Leslie R. Sheeler

Octreotide Treatment of Acromegaly: A Randomized, Multicenter Study

OBJECTIVE To determine the effects of the somatostatin analog, octreotide acetate, in patients with acromegaly. DESIGN Double-blind, randomized trial. SETTING Fourteen university-affiliated medical centers. PATIENTS One hundred fifteen acromegalic patients, 70% of whom had persistent disease after pituitary surgery or radiotherapy. INTERVENTION Subcutaneous octreotide, 100 micrograms, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 micrograms octreotide subcutaneously every 8 hours for 6 months. RESULTS After 2 weeks of treatment, a single 100-micrograms injection reduced mean serum growth hormone (GH) to 30% of the pretreatment concentration within 2 hours. The integrated mean GH level was reduced over 8 hours from 39 +/- 11 micrograms/L to 9 +/- 2 micrograms/L (P less than 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P less than 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 micrograms/L by 300 micrograms of octreotide and from 29 +/- 5 micrograms/L to 9 +/- 2 micrograms/L by 750 micrograms of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500 +/- 400 U/L after 300 and 750 micrograms octreotide, respectively. Integrated mean GH levels were reduced to < 5 micrograms/L in 53% (95% CI, 39% to 67%) and 49% (CI, 35% to 63%), and IGF-1 levels were normal in 68% (CI, 54% to 82%) and 55% (CI, 40% to 70%) of patients receiving low- and high-dose octreotide, respectively. A substantial decrease in headache, amount of perspiration, joint pain, and finger circumference occurred in two thirds of the patients. The pituitary size was reduced in 19% (CI, 5% to 33%) and 37% (CI, 22% to 52%) of patients receiving 6 months of low- and high-dose octreotide, respectively. Ten percent and 13% of patients in each treatment group developed transient diarrhea; 10% and 14%, biliary sludge; and 6% and 18%, cholelithiasis, respectively. CONCLUSION Octreotide effectively decreased GH and IGF-1 concentrations in 53% and 68% of patients, respectively. The higher dose resulted in increased frequency of tumor shrinkage but added no biochemical or clinical benefit.

Cushing's syndrome and pregnancy

Women with active Cushings syndrome rarely conceive. Only about 69 pregnancies have been reported in women with Cushings syndrome, 60 of whom had maternal and fetal complications. Fourteen of the women have had therapy with unilateral adrenalectomy, bilateral adrenalectomy, pituitary surgery with selective adrenomectomy, or pituitary radiation.

Erdheim-chester disease. Case report and review of the literature

Erdheim-Chester disease is a distinctive pathologic and radiographic entity characterized by bilateral, symmetric sclerosis of the metaphyseal regions of long bones and infiltration of foamy, lipid-laden histiocytes. Clinically, it ranges from an asymptomatic, focal process to a fatal, systemic disease. All previously reported cases of Erdheim-Chester disease are reviewed and a new case with diabetes insipidus, partial hypopituitarism, histiocytic skin lesions, and retro-orbital tumors is presented. An 11-year follow-up reveals progression from a benign, limited process to a progressive, systemic disease. Patients with Erdheim-Chester disease show markedly disparate clinical courses and some features similar to Hand-Schüller-Christian disease. They need careful monitoring and further attempts at treatment.

The natural history of untreated microprolactinomas.

The development of radioimmunoassay (RIA) for prolactin (PRL) and sensitive high-resolution computed tomography (HRCT) has resulted in documentation of large numbers of microprolactinomas (microPRL). To try to define the rate and prevalence of tumor growth, the authors performed serial HRCT scans in 38 untreated patients, an average of 31.7 months apart. In no patient, including two patients with exuberant rises in PRL, was there any evidence of subtle tumor growth. The authors conclude that the majority of patients with microPRL have a benign course, with tumor growth occurring, if at all, over a period of years.

Pituitary Apoplexy: A Complication of Cardiac Surgery

Pituitary apoplexy occurred in 3 patients in the immediate postoperative period following cardiac operation with cardiopulmonary bypass. In this setting, this complication is extremely rare and not widely recognized. Precipitating factors may be related to the extracorporeal bypass apparatus, anticoagulation, low cerebral blood flow, and even anesthetic agents. Neurosurgical decompression can be safely performed in the early postoperative period following open-heart operations.

Adrenal carcinosarcoma presenting in a woman with clinical signs of virilization: A case report with immunohistochemical and ultrastructural findings

An adrenal carcinosarcoma is reported in a 29-year-old female presenting with clinical signs of virilization. This is the first reported case of a functioning adrenal carcinosarcoma in the English language literature. The tumor measured 12.5 cm in greatest dimension, weighed 610 g, and consisted of large areas of typical adrenal cortical carcinoma that was, however, interspersed with multiple foci of sarcoma. Rhabdomyosarcomatous elements were identified and confirmed both immunohistochemically and ultrastructurally. After radical resection, the patient received adjuvant mitotane therapy but developed rapid local and metastatic recurrence. Systemic chemotherapy was unsuccessful, and the patient died 8 months after surgery.

Adrenal insufficiency secondary to carcinoma metastatic to the adrenal gland

Four patients are reported in whom adrenocortical insufficiency developed consequent to carcinoma metastatic to the adrenal glands. Recognition and treatment of this entity may lead to palliation of symptoms and prolongation of useful life. The computerized axial tomographic scanner is a valuable diagnostic aid in diagnosing adrenal enlargement.

Spontaneous resolution of Cushing's syndrome after pregnancy

Pregnancy is a rare occurrence in women with Cushings syndrome. Even more uncommon is the exacerbation of Cushings syndrome during pregnancy and spontaneous resolution post partum. We report one such case in which biochemical and radiologic findings suggested adrenocorticotropic hormone-dependent disease.

Pleural Effusion Resulting from Metastatic Papillary Carcinoma of the Thyroid

We present a patient with a symptomatic pleural effusion resulting from papillary carcinoma of the thyroid metastatic to the pleura. Distinctive features include clinically evident pleural metastasis and the presence of psammoma bodies in the pleural fluid, which are characteristic (albeit not pathognomonic) of papillary carcinoma of the thyroid.

Insulin antibodies and hypoglycemia in diabetic patients. Can a quantitative analysis of antibody binding predict the risk of hypoglycemia

We report a noninsulin-dependent diabetes mellitus (NIDDM) patient with spontaneous, severe hypoglycemic reactions and the presence of insulin antibodies. He had a remote antecedent history of beef-pork insulin therapy as well as exposure to hydralazine. Detailed insulin binding kinetic studies were performed in this patient as well as in six other insulintreated diabetic patients with anti-insulin antibodies (three with and three without an obvious cause of hypoglycemia). Sera from the current patient and five of the six other diabetic patients (one NIDDM, four IDDM) revealed two types of binding sites: high-affinity with low capacity (Kd′, 0.4–12.4×10−9 mol/L; binding capacity, 0.6–659 mU/L) and low-affinity with high capacity (Kd′, 0.3 to 35.7×10−7 mol/L; binding capacity; 202–113,680 mU/L). One NIDDM patient had only high-affinity antibodies (Kd′ 22.9 ×10−9 mol/L; binding capacity of 78 mU/L). Type of diabetes mellitus, insulin antibody titers or their binding capacities, insulin levels (total, bound, or free), and bioavailable insulin were not related to hypoglycemic reactions. Two calculated values by the method described tended to discriminate patients with and without hypoglycemia. The calculated amount of low-affinity antibody bound insulin ranged from 69.4–2090 mU/L vs <4–70.6 mU/L in patients with and without hypoglycemia, respectively. The best discrimination was afforded by the percent saturation of low-affinity binding sites; values were clearly higher in the patients with hypoglycemia (2.5–34.4 %) than in those without hypoglycemia (not detectable, 0.06, 0.15 %). Consideration of the possible drug-associated insulin antibody formation in insulin-treated diabetics and the novel quantitative analysis of the antibody binding kinetics should prove, helpful in evaluating patients with high insulin antibody titers and assessing the risk of hypoglycemia.