Biomedical subjects

M A Zeiger

Publications and source records attributed to M A Zeiger.

At least 37 records · Page 2Linked to original sources

PubMed1997

Telomerase activity in the differential diagnosis of papillary carcinoma of the thyroid.

BACKGROUND: Although fine-needle aspiration (FNA) is 90% sensitive in the detection of papillary carcinoma (PC) of the thyroid, its specificity has been reported as low as 52%. Consequently, patients who have an FNA suspicious for PC may undergo operation for a benign process. The ribonucleoprotein telomerase has been noted to be activated in a wide variety of carcinomas. We examined 30 PCs for telomerase activity to determine whether this would be a useful adjunct to FNA in the diagnosis of lesions suspicious for PC. METHODS: Standard telomere repeat amplification protocol assays were performed on fresh frozen tissue samples from 30 PCs, 3 benign nodules, and 10 normal thyroids. RESULTS: Telomerase activity was documented in 20 of 30 (67%) of the PCs, 0 of 3 benign nodules, and 0 of 10 normal thyroids. In all, 11 of the 20 PCs had FNA cytology that was nondiagnostic of PC, and 2 of the benign nodules had FNA that was suspicious for PC. CONCLUSIONS: The telomerase assay appears useful in the distinction of benign from malignant thyroid lesions that have FNA suspicious for but not diagnostic of PC. On the basis of these findings, a prospective trial examining telomerase activity in FNAs suspicious for thyroid cancer has been initiated.

Biopsy, Needle↗

PubMed1997

Polymerase chain reaction-based microsatellite analysis of fine-needle aspirations from Hürthle cell neoplasms.

Fine-needle aspiration (FNA) of the thyroid is the sine qua non in the preoperative evaluation of thyroid nodules. Despite this, cytological examination of FNA cannot differentiate malignant from benign Hürthle cell neoplasms. We have previously shown that Hürthle cell carcinomas harbor more genetic alterations on chromosomal arms 1q and 2p than Hürthle cell adenomas, and that all Hürthle cell neoplasms have a significantly higher frequency of alterations on chromosomal arm 1p compared with normal thyroid. To determine if these genetic alterations could be detected in FNA samples, we examined DNA from FNAs that were available from eight Hürthle cell neoplasms. Polymerase chain reaction (PCR) amplification of DNA demonstrated either direct correlation with alterations seen in the tumor samples or in some instances, additional chromosomal alterations. We conclude that PCR-based microsatellite DNA analysis of preoperative FNA samples from Hürthle cell neoplasms can potentially distinguish Hürthle cell carcinomas from adenomas and that with further validation and perfection, this technique may allow more optimal surgical management of patients with these lesions.

Adenocarcinoma↗

PubMed1997

Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice.

Thyroid cell growth and function are regulated by hormones and growth factors binding to cell surface receptors that are coupled via G proteins, Gs and Gq, to the adenylyl cyclase and phospholipase C signal transduction systems, respectively. Activating mutations of the TSH receptor and G alpha s have been documented in subsets of thyroid neoplasms. To test the oncogenic potential of activated G alpha s in transgenic mice, we used the cholera toxin A1 subunit that constitutively activates G alpha s and used the rat thyroglobulin gene promoter for targeting this transgene (TGCT) to thyroid follicular cells. Three (M1392, F1358, and F1286) of six founders identified were able to transmit the transgene to their offspring and thyroid glands from these mice contained elevated levels of cAMP. Concentrations of serum thyroxine were elevated as early as 2 months of age (M 1392 and F 1286). F1358 mice were euthyroid until 8 months of age, at which time they developed hyperthyroidism. All three TGCT lines developed thyroid hyperplasia independent of their thyroxine levels. DNA image analysis of thyroid follicular cells from both the hyper and euthyroid mice showed that DNA index and "S+G2/M" phase were increased compared with normal, changes similar to that seen in poor prognosis human carcinomas. These data suggest that the G alpha s-adenylyl cyclase-cAMP pathway has an important role in thyroid hyperplasia and the transgenic mouse models reported herein will allow further examination of the role of this pathway in thyroid oncogenesis.

Adenylyl Cyclases↗

PubMed1997

Papillary carcinoma of the thyroid: can operative management be based solely on fine-needle aspiration?

BACKGROUND: Fine-needle aspiration cytology is sensitive for detecting malignancies such as papillary carcinoma of the thyroid gland. Because fine-needle aspiration specificity for papillary carcinoma of the thyroid is variable, routine intraoperative frozen section is often advocated. STUDY DESIGN: To define the roles of fine-needle aspiration and frozen section in papillary carcinoma of the thyroid gland, we reviewed data from 82 patients who underwent thyroidectomy between August 1989 and August 1995 for papillary carcinoma of the thyroid cytology. Results of fine-needle aspirations were grouped into three categories: diagnostic of papillary carcinoma of the thyroid; diagnostic of follicular-variant of papillary carcinoma of the thyroid; or suspicious for papillary carcinoma of the thyroid. Definitive diagnoses were made on permanent histology. RESULTS: A fine-needle aspiration revealing papillary carcinoma of the thyroid was 98 percent specific for cancer or 100 percent specific for follicular-variant of papillary carcinoma of the thyroid. A fine-needle aspiration that was suspicious for papillary carcinoma of the thyroid (n = 24) was only 54 percent specific for cancer. On the basis of gross intraoperative findings, 5 of these 24 patients underwent total thyroidectomy without frozen section, and all had carcinoma. The other 19 had frozen section analysis. Of the 5 patients with cancer detected by frozen section, 4 had cancer on permanent histology. Findings on frozen section demonstrated a follicular neoplasm in the other 14 patients, of which 4 ultimately were cancer. CONCLUSIONS: When papillary carcinoma of the thyroid or follicular-variant of papillary carcinoma of the thyroid is definitively diagnosed on fine-needle aspiration, the surgeon can perform definitive thyroidectomy without frozen section because of the high specificity for cancer. If the fine-needle aspiration is suspicious for papillary carcinoma of the thyroid, the incidence of cancer is 54 percent, and patients with these conditions should undergo surgery with frozen section. When either gross findings or frozen sections suggest malignancy, definitive thyroidectomy can be performed because 90 percent of such cases will be cancer. If frozen section is not diagnostic of malignancy, a thyroid lobectomy/isthmusectomy is recommended because 71 percent have a benign lesion. This systematic approach to papillary carcinoma of the thyroid will obviate unnecessary frozen sections while maintaining excellent diagnostic specificity.

Adolescent↗

PubMed1996

An allelotype of papillary thyroid cancer.

Although papillary carcinoma accounts for approximately 70% of all thyroid cancers, preliminary studies of allelic loss have thus far not identified any areas of chromosomal deletion. We evaluated 30 papillary thyroid carcinomas for chromosomal loss/allelic imbalance by testing at least 2 microsatellite markers from every autosomal arm. Fifteen of the 30 tumors tested exhibited loss of heterozygosity/allelic imbalance (LOH/AI) at one or more loci. Chromosomal arms with frequent LOH/AI included 4q, 5p, 7p and 11p. An average of 1.1 chromosomal arms displayed LOH/AI in each individual tumor. Therefore, 4q, 5p, 7p and, to a lesser extent, 11p display significant LOH/AI in papillary thyroid cancer, which indicates the presence of putative tumor-suppressor gene loci at these chromosomal arms.

Alleles↗

PubMed1996

Adenoviral infection of thyroid cells: a rationale for gene therapy for metastatic thyroid carcinoma.

BACKGROUND: Patients with thyroid carcinoma experience excellent long-term survival; however, up to 16% will die of their disease. We have transformed a rat thyroid follicular cell line (FRTL-5) with a gene (TGCT) that mimics a known mutation associated with thyroid neoplasms. These cells form subcutaneous tumors that metastasize to lung in nude mice. METHODS: In anticipation of developing gene therapy against this thyroid carcinoma model, we (1) tested whether adenovirus containing the beta-galactosidase gene could infect FRTL-5 cells and neonatal rat thyroid and (2) evaluated the ability to kill FRTL-5 cells by transfecting them with a transgene in which the thyroglobulin promoter (TG) directed the expression of herpes simplex virus type I thymidine kinase (HSV1TK) and treating TG-HSV1TK-transfected cells with 5 micrograms/ml ganciclovir. RESULTS: Nearly 100% of the TG-HSV1TK but only 5% of control cells were killed by addition of ganciclovir. Histochemical staining for beta-galactosidase activity demonstrated infection of FRTL-5 cells and neonatal rat thyroid tissue by adenovirus beta-galactosidase. CONCLUSIONS: These data demonstrate the feasibility of using adenovirus as vector to infect thyroid cells in vivo and provide a rationale for development of gene therapy for treatment of thyroid cancer.

Adenoviridae↗

PubMed1996

Parathyroidectomy in Maryland: effects of an endocrine center.

BACKGROUND: Surgery for hyperparathyroidism is associated with high cure rates and low morbidity and mortality when performed by experienced surgeons. We wanted to determine whether referral of patients with hyperparathyroidism to an endocrine surgery center has an impact on patient outcomes and costs. METHODS: Data from 901 patients who underwent parathyroidectomy recorded in the Maryland inpatient discharge database between 1990 and 1994 at 52 hospitals were compared with 169 consecutive patients who underwent surgical exploration by one surgeon (R.U.) at the Johns Hopkins Hospital. RESULTS: Although in 47 of 52 hospitals fewer than 10 parathyroidectomies were performed each year, in these hospitals four of five related deaths occurred before patient discharge. The percentage of parathyroidectomies in Maryland performed by one endocrine surgeon has increased from 8% in 1990 to 21% in 1994 and is associated with a 97% cure rate and no mortality. Moreover, while hospital length of stay (LOS) in the state has decreased from 7 to 3.1 days, LOS for the high-volume provider has declined to a mean of 1.3 days. CONCLUSIONS: Patients with hyperparathyroidism are increasingly referred to an endocrine surgery center, which results in a high cure rate, low morbidity, no mortality, and a shorter LOS. Improved surgical outcomes and lower costs depend on an experienced surgeon and argue for the referral of these patients to endocrine surgery centers.

Academic Medical Centers↗

PubMed1996

Transformation of rat thyroid follicular cells stably transfected with cholera toxin A1 fragment.

Activating mutations of the alpha subunit of the G protein G(s) (G(s)alpha) have been identified in thyroid adenomas and well-differentiated thyroid carcinomas. To examine the role of activating mutations of G(s)alpha in thyroid neoplasia, we transfected rat follicular thyroid (FRTL-5) cells with a transgene in which the cholera toxin A1 subunit (CTA1) is expressed under the control of the rat thyroglobulin gene promoter (TG). This transgene recapitulates effects of the activating mutation of G(s)alpha by its ability to ADP-ribosylate and thereby inhibit GTPase activity of endogenous G(s)alpha molecules. To assess the effect of G(s)alpha activation on cell growth, TGCTA1, or control, pM AM neotransfected FRTL-5 cells (10(4)-10(6)) were injected s.c. into nude mice. TGCTA1-transfected FRTL-5 cells grow in nude mice, whereas control cells do not. Tumor histology revealed increased mitotic activity, infiltration of skeletal muscle, perineural invasion, and plugging of lymphatic spaces. In addition, nude mice injected with TGCTA1 transfected cells or xenografted with the tumors developed metastases to lung. These results indicate that activation of G(s)alpha and constitutive production of cAMP in FRTL-5 cells can result in TSH-independent cellular proliferation and neoplastic transformation.

Adenosine Diphosphate Ribose↗

PubMed1996

Increased cyclic adenosine 3',5'-monophosphate inhibits G protein-coupled activation of phospholipase C in rat FRTL-5 thyroid cells.

Thyroid cell growth and function are regulated by several hormones and growth factors that bind to cell surface receptors coupled via G proteins, Gs and Gq, to stimulation of adenylyl cyclase and phospholipase C (PLC), respectively. We created a permanently transfected FRTL-5 cell line (TG8) in which the thyroglobulin gene promoter directs expression of the cholera toxin (CT) A1 subunit (CTA1). CTA1 catalyzes ADP ribosylation of Gs alpha, which results in persistent activation of Gs alpha. Activated Gs alpha causes constitutive stimulation of adenylyl cyclase and increases levels of intracellular cAMP. Because G protein-coupled signaling pathways exhibit cross-talk, we compared TG8 cells to FRTL-5 cells transfected with the neomycin resistance gene (TG4) to determine whether constitutive stimulation of adenylyl cyclase influences the PLC pathway. PLC activity was assessed by measuring levels of total inositol phosphates (IPs) in TG4 and TG8 cells that had been preincubated with myo-[3H]inositol for 2 days. Baseline values of [3H]IP production were similar for the two cell lines. Incubation of TG4 control cells with 10(-8) M TSH, 300 microM ATP, and 100 microM norepinephrine for 60 min stimulated 2.5-, 8.1-, and 3.4-fold increases, respectively, in [3H]IP production over the control value. By contrast, there was no [3H]IP response to any of these ligands in TG8 cells. TG8 cells exhibit a decrease in [35S]adenosine 5'-(gamma-thio)triphosphate binding to their cell surface compared to TG4 control cells counterparts, but no decrease in [125I]TSH binding. Treatment of TG4 cells with 100 ng/ml CT, 50 microM forskolin, or 1 mM 8-bromo-cAMP for 2 days reproduced the loss of ligand-stimulated [3H]IP synthesis present in TG8 cells. Although levels of immunoreactive Gq alpha and Gq alpha 11 were normal in TG8 cells, sodium fluoride-induced [3H]IP production was also inhibited. Levels of immunoreactive PLC beta 3, the dominant subtype of PLC beta in FRTL-5 cells, were not altered in TG8 cells or by CT treatment of TG4 cells. These data indicate that elevated levels of cAMP can inhibit the activity of G protein-coupled PLC. Further study of this model will elucidate our understanding of the exact mechanism responsible for this interaction.

Adenosine Triphosphate↗

PubMed1995

Loss of heterozygosity on the short arm of chromosome 3 in sporadic, von Hippel-Lindau disease-associated, and familial pheochromocytoma.

Pheochromocytomas occur sporadically and are associated with several dominantly inherited cancer syndromes, including von Hippel-Lindau (VHL) disease. We examined 14 pheochromocytomas (four from VHL patients, nine from sporadic patients, and one from a patient with familial pheochromocytoma) for loss of heterozygosity on chromosome arm 3p by using the polymerase chain reaction and restriction fragment length polymorphisms at eight loci. Loss of heterozygosity was detected in 8 of 14 pheochromocytomas examined: in three of the four VHL-associated tumors, in four of the nine sporadic tumors, and in the familial pheochromocytoma-associated tumor. Deletion of the inherited wild-type VHL allele was demonstrated in both informative VHL-associated pheochromocytomas, demonstrating involvement of VHL in pheochromocytoma development. However, because VHL mutations have not been detected in sporadic pheochromocytomas, VHL and/or another chromosome arm 3p gene may be involved in the etiology of these tumors.

Adrenal Gland Neoplasms↗

PubMed1994

Loss of heterozygosity on the short arm of chromosome 3 in mesothelioma cell lines and solid tumors.

Cytogenetic analysis of mesothelioma cell lines and solid tumors has documented non-random chromosomal abnormalities on the short arm of chromosome 3 from 3p14 to 3p25. We therefore examined nine mesothelioma cell lines, their corresponding tumors, and 15 additional mesothelioma tumors for loss of heterozygosity on 3p from 3p13 to 3p25.5 by polymerase chain reaction and restriction fragment length polymorphism analysis at 8 loci: D3S3, D3S30, D3S6, D3S2, D3S32, D3F15S2, THRB, and VHL. Loss of heterozygosity was documented by loss of one of two alleles in the tumor DNA whose corresponding normal DNA was heterozygous and was documented in four of nine mesothelioma cell lines and six of 15 mesothelioma tumors or a total of 42% of the mesotheliomas evaluated. This study suggests the involvement of a gene on the short arm of chromosome 3 in the development of mesotheliomas.

Alleles↗

PubMed1994

An in vitro model of thyroid neoplasia: permanently transfected FRTL-5 cells with thyroglobulin promoter-cholera toxin A1 subunit minigene.

BACKGROUND: Activating mutations of protein Gs alpha that stimulates adenylyl cyclase are present in a subset of thyroid adenomas. Cholera toxin A1 subunit (CT) mimics these mutations via adenosine diphosphate-ribosylation of Gs alpha. METHODS: To test the role of activated Gs alpha in thyroid neoplasia we developed an in vitro model. With molecular genetic techniques a transgene (TG-CT) in which the thyroglobulin gene (TG) promoter directs expression of CT was made. This transgene was transfected into rat thyroid follicular cells (FRTL-5). Integration of TG-CT transgene and its expression were examined. RESULTS: Polymerase chain reaction of DNA from transfected FRTL-5 cells identified the TG-CT transgene in six cell lines. The TG-CT transfected clones exhibited up to a 65-fold (1.29 +/- 0.37 pmols cyclic adenosine monophosphate (cAMP)/micrograms DNA) increase in cAMP over nontransfected FRTL-5 cells (0.02 +/- 0.001 pmols cAMP/micrograms DNA). Insulin, a known stimulator of the TG promoter, further induced CT gene expression and led to a 209-fold (10.43 +/- 0.10 pmols cAMP/micrograms DNA) increase in cAMP over nontransfected cells (0.05 +/- 0.00 pmols cAMP/microgram DNA). CONCLUSIONS: By mimicking a known mutation associated with thyroid neoplasms, these permanently transfected FRTL-5 cell lines will serve as a model to examine the long-term potential neoplastic effects of activated Gs alpha on thyroid follicular cells.

Animals↗

PubMed1993

Effective reversibility of the signs and symptoms of hypercortisolism by bilateral adrenalectomy.

BACKGROUND: The long-term outcome of bilateral adrenalectomy in the management of patients with Cushing's syndrome has not been previously well studied. METHODS: We reviewed our long-term results in 34 patients treated with bilateral adrenalectomy between 1983 and the present. Fourteen presented with occult or metastatic ectopic adrenocorticotropic hormone (ACTH) syndrome, 10 with failed treatment of Cushing's disease, five with primary micronodular and four with massive macronodular adrenocortical disease and one with indeterminate cause of Cushing's syndrome. RESULTS: All patients underwent bilateral adrenalectomy. Of 19 patients who required antihypertensive medications before operation, 15 (79%) had significant improvement and were either off all antihypertensive medication or required less medication after operation. Of 7 patients who required medications for diabetes mellitus, after operation 6 (86%) required no medication or changed from injections to oral hypoglycemic agents. Of 9 patients with mood changes or depression, the symptoms of 8 (88%) resolved. Of 29 patients with documented weight gain, 23 (79%) showed marked weight loss. Of 13 hirsute patients, 10 (77%) had resolutions of symptoms. Of 21 patients with complaints of fatigue, the symptoms of 16 (76%) resolved. Of 8 women with amenorrhea, 6 (75%) had resolution of symptoms. Each patient in the primary adrenocortical disease group, except one with residual fatigue, had complete resolution of his or her symptoms. There was no difference in resolution of symptoms between the ectopic ACTH and Cushing's disease groups. Six patients died: in the ectopic ACTH group one died of suicide at 1 month, and four of metastatic tumor at 9, 24, 25, and 48 months, and the patient with macronodular adrenocortical hyperplasia died of a myocardial infarction at 30 months. The remainder of the patients have been followed for a mean of 32 months (3 to 67 months). None of the patients had any evidence of recurrent hypercortisolism. CONCLUSIONS: We conclude that bilateral adrenalectomy is a safe, effective, and long-lasting method to ameliorate the devastating signs and symptoms of hypercortisolism in patients with Cushing's syndrome.

ACTH Syndrome, Ectopic↗

PubMed1993

Gs alpha--identification of a gene highly expressed by insulinoma and other endocrine tumors.

BACKGROUND: The isolation of mRNA molecules that are either uniquely or more highly expressed by tumor and not normal tissue is a powerful tool in the study of cell regulation and growth. To this end we constructed a complementary DNA (cDNA) library from messenger RNA (mRNA) isolated from a human insulinoma and, by differential hybridization with cDNA from both normal pancreas and insulinoma, isolated clones more highly expressed by insulinoma. METHODS: Total RNA was isolated from human insulinoma and normal pancreas and purified to mRNA by oligo (dT) column. An insulinoma cDNA library was constructed and screened with 32P-labeled cDNA from pancreas and insulinoma. Northern blots from insulinoma, pancreas, carcinomas, normal endocrine tissues, and endocrine tumors were then probed with the 32P-labeled inserts. RESULTS: Two clones that consistently hybridized with 32P cDNA from insulinoma and not pancreas proved to represent mRNAs for insulin and the alpha subunit of the Gs protein. There was a markedly higher expression (30-fold) of the gene for Gs alpha in mRNA from insulinoma compared with normal pancreas by Northern blot analysis. We found Gs alpha to be more highly expressed by a pheochromocytoma, a corticotropin-producing islet cell tumor of the pancreas, and a corticotropin-producing thymic carcinoid (up to 35-fold) compared with normal pancreas, whereas normal endocrine tissues, a parathyroid adenoma, thyroid follicular adenoma, gastrinoma, and several carcinomas showed no expression. CONCLUSIONS: This study showed that Gs alpha is highly expressed in insulinoma and certain endocrine tumors. It is not expressed in several cancers or normal endocrine tissues. Others have implicated mutated Gs proteins in the tumorigenesis of pituitary and thyroid tumors. G proteins are also known to mediate hormonal transmembrane signaling. Its overexpression in four of seven endocrine tumors tested suggests that it may have a role in the unregulated hormone secretion and/or a role in the tumorigenesis of differentiated endocrine tumors.

DNA↗

PubMed1992

Surgical strategy in the management of non-small cell ectopic adrenocorticotropic hormone syndrome.

BACKGROUND: Non-small cell ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of hypercortisolism that may require surgery for either curative resection or palliative adrenalectomy. METHODS: We report our surgical experience with 41 patients with ectopic ACTH syndrome and no evidence of small cell lung cancer at initial evaluation. RESULTS: All 41 patients had documented hypercortisolism secondary to ectopic production of ACTH. Based on imaging study results, we determined that 21 patients had localized/resectable disease; eight patients had metastatic disease, and 12 patients had occult disease at examination. Of the 21 patients with localized disease, 16 (76%) were cured of ectopic ACTH by surgery (15 bronchial carcinoid, one pheochromocytoma). Patients with bronchial carcinoid had the greatest probability for cure of ectopic ACTH syndrome, and patients with thoracic primary tumor were more likely to be cured than patients with abdominal primaries. Of the eight patients who had metastatic disease, none were cured of the disease; five patients underwent bilateral adrenalectomy, and three patients were given medical therapy. Only one patient was alive after 5 years. Of the 12 patients who had occult disease, four patients were eventually cured of the disease (three bronchial carcinoid, one thymic carcinoid); one patient died of disease (small cell lung cancer), and seven patients still have occult disease. Nine of 12 patients with occult disease underwent bilateral adrenalectomy for surgical management of hypercortisolism. CONCLUSIONS: This study suggests that the most common primary focus of ectopic ACTH production is within the thorax with 25 of 34 (74%) identifiable tumors originating within either the thymus or bronchus. Adrenalectomy offers excellent palliation of hypercortisolism secondary to either occult or metastatic disease. Patients who initially have localized disease usually have bronchial carcinoids and have a high probability of cure with surgical resection (81%).

ACTH Syndrome, Ectopic↗

PubMed1992

Thymic carcinoid in association with MEN syndromes.

Although carcinoid tumors in association with multiple endocrine neoplasia syndrome (MEN) has been well described, thymic carcinoid in association with MEN is extremely rare (only 23 cases in the world literature). A patient with thymic carcinoid and MEN-I was treated with surgical resection and postoperative radiation therapy, which was later followed by subtotal parathyroidectomy for hyperparathyroidism. Four years later, a symptomatic recurrence of his thymic carcinoid was resected from below his right clavicle. Six years after his original operation, the patient came to the hospital with pancreatitis, and a 5 cm, distal, pancreatic metastasis was resected. He now has symptomatic paraspinal and pleural metastases and is receiving somatostatin. Review of the world's literature shows that the majority of patients with thymic carcinoid and MEN-I are men with an average age of 37 years. Their clinical course is indolent, and surgery represents the only means of cure. Adjuvant chemotherapy and radiation therapy confer no survival advantage. The surgical decision making involved in treating a patient with thymic carcinoid and hyperparathyroidism associated with MEN is also discussed.

Adult↗

PubMed1991

Primary bilateral adrenocortical causes of Cushing's syndrome.

Nontumorous primary adrenal causes of Cushing's syndrome are exceedingly rare. Herein we review our results with seven patients in whom there is biochemical evidence of a primary (adrenocorticotropin independent) bilateral adrenal cause of endogenous hypercortisolism. Each patient had low plasma adrenocorticotropin levels. All patients had elevated 24-hour urinary free cortisol levels and 17-hydroxycorticosteroids that were not suppressed by high-dose dexamethasone. Plasma levels of adrenocorticotropin and cortisol were not elevated by ovine corticotropin-releasing factor. No patient had a gradient between petrosal and peripheral adrenocorticotropin levels. No pituitary tumors were detected by magnetic resonance imaging or computed tomography. Five of six patients who underwent iodocholesterol scanning showed bilateral adrenal activity. Computed tomographic and magnetic resonance imaging of the abdomen demonstrated bilateral small adrenal glands in three patients, an adrenal mass in one patient with Carney's complex, and massively enlarged glands in three patients. Each patient underwent bilateral adrenalectomy and was given glucocorticoid and mineralocorticoid replacement. Pathologic examination of four of these bilateral adrenal specimens revealed primary pigmented micronodular adrenocortical disease, with adrenal gland weights between 2.5 and 13.4 gm (mean 5.2 gm). However, the remaining three patients had primary adrenocorticotropin-independent bilateral macronodular adrenocortical disease with adrenal gland weights between 32 and 81 gm (mean 52 gm). Although each of the patients with primary pigmented micronodular adrenocortical disease was cured by bilateral adrenalectomy through a posterior approach, two of the three patients required an anterior approach. We conclude that Cushing's syndrome can arise through two distinct forms of primary bilateral adrenal cortical disease. Computed tomography is important in evaluation of these patients because the size of the adrenal glands influences the surgical approach.

Adolescent↗

PubMed1991

The significance of gastrinomas found in peripancreatic lymph nodes.

A patient with Zollinger-Ellison syndrome (ZES) was found to have a solitary, extrapancreatic, extraintestinal gastrinoma in a peripancreatic lymph node. Preoperative studies did not show the location of the tumor. After excision of the gastrinoma the patient's fasting serum gastrin level dropped from preoperative levels of 596 pg/ml to 120 pg/ml (normal, less than 200 pg/ml). Fasting and stimulated gastrin levels have remained within the normal range at 18 months follow-up. This patient had previously undergone antrectomy, so it could not be determined if this tumor represented a primary lymph node gastrinoma or metastasis from an unrecognized tumor that may have been present in the resected stomach or duodenum. The outcome of this case confirms the previous reports that ZES can be controlled after resection of gastrinomas that were contained within abdominal lymph nodes, even if a primary enteropancreatic tumor is not found. Our results also support the use of an aggressive operative search aimed at eradication of the tumor in patients with ZES even if preoperative localization studies fail to identify the site of the gastrinoma.

Adenoma, Islet Cell↗