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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

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

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

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

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

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

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

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

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

Hyperparathyroidism due to primary cystic parathyroid hyperplasia.

Cysts of the parathyroid glands are uncommon, and functioning parathyroid cysts that cause primary hyperparathyroidism are rare. A 63-year-old man had primary hyperparathyroidism because of cystic hyperplasia of all four parathyroid glands. He also had squamous cell carcinoma of the soft palate, chronic renal failure, hypertension, type-4 renal tubular acidosis, a hyperplastic thyroid adenoma, and hyporeninemic hypoaldosteronism. To our knowledge, this is the first patient to be described with hyperparathyroidism due to multiple parathyroid cysts. The finding of cystic involvement of all four glands supports the theory that at least some parathyroid cysts are either a result of a common embryologic defect or of retention of parathyoid secretions rather than of cystic infarction of parathyroid adenomas.

Cysts

Parathyroid cysts.

Cystic neck masses may be accurately diagnosed by sonography, and some nonfunctioning parathyroid cysts can be cured by percutaneous aspiration. Primary hyperparathyroidism should be considered in all patients with cystic neck masses. Parathyroid cysts can often be recognized from the characteristics of the cyst fluid which is usually clear and colorless, contains elevated parathyroid hormone levels and normal or low thyroid hormone levels, and may contain parathyroid cells. Parathyroid cysts may be multiple; all four parathyroid glands should therefore be identified and appropriately removed or hyperparathyroidism may persist.

Adult

Significance of lymph node metastasis in differentiated thyroid cancer.

In age-matched patients with differentiated carcinoma of the thyroid, the tumor recurred in 32 per cent of those with lymph node metastases and in 14 per cent of those without lymph node metastases. Twenty-four per cent of patients with nodal involvement at the initial examination died of thyroid cancer, whereas only 8 per cent of those without nodal involvement died of thyroid cancer. In patients less than forty years old, there were no deaths in those without nodal metastases bu there were three deaths (11 per cent) in patients with nodal metastases. In patients more than forty years old, nine (41 per cent) iwth nodal metastases died of tumor, and four (15 per cent) without nodal metastases died of tumor. In the presence of positive nodes the death rate was substantially greater in the older than in the younger patients. Nodal involvement has an adverse effect on prognosis, but appears to be less important than the age of the patient.

Adult