Faculty Bibliography

OBJECTIVE: To study whether a program of brief, intensive, inpatient intervention could improve glycemic control in an indigent, minority population with uncontrolled diabetes unresponsive to outpatient treatment. METHODS: Patients with uncontrolled diabetes unresponsive to treatment in our outpatient Diabetes Clinic were admitted to our inpatient Diabetes Unit, where their care was directed by the Diabetes Team (an attending diabetologist, an endocrinology fellow, two nurses, and two nutritionists). Of 108 patients admitted, data were available for 96. Patients from minority populations constituted 91.7% of the group. All patients were indigent. The mean duration of stay was 4.3 days. After dismissal, patients underwent follow-up again in our Diabetes Clinic. During the 540-day follow-up period, 25 patients were electively readmitted when satisfactory improvement in glycemic control was not achieved. Hemoglobin A1c levels were averaged and plotted for the group at defined time points up to 360 days before admission and up to 540 days after admission. RESULTS: During the year before admission, hemoglobin A1c increased slowly from 10.1 +/- 0.3% (mean +/- standard error) at day -360 to 10.3 +/- 0.2% at day -210 (F5 = 29; P<0.01) and then rapidly to 11.4 +/- 0.2% at admission (F7 = 1,541; P<0.001). After admission, hemoglobin A1c declined rapidly to 9.5 +/- 0.2% at day 90 (F4 = 121; P<0.005), plateaued at that level until day 240, and then declined again slowly to 9.0 +/- 0.3% at day 540, the end of the follow-up period (F10 = 70; P<0.01). All hemoglobin A1c levels 30 days or more after admission were significantly lower than the mean level at admission (P<0.05 at day 30 and P<0.001 from day 45 to day 540). CONCLUSION: Brief, intensive, inpatient intervention in an indigent, minority population with uncontrolled diabetes unresponsive to outpatient treatment produced and sustained a significant improvement in glycemic control. This mode of treatment is a practical approach to achieving the improvement in glycemic control that the Diabetes Control and Complications Trial demonstrated to be effective in delaying the onset and slowing the progression of diabetic retinopathy, nephropathy, and neuropathy.

Despite nearly six decades of epidemiological studies, meta-analyses, and reviews, there is still considerable controversy in the literature about the question, does postmenopausal estrogen administration increase the risk of breast cancer? In an effort to resolve the controversy, a number of animal, biochemical, and clinical investigative studies in this field have been reviewed. The following summary formulation is proposed: 1. Administration of estrogen is inherently capable of promoting the growth of breast cancer, and therefore of increasing the incidence of clinical breast cancer. 2. Human response to estrogen is like that of the low-cancer-incidence strains of mice studied by Lacassagne, in that large doses and prolonged administration are required to induce clinical breast cancer. 3. The blood levels of estradiol produced by the usual doses of postmenopausal estrogen are relatively low, equivalent to those of the follicular phase of the menstrual cycle. These levels may be near the threshold for producing breast-cancer-promoting effects; therefore, the tumor response will vary greatly in different populations, depending on genetic susceptibility factors: a. The prevalence of a family history of premenopausal breast cancer in a first-degree relative. b. The prevalence of abnormal BRCA1, BRCA2, and p53 genes. c. The prevalence of increased 16 alpha-hydroxylation of estradiol. d. The prevalence of smokers who are slow acetylators. 4. Consumption of alcohol (5 grams or more daily) along with the postmenopausal estrogen administration results in elevation of blood estradiol levels to values equivalent to those of the periovulatory peak of the menstrual cycle, which may be well above the threshold for producing breast-cancer-promoting effects in all women. The risk for cancer will therefore be uniformly increased in women who use alcohol and take estrogen. 5. Increased risk of breast cancer from postmenopausal estrogen administration can be eliminated by taking two synergistic steps: a. Eliminating alcohol consumption, or at least keeping it well below an average of 5 grams daily (equivalent to 2/3 ounce of whiskey or 3 ounces of wine). b. Diminishing the capacity to 16 alpha-hydroxylate estradiol, either through pharmacological agents such as indole-3-carbinol or through increased consumption of cruciferous vegetables. It is concluded that despite the inherent ability of postmenopausal estrogen therapy to increase the risk of breast cancer in theory, the increased risk can be eliminated in practice by minimizing or eliminating consumption of alcohol and ingesting pharmacological or dietary agents that reduce the 16 alpha-hydroxylation of estradiol.

STUDY OBJECTIVES: To determine whether bone imaging with 99mTc methylene diphosphonate is a specific method of making the diagnosis of costochondritis in patients with chest pain who rule out for myocardial infarction. DESIGN: Nonblinded prospective controlled study in 20 patients and 10 control subjects. SETTING: Inpatient medical service of a tertiary teaching hospital. PATIENTS: Two hundred consenting patients admitted to the hospital with chest pain and suspected myocardial infarction were examined. Those in whom acute myocardial infarction was ruled out were evaluated for the clinical signs of costochondritis, ie, tenderness over one or more costochondral junctions. Twenty patients who met the clinical criterion gave informed consent and were subjected to bone imaging. Ten control subjects with cancer who did not have clinical signs of costochondritis underwent bone imaging to rule out metastatic disease (normal in all cases). INTERVENTIONS: Bone imaging with I.V. 99mTc methylene diphosphonate. MEASUREMENTS: Bone scans of the investigative patients and the control subjects were read by two independent nuclear medicine specialists. RESULTS: Sixteen of the 20 patients with clinically diagnosed costochondritis showed increased technetium uptake at all costochondral junctions bilaterally; six of them also had increased uptake elsewhere on the chest wall (sternum, manubrium, or first rib). All 10 of the control patients likewise showed increased technetium uptake at all costochondral junctions bilaterally. CONCLUSIONS: Bone imaging with 99mTc methylene diphosphonate is not a specific method of making the diagnosis of costochondritis.

This review pertains to gonadal function in men with human immunodeficiency virus (HIV) infection, who often exhibit clinical and biochemical evidence of hypogonadism. Hypogonadotropic hypogonadism appears to be the most commonly encountered abnormality, although complete anterior pituitary insufficiency and primary gonadal failure have been reported. Levels of sex hormone-binding globulin (SHBG) are either unchanged or increased. Plasma levels of estrogens, progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and prolactin vary. Pathologically, except for involvement by opportunistic infections, no significant abnormality in the hypothalamic-pituitary area has been described, but evidence of orchitis is commonly present. The cause(s) of these abnormalities remains unclear. The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis. Further studies are needed to clarify the cause(s) of testicular dysfunction in HIV-infected men and its clinical significance, treatment, relevance to the progression of HIV infection, and influence on the immune system.

PURPOSE: To determine whether consultation by an individual endocrinologist or by a multidisciplinary diabetes team (endocrinologist, diabetes nurse educator, and registered dietitian) can impact length of hospital stay of patients with diabetes. PATIENTS AND METHODS: Hospital stays of consecutive patients with a principal diagnosis of diabetes were compared. Forty-three patients were seen by an individual endocrine consultant and 27 were managed by the internist alone. Thirty-four patients were seen in consultation by the diabetes team. All consultations were performed at the request of the primary physician. There were no statistically significant differences among groups with respect to age, duration of diabetes, admitting diagnosis, glucose levels, or concomitant acute or chronic illness. RESULTS: Average length of stay of diabetes-team patients was 3.6 +/- 1.7 days, 56% shorter than the value, 8.2 +/- 6.2 days, of patients in the no-consultation group (P < 0.0001), and 35% shorter than the value, 5.5 +/- 3.4 days, of patients who received a traditional individual endocrine consultation (P < 0.05). The length of stay correlated with time from admission to consultation (regression equation: y = 3.92 + [1.09 x time to consultation]; r = .55; P < 0.0001). The slope (1.09) indicates that each 1-day delay in consultation resulted in a 1-day increase in length of stay. CONCLUSIONS: Length of stay was lowest in patients who received diabetes-team consultation. Three million Americans are hospitalized annually with diabetes at a cost of $65 billion. A team approach to their inpatient care may reduce their hospital stays, resulting in considerable health and economic benefits.

The 24-h mean plasma concentration of total testosterone (T) was measured in 33 healthy, regularly cycling, nonobese women between 21 and 51 yr of age. Percent free T was measured in 17 of them. Plasma dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were measured in 24 of them, and the DHEA-to-T and DHEAS-to-T ratios were calculated. It was found that the concentration of total T showed a steep decline with age; the regression equation was: T (nanomoles per L) = 37.8 x age-1.12 (r = -0.54; P < 0.003). According to this equation, the expected T concentration of a woman of 40 would be 0.61 nmol/L, about half that of a woman of 21 (1.3 nmol/L). The percent free T did not vary significantly with age, so free T concentration likewise showed a steep decline with age. The DHEA-to-T and DHEAS-to-T ratios were both age invariant, clearly because the levels of DHEA and DHEAS also decline steeply with age, as previously reported.

The literature findings on endogenous hormonal profiles in women with breast cancer are reviewed in detail. It is concluded that four sets of findings are valid: (1) diminished adrenal androgen production, probably genetic, in women with premenopausal breast cancer; (2) ovarian dysfunction (luteal inadequacy plus increased testosterone production) in breast cancer at all ages; (3) increased 16 alpha-hydroxylation of estradiol in breast cancer at all ages; and (4) evidence that prolactin is a permissive risk factor for breast cancer, and that the pregnancy-induced decrease in prolactin levels may account for the protective effect of early pregnancy against breast cancer.

It is known that there is an inverse relationship between the serum levels of insulin and sex hormone-binding globulin (SHBG) in women, but the relationship in men has not been reported. It is not known whether changes in the one cause changes in the other, or whether they change in opposite directions in response to some third factor. Because obesity raises insulin levels and lowers SHBG levels in both sexes, we proposed to study the cause-effect question by determining whether the relationship between changes in SHBG and insulin levels during active weight loss. We studied 70 healthy weight-stable men with body mass index (BMI) from 20.7-94 (normal, 22.5 +/- 2.5) and restudied 17 of them during diet-induced weight loss. Fasting serum insulin levels in the weight-stable men showed a positive linear correlation with BMI, increasing 1 microU/mL per unit increase in BMI (P < 0.0001). SHBG levels in the weight-stable men showed a negative linear correlation with BMI, decreasing 0.2 nmol/L per unit increase in BMI (P < 0.0002). In the weight-stable men, there was an inverse hyperbolic correlation between SHBG and insulin levels; SHBG (nmol/L) = 13.1 + [30.1 divided by insulin (microU/mL)] (P < 0.002). During weight loss, insulin levels decreased at an average rate of 6.1 microU/mL per unit decrease in BMI, a much higher slope than the positive slope vs. BMI in weight stable men. During weight loss, SHBG levels increased at an average slope of 0.43 nmol/L per unit decrease in BMI, much higher than the negative slope of 0.2 nmol/L per unit increase in BMI in weight-stable men. Values for the SHBG vs. insulin coordinates in the weight-losing subjects did not differ significantly from those expected from the SHBG vs. insulin equation in weight-stable subjects. The stability of the SHBG-insulin relationship during weight loss despite the profoundly altered relationship of each separate component to BMI strongly suggests a close metabolic link between SHBG and insulin. As SHBG is not known to alter the production or metabolism of insulin, whereas insulin has been shown in vitro to decrease the synthesis of SHBG, it seems a reasonable conclusion that the predictable inverse relationship between serum insulin and SHBG indicates that insulin controls SHBG synthesis in vivo.