmol/L; P = 0.058), dominant petrosal sinus AVP was significantly elevated in patients with CD compared to normal volunteers at 3 min (269 +/- 122 vs. 45.1 +/- 30.0 pmol/L; P < 0.05) and 5 min (315 +/- 120 vs 40.2 +/- 23.6 pmol/L; P < 0.05) after ovine CRH administration. Peripheral venous AVP levels were similar in all groups. We conclude that lateralization of AVP secretion occurs in both patients with CD and normal volunteers, but there is greater CRH-stimulated AVP secretion in the inferior petrosal sinuses of patients with CD.

Adrenocorticotropic Hormone↗
PubMed1996

Microvascular anatomy of dural arteriovenous abnormalities of the spine: a microangiographic study.

Although most vascular abnormalities of the spinal cord are now ascribed to an abnormal communication between a dural artery and a medullary vein on the dura near a sensory nerve root, these lesions are too small for their anatomy to be demonstrated directly by spinal arteriography. Thus, it is unknown whether the site of dural arteriovenous shunting is an arteriovenous malformation (AVM), implying a congenital origin, or is a direct arteriovenous fistula (AVF), implying an acquired etiology. The authors treated six patients by en bloc resection of the involved dural root sleeve, proximal nerve root, and adjacent spinal dura. All of the patients presented with myelopathy and their arteriograms were consistent with a spinal dural vascular malformation. The lesions occurred between T-6 and T-12, levels at which clinical deficits from such resection are minimal. The dural artery or medullary vein associated with the vascular malformation was cannulated and a dilute solution of barium sulfate was injected during sequential fine-grain radiography. In all of the lesions the artery split into daughter vessels that coalesced one to three times to form a skein of arterial loops in the dura that invariably emptied into a medullary vein without an intervening capillary plexus. Several medium-to-small collateral vessels arising from adjacent intercostal or lumbar arteries were commonly present in the dura and converged at the site of the AVF to join a single medullary vein. These results show that spinal dural AVMs are direct AVFs that link the dural branch of the radiculo-medullary-dural artery with the intradural medullary vein. They also provide an anatomical explanation for the presence of a multiple segmental arterial supply and a single draining medullary vein of spinal dural AVFs, and the propensity for reestablishment of flow through the arteriovenous shunt after embolic occlusion.

Adult↗
PubMed1995

Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium.

OBJECTIVE: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas. DESIGN AND PATIENTS: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas. SETTING: Tertiary referral hospital. MEASUREMENTS: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9). RESULTS: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions. CONCLUSION: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.

Adult↗
PubMed1995

Venographic surveillance of tunneled venous access devices in adult oncology patients.

BACKGROUND: Tunneled venous access devices (VADs) are often essential in the care of patients with advanced malignancies, but they carry an uncertain risk of thrombosis. METHODS: To determine the incidence of venoocclusion related to silicone VADs in a population of adult oncology patients, we prospectively studied 50 individuals with upper extremity venograms approximately 6 weeks after their VADs had been implanted. Twenty-one of these patients were reevaluated with venograms approximately 12 weeks after catheterization. In addition, venograms were performed on a separate group of 24 patients who needed catheterization of axillary-subclavian veins that had been catheterized in the past. RESULTS: The 6-week venograms in the prospective study showed partial venous obstruction in 15 patients (30%), whereas three (6%) had developed symptomatic total venoocclusion by this time. The 12-week venograms showed two additional complete occlusions. Venograms of 30 previously catheterized veins showed complete venoocclusion in nine (30%), although only two had a history of thrombosis. CONCLUSIONS: Our observations indicate that VADs frequently cause partial venoocclusion within the first 6 weeks of catheterization and that permanent venous damage from VADs is common, even without a history of VAD-related thrombosis.

Adult↗
PubMed1995

Role of preoperative iodocholesterol scintiscanning in patients undergoing adrenalectomy for Cushing's syndrome.

BACKGROUND: Iodocholesterol scintiscanning (IS) is a noninvasive, functional diagnostic test. We report our experience with IS as an adjunct for adrenal surgery for Cushing's syndrome. METHODS: Between April 1983 and October 1994, 23 patients with Cushing's syndrome from benign primary adrenal disease underwent IS and computed tomography (CT) and/or magnetic resonance imaging (MRI). Twelve patients had unilateral adrenal involvement with a solitary adenoma (n = 11) or unilateral multinodular disease (n = 1), and 11 patients had bilateral adrenal disease. RESULTS: In patients with Cushing's syndrome caused by unilateral adrenal disease, IS was 100% specific and 100% sensitive, whereas in two cases CT/MRI incorrectly showed bilateral disease. In patients with Cushing's syndrome with bilateral adrenal involvement, IS had one false-negative result with nonvisualization. CT/MRI showed unilateral disease in four cases and no abnormalities in two. All patients in this series were cured of Cushing's syndrome after unilateral adrenalectomy in 11 cases and bilateral adrenalectomy in 12 cases. CONCLUSIONS: IS is a highly sensitive and specific imaging modality and is an essential adjunct to biochemical testing in planning adrenal resections for Cushing's syndrome caused by primary adrenal disease.

Adenoma↗
PubMed1995

Adrenocorticotropic hormone-secreting pheochromocytomas: the exception to the rule.

BACKGROUND: Operative management of pheochromocytomas dictates resection of the involved adrenal and exploration-resection of the contralateral gland if enlarged. We describe an exception to this rule. METHODS: We report the largest series of patients with adrenocorticotropic hormone (ACTH)-secreting pheochromocytomas and review the world literature. RESULTS: Four patients presented with findings of adrenocorticoid and catecholamine excess, as well as elevated levels of plasma ACTH, urinary metanephrines, and urinary free cortisol. Abdominal computed tomography scans revealed bilateral adrenal hyperplasia, and magnetic resonance imaging scans showed a unilateral adrenal mass with a bright T2 signal suggesting a pheochromocytoma. Two patients underwent adrenal venous sampling localizing ACTH secretion to the pheochromocytoma. All underwent unilateral adrenalectomy for a benign tumor without morbidity or death, leaving the contralateral hyperplastic adrenal in situ. After operation all patients experienced normalization of their levels of plasma ACTH, urinary metanephrines, and urinary free cortisol with resolution of symptoms. Combining our series with previously reported cases of ACTH-secreting pheochromocytomas, almost all are benign (20 of 21), in contrast to most ACTH-secreting tumors. CONCLUSIONS: ACTH-secreting pheochromocytomas are the exception to the rule; unilateral adrenalectomy is curative and the contralateral hyperplastic adrenal can be preserved. This approach results in resolution of both syndromes of hormone excess and preserves long-term adrenal function.

17-Hydroxycorticosteroids↗