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Biomedical subjects

O H Clark

Publications and source records attributed to O H Clark.

At least 19 recordsLinked to original sources
PubMed1992

Normocalcemic hyperparathyroidism. Biochemical and symptom profiles before and after surgery.

Patients with normocalcemic hyperparathyroidism represent a diagnostic and therapeutic challenge. It is unclear to what extent these patients benefit from surgery in terms of correction of their serum chemistry abnormalities and their symptoms. We studied 142 patients: 23 with normocalcemic hyperparathyroidism (serum calcium levels below 2.62 mmol/L), 35 with intermittent hypercalcemia, and 84 with hypercalcemic hyperparathyroidism. Serum chemistry analyses and a standardized questionnaire of symptoms were completed before and after surgery. Overall, patients in the normocalcemic group reported a similar frequency of preoperative symptoms; had a similar reduction in postoperative symptoms; and had a similar normalization of serum calcium, parathormone, and phosphate levels as those in the two control groups. This study indicates that factors other than elevated serum calcium levels are in large part responsible for the symptoms of hyperparathyroidism and that these patients benefit from operation.

Adenoma↗
PubMed1992

Use of color Doppler imaging in the distinction between thyroid and parathyroid lesions.

To determine whether the use of color Doppler imaging in conjunction with standard high-resolution 10-MHz ultrasound could increase the screening sensitivity in distinguishing between thyroid and parathyroid lesions in the detection of parathyroid disease, we studied 32 patients with hyperparathyroidism with both modalities who were subsequently treated surgically. Among these 32 patients, parathyroid lesions were predominantly avascular (n = 21, average size 0.9 x 0.6 cm) but with increased size demonstrated some vascularity (n = 9, average size 2.1 x 1 cm, 32%). Of these 32 patients, 46.6% had thyroid lesions as well. Thyroid lesions were avascular when small (n = 26 lesions, average size 0.5 x 0.5 cm) but tended to demonstrate vascularity (n = 14, 35%) at about 1 cm in size or greater. Although the addition of color Doppler imaging enabled the differentiation of vessel from soft-tissue abnormalities and some distinction between parathyroid and thyroid lesions, it had no effect on overall sensitivity (65%) in the detection of parathyroid disease.

Adult↗
PubMed1992

Hyperparathyroidism in multiple endocrine neoplasia syndrome.

BACKGROUND: We analyzed clinical findings and results of parathyroidectomy in 42 patients treated from 1936 to 1988 at the University of California, San Francisco (UCSF) for primary hyperparathyroidism and multiple endocrine neoplasia (MEN) syndrome to document results of parathyroidectomy and reasons for failed parathyroid operations. METHODS: Of the 42 patients (38 had MEN 1 syndrome; 4 had MEN 2A syndrome), 40 patients were treated surgically: 29 had initial parathyroidectomy at UCSF; 11 were referred to UCSF because of MEN syndrome. Eight of these 11 patients required reoperation for persistent or recurrent hyperparathyroidism. Patients with hyperplasia were treated with subtotal parathyroidectomy; the glands of those patients with solitary or double adenomas were removed with or without biopsy of the normal appearing glands. RESULTS: Overall, in seven (50%) of 14 patients with hyperplasia, three (16%) of 19 patients with solitary adenoma, and one (14%) of seven patients with double adenomas, recurrent or persistent hyperparathyroidism developed. Failure in patients with hyperplasia was due to missed supernumerary glands (13%) and missed ectopic glands (33%). Failure occurred in patients with solitary (three patients) or double (one patient) parathyroid tumors because of unrecognized hyperplasia. None of the four patient with MEN 2A syndrome had persistent or recurrent disease, but hypoparathyroidism developed in one patient; hypoparathyroidism developed in three patients with MEN 1 syndrome. CONCLUSIONS: These data suggest that although many patients with primary hyperparathyroidism and MEN syndrome have multiple abnormal parathyroid glands, two populations of patients exist; one population has solitary or double adenomas and recurrence is uncommon, whereas the other population of patients has hyperplasia and persistent or recurrent disease is common.

Adenoma↗
PubMed1992

Reoperative thyroid surgery.

BACKGROUND: Patients with thyroid cancer are sometimes denied repeat thyroid operations for fear of an increased risk of complications. METHODS: We therefore reviewed our experience in 114 patients with benign or malignant thyroid tumors who underwent 116 thyroid reoperations with or without other procedures. All patients had undergone at least one prior thyroid operation and 16 patients had undergone from two to four thyroid operations before referral. The initial histologic diagnosis before reoperation was thyroid carcinoma in 79 patients, papillary carcinoma in 47 patients, follicular carcinoma in 17 patients, medullary carcinoma in 9 patients, and Hürthle cell carcinoma in 6 patients. Benign disease was present in 35 patients. In 62 patients with cancer, reoperations were performed because of suspected persistent or recurrent disease; one of these patients underwent two reoperations by us. In 17 patients reoperation was to complete total thyroidectomy, primarily so that radioactive iodine could be used to scan for and treat metastatic disease. RESULTS: Among the 116 reoperations, 102 were completion total thyroidectomy, 8 were near-total or subtotal thyroidectomy, and 6 were completion lobectomy. Histologic examination at reoperation revealed thyroid carcinoma in 51 cases (64%) among the 79 patients who had undergone 80 operations for previous thyroid cancer. Recurrent or persistent cancer was present in 49 of 63 (78%) reoperations for patients with papillary, medullary, and Hürthle cell cancer but in only 2 of 17 (12%) patients with follicular cancer. Cancer also occurred in 8 cases (22%) of the 36 reoperations in 35 patients who initially had benign lesions. Complications included one permanent and one transient palsy of the recurrent laryngeal nerve; both occurred on the side of a previous partial or subtotal lobectomy. Other complications included temporary hypoparathyroidism in four patients, seromas in two patients, and a keloid in one patient. CONCLUSIONS: This study documents that reoperations can be performed with minimal morbidity. Thus patients should not be denied the chance to undergo removal of a persistent tumor or the remnant normal thyroid tissue because of the fear of complications.

Adolescent↗
PubMed1991

Calciphylaxis in secondary hyperparathyroidism. Diagnosis and parathyroidectomy.

Calciphylaxis is a rare, severe complication of secondary hyperparathyroidism. Patients present with painful, violaceous, mottled skin lesions of the upper and lower extremities, which become necrotic and produce nonhealing ulcers. Gangrene of fingers and toes frequently requires amputation, produces nonhealing wounds, and can lead to sepsis and death. We reviewed the clinical course of five patients with calciphylaxis treated in our institution. The three men and two women (aged 47 to 72 years) had secondary hyperparathyroidism from chronic renal failure. All patients had severe pruritus, painful ulcers, and severe hyperphosphatemia with elevated serum calcium-phosphate product (greater than 12 mmol2/L2), but the serum parathyroid hormone levels were only moderately elevated. Most patients had medical calcification of medium and small blood vessels, and some had soft-tissue calcification visible on roentgenography. Treatment consisted of local wound care, antibiotics, phosphate-binding agents, and parathyroidectomy. Two patients died of uncontrollable sepsis. The three survivors had dramatic improvement of pain and ulcers after parathyroidectomy. Calciphylaxis is a limb- and life-threatening complication of secondary hyperparathyroidism. Diagnosis can be made by recognizing the characteristic painful skin lesions, ulcers, and gangrene of the digits, and patients should be treated with subtotal parathyroidectomy.

Aged↗
PubMed1991

Diagnosis and management of asymptomatic hyperparathyroidism: safety, efficacy, and deficiencies in our knowledge.

Several recent articles question whether patients with asymptomatic hyperparathyroidism and minimal hypercalcemia should be treated by parathyroidectomy. We therefore reviewed our experience in 103 consecutive patients with primary hyperparathyroidism who were treated by parathyroidectomy to determine, first, how many of these patients had asymptomatic or symptomatic hyperparathyroidism, and second, did these patients benefit from parathyroidectomy? We also analyzed the safety of parathyroidectomy in 426 consecutive patients, including 79 who required reoperation for hyperparathyroidism, specifically looking for complications and the outcome of these procedures. Our study documents the following: (1) only 2 of 103 (2%) patients referred for parathyroidectomy had "true" asymptomatic hyperparathyroidism; (2) only symptoms of fatigue, bone pain, and weight loss correlated with the degree of hypercalcemia, whereas muscular weakness, psychiatric symptoms, nocturia, polyuria, recent memory loss, constipation, and nephrolithiasis did not; (3) only 1 of 15 patients who were referred as asymptomatic were truly asymptomatic after more thorough questioning, and all 14 improved following parathyroidectomy; (4) 81% of the patients who were referred with symptoms improved following parathyroidectomy; and (5) permanent complications occurred in only 4 patients. All but 1 had reoperations for persistent or recurrent hyperparathyroidism (3 vocal cord paralyses and 1 hypoparathyroidism requiring autotransplantation of cryopreserved parathyroid tissue). There was 1 death of an 84-year-old woman with hypercalcemic crisis. Thus, most patients with hyperparathyroidism are symptomatic and benefit symptomatically and metabolically from parathyroidectomy, which is a safe operation.

Female↗
PubMed1991

Thyroid cancer.

There have been important recent advances in our understanding of the biologic nature of thyroid cancer and in the early diagnosis of the disease. Despite these advances, there is still considerable controversy over the management of thyroid cancer, including the extent of surgery, the indications for the use of iodine-131, the effectiveness of thyroid-stimulating hormone suppression, and the prediction of outcome. In this review, the current status of the diagnosis and management of the various types of thyroid cancer are carefully reviewed and extensively documented.

Humans↗
PubMed1991

Increased stimulatory G protein in neoplastic human thyroid tissues.

Prior studies in our laboratory have shown that thyroid neoplasms produce increased amounts of cyclic adenosine monophosphate (cAMP). Thyroid-stimulating hormone receptors act through the stimulatory G protein (Gs) to activate adenylate cyclase, the enzyme responsible for cAMP production. The purpose of this study is to measure the activity and amount of Gs in human normal and neoplastic thyroid tissue to see whether alterations in Gs are responsible for the increased cAMP production seen in thyroid neoplasms. Four tumors with a high TSH-stimulated cyclase activity of 497.6 +/- 71.9 pmol/mg/30 min versus 35.9 +/- 13.5 pmol/mg/30 min for normal tissue from the same patients were studied. In reconstitution studies measuring Gs activity, neoplastic thyroid tissue produced 637 +/- 106 pmol cAMP/mg S49/mg thyroid membrane min versus 363 +/- 133 pmol cAMP/mg 549/mg thyroid membrane/min produced by normal thyroid tissue. Qualitative assessments of the amount of Gs present with cholera toxin-mediated adenosine diphosphate ribosylation showed increased Gs in thyroid tumors. Western blotting with antibodies directed against Gs showed a 3.3 +/- 0.6-fold increase in the amount of Gs in these thyroid tumors. These experiments identify an increase in the amount of an otherwise normal Gs as the biochemical defect responsible for the increased cAMP production in this group of tumors.

Adenocarcinoma↗
PubMed1991

Insulinomas associated with multiple endocrine neoplasia type I: the need for a different surgical approach.

Insulinomas are usually solitary (greater than 90%) benign pancreatic tumors readily cured by enucleation or resection. To determine whether the 4% of insulinomas associated with multiple endocrine neoplasia type 1 (MEN-I) require a different surgical approach, we analyzed our experience in seven patients with MEN-I insulinomas treated during the past 28 years at the University of California, San Francisco, and 53 patients reported in the English literature. We found: (1) MEN-I insulinomas were associated with an antecedent history of other endocrinopathy or a family history of MEN-I in six of our seven patients, allowing preoperative identification of these patients. (2) All seven of our patients had hyperparathyroidism and four had pituitary tumors. Overall 83.6% of patients had hyperparathyroidism and 45.4% had pituitary tumors. (3) In our patients, MEN-I insulinomas were usually multiple (median 3; range 1 to 14). Overall, 76.3% of patients had multiple islet cell tumors. (4) Distal subtotal pancreatectomy with enucleation of any tumors identified in the head of the gland was done in five of our patients. Four are now normoglycemic and one is diabetic. Enucleation alone failed in one patient. The seventh patient was diagnosed at autopsy. Because the diagnosis of MEN-I can generally be made, preoperative strategy can address the unique pathologic features of insulinomas associated with MEN-I. The tumors are usually multiple, so local resection will fail. We recommend subtotal pancreatectomy in addition to enucleation of tumors in the head of the pancreas.

Adolescent↗
PubMed1990

Two G protein oncogenes in human endocrine tumors.

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes. The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary. The mutant alpha i2 gene is a putative oncogene, referred to as gip2. In addition, gsp mutations were found in 18 of 42 GH-secreting pituitary tumors and in an autonomously functioning thyroid adenoma. These findings suggest that human tumors may harbor oncogenic mutations in various G protein alpha chain genes.

Amino Acid Sequence↗
PubMed1990

Results of surgical treatment for hyperparathyroidism associated with renal disease.

Recently, the role and timing of surgery for treating secondary and tertiary hyperparathyroidism (HPT) have been questioned. In order to delineate the indications for surgery in these patients, a retrospective analysis of 53 consecutive patients treated with parathyroidectomy was conducted. Subtotal thyroidectomy was done in 37 of 45 patients undergoing their initial operations for HPT. Eight additional patients were referred after failed operations. Of 33 patients with preoperative bone pain, 70% improved. Joint pain improved in 87% of 30 patients, pruritus improved in 81% of 27 patients, and preoperative malaise improved in 73% of 33 patients after parathyroidectomy. Abdominal pain and irritated eyes were unlikely to improve. The best predictors of a successful outcome were a markedly elevated preoperative immunoreactive parathyroid hormone (mid-region) level and an elevated alkaline phosphatase level. There were no perioperative deaths. One patient (1.6%) had a recurrent laryngeal nerve injury, and one patient required reoperation for a neck hematoma. No patient had permanent hypoparathyroidism, but transient hypocalcemia (less than 7 mg/dL) occurred in 22%. Postoperative hypocalcemia correlated with elevated preoperative alkaline phosphatase levels (r2 = 0.247).

Adult↗
PubMed1990

Iodide-induced hypothyroidism in patients after thyroid resection.

The purpose of this investigation was to determine whether an intrinsic defect in thyroid hormone production is required for the development of iodide-induced hypothyroidism or does it also develop in TSH-stimulated normal thyroid tissue. To answer this question, we studied the response to iodine administration (180 mg iodide daily for 3-4 months) in eight euthyroid patients who had had partial thyroidectomies 2 months to 10 years previously for benign thyroid nodules, and in three euthyroid control subjects. In all 11 euthyroid patients, basal serum TSH concentrations increased during iodide administration. In six of the eight patients who had previous thyroid operations and in two of the three control patients, basal serum TSH concentrations increased into the abnormal range (greater than 6 U ml-1). Increased serum TSH concentrations were noted as early as 1 week after potassium iodide had been started and the increased levels persisted during the period of iodide administration. Although basal values for serum TSH concentration were initially within the normal range, those patients with highest basal serum TSH values developed the greatest increase in TSH in response to potassium iodine. Among the eight patients treated by partial thyroidectomy, serum T4 concentrations decreased in five, serum T3 concentration decreased in three and all five developed mild symptoms of hypothyroidism while receiving iodide. Serum T4 concentrations also decreased slightly in two of the three control patients. Serum total iodine levels increased from 7.0 +/- 0.5 to 315.7 +/- 108.6 g dl-1 (mean-+/- standard error) during potassium iodide administration, but there was no correlation between the level of serum iodide concentration achieved and inhibition of thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Persistent and recurrent hyperparathyroidism: assessment with gadopentetate dimeglumine-enhanced MR imaging.

The effect of gadopentetate dimeglumine on signal intensity of abnormal parathyroid glands was assessed in 14 patients with persistent and recurrent hyperparathyroidism. Non-contrast material-enhanced T1- and T2-weighted spin-echo images were compared with T1-weighted images obtained 1 minute and 10 minutes after administration of gadopentetate dimeglumine. Percentage of contrast between the abnormal gland and surrounding tissue was determined with the use of skeletal muscle, subcutaneous fat, and thyroid gland as reference tissues. All 11 abnormal parathyroid glands showed low to intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Gadopentetate dimeglumine significantly increased the signal intensity enhancement ratio of all abnormal parathyroid glands, causing increased percentage of contrast relative to the thyroid gland and skeletal muscle on T1-weighted images. However, the percentage of contrast relative to these tissues was even greater on nonenhanced T2-weighted images. Thus, gadopentetate dimeglumine can substantially enhance the signal intensity of abnormal parathyroid glands and improve differential contrast with some neighboring tissues on T1-weighted images, but it does not improve contrast with surrounding tissue beyond that achieved on T2-weighted images.

Adipose Tissue↗
PubMed1990

Actin architecture of cultured human thyroid cancer cells: predictor of differentiation?

The actin cytoskeleton is important for cell structure and motility. A disordered actin architecture has been correlated with a high metastatic potential in melanoma, fibrosarcoma, and colon cancer models. Thyrotropin is known to induce growth and differentiation in cultured thyroid cells, whereas the carcinogenic phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) causes dedifferentiation and malignant transformation in many cell lines. We therefore assessed the effect of thyrotropin and TPA on the actin architecture of FTC-133 human follicular thyroid cancer cells in continuous culture. Staining of filamentous actin with rhodamine phalloidin showed that 1 mU/ml or 30 mU/ml thyrotropin-induced actin polymerization was detectable at 1 hour but more notable at 24 hours. Similarly TPA (0.008 to 10 mumol/L) caused rapid actin fiber disruption and redistribution to the cell periphery. Secondary antibody staining for alpha-actinin, a protein that binds and crosslinks actin, was more prominent after treatment with thyrotropin but decreased after TPA. These findings indicate that the actin cytoskeleton has a dynamic response to trophic factors. Thyrotropin promoted actin polymerization, but TPA caused depolymerization. These effects may correlate with cellular alpha-actinin levels. Actin architecture may therefore reflect the state of differentiation of thyroid tumor cells.

Actin Cytoskeleton↗
PubMed1990

Surgery in the treatment of thyroid cancer.

Patients with thyroid cancers offer a clinical challenge to the physician and surgeon for both treatment and research. It is evident that preoperative, intraoperative, and postoperative management can all favorably affect the clinical outcome. This demands close cooperation among internist, endocrinologist, radiotherapist, and surgeon. As surgeons, we advocate total thyroidectomy for most thyroid cancers, when it can be done safely, because recurrences will be minimized and the subsequent use of radioactive iodine treatment is facilitated. In the hands of an experienced thyroid surgeon, total thyroidectomy can be accomplished with a minimum of risk. In the future we hope to be able to identify patients at highest risk for aggressive tumor behavior and select these patients for the most aggressive treatment plans. In other cases early detection by surveillance of patients at risk for thyroid cancer, particularly medullary thyroid cancer, has already favorably affected prognosis by allowing treatment at an earlier stage of disease.

Adenocarcinoma↗