Fatty acid composition of adipose tissue, an indication of dietary fatty acids, and breast cancer prognosis.

PURPOSE: Fatty acid composition of adipose tissue is an indicator of the long-term ingestion pattern of several specific fatty acids. There is good correlation of antecedent diet with the essential fatty acids, and there is reflection of the diet with the fatty acids that can be synthesized. The relationship between the fatty acid levels and lymph node status and clinical outcome was examined. METHODS: At the time of diagnostic surgery, 161 women with clinical stage T1NO breast cancer had subcutaneous adipose tissue (breast and abdominal) aspirated. The concentrations of 35 fatty acids, seven summed classes, and six fatty acid groups were measured by capillary gas chromatography. Lymph node status was determined with axillary dissection, and patients were followed-up (mean, 7.3 years) for clinical outcome. RESULTS: There was no significant association of any adipose tissue fatty acids with overall survival, although few (16 of 161 women) died of breast cancer. However, the odds of having positive lymph nodes (57 of 161 women) were significantly higher for women with a greater adipose tissue proportion of oleic acid (odds ratio [OR], 7.56; 95% confidence interval [CI], 1.78 to 32.1) or total saturated acids (OR, 8.43; 95% CI, 1.48 to 40.0) and significantly lower with a higher proportion of trans fatty acids (OR, 0.24; 95% CI, 0.07 to 0.77), as assessed by multivariate logistic regression. CONCLUSION: These data support previous research with dietary questionnaire methodology, suggesting that specific dietary fatty acids may be associated with breast cancer promotion. Further research with long-term clinical follow-up is necessary to investigate these observations in large, diverse populations before dietary recommendations can be envisioned.

Is body fat topography a risk factor for breast cancer?

OBJECTIVE: To determine whether body fat distribution is associated with the onset of breast cancer. DESIGN: Case-control study. SETTING: Memorial Sloan-Kettering Cancer Center, New York, New York. PATIENTS: Three hundred thirteen healthy, white women, born in the United States. MEASUREMENTS: Waist and hip circumferences were measured on the day before diagnostic breast surgery, and an extensive risk assessment of clinical and family history data was done. After the results of diagnostic breast surgery were obtained, study participants were divided into three groups: women with breast cancer (n = 156); controls (n = 126) with benign tissue at biopsy and an average risk for breast cancer; and high-risk women (n = 31), defined as being at a risk for breast cancer development of 1% per year, based on rigorous histologic or clinical criteria. RESULTS: The waist-to-hip ratios (WHR) were identical (mean +/- SD) in case patients (0.80 +/- 0.06), controls (0.80 +/- 0.06), and high-risk women (0.80 +/- 0.08). Further, no trend could be detected between increasing WHR and breast cancer risk; the estimated relative risk for cancer incidence in women with WHR greater than or equal to 0.81 was 0.78 (95% Cl, 0.36 to 1.71), compared with women with WHR of less than 0.73. No difference in WHR was noted between the case patients and controls when analyzed separately according to menopausal status, age, absolute weight, or relative weight. CONCLUSION: In the women studied, body fat topography as defined by WHR was not associated with breast cancer development.

Four cycles of chemotherapy and regional radiation therapy for clinical early-stage and intermediate-stage Hodgkin's disease.

To achieve a high percentage of durable complete remissions (CR) and prolonged survivals and reduce toxicity in patients with early-stage and intermediate-stage Hodgkin's disease, a randomized trial of four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa, bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT) was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5 years, the percentage of patients in CR was 90%, with freedom from progression of 89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of 59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and overall survival of 91% (P greater than 0.15). The median follow-up was 65 months (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2 relapses and 2 deaths. Short-term toxicity except for transient leukopenia was less for TBV and RT than for MOPP and RT. Good results are achievable with combined treatment without excessive toxicity.

The diagnosis and management of hypomagnesemia: a unique treatment approach and case report.

Hypomagnesemia is a common but frequently overlooked electrolyte disorder that occurs as part of a complex metabolic profile. It often is associated with a spectrum of nonspecific symptoms secondary to other electrolyte deficiencies. These symptoms then are associated with the primary illness, thereby masking the presence of this disorder. In most clinical situations, magnesium deficiency is transitory and responds well to short-term supplementation. Certain populations of patients with cancer may have an increased risk of developing severe hypomagnesemia requiring continued supplementation; patient populations receiving aminoglycoside antibiotics or cisplatin therapy are considered to be high-risk groups. This paper describes the causes, signs, and symptoms of chronic hypomagnesemia; patient populations at risk of developing this disorder; and a unique treatment approach using a subcutaneous pump infusion system. A case study illustrates the complexity of clinical and nursing management of this disorder.

Metabolic consequences of (regional) total pancreatectomy.

Little information has been reported on the metabolic characteristics of the totally pancreatectomized patient or the efficacy of medical management after radical pancreatic surgery. The prospective evaluation of 49 such patients, with 31% followed for 48 or more months, forms the basis of this report. The major immediate postoperative challenge is control of diarrhea and weight stabilization. Chronically patients have an increased daily caloric requirement (mean +/- SE, 56 +/- 1 kcal/kg), not wholly explained by moderate steatorrhea (fecal fat excretion, 16% +/- 2% of unrestricted fat intake). Despite persistent malabsorption, deficiencies in fat-soluble vitamin, magnesium, and trace element serum levels can be prevented in most patients. Pancreatogenic diabetes is characterized by (1) absence of the major glucoregulatory hormones insulin and glucagon, (2) instability, and (3) frequent hypoglycemia, with the latter parameters improving with rigorous home glucose monitoring. No patient has developed clinically overt diabetic micro- or macrovascular disease. Performance status in long-term survivors has been reasonable. However adverse chronic sequelae of the operation occur and include an unusual frequency of liver disease, characterized by accelerated fatty infiltration, and osteopenia, with an 18% reduction in radial bone mineral content noted in pancreatectomized patients studied more than 5 years after surgery.

The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia.

With the euglycemic clamp technique, we evaluated the effects of graded doses of insulin on glucose turnover rates and forearm lactate balance in five weight-losing patients with cancer before surgery and five age- and weight-matched healthy volunteers (control subjects). Insulin was infused sequentially at increasing rates of 0.5 (low physiologic), 1.0 (high physiologic), and 4.0 (supraphysiologic) mU/kg.min for 120 minutes each. Concurrently, rates of glucose appearance and disappearance were derived from [3-3H] glucose infusion. The mean postabsorptive rate of glucose appearance in patients (2.9 +/- 0.1 mg/kg.min) was significantly higher (p less than 0.02) than that of control subjects (1.98 +/- 0.16 mg/kg.min). Complete suppression of endogenous glucose production occurred at high physiologic insulin concentrations. With progressive insulin infusion, the rate of glucose disappearance increased to 3.6 +/- 1.2, 8.7 +/- 0.8, and 13.7 +/- 1.1 mg/kg/min in control subjects and 2.9 +/- 0.4, 5.3 +/- 0.3, and 10.9 +/- 0.9 mg/kg.min in patients, significantly different from that of control subjects (p less than 0.05) during the intermediate (high physiologic) insulin infusion. A comparable slight increase in arterial plasma lactate concentration was observed in both groups with progressive hyperinsulinemia. Baseline peripheral lactate flux was identical in patients (-272 +/- 56 nmol/100 gm.min) and in controls (-271 +/- 57 nmol/100 gm.min). Progressive physiologic hyperinsulinemia resulted in significantly (p less than 0.05) augmented peripheral lactate efflux in patients (-824 +/- 181 nmol/100 gm.min) compared with control subjects (-287 +/- 64 nmol/100 gm.min). Supraphysiologic insulin abolished this increased lactate efflux in patients. Postabsorptive rates of endogenous glucose appearance in weight-losing patients with cancer were elevated, but complete suppression was achieved with insulin concentrations in the physiologic range. Total body glucose use was diminished in these patients, consistent with a state of insulin resistance. This impaired insulin action on peripheral glucose use was associated with an increase in peripheral lactate release in patients.

Insulin secretion and action in patients with pancreatic cancer.

The authors investigated insulin secretory capacity and insulin action in 11 preoperative patients with pancreatic carcinoma and 15 age-matched and weight-matched healthy subjects (C). Five patients were classified as diabetic (D), two as impaired glucose tolerant (IGT), and four as nondiabetic (ND). Postabsorptive serum insulin levels (mean +/- SE, in uU/ml) in D (12 +/- 2), IGT (17 +/- 7), and ND (10 +/- 2) were comparable. After administration of 100 g of oral glucose, peak insulin achieved in D (60 +/- 11) was lower than in IGT (101 +/- 26) and ND (83 +/- 20), whereas peak insulin levels in IGT and ND were significantly (P less than 0.05) higher than in C (45 +/- 6). Comparable insulin response to nonglucose stimuli was documented in all subjects using the slow arginine infusion test with mean serum insulin of 27 +/- 4 in D, 28 +/- 6 in IGT, 34 +/- 10 in ND, and 32 +/- 5 in C. In six patients (P) and six controls, insulin action was assessed by the euglycemic hyperinsulinemic clamp technique, with glucose turnover rates estimated by [3-3H]glucose infusion. Steady-state plasma glucose concentrations were maintained at 92 +/- 3 (P) and 91 +/- 1 mg/dl (C). After insulin infusion at the rate of 1.0 mU/kg/min, comparable high physiologic insulin levels were observed in P (73 to 104 uU/ml) and in C (81 to 103 uU/ml). Postabsorptive rates of endogenous glucose appearance (Ra) were higher in P (2.86 to 3.02 mg/kg/min) than in C (1.50 to 2.80 mg/kg/min). At high physiologic insulin concentrations, negative Ra values were documented in all subjects, and complete suppression of Ra was assumed. Total body glucose use (M) was consistently lower in P (3.90 to 6.40 mg/kg/min) than in C (6.98 to 10.40 mg/kg/min), consistent with a state of insulin resistance. Patients with pancreatic cancer manifest insulin resistance by virtue of a decrease in total body glucose use (M) and decreased insulin response to glucose due to either inherent beta cell dysfunction or decreased islet cell mass. The latter is not identifiable by histologic morphology.

Adrenal insufficiency in the cancer patient: implications for the surgeon.

Aspects of acute and chronic adrenal insufficiency of interest to surgeons who treat cancer patients are reviewed. Clinical features and the management of both primary and secondary types are considered with reference to classification, aetiology, diagnosis and treatment. Specifically considered are the management of patients with Addison's disease and metastases. Prompt recognition and treatment of adrenal insufficiency can avert potentially life-threatening situations.

Clinical manifestations of cancer-related hypercalcemia.

Hypercalcemia is a potentially lethal endocrine disorder occurring in 10% to 20% of cancer patients at some time during the course of their disease. Clinical manifestations vary in severity, depending on the degree and duration of hypercalcemia, rapidity of onset, patient's age, performance status, sites of metastases, previous antineoplastic therapy, and the presence of hepatic or renal dysfunction. The clinical features of hypercalcemia are protean and affect multiple organ systems, resulting most prominently in neurologic, gastrointestinal, renal, cardiovascular, and musculoskeletal morbidity. Recognition of the disorder requires a high index of suspicion because many of its symptoms, such as nausea, anorexia, weakness, fatigue, lethargy, and confusion, are non-specific and, in the patient with a malignancy, can result from other complications of the primary disorder. If identified appropriately as being related to hypercalcemia, such symptomatology is potentially reversible with treatment. Whereas in the ambulatory general medical population the most common cause of hypercalcemia is primary hyperparathyroidism, in cancer patients and hospitalized patients in general, the most common cause is malignancy. Hypercalcemia in cancer patients is, in most cases, due to advanced metastasized disease. Diagnostic tests are useful in the differential diagnosis of hypercalcemia, and such tests, together with an accurate history and careful clinical observation, permit the best therapeutic approach to an individual patient.

Bone mineralization in women following successful treatment of Hodgkin's disease.

PURPOSE: Women with Hodgkin's disease in whom a cure has been achieved may be at risk for osteoporosis because of therapy-induced premature menopause. Our objective was to gather information regarding the integrity of bone mass in such long-term cancer survivors. SUBJECTS AND METHODS: Bone mineral density was measured using photon absorptiometry in five groups of women: 11 patients with Hodgkin's disease and ovarian failure (Group I); six patients with Hodgkin's disease and ovarian failure who received estrogen replacement (Group II); 15 patients with Hodgkin's disease and normal ovarian function (Group III); 16 premenopausal control subjects (Group IV); and 11 postmenopausal control subjects (Group V). All patients with Hodgkin's disease were in remission and had completed treatment more than five years earlier. RESULTS: Subjects in Group I were found to have significantly decreased radial (p = 0.0009), lumbar spine (p = 0.002), and femoral neck (p = 0.0001) bone mineral density measurements compared with those in subjects in Group IV; the bone mineral density measurements at all sites of subjects in Group I were no different than those of subjects in Group V. Subjects in Group III had bone density measurements that were similar to those in Group IV, although the radial bone mineral density value was significantly lower (p = 0.0004). Determination of serum gonadotropins and estradiol was consistent with the menstrual status defining the five groups. No secondary causes for decreased bone mineral density values could be detected, since the mean serum levels of parathyroid hormone, calcium, phosphorus, and vitamin D metabolites were similar among the groups, and all prolactin levels were normal. CONCLUSION: We have identified a new population of patients with a high risk of osteoporosis, and these results emphasize the importance of treatment-related ovarian failure in the pathogenesis of osteoporosis.

Testicular failure in patients with extragonadal germ cell tumors.

Eight patients with mediastinal or retroperitoneal germ cell tumors who had undergone testicular biopsy or orchiectomy were retrospectively analyzed for primary testicular abnormalities, subfertility, and abnormal sex hormone levels. Testicular tissue was abnormal in all patients, revealing peritubular fibrosis (six), decreased spermatogenesis (eight), interstitial edema (five), Sertoli cells only (one), and Leydig cell hyperplasia (two). Detailed hormone analysis in five patients revealed elevations of luteinizing hormone in four, decreased serum testosterone in two, elevations of estradiol in two, and elevation of human chorionic gonadotropin in one patient. A history of infertility was documented 2 months to 13 years before presentation in four patients and suspected in another. Extragonadal germ cell tumors, like their testicular counterparts are associated with primary germ cell defects, some of which seem to be independent of gonadotropin production by the tumor. In addition, the rather high incidence of antecedent infertility suggests that either a congenital or acquired primary germ cell defect contributes to defective spermatogenesis and the development of cancer in incompletely migrated germ cells.

Endocrine and exocrine profiles of men with testicular tumors before orchiectomy.

In 15 patients with germ cell testicular tumors serum hormone profiles and semen analysis before orchiectomy were evaluated to determine the incidence of defective spermatogenesis associated with testicular tumors. Defective spermatogenesis was noted in 10 patients (66 per cent) on the basis of low sperm concentration, motility or semen volume. Of the 10 patients 7 had sperm concentrations less than 10 million per cc. Endocrine abnormalities occurred in 10 patients, the most common of which were elevations in serum human chorionic gonadotropin and estradiol, and a relative decrease in follicle-stimulating hormone. Three patients who presented with subfertile semen analyses were treated with orchiectomy alone. Repeat semen analyses 4 to 12 months after orchiectomy showed improvement in spermatogenesis and 2 patients achieved a normal semen analysis. Endocrine abnormalities and defective spermatogenesis are common in patients with testicular tumors. These abnormalities precede orchiectomy and imply that a primary germ cell defect exists in these patients.

Semen cryopreservation and artificial insemination for Hodgkin's disease.

Seventy-nine men with Hodgkin's disease were treated with chemotherapy protocols at Memorial Sloan-Kettering Cancer Center and had pretreatment semen analysis performed at the area semen bank. The patients were evaluated to determine: the quality of pretreatment semen, the effect of treatment on spermatogenesis, and the success rate of artificial insemination after semen cryopreservation. Pretreatment sperm concentration, fresh motility, fresh progression, postthaw motility and postthaw progression were all significantly decreased in men with Hodgkin's disease compared with normal controls. Posttreatment semen analysis in 44 men showed azoospermia in 80%, sperm concentration, less than or equal to 10 X 10(6)/mL in 11%, and sperm concentration greater than 10 X 10(6)/mL in 9%. Eleven couples attempted artificial insemination using cryopreserved semen, thus far resulting in three pregnancies. Semen cryopreservation and artificial insemination offer a partial solution to posttreatment azoospermia in this population, but further methods are needed to minimize gonadal toxicity without compromising therapy for Hodgkin's disease.

Pituitary and testicular hormonal function after treatment for germ cell tumours.

The endocrine effects of cisplatin based chemotherapy in patients with germ cell tumours were studied in twenty-two patients 9+ to 24+ months after completing treatment. The mean basal FSH and stimulated LH and FSH levels were found to be elevated in treated patients when compared to untreated controls. Serum testosterone levels in treated patients were similar to those in untreated controls. Mean basal LH and FSH levels tended to return toward normal in those patients treated more than 18 months prior to study, and were lower in patients less than 25 years of age at the time of treatment when compared to those aged over 25. These data demonstrate that compensated hypogonadism is common after treatment for metastatic germ cell tumours, that young patients appear to be more resistant to the effects of cisplatin based chemotherapy, and that these effects tend to recover with time.

Gonadal dysfunction in patients treated for metastatic germ-cell tumors.

The effects of chemotherapy on endocrine function were assessed in 22 previously treated patients with germ-cell tumors and compared with the endocrine function of six previously untreated patients. Baseline and stimulated serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, thyroid-stimulating hormone (TSH), prolactin, and thyroxine (T4) were obtained. Baseline LH levels were elevated in both groups of patients, whereas basal FSH levels were significantly elevated only in treated patients (P less than .001). Following gonadotropin-releasing hormone (GnRH), levels of LH (P = .051) and FSH (P = .003) were greater in treated patients than in untreated control patients. No abnormalities of thyroid function or prolactin responsiveness were observed. Patients younger than 25 years of age at the time of treatment had lower serum levels of LH and FSH following chemotherapy than patients older than 25. Evidence for partial recovery of gonadal function was present with patients treated more than 18 months before study having lower levels of LH and FSH than those patients studied less than 18 months after treatment. These data demonstrate that frequent gonadal dysfunction exists in untreated patients with germ-cell tumors and that chemotherapy induces additional injury to both Leydig cells and the germinal epithelium. Further studies with long-term follow-up are necessary to define the pattern of gonadal recovery and to assess the potential sequelae of endogenous gonadotropin hypersecretion.

Total pancreatectomy increases the metabolic response to glucagon in humans.

To evaluate the impact of glucagon deficiency on the response to glucagon replacement, we infused physiological doses of glucagon (1.25 ng/kg X min) into 9 totally pancreatectomized (PX) diabetic patients (C-peptide, undetectable) 1) for 24 h during their usual diet and insulin regimen and/or 2) for 6 h in a fasted insulin-withdrawn state. During both glucagon infusions, plasma glucagon rose from 46 +/- 2 (+/- SE) pg/ml (0-10% 3500 mol wt glucagon) to 112 +/- 9 pg/ml. In the 24-h study (n = 4), glucagon significantly increased mean 24-h glucose levels (272 +/- 27 mg/dl; P less than 0.05) and glycosuria (29 +/- 5 g/day; P less than 0.01) compared to preinfusion (158 +/- 14 mg/dl and 4 +/- 4 g/day, respectively) and postinfusion (200 +/- 35 mg/dl and 3 +/- 2 g/day) control periods. Blood ketones did not change. The 24-h glucagon infusion significantly lowered the fasting levels of the glucogenic amino acids aspartate (43%; P less than 0.01), threonine (46%; P less than 0.05), serine (46%; P less than 0.02), glycine (47%; P less than 0.01), and methionine (34%; P less than 0.02). Fasting alanine levels decreased from 835 +/- 236 to 393 +/- 66 microM (P less than 0.05). The 6-h glucagon infusion caused a 101 +/- 14 mg/dl maximal plasma glucose increment in PX (n = 8) vs. 33 +/- 11 in 5 insulin-withdrawn type I diabetic patients serving as controls (P = 0.022). Furthermore, when glucagon was infused at a higher rate (3 ng/kg X min) in 12 additional type I diabetic patients, the mean maximal plasma glucose increment (54 +/- 15 mg/dl) was still less than half that in PX, despite a 3-fold higher infusion plasma glucagon level (326 +/- 37 pg/ml). The 6-h glucagon infusion caused a significant decrease in the concentrations of glucogenic amino acids in the glucagon-deficient patients, but not in the type I diabetic patients. We conclude that 1) glucagon replacement in the PX patient markedly alters blood glucose and glucogenic amino acids, but not ketone levels; and 2) the metabolic response to glucagon is considerably more pronounced in PX patients than in type I diabetic patients. These data suggest that glucagon responsiveness is enhanced in the chronic hormone-deficient state.

Glucagon immunoreactivity and chromatographic profiles in pancreatectomized humans. Paradoxical response to oral glucose.

The nature and origin of plasma immunoreactive glucagon (IRG) after pancreatectomy in humans remains controversial. Low plasma IRG levels and heterogeneity hamper accurate assessment. We studied plasma IRG levels and profiles in 12 patients 2-57 mo after a total pancreatectomy (with antrectomy and duodenectomy) for cancer (N = 9) or chronic pancreatitis (N = 3). After oral glucose, plasma IRG (with the COOH-terminal-specific 30K glucagon antibody) rose from 59 +/- 7 to a peak of 113 +/- 17 pg/ml at 60-120 min. Chromatographic profiles revealed four distinct IRG fractions. In every patient a plasma IRG fraction of 9000-15,000 Mr, detectable basally, increased markedly after oral glucose and accounted for the rise in total IRG observed in plasma. Nine of the 12 pancreatectomized subjects had no detectable 3500-Mr glucagon and the remaining 3 had very low levels. For the group as a whole, 3500-Mr IRG comprised 1-2% of the total recovered IRG. Two patients were also studied before pancreatectomy: suppressibility of glucagon (Mr 3500) was evident. After surgery this paradoxical response to oral glucose was demonstrated. Reproducibility of these responses was confirmed in two patients studied twice over 2 yr. Diabetic controls without pancreatectomy did not show this response. The absence or marked reduction of pancreatic glucagon was confirmed in five of the pancreatectomized patients after intravenous arginine or oral protein. Normal basal plasma IRG and profiles, oral glucose suppressibility, and arginine stimulation were present in five control patients with unresectable pancreatic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance.

To evaluate the role of glucagon in insulin-mediated glucose metabolism, we studied four men and four women, ranging in age from 30-73 yr (mean +/- SEM, 54 +/- 5) who had undergone complete pancreatic resection for cancer or chronic pancreatitis 16-58 mo previously. The patients had undetectable C-peptide levels and established lack of biologically active 3500 mol wt glucagon. Euglycemic insulin clamp studies were performed with a 40 mU X m-2 X min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng X kg-1 X min-1). In four patients, hepatic glucose production was determined by a primed-constant infusion of 3-[3H]glucose. Monocyte insulin-binding studies, pre- and postglucagon, were performed in all patients. The 72-h glucagon infusion, resulting in mean plasma glucagon levels of 124 +/- 7 pg/ml, caused a significant rise in the mean plasma glucose level (249 +/- 8 versus 170 +/- 13 mg/dl preglucagon) and a sixfold increase in mean 24-h glucose excretion. Both with and without glucagon, euglycemic hyperinsulinemia achieved identical and complete suppression of hepatic glucose production. The mean glucose utilization rate (4.70 +/- 0.36 mg X kg-1 X min-1 preglucagon) was significantly decreased by glucagon replacement (3.83 +/- 0.31 mg X kg-1 X min-1, P less than 0.02). Mean glucose clearance was also diminished with glucagon (4.49 +/- 0.32 versus 5.73 +/- 0.45 ml X kg-1 X min-1 preglucagon, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of bromocriptine in a patient with generalized resistance to thyroid hormone.

A 50-yr-old man with a large goiter had elevated serum levels of T4 (22 micrograms/dl), T3 (228 ng/dl), and free T4 (6.6 ng/dl), a high 24-h 131I-thyroidal uptake (69%), and an elevated TSH level (3.6 microU/ml), as well as hyperresponsiveness of TSH to TRH (peak TSH, 47 microU/ml). Normal serum alpha-subunit concentrations and sella turcica films mitigated against the presence of a pituitary tumor. A normal basal metabolic rate and minimally elevated concentration of testosterone-estradiol binding globulin were consistent with generalized resistance to thyroid hormone. Mild lactotroph resistance was also present. The patient was given bromocriptine for 16 months (2.5-10 mg daily). Basal serum TSH levels decreased (less than 0.3-2 microU/ml), as did the TSH response to TRH; serum T4 levels (14-17 micrograms/dl); and 24-h 131I-thyroidal uptake (28%) were reduced. Serum T3 levels, however, changed little. The thyroid gland decreased to normal size, and the basal metabolic rate and testosterone-estradiol binding globulin remained normal. Bromocriptine was stopped for 4 months. Serum TSH increased to 4.5 microU/ml; T4 and T3 increased to 27 micrograms/dl and 328 ng/dl; the patient became clinically mildly hyperthyroid. Thus, bromocriptine in this patient was useful in decreasing TSH secretion and decreasing goiter size, while maintaining clinical euthyroidism. Only a small amount of TSH was necessary to maintain iodine uptake and thyroid hormone synthesis and secretion in a responsive thyroid gland. We speculate that this patient may be secreting a highly bioactive form of TSH and/or have increased thyroid sensitivity to TSH.

Virilizing hilus (Leydig) cell tumor of the ovary: the challenge of an accurate preoperative diagnosis.

A 73-year-old woman developed temporal balding and "hoarseness" over a 3-year interval. Investigation including extensive endocrinologic screening, abdominal computed tomography scanning, pelvic ultrasonography, iodocholesterol (NP-59) adrenal scanning, and selective retrograde venous sampling revealed only an elevated serum testosterone level without localization of the source. At laparotomy a 2.0 cm left ovary was found to contain a hilus (Leydig) cell tumor. The testosterone level in a blood sample from the left ovarian vein obtained intraoperatively was 9000 ng/dl, whereas a blood sample from the right ovarian vein contained 213 ng/dl. One week later her peripheral blood testosterone level was normal (8 ng/dl). The records of six other patients with ovarian hilus cell tumors were reviewed from the Memorial Hospital Registry (from 1959 to 1982). All tumors were small (ovaries were 2 to 4 cm in diameter) and benign. The average patient's age was 63 years (range: 57 to 73 years). Only three of the seven patients in our series were first seen with virilization; the tumors in the remaining four patients were found incidentally. Ovarian hilus cell tumors are rare and are difficult to diagnose, but surgeons and endocrinologists should think of this tumor when they investigate older female patients with virilization. Careful intraoperative examination of even normal-appearing ovaries is imperative, particularly if no adrenal disease is found.