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Biomedical subjects

E L Mazzaferri

Publications and source records attributed to E L Mazzaferri.

At least 19 recordsLinked to original sources
PubMed1992

Intervention in Graves' disease. Choosing among imperfect but effective treatment options.

Graves' disease is an autoimmune disorder that comprises the triad of diffuse toxic goiter, ophthalmopathy, and infiltrative dermopathy, although all three are not necessarily present in a given patient. The manifestations of Graves' disease vary, depending on the patient's age and other factors. Choice of therapy is influenced by the patient's age, history of heart disease, pregnancy status, expectations, and preferences. Most patients are treated with either radioactive iodine (sodium iodide I 131 [Iodotope]) or the antithyroid drugs propylthiouracil or methimazole (Tapazole). Antithyroid drugs may be more effective in producing long-term remission if levothyroxine sodium (Levothroid, Levoxine, Synthroid) is added to the regimen after the patient becomes euthyroid. Hypothyroidism occurs in many patients following 131I therapy but is also seen in a substantial number of patients who have been treated with thyroidectomy and even in some who have taken antithyroid drugs. Long-term follow-up is necessary, regardless of type of initial treatment, and should include an annual physical examination and measurement of serum concentrations of thyrotropin and the free thyroxine index, both of which should be maintained in the normal range.

Antithyroid Agents↗
PubMed1992

Detection of the PTC/retTPC oncogene in human thyroid cancers.

We have investigated the PTC/retTPC oncogene, an activated form of ret proto-oncogene with a specific rearrangement, in thyroid malignancies. Southern analysis was used to screen 36 thyroid papillary carcinomas (PC), 22 normal thyroid tissues from glands with PC elsewhere, three follicular carcinomas, eight follicular adenomas and 30 other non-malignant thyroids. Rearrangements were detected in four PCs (11%) using probes derived from the ret proto-oncogene. Genomic breakpoints from a PC and a PC cell line (TPC-1) were cloned and sequenced. The rearrangement points of ret proto-oncogene were found in the intron between the exon for the transmembrane domain and the first exon for the tyrosine kinase domain. Furthermore, the PTC/retTPC chimeric transcripts were detected in two PCs with the rearrangement by reverse transcription polymerase chain reaction. Distant metastases were present in 50% (2/4) of PCs with the rearrangement, but in only two out of 32 PCs without a detectable rearrangement (P = 0.05, Fisher exact test). Our study suggests that the rearrangement of the ret proto-oncogene may be involved in the development of distant metastases in patients with papillary thyroid carcinomas. However, a larger clinical study will be required to verify this observation.

Adolescent↗
PubMed1991

Multiple endocrine neoplasia.

The multiple endocrine neoplasia (MEN) syndromes are well-defined disorders characterized by familial inheritance of specific endocrine tumors. The parathyroid, endocrine, pancreas, and pituitary tumors of MEN-1 are described by frequency and symptomatology. The effectiveness of surgery, symptomatic therapy, and panendocrine suppression by the somatostatin congener octreotide are discussed. Evidence indicates that the MEN-1 gene is located on chromosome 11 and tightly linked markers can help identify family members at risk for inheriting the gene. In MEN-2, the effectiveness of biochemical screening for thyroidal C-cell neoplasms and early thyroidectomy are described. New imaging techniques have been developed to identify medullary thyroid carcinoma and pheochromocytoma in MEN-2. Genetic analysis has identified markers on chromosome 10 closely linked to the MEN-2a gene, allowing better identification of family members likely to develop the syndrome.

Adrenal Gland Neoplasms↗
PubMed1991

Calcitonin gene-related peptide: 24-hour profile and responses to volume contraction and expansion in normal men.

Plasma immunoreactive calcitonin-gene related peptide (CGRP) concentrations were measured in 10 normal male subjects, aged 23-34 yr, who were studied under 3 separate conditions at intervals of at least 1 week. In phase 1, plasma CGRP concentrations were measured hourly for 24 h during normal activity; in phase 2, the CGRP response to diuretic-induced volume depletion and upright posture was measured over 3 h; in phase 3, the CGRP response to volume loading and supine posture was measured over 4 h. During phase 1, the mean 24-h plasma CGRP concentration averaged 30 +/- 16 pmol/L; hourly CGRP concentrations ranged from 25-37 pmol/L over 24 h and oscillated from 16% below to 27% above the mean 24-h CGRP value, changes that were highly significant (P = 0.005). The peaks were at 0600 and 0700 h, while the nadirs were at 1200 and 2000 h. No significant difference was found between fasting CGRP at 0800 h and levels taken 1, 2, and 3 h postprandially (P = 0.68). During phase 2 (volume depletion and upright) mean plasma CGRP rose significantly, going from a baseline of 42 +/- 8 pmol/L at 0800 h to a peak of 60 +/- 10 pmol/L at 1100 h (P = 0.0005). The percent CGRP increment was relatively small (26% to 42%) compared to the rise in PRA (518% to 1033%) and aldosterone concentrations (333% to 465%). Hematocrit increased from 40.5 +/- 0.7% to 45.8 +/- 0.7% (P = 0.0001) in phase 2, while serum osmolality did not change significantly. In phase 3 (volume loading and supine), plasma CGRP did not change significantly, while PRA and aldosterone concentrations fell significantly (P = 0.0001); neither serum osmolality nor hematocrit changed significantly. We conclude that plasma CGRP concentrations fluctuate spontaneously and significantly during the day, and rise in response to volume depletion. The reasons for the CGRP fluctuations seen over 24 h, which are not apparent from this study, may be related to changes in vascular volume or other as yet unidentified factors. These studies are consistent with the concept that CGRP, acting either directly or through the renin-aldosterone system, may have a role in regulating peripheral vascular tone or controlling vascular volume.

Adult↗
PubMed1990

Cystic thyroid nodules. The dilemma of malignant lesions.

A retrospective study of 221 surgically resected thyroid nodules disclosed that 71 (32%) were cystic and 150 (68%) were solid lesions. Ultrasonography correctly characterized cystic nodules in all but one case. Comparing cystic and solid nodules, there were no differences in patient demographics (mean ages, 47.7 +/- 1.8 SEM vs 45.9 +/- 1.2 years; sex, 78% females both groups), the proportion that were solitary (39% vs 40%), or the nodule size (49% vs 47% greater than or equal to 2 cm in diameter). Of cystic thyroid lesions, 4% were simple cysts, 82% were degenerating benign adenomas or colloid nodules, and 14% were malignant compared with 23% of solid lesions that were malignant. Most cystic lesions (81%) contained bloody fluid. One benign true cyst was filled with thick brown fluid, while clear yellow fluid was repeatedly aspirated from one malignant cystic nodule. Malignant fine-needle aspiration cytology was the best predictor of cancer (100%). Much less predictable were signs of local compression or invasion (43%), a history of head or neck irradiation (33%), cyst recurrence after aspiration (29%), or an increase in the cystic nodule's size (7%). Indeterminate cytology identified malignancy with about half the frequency in cystic lesions as compared with solid nodules (13% vs 27%). The only false-negative fine-needle aspiration cytology occurred in a cystic lesion. In patients with cystic papillary cancers, needle aspirates contained insufficient material for diagnosis in 20% that occurred in no patient with solid papillary carcinoma. The sensitivities and specificities of fine-needle aspiration cytology for solid nodules were 100% and 55%, and for cystic nodules were 88% and 52%. Thus, cystic lesions are as likely as solid thyroid lesions to harbor a malignancy that cannot be predicted from the cyst's clinical characteristics or the patient's demographic data. Although fine-needle biopsy is the best predictor of malignancy in either cystic or solid thyroid lesions, it is slightly less reliable when a thyroid lesion is fluid filled rather than solid. We believe that most cysts not abolished by aspiration should be surgically excised.

Adult↗
PubMed1990

Gastric inhibitory polypeptide mechanisms of augmenting insulin secretion.

The cellular mechanisms whereby gastric inhibitory polypeptide (GIP) augments glucose-dependent insulin secretion remains poorly defined. Since glucose-dependent insulin secretion is modulated by membrane associated phospholipase A2 (PLA2) and intracellular lipoxygenase (LPX) and cyclooxygenase (CO) we hypothesize that GIP's augmentation of insulin secretion involves these enzyme systems. Neonatal rat pancreatic islet cell cultures were preincubated with 5.6mM glucose for 60 minutes. The cultures were then stimulated for 60 minutes with 16mM glucose alone or with GIP with or without the addition of PLA2, LPX, and CO inhibitors. Insulin secretion significantly increased (P less than 0.05) when the glucose concentration was raised from 5.6 to 16mM glucose and this was further augmented by the addition of GIP (P less than 0.05). PLA2 inhibitors significantly (P less than 0.025) decreased 16mM glucose insulin secretion but this was restored by the simultaneous addition of GIP. LPX inhibitors significantly (P less than 0.01) decreased glucose-dependent insulin secretion and this decrease persisted despite the addition of GIP. Simultaneous treatment of islet cell cultures with GIP and CO inhibitors yielded insulin responses that were indistinguishable from CO inhibition alone. These studies suggest that GIP exerts its influence in part by modulating membrane associated PLA2 activity. Furthermore, the formation of intracellular LPX products appears to be a pivotal step in the insulinotrophic action of GIP.

Analysis of Variance↗
PubMed1990

Thyrotoxicosis. Results and risks of current therapy.

Effective therapy for thyrotoxicosis hinges on prompt recognition of the syndrome. When the diagnosis is suspected clinically but is not certain, the free thyroxine index is the most cost-effective test to order initially. The thyroidal radioactive iodine (123I) uptake is measured to differentiate Graves' disease from thyroiditis and other forms of thyrotoxicosis. Definitive therapy includes antithyroid drugs, iodine 131, and surgery. Patient preference has a large role in the final therapeutic choice.

Adrenergic beta-Antagonists↗
PubMed1989

Sensitivity, specificity, and cost-effectiveness of the sensitive thyrotropin assay in the diagnosis of thyroid disease in ambulatory patients.

The sensitivity and specificity of two sensitive thyrotropin assays were compared with those of other standard thyroid function tests in 544 ambulatory subjects who were clinically euthyroid, thyrotoxic, or hypothyroid. Both sensitive thyrotropin assays had the highest sensitivity and specificity (95%/89% and 92%/95%), following by estimated free thyroxine (T4) level (82% and 94%), calculated free T4 index (78% and 93%), and free triiodothyronine index (86% and 88%). Sensitivity of the two thyrotropin assay kits in the diagnosis of thyrotoxicosis was 86% and 95%, and that in the diagnosis of hypothyroidism was 92% and 94%. Other tests were nearly as sensitive in the diagnosis of thyrotoxicosis but not hypothyroidism. A cost analysis of a testing strategy that used either total T4, free T4 index, or sensitive thyrotropin assay alone as the first-line thyroid test disclosed that to establish the patient's thyroid metabolic status would have cost $11,093, $14,536, and $24,902, respectively, using each test first. We suggest that, at current prices, routine use of the thyrotropin assay as a first-line test in ambulatory patients is not as cost-effective as the free T4 index.

Adult↗
PubMed1989

Thyroid function tests. Guidelines for interpretation in common clinical disorders.

While a wide variety of thyroid function tests are currently available, all are sometimes abnormal in patients without thyroid disease. To interpret test results properly, the clinician needs to be aware of factors altering thyroid function tests. In every instance, the clinician needs to begin by asking whether the patient is thyrotoxic or hypothyroid and then should order a test to substantiate or exclude the diagnosis. In this way, accurate and early diagnosis of thyroid dysfunction can be routinely established.

Algorithms↗
PubMed1989

Hemoptysis as the presenting manifestation of thyroid carcinoma. A case report.

An unusual case of a 61-year-old man who had hemoptysis as the major presenting manifestation of radiation-induced thyroid carcinoma is reported. The diagnosis was made by bronchoscopic removal of a polypoid lesion that was a direct extension of tumor through the trachea. Bronchoscopy is an effective and reliable means of establishing the diagnosis in this unusual subset of patients with thyroid carcinoma invading the trachea, and should be considered as the first diagnostic procedure in a patient with a thyroid mass and hemoptysis.

Bronchoscopy↗
PubMed1988

Solitary thyroid nodule: diagnosis and management.

Thyroid nodules are common. Most are benign lesions since clinically important thyroid carcinoma is a relatively rare disease. The most sensitive and specific test for the diagnosis of thyroid cancer is fine-needle aspiration biopsy, but its diagnostic accuracy depends upon whether or not one excises all suspicious nodules, thus including them as correctly diagnosed. Nevertheless, fine-needle aspiration biopsy is the most sensitive, specific, and cost-effective test for thyroid cancer. Therapy depends upon the cause of the thyroid nodule.

Adenoma↗
PubMed1988

Effect of source of dietary fats on serum glucose, insulin, and gastric inhibitory polypeptide responses to mixed test meals in subjects with non-insulin dependent diabetes mellitus.

We recently demonstrated that normal subjects given mixed test meals of varying fatty acid composition showed significantly greater serum insulin responses to meals enriched with polyunsaturated fat as compared to those in which the fat content was derived from saturated fatty acids. To determine if a similar phenomenon occurs in subjects with non-insulin dependent diabetes mellitus (NIDDM), serum glucose, insulin, C-peptide, and gastric inhibitory polypeptide (GIP) responses to three mixed test meals of varying fatty acid composition were assessed in twelve subjects with NIDDM. Baseline means (+/- SEM) fasting serum glucose concentration was 205 +/- 15 mg/dl and mean glycosylated hemoglobin was 8.5 +/- 0.5%. Fatty acids in the test meals were either saturated fats, or polyunsaturated fats derived from vegetables or fish. Each test meal provided 40% of the subjects' calculated daily caloric requirement and contained approximately 45% carbohydrate, 40% fat, and 15% protein. No appreciable differences in serum glucose, insulin, and C-peptide responses occurred during the three mixed test meals. Although GIP values were higher in the saturated fat and the vegetable meals when compared to the fish meal, the differences did not reach statistical significance. The inability of NIDDM subjects to evoke a greater insulin response to polyunsaturated fatty acids than to saturated fatty acids suggests another pathogenetic factor contributing to their glucose intolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗