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Biomedical subjects

A M Lawrence

Publications and source records attributed to A M Lawrence.

At least 91 records · Page 5Linked to original sources
PubMed1984

Adult nesidiodysplasia.

Subtotal pancreatectomy specimens from two adults with hyperinsulinemic hypoglycemia and one adult with watery diarrhea syndrome were investigated. All three specimens were originally diagnosed as "nesidioblastosis"; none had a neoplasm, and all patients were cured of their endocrine dysfunction by the surgical procedure. Tissue samples were studied by light microscopy and light microscopic immunohistochemistry for serotonin, ACTH, bombesin, calcitonin, gastrin, glucagon, insulin, HPP, somatostatin, and VIP. The results were compared with those obtained from the parallel study of ten adult pancreata obtained at autopsy from patients without pancreatic disease or endocrine dysfunction. The total endocrine cell mass was not notably greater in the pancreata from patients with endocrine dysfunction than in the controls. Both groups had an estimated 95% of the endocrine cell population organized in islets while the remaining 5% was irregularly dispersed amidst the exocrine ducts and acini. Findings more conspicuous in patients with endocrine dysfunction but not absent in the controls included: large islets, islets with irregular contours and ragged edges, and large individual islet cells with abundant cytoplasm and bizarre nuclei. Immunoreactivity for insulin, glucagon, and somatostatin was demonstrated in all cases; the ratio among these hormones in the patients with endocrine dysfunction and in the controls was similar. In the patients with hyperinsulinemic hypoglycemia, step sections sequentially stained for insulin and somatostatin showed a close topographic relationship between these cell types. In the patient with the watery diarrhea syndrome, VIP immunoreactive cells were easily identified admixed with exocrine components; they were only rarely seen within islets. We suggest that the hyperinsulinemic hypoglycemia in these adults was not due to simple quantitative abnormalities in total endocrine cell mass nor to its maldistribution nor to lack of topographic proximity between insulin and somatostatin cells. We speculate that the syndrome may be based on still unknown derangements of insulin secretion, release, and/or its degradation. In the case of the watery diarrhea syndrome, the readily identifiable VIP immunoreactive cells represent the emergence of a functional expression regarded as ectopic for the endocrine cells of the pancreas. We conclude that nesidioblastosis per se cannot be viewed as the structural basis of these endocrine dysfunctions since many of its features were present in control pancreata lacking any such association.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Successful adrenal autotransplantation in Cushing's disease.

Since Cushing's disease was delineated as a distinct entity, a wide array of therapeutic modalities has been employed to treat its symptoms, which are primarily the result of hypercortisolism. With the advent of pituitary polytomography and the concept of microadenomas, a wave of enthusiasm has developed in recent years in favor of transsphenoidal microdissection. In a recent national survey, however, one third of 30 endocrinologists reported cure rates below 60% and, according to several respondents, recurrence was a serious problem at 50% or greater incidence. We report on four patients treated by bilateral adrenalectomy and autotransplantation. They were weaned off all corticosteroid medication for up to 6 years. Two of the four patients have demonstrable iodocholesterol uptake at the site of autotransplantation. We also report on three additional patients who are taking reduced doses of cortisone. All seven patients have no demonstrable iodocholesterol uptake in the adrenal fossae or other possible ectopic sites. We believe that bilateral adrenalectomy with autotransplantation is a worthy alternative in the long-term treatment of Cushing's disease.

19-Iodocholesterol↗
PubMed1984

Parathyroid carcinoma: biochemical and pathologic response to DTIC.

Parathyroid carcinoma is a rare cause of hyperparathyroidism. Cure results from successful en bloc resection. However, because of its rarity, the malignant nature may not be appreciated at the initial operative procedure and as a result, definitive resection may not be accomplished. However, even with extensive en bloc resections, local recurrences do occur and patients die of metabolic derangements associated with hypercalcemia. Thus in addition to operative intervention, palliative chemotherapy may be required to control the hypercalcemia. Radiotherapy has been unsuccessful. A single case of nonfunctioning parathyroid carcinoma responding to treatment with methotrexate, Adriamycin, cyclophosphamide, and CCNU has been reported. We report a case of recurrent functioning parathyroid carcinoma treated with dacarbazine (DTIC) in which biochemical and pathologic evidence of at least a partial response was seen. The patient, a 33-year-old woman, had undergone five previous neck explorations during a 26-month period for aggressive locally recurrent disease. Before DTIC therapy the intact parathyroid hormone (PTH) level was 1032 pg Eq/ml (normal 163 to 347 pg Eq/ml) and the serum calcium level was 16.8 mg/dl (normal 8.8 to 10.0 mg/dl). After a course of DTIC there was a marked improvement in her clinical status and biochemical parameters (intact PTH 545 pg Eq/ml; serum calcium 11.8 mg/dl). For 2 months her condition stabilized, with PTH levels between 700 and 760 pg Eq/ml and serum calcium levels between 10.2 and 16.0 mg/dl. With a slowly progressive rise in biochemical parameters a second course of DTIC was initiated and a marked drop in serum calcium levels (5.7 mg/dl) occurred, but PTH levels remained unchanged. A progressive course of septicemia, malnutrition, and disseminated intravascular clotting ultimately lead to her death 4 weeks later. At autopsy examination the tumor was confined to the neck. Grossly and microscopically there was extensive central as well as peripheral necrosis of the tumor, which was thought to be the result of the cytotoxic effect of DTIC. From this experience and because of the grim prognosis in patients with recurring parathyroid carcinoma, it may be that aggressive use of chemotherapy with DTIC early in the course of treatment should be considered.

Adult↗
PubMed1984

Hyperparathyroidism unmasked by the treatment of hypothyroidism secondary to Hashimoto's thyroiditis.

Primary hyperparathyroidism masked by untreated hypothyroidism was first noted by Kissin and Bakst in 1947; since then there has been only a single case reported. As a result, it has been thought to be a rare complex of parathyroid disease. During the past 17 years we observed 17 patients who developed primary hyperparathyroidism after their treatment for hypothyroidism (secondary to Hashimoto's thyroiditis) with thyroxine had been well underway. The patients were all women whose ages ranged between 16 and 76 years. The clinical and biochemical manifestations of hyperparathyroidism were noted 2 months to 30 years after thyroxine therapy. All patients underwent standard subtotal parathyroidectomy. Fourteen patients had a single parathyroid adenoma and three had multiglandular adenomatous hyperplasia. It is of interest that all 17 patients were found to have Hashimoto's thyroiditis, based on antimicrosomal antibody titers or histopathologic criteria. Thus we present a series of patients who developed primary hyperparathyroidism in a background of Hashimoto's thyroiditis and hypothyroidism treated with thyroxine. We are intrigued by the association of hyperparathyroidism and Hashimoto's chronic thyroiditis. From this experience it seems appropriate to evaluate parathyroid function in patients with hypothyroidism secondary to Hashimoto's thyroiditis before the initiation of treatment with thyroxine and at intervals thereafter.

Adenoma↗
PubMed1983

Immunoreactive thyroid stimulating hormone (TSH)(: association with synaptosomally-rich fractions in the rat hypothalamus.

The subcellular compartmentalization of brain thyroid stimulating hormone (TSH) in the hypothalamus of the rat was investigated using differential and discontinuous sucrose density gradient centrifugation. When the mitochondrial fraction (P2) was layered on a discontinuous sucrose density gradient (0.32-1.4 M) and centrifuged for 60 min at 72,000 g, TSH recovered from the gradient was found, by double antibody radioimmunoassay, to be associated preferentially with the synaptosomally-rich layers. The separation was monitored by electron microscopic examination of all fractions obtained throughout the procedure. The addition of a large excess of either [125I]-labeled or unlabeled pituitary TSH at the time of homogenization did not influence the amount of immunoreactive TSH associated with the synaptosome-rich fractions, and both the unlabeled and labeled hormone were recoverable in the final supernatant indicating that the simple addition of peptide to hypothalamic homogenates did not result in any preferential association to any particular subcellular fraction. The apparent association of this brain-based pituitary peptide was not, therefore, an artifact of the homogenization process. It is concluded that an association exists between immunoassayable TSH and brain-based synaptosomes in homogenates of the rodent hypothalamus.

Animals↗
PubMed1983

Subtotal parathyroidectomy for primary hyperparathyroidism. Long-term results in 292 patients.

Subtotal parathyroidectomy was performed in a consecutive series of 292 patients with primary hyperparathyroidism. We evaluated the long-term postoperative results during a period of 16 years. Patients ranged in age from 14 to 83 years and included 176 women and 116 men. Of these, 16% had a history of exposure to radiation in childhood or adolescence, while thyroid disease requiring some form of thyroidectomy coexisted in 91 (31%) of the patients. Histologic information on three or more parathyroid glands was obtained in 73% of the cases. We considered 285 patients (97.6%) cured after their first operation. The remaining seven patients (2.4%) had persistent hyperparathyroidism. However, five were cured after a sternum-splitting mediastinal exploration and one after a second neck exploration. The seventh remains hypercalcemic despite a subsequent mediastinal exploration. Temporary postoperative hypoparathyroidism occurred in 10% of our cases and permanent hypoparathyroidism in 1%. There have been no instances of recurrent hyperparathyroidism.

Adenocarcinoma↗
PubMed1983

Fine needle aspiration biopsy of thyroid nodules.

The clinical value of the fine needle aspiration of thyroid nodules was evaluated by comparing preoperative cytology to subsequent pathology in 109 patients undergoing thyroidectomy. Preoperative cytology was reported as insufficient cellular material (31 patients), benign goiter (27 patients), follicular neoplasm (22 patients), thyroiditis (12 patients), suspicious for papillary carcinoma (nine patients), Hurthle cell neoplasm (five patients), medullary carcinoma (one patient), lymphoma (one patient), and metastatic adenocarcinoma (one patient). Operative findings demonstrated that the overall sensitivity of fine needle aspiration in diagnosing thyroid neoplasia (carcinoma or adenoma) was 88% and its specificity was 80%. Operation verified the cytologic diagnosis of medullary carcinoma, lymphoma, metastatic adenocarcinoma, and seven of nine papillary carcinomas. Of the five patients with an aspiration biopsy diagnosis of Hurthle cell neoplasm, three patients had carcinoma and one had an adenoma. Four carcinomas and 12 follicular adenomas were found in patients with a cytologic diagnosis of follicular neoplasm. Thyroiditis was confirmed at operation in all 12 patients with this diagnosis on fine needle aspiration. One carcinoma was found in the 27 patients with benign goiter diagnosed on cytology. Fine needle aspiration is a valuable tool that can lead to earlier diagnosis and treatment of thyroid cancer. However, a negative aspiration does not supplant good clinical judgement in determining the need for thyroidectomy.

Adenocarcinoma↗
PubMed1983

Extrahypothalamic brain luteinizing hormone: characterization by radioimmunoassay, chromatography, radioligand assay and bioassay.

We have recently reported that luteinizing hormone (LH) is present in the hypothalamus of rats. It has chromatographic and biologic characteristics similar to pituitary LH. In this report we focus on extrahypothalamic LH that is widely distributed in the rodent central nervous system. This material has a chromatographic profile similar to that of pituitary LH. Serial dilution of this material is parallel with dilutions of rat pituitary LH in the immunoassay. Brain extracts are active in the testis LH radioligand receptor assay and in the rat interstitial cell testosterone secretion bioassay. Prior incubation of extract with LH antibody significantly attenuated both of these activities. Thus, extrahypothalamic LH has immunologic, chromatographic, and biologic characteristics similar to hypothalamic and pituitary LH.

Animals↗
PubMed1983

Parathyroid cysts: a report of eleven cases including two associated with hyperparathyroid crisis.

Eleven parathyroid cysts were found in 325 patients who underwent parathyroid operations. Ten cysts were located in the neck and one was located in the mediastinum. The cysts ranged in size from 1.6 to 10 cm with a mean of 3.9 cm. The patients who had cysts included six women and five men, and their ages ranged from 28 to 72 years with a mean of 51 years. In contrast to other reports that have suggested that most parathyroid cysts are nonfunctional, all but one of our patients had hyperparathyroidism, as evidenced by hypercalcemia, hypophosphatemia, and elevated parathyroid hormone level, which was corrected by cyst removal. The nonfunctional cyst first appeared to be an asymptomatic neck mass. Two patients had acute hyperparathyroid crises, which required emergency operations. It is postulated that the crises may have been the result of spontaneous necrosis of preexisting parathyroid adenomas. This is supported by the pathologic findings of degeneration and early organization as well as by the presence within the cyst of sanguineous fluid that contained a parathormone concentration greater than 100 times normal serum levels.

Acute Disease↗
PubMed1983

Effects of radiation on parafollicular C cells of the thyroid gland.

While radiation has well-recognized effects on follicular cells of the thyroid gland, those on parafollicular C cells are not yet established. Low-dose radiation that has been proved to be nonablative and carcinogenic to follicular cells was administered to 8-week-old Long-Evans rats to study the changes in C cell number and function. Circulating calcitonin levels were significantly reduced in animals that had undergone radiation at age 24 months. Mean calcitonin values were 0.66 (+/- 0.20) ng/ml and 1.64 (+/- 0.59) ng/ml for control males and females compared with 0.14 (+/- 0.06) ng/ml and 0.11 (+/- 0.01) ng/ml for males (P less than 0.05) and females (P less than 0.001) that had undergone radiation, respectively. These levels correlated well with C cell population density in thyroid glands in the control group and in the group that had undergone radiation as evidenced by light microscopy. Routine hematoxylin and eosin staining showed C cell hyperplasia in 77% of control animals of both sexes compared with 4% in animals that had undergone radiation (P less than 0.005). Immunoperoxidase staining with an anticalcitonin antibody showed virtual absence of C cells in most animals that had undergone radiation compared with diffusely scattered cells in animals in the control group. Medullary carcinomas occurred in 14% of animals in the control group compared with 3% of animals that had undergone radiation (P less than 0.05). These data indicate that the radiation dosage that is carcinogenic to the follicular epithelium causes lethal injury to C cells and thus suggest that C cells are more sensitive to radiation than are follicular cells. This increased sensitivity could explain the virtual absence of C cells, decrease in calcitonin levels, and reduced numbers of medullary carcinomas in the animals that had undergone radiation.

Animals↗
PubMed1983

Successful autotransplantation of parathyroid adenomas in seven patients.

The autotransplantation of normal as well as adenomatous parathyroid tissue is currently being used with increasing frequency. In the present report, we describe our experiences with the successful transplantation of adenomatous or hyperplastic parathyroid tissue in seven patients. Prior to transplant surgery, six of these patients had recurrent or persistent primary hyperparathyroidism. The last patient was on hemodialysis for chronic renal failure and was presumed to have tertiary hyperparathyroidism. A large superior mediastinal parathyroid adenoma was found at a second neck exploration. In all patients, the only remaining parathyroid tissue was either adenomatous or hyperplastic. A total of 30 to 75 mg of this parathyroid tissue was diced and transplanted into single subfascial pockets of the forearm muscles (6) or sternocleidomastoid muscle (1). Following transplantation, all patients required transient calcium and vitamin D supplements for six to 12 weeks. In follow-up studies of ten months to 12 years, all patients have remained eucalcemic with normal parathyroid hormone levels. The use of a single subfascial pocket (versus the popular method of multiple implants) may explain the lack of recurrent hyperparathyroidism in our small population.

Adenoma↗
PubMed1982

Incidental asymptomatic adrenal masses detected by computed tomographic scanning. Is operation required?

Until recently, adrenal masses came to clinical attention either from local symptoms due to massive enlargement or from manifestations of excess hormones production. During the last year, an adrenal mass was identified as an incidental finding in nine patients undergoing abdominal computed tomographic (CT) scanning for unrelated problems. These five men and four women ranged in age from 41 to 73 years. Eight were hypertensive. After the CT scan, each was evaluated for catecholamine or steroid hypersecretion. Only one had clearly elevated urinary vanillylmandelic acid, metanephrine, and catecholamine levels. Equivocal evidence of catecholamine excess was seen in five patients who had slight elevation of one urinary metabolite or of plasma epinephrine or norepinephrine levels. Three patients had no evidence of medullary or cortical hyperfunction on repeated testing. Eight patients were good operative risks and underwent unilateral adrenalectomy without complication. Masses ranging in size from 1 to 4 cm were found in each. These included four cortical adenomas, two adrenal cysts, one adrenal lipoma, and one pheochromocytoma. The pheochromocytoma occurred in the patient with strong biochemical evidence of disease. With wider application of CT imaging, increasing numbers of asymptomatic adrenal masses will be detected. Care in interpreting the clinical significance of these masses and caution in recommending treatment are required.

Adenoma↗
PubMed1982

Growth hormone (GH) immunoreactivity in the rodent and primate CNS: distribution, characterization and presence posthypophysectomy.

Using a specific sensitive radioimmunoassay, the distribution of growth hormone (GH) immunoreactivity in the rodent and primate central nervous system (CNS) was determined. Highest levels of extractable growth hormone-like materials were obtained from the rat amygdaloid nucleus, although other areas including cortex, hippocampus and the thalamus, contained immunoreactive material. Primate hypothalamus showed the highest levels of growth hormone immunoreactivity but it was also detectable in all regions examined. Forty-eight days posthypophysectomy, levels of GH immunoreactivity did not change in most rodent CNS areas studied. Moreover, levels in the amygdaloid nucleus and hypothalamus, although demonstrating an initial fall, actually rose above control levels several weeks following hypophysectomy. Dispersed CNS cells from both intact and hypophysectomized rats continuously released a GH-like material into the growth medium during a 20-day period of tissue culture. This phenomenon was suppressed with the addition of somatostatin to the growth medium. Characterization of this readily extractable GH-like material using column chromatography, parallel displacement curves, and biologic assay in the hypophysectomized rat showed a similarity between the CNS growth hormone-like material and its pituitary counterpart. The blood-brain barrier was found to be most likely intact to circulating pituitary growth hormone lending further support to the CNS origin of this biologically active and immunoreactive GH-like material in the brain.

Amygdala↗
PubMed1982

Prior irradiation and the development of coexistent differentiated thyroid cancer and hyperparathyroidism.

Twelve patients with coexistent well-differentiated thyroid carcinoma and primary hyperparathyoidism were studied to determine the frequency of previous radiation exposure. Eight were found to have received prior irradiation. External radiation was administered to the head and neck region for benign conditions such as tonsillar enlargement, acne, scrofula, and thyroid enlargement. One patient received 131I therapy for carcinoma of the thyroid. The observation that 67% of the patients in this series had previous radiation to the head and neck strongly implicates radiation exposure in the development of coexistent well-differentiated thyroid carcinoma and hyperparathyroidism.

Adult↗
PubMed1982

Growth hormone (GH), thyroid-stimulating hormone (TSH), and luteinizing hormone (LH)-like peptides in the rodent brain: non-parallel ontogenetic development with pituitary counterparts.

Brain and anterior pituitary growth hormone (GH), thyroid-stimulating hormone (TSH) and luteinizing hormone (LH) were measured during fetal, neonatal, and pubertal life and into adulthood. Immunoassayable GH and TSH could be found in the fetal whole brain before their detection in the fetal pituitary. Developmental patterns of pituitary and brain hormones differed in that pituitary hormones showed a gradual rise in levels from birth to puberty at approximately 20 days of age. Biochemically similar, brain-based peptides demonstrated a remarkable preparturitional surge in concentrations that was limited to a few days immediately preceding birth. Twenty-four hours after birth, brain GH, TSH, and LH had dropped to levels equal to or less than concentrations in the neonatal pituitary and subsequently rose to adult levels around the time of puberty. In these studies it could be shown that both the placental-fetal barrier and the neonatal blood-brain barrier were intact. These observations indicate the presence of two biochemically and immunologically similar but topographically distinct pools of peptides present in the developing brain and in the anterior pituitary gland.

Aging↗