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B M Biller

Publications and source records attributed to B M Biller.

At least 19 recordsLinked to original sources
PubMed2000

Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial.

BACKGROUND: Growth hormone-deficient adults have increased cardiovascular mortality. Growth hormone replacement may affect cardiovascular risk. Inflammation plays an important role in atherosclerosis, and inflammatory markers are predictive of cardiovascular events. OBJECTIVE: To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors. DESIGN: Randomized, single-blind, placebo-controlled trial. PATIENTS: 40 men with adult-onset growth hormone deficiency. INTERVENTION: Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level. MEASUREMENTS: Anthropometric, hemoglobin A1c, and central fat values were assessed every 6 months. Levels of glucose, insulin, insulin-like growth factor I, and lipids were measured at 1, 3, 6, 12, and 18 months. C-reactive protein, serum amyloid polypeptide A, inteleukin-6, and lipoprotein(a) levels were determined at baseline and 6 and 18 months. RESULTS: C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients (differences between groups, -1.9 +/- 0.6 mg/L [P = 0.0027] and -1.3 +/- 0.5 ng/L [P = 0.013], respectively). Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance (difference between groups, -2.4 +/- 1.2 mg/L; P = 0.056). Serum cholesterol levels, low-density lipoprotein cholesterol levels, and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients (differences between groups, -0.86 +/- 0.17 mmol/L [-33.2 +/- 6.6 mg/dL] [P < 0.001], -0.63 +/- 0.20 mmol/L [-24.5 +/- 5.9 mg/dL] [P < 0.001], and -0.56 +/- 0.26 [P = 0.040], respectively), but the decrease was not maintained from month 6 to month 18. Lipoprotein(a) levels increased (difference between groups, 22.0 +/- 8.0 mg/L; P = 0.0096). Short-term increases occurred in glucose levels, insulin levels, and insulin-to-glucose ratios (differences between groups, 0.54 +/- 0.16 mmol/L [9.6 +/- 2.8 mg/dL] [P = 0.0018], 37.9 +/- 9.6 pmol/L [P < 0.001], and 6.0 +/- 1.8 [P = 0.0025], respectively), but only the increase in glucose level was maintained over the long term (difference between groups, 0.56 +/- 0.17 mmol/L [10.0 +/- 3.1 mg/dL]; P = 0.0026). Hemoglobin A1c values did not change. Truncal fat-to-total fat ratios decreased (difference between groups, -0.018 +/- 0.007; P = 0.0087). CONCLUSIONS: Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers, decreases central fat, and increases lipoprotein(a) and glucose levels without affecting lipid levels.

Adipose Tissue↗
PubMed2000

Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency.

Adults with acquired GH deficiency (GHD) have been shown to have osteopenia associated with a 3-fold increase in fracture risk and exhibit increased body fat and decreased lean mass. Replacement of GH results in decreased fat mass, increased lean mass, and increased bone mineral density (BMD). The possible differential effect of withdrawal of GH replacement on body composition compartments and regional bone mass is not known. We performed a randomized, single blind, placebo-controlled 36-month cross-over study of GH vs. placebo (PL) in adults with GHD and now report the effect of withdrawal of GH on percent body fat, lean mass, and bone density, as measured by dual energy x-ray absorptiometry. Forty men (median age, 51 yr; range, 24-64 yr) with pituitary disease and peak serum GH levels under 5 microg/L in response to two pharmacological stimuli were randomized to GH therapy (starting dose, 10 microg/kg x day, final dose 4 microg/kg x day) vs. PL for 18 months. Replacement was provided in a physiological range by adjusting GH doses according to serum insulin-like growth factor I levels. After discontinuation of GH, body fat increased significantly (mean +/- SEM, 3.18 +/- 0.44%; P = 0.0001) and returned to baseline. Lean mass decreased significantly (mean loss, 2133 +/- 539 g; P = 0.0016), but remained slightly higher (1276 +/- 502 g above baseline; P = 0.0258) than at study initiation. In contrast to the effect on body composition, BMD did not reverse toward pretreatment baseline after discontinuation of GH. Bone density at the hip continued to rise during PL administration, showing a significant increase (0.0014 +/- 0.00042, g/cm2 x month; P = 0.005) between months 18-36. Every bone site except two (radial BMD and total bone mineral content), including those without a significant increase in BMD during the 18 months of GH administration, showed a net increase over the entire 36 months. Therefore, there is a critical differential response of the duration of GH action on different body composition compartments. Physiological GH administration has a persistent effect on bone mass 18 months after discontinuation of GH.

Absorptiometry, Photon↗
PubMed2000

Clinical and reimbursement issues in growth hormone use in adults.

Data published in the past decade have demonstrated that adults who are deficient in growth hormone (GH) experience deleterious clinical consequences without treatment. In 1996, the Food and Drug Administration approved the use of GH in adults who were GH deficient as a result of hypothalamic or pituitary disease. However, there are other conditions in adults for which GH treatment has also been approved (acquired immune deficiency syndrome [AIDS]-related wasting) or for which it is being considered, such as aging, catabolic states, and cardiomyopathy. Clinical issues revolve around the rationale for treatment; the diagnostic evaluation; the effects of GH therapy on body composition, bone density, lipids, and cardiac function; and appropriate dosing and follow up. Clearly, the use of GH in adults raises reimbursement issues as well. In this article, Dr. Beverly M.K. Biller provides an overview of the rationale for the treatment of adult-onset GH deficiency and reviews its etiology and clinical features as well as reimbursement and utilization issues related to treatment. Dr. Mary Lee Vance discusses various assays and criteria used in the diagnostic evaluation of the patient with adult-onset GH deficiency. Dr. David L. Kleinberg focuses on the effects of GH therapy on body composition, bone density, lipid profiles, and cardiac function, as well as on reimbursement issues regarding body composition studies. To complete the clinical portion of this session, Dr. David M. Cook addresses dosing and follow up. To address economic implications, Dr. Terry Gordon provides the payer's perspective on the diagnosis and treatment of adult-onset GH deficiency.

Adult↗
PubMed1999

Long-term mortality after transsphenoidal surgery for Cushing disease.

BACKGROUND: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported. OBJECTIVE: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques. DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996. INTERVENTION: Transsphenoidal adenomectomy and as-needed adjunctive therapy. MEASUREMENT: Record review with follow-up interview. RESULTS: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2). CONCLUSION: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.

Adenoma↗
PubMed1999

A new clinical option for hormone replacement therapy in women with secondary amenorrhea: effects of cyclic administration of progesterone from the sustained-release vaginal gel Crinone (4% and 8%) on endometrial morphologic features and withdrawal bleeding.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of 2 doses of a transvaginal polycarbophil-based progesterone gel (4% and 8%) in hormone replacement therapy. STUDY DESIGN: This multicenter, randomized, parallel-group, open-label 3-month study included 127 women with secondary amenorrhea. Estrogenized patients applied transvaginal progesterone (4% or 8%) every other day for 6 doses per month. Efficacy was based on endometrial biopsy findings and withdrawal bleeding. McNemar's test was used to compare incidence of adverse events before and during treatment. RESULTS: Progestational changes were found in 92% (Crinone 4%) and 100% (Crinone 8%) of patients with evaluable biopsies. Withdrawal bleeding was experienced by 81% (Crinone 4%) and 82% (Crinone 8%) of the patients. No patient experienced any serious side effect related to treatment. The incidence of most side effects, including psychologic symptoms, decreased with progesterone treatment compared with estrogen alone therapy. Compliance exceeded 98% for both doses. CONCLUSIONS: Crinone is a novel, effective, and well-tolerated option for hormone replacement therapy in women with secondary amenorrhea.

Administration, Intravaginal↗
PubMed1999

Guidelines for the diagnosis and treatment of hyperprolactinemia.

Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. While it can occur in men, it occurs more commonly in women. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult population to as high as 9-17% in women with reproductive disorders. There are many possible causes of hyperprolactinemia, falling into three general categories: physiologic, pharmacologic and pathologic. When specific treatable underlying causes have been eliminated and in cases of severe hyperprolactinemia, the most likely cause is a prolactin (PRL)-secreting pituitary adenoma. Microadenomas should be treated medically, with a dopamine agonist, if there is an indication for therapy (such as amenorrhea, infertility or bothersome galactorrhea). If there is no indication for therapy, microadenomas may be followed conservatively, as growth is uncommon. Macroadenomas may grow larger; medical therapy is recommended initially, with neurosurgical evaluation reserved for specific clinical situations, such as failure of medical therapy and evidence of mass effect despite medical therapy. In the United States, the dopamine agonists indicated for treatment of hyperprolactinemia are bromocriptine and cabergoline. Bromocriptine is usually given once or twice daily, while cabergoline has a long duration of action and is given once or twice weekly. Results of comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (PRL suppression, restoration of gonadal function) and tolerability.

Adult↗
PubMed1999

Diagnostic evaluation of hyperprolactinemia.

A serum prolactin (PRL) level is obtained in response to a specific clinical presentation, including symptoms of hyperprolactinemia (such as amenorrhea and galactorrhea); serum PRL measurement may also be performed as part of an infertility evaluation. An initial level above the normal range should be followed by a repeat level from a blood sample drawn in the morning with the patient in a fasting state. The medical history and a few laboratory tests can eliminate the most common physiologic and pharmacologic causes of hyperprolactinemia, including pregnancy, primary hypothyroidism and treatment with drugs (such as neuroleptics) that reduce dopaminergic effects on the pituitary. In the absence of such causes, radiologic imaging of the sella turcica is necessary to establish whether a PRL-secreting pituitary adenoma or other lesion is present. The vast majority of patients are treated medically, with dopamine agonist drugs. Surgery is reserved for the patient with the uncommon tumor that does not respond to medical therapy or has a large cystic component or for the occasional patient who cannot tolerate dopamine agonists or who experiences pituitary apoplexy.

Amenorrhea↗
PubMed1998

Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly.

To analyze the long term outcome after multimodality therapy for acromegaly, a retrospective review was performed on 162 patients who underwent transsphenoidal surgery at Massachusetts General Hospital between 1978 and 1996. The surgical cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was 57% overall. The surgical cure rate was significantly dependent on tumor size, but was not dependent on age or sex. An improvement in the surgical cure rate was noted over the course of the review, from 45% before 1987 to 73% since 1991. Long term follow-up was obtained in 99% of U.S. residents (149 of 151), with a mean follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical remission as determined by normalization of serum insulin-like growth factor I levels or by GH suppression after oral glucose tolerance testing at last contact or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery in those patients who initially met the criteria for surgical cure. The 10-yr survival rate was 88%, and there were 12 deaths at postoperative intervals of 2-12 yr, with the most common cause of death being cardiovascular disease. A Cox proportional hazards model showed that patient-years with persistent disease carried a 3.5-fold [95% confidence interval (CI), 1.0-12; P = 0.02] relative mortality risk compared to those patient-years in remission. A Poisson person-years regression analysis showed no significant difference in survival between those 86 patients cured at operation and an age- and sex-matched sample from the U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3-2.2; P = 0.35]. A similar analysis on the entire group of 149 patients showed no significant difference in survival from that in a control sample (SMR, 1.16; 95% CI, 0.66-2.0; P = 0.3). Mortality risk for patient-years with persistent active disease after unsuccessful treatment vs. that in the U.S. population sample remained increased (SMR, 1.8; 95% CI, 0.9-3.6; P = .05). This analysis suggests that the decreased survival previously reported to be associated with acromegaly can be normalized by successful surgical and adjunctive therapy.

Acromegaly↗
PubMed1998

Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency.

GH replacement of adults with acquired GH deficiency (GHD) results in body composition changes including increases in lean mass and bone mineral density. However, the effects of long-term GH therapy on cognitive function are largely unknown, and there are conflicting data regarding quality of life. We performed a randomized, double-blind, placebo-controlled study of GH replacement in adults with GHD and measured cognition and sense of well-being using standardized psychometric tests before and after therapy. Forty men (median age 51 yr, range 24-64 yr) with a history of pituitary disease were randomized to GH therapy (starting dose, 10 +/- 0.3 micrograms/kg per day: mean treatment dose, 4 +/- 2 micrograms/kg per day) vs. placebo for 18 months, and GH doses were adjusted according to serum insulin growth factor-I levels. At baseline, the patients displayed a full-scale intelligence quotient (IQ) score nearly 1 SD above the normal mean. Mean scores on all cognitive tests fell within normal limits, and on many tests, fell above the mean. On tests of verbal learning and delayed visual memory, mean test scores fell below the mean (although within normal limits), suggestive of a relative compromise in the area of memory performance. Following 18 months of GH replacement therapy, there were no significant changes in cognitive function or quality of life. We conclude that acquired GHD in adult men is not associated with significant alterations in cognitive function as assessed by standardized tests, and chronic low-dose GH replacement therapy does not result in significant beneficial effects on cognitive function or quality of life. Although previous studies have suggested that GH replacement in adults with acquired GHD may improve quality of life, our data do not support the use of physiological GH replacement in GHD men for this indication.

Adult↗
PubMed1997

Clinical and biochemical evaluation of Cushing's syndrome.

Over the past decade, several advances have been made in our understanding of the molecular pathogenesis of pituitary adenomas, and novel diagnostic tests for the diagnosis and differential diagnosis of Cushing's syndrome have been developed. Although established in the late 1970s, measurement of UFC has emerged as the most sensitive and specific test to screen for and confirm the presence of Cushing's syndrome. The combined CRH/DST is potentially a useful adjunct in patients with probable pseudo-Cushing's syndrome and borderline elevated urinary cortisol levels. Improved assays for circulating ACTH levels are now used as the first test in differentiating ACTH-dependent from ACTH-independent sources. HDDST with the revised reference ranges for UFC currently remains the primary test for differentiating pituitary from ectopic ACTH secretion. However, the CRH test may replace the HDDST in the foreseeable future because of its lower rate of false-positive and false-negative results. IPSS has been established as an integral part of the evaluation of patients with suspected Cushing's disease and no conclusive (> 0.8 to 1 cm) pituitary adenoma. Advances in the radiolabeling of small peptides, such as somatostatin analogs, may facilitate the search for occult ectopic sources.

Adrenocorticotropic Hormone↗
PubMed1997

Body composition and endocrine function in women with acquired immunodeficiency syndrome wasting.

The acquired immunodeficiency syndrome (AIDS) wasting syndrome is a devastating complication of human immunodeficiency virus (HIV) infection characterized by progressive weight loss and severe inanition. In men, the wasting syndrome is characterized by a disproportionate decrease in lean body mass and relative fat sparing. In contrast, relatively little is known about the gender-specific changes in body composition that characterize AIDS wasting in women. Three groups of women were studied to determine body composition and hormonal changes with respect to stage of wasting [nonwasting (NW; weight >90% ideal body weight; weight loss <10% of preillness maximum; n = 12), early wasting (EW; weight >90% ideal body weight; weight loss >10% of preillness maximum; n = 10), and late wasting (LW; weight <90%; n = 9)] and compared with a control group of 12, healthy, age-matched women. Weight loss averaged 6 +/- 6% (NW), 15 +/- 6% (EW), and 20 +/- 8% (LW) in the three groups. Lean, fat, and muscle masses were determined by dual energy x-ray absorptiometry and urinary creatinine excretion. Subjects were 36 +/- 5 yr of age (mean +/- SD) with a CD4 cell count of 379 +/- 239 cells/mm3. The body mass index was 24.4 +/- 2.6 kg/m2 (NW), 22.2 +/- 1.2 kg/m2 (EW), 18.2 +/- 2.0 kg/m2 (LW), and 24.3 +/- 2.6 kg/m2 (controls; P < 0.01, NW vs. EW; P < 0.0001, NW vs. LW). Lean body mass indexed for height was 15.7 +/- 2.4 kg/m2 (NW), 14.8 +/- 2.0 kg/m2 (EW), and 13.7 +/- 1.2 kg/m2 (LW) and was decreased significantly only in the LW group (P < 0.05 vs. NW). Muscle mass was 96% (NW), 94% (EW), and 78% (LW) of that predicted for height (P < 0.05, NW vs. LW). In contrast, fat mass indexed for height was decreased significantly among patients in both the EW and LW groups [8.7 +/- 1.9 kg/m2 (NW), 6.5 +/- 1.9 kg/m2 (EW), and 3.7 +/- 1.4 kg/m2 (LW); P < 0.05, NW vs. EW; P < 0.001, NW vs. LW). Expressed as a percentage of the value in nonwasting HIV-positive controls (NW), the relative loss of fat was greater than the loss of lean mass with progressive degrees of wasting [EW, 25% vs. 6% (fat vs. lean); LW, 58% vs. 13%]. The prevalence of amenorrhea was 20% among study subjects [17% (NW), 10% (EW), and 38% (LW)]. The percent predicted muscle mass was significantly lower in subjects with amenorrhea (74 +/- 8%) compared to that in eumenorrheic HIV-positive subjects (94 +/- 4%; P < 0.05). Estradiol levels were lower among subjects with amenorrhea (17.6 +/- 21.8 pg/mL) compared to eumenorrheic HIV-positive (48.9 +/- 33.6 pg/mL) and control (68.3 +/- 47.6 pg/mL) subjects and did not correlate with body composition. Mean free testosterone, but not total testosterone, levels were decreased in subjects with EW and LW compared to those in age-matched healthy controls, but not compared with those in NW [0.9 +/- 0.6 ng/dL (NW), 0.7 +/- 0.4 ng/dL (EW), 0.6 +/- 0.3 ng/dL (LW), and 2.0 +/- 2.4 ng/dL (controls); P < 0.05, EW vs. controls and LW vs. controls] and correlated with muscle mass (r = 0.37; P < 0.05). The percentages of women with free testosterone levels below the age-adjusted normal range were 33% (NW), 50% (EW), and 66% (LW). Dehydroepiandrosterone sulfate levels were also low in the subjects with LW compared to those in the control group [98 +/- 85 microg/dL (NW), 102 +/- 53 microg/dL (EW), 55 +/- 46 microg/dL (LW), and 132 +/- 68 microg/dL (controls); P < 0.05 LW vs. controls] and were correlated highly with free testosterone levels (r = 0.73; P < 0.00001) and also with muscle mass (r = 0.48; P < 0.01). These data demonstrate that women lose significant lean body and muscle mass in the late stages of wasting. However, in contrast to men, women exhibit a progressive and disproportionate decrease in body fat relative to lean body mass at all stages of wasting, consistent with gender-specific effects in body composition in AIDS wasting. (ABSTRACT TRUNCATED)

Absorptiometry, Photon↗
PubMed1996

Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial.

BACKGROUND: Patients with adult-onset growth hormone deficiency have reduced bone density and increased fat mass. Growth hormone at high doses may decrease body fat in these patients, but the effects of growth hormone at more physiologic doses on bone density and body composition have not been convincingly shown. OBJECTIVE: To determine whether long-term growth hormone therapy at a dose adjusted to maintain normal insulin-like growth factor 1 (IGF-1) levels has clinical effects in patients with adult-onset growth hormone deficiency. DESIGN: Randomized, placebo-controlled study. SETTING: Tertiary referral center. PATIENTS: 32 men with adult-onset growth hormone deficiency. INTERVENTION: Growth hormone (initial daily dose, 10 micrograms/kg of body weight) or placebo for 18 months. The growth hormone dose was reduced by 25% if IGF-1 levels were elevated. MEASUREMENTS: Body composition and bone mineral density of the lumbar spine, femoral neck, and proximal radius were measured by dual energy x-ray absorptiometry at 6-month intervals. Markers of bone turnover were also measured during the first 12 months of the study. RESULTS: Growth hormone therapy increased bone mineral density in the lumbar spine by a mean (+/- SD) of 5.1% +/- 4.1% and bone mineral density in the femoral neck by 2.4% +/- 3.5%. In the growth hormone group, significant increases were seen in the following markers of bone turnover: osteocalcin (4.4 +/- 3.6 mg/L to 7.2 +/- 4.6 mg/L) and urinary pyridinoline (39.0 +/- 19.8 nmol/mmol of creatinine to 55.7 +/- 25.5 nmol/mmol of creatinine) and deoxypyridinoline (8.4 +/- 7.1 nmol/mmol of creatinine to 14.9 +/- 9.4 nmol/mmol of creatinine). Percentage of body fat in the growth hormone group decreased (from 31.9% +/- 6.5% to 28.3% +/- 7.0%), and lean body mass increased (from 59.0 +/- 8.5 kg to 61.5 +/- 6.9 kg). These changes were significant compared with corresponding changes in the placebo group (P < 0.01 for all comparisons). CONCLUSIONS: Growth hormone administered to men with adult-onset growth hormone deficiency at a dose adjusted according to serum IGF-1 levels increases bone density and stimulates bone turnover, decreases body fat and increases lean mass, and is associated with a low incidence of side effects.

Adult↗
PubMed1996

Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with that in normal men--a clinical research center study.

It is not known how patients who acquire GH deficiency (GHD) in adulthood differ in measures of GH secretion from normal adults. To characterize measures of GH secretion in such patients compared to those in normal subjects, we studied 23 men (median age, 51 yr; range, 32-62 yr) with adult-onset pituitary disease, defined as GH-deficient based on having no detectable GH response to two pharmacological agents, and 17 normal men. Patients less than 50 yr old received insulin (0.1 U/kg, i.v.) and clonidine (0.15 mg, orally), whereas those 50 yr of age or older as well as normal controls received arginine (30 g, i.v.) and clonidine. Patients were compared to normal men by investigating GH sampling every 10 min for 24 h and serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGFBP-3, and GH-binding protein. Frequent venous sampling of GH was analyzed in terms of mean 24-h levels, pooled 24-h GH, mean levels over the 12 h between 2000-0800 h (mean overnight GH level), and pulse analysis (pulses per 24 h and pulse amplitude) by the Pulsar computer program. Although there were significant differences between the two groups for almost all measures of GH secretion, overlap between the groups was always present. GH levels measured using a highly sensitive chemiluminescence assay on 24-h pools derived from frequent sampling displayed the least overlap between the two groups, as only 2 of 17 normal controls overlapped with the GHD patients. The pooled 24-h GH level using this technique was significantly lower in patients with GHD than in controls (0.117 +/- 0.021 vs. 0.861 +/- 0.098 micrograms/L; P < 0.0001). In the analysis of frequent GH sampling using a standard immunoradiometric assay, mean overnight GH levels provided the best separation between the two groups, as all 23 patients had values of 0.6 microgram/L or less, and 13 of 17 normal controls had values greater than 0.6 microgram/L. The mean overnight GH level in patients was 0.6 +/- 0.0 microgram/L compared to 1.0 +/- 0.1 microgram/L in controls (P < 0.0001). The mean 24-h GH level in patients was 0.5 +/- 0.0 microgram/L compared to 0.8 +/- 0.1 microgram/L in normal controls (P < 0.0001). GH pulse frequency and pulse amplitude were also reduced in patients with GHD compared to those in normal controls [1.7 +/- 0.5 vs. 5.1 +/- 0.5 pulses/24 h (P < 0.0001) and 0.6 +/- 0.1 vs. 2.8 +/- 0.4 microgram/L (P < 0.0001), respectively]. The mean serum IGF-I level was significantly lower in patients with GHD than in normal controls (106.7 +/- 8.0 vs. 218.7 +/- 16.7 microgram/L; P < 0.0001). Three of 23 patients overlapped with control values. Mean serum levels of IGFBP-3 and the serum IGF-I/IGFBP-2 ratio were also significantly lower in patients than in controls, but values overlapped substantially. We conclude that overlap occurs on measures of GH secretion between normal men and men identified as GH deficient despite a stringent definition of GHD. The best separation was obtained using pooled 24-h GH levels determined by a highly sensitive chemiluminescence assay.

Adult↗
PubMed1996

Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline.

Dopamine agonist administration is the primary therapy for macroprolactinomas, but bromocriptine is the only agent approved in the United States. Its use is limited by a high incidence of side effects, a short duration of action, and a lack of effectiveness in some patients. Cabergoline is a long-acting dopamine agonist specific for the D2 receptor that is more effective and better tolerated than bromocriptine in women with microadenomas or idiopathic hyperprolactinemia. However, experience with cabergoline in the treatment of patients with macroadenomas is limited. We report the first study of chronic administration of cabergoline conducted exclusively in patients with macroprolactinomas. Fifteen patients (8 women, 7 men) ages 18-76 yr were studied in an open-label 48-week dose escalation trial of cabergoline administered once per week. Eleven patients had received prior therapy with other dopamine agonists. Mean prolactin (PRL) levels decreased by 93.6%, and normal levels were attained in 73% of patients at doses of 0.5-3.0 mg per week. Three of five patients who had failed to normalize PRL on prior dopamine agonists achieved normal levels. Gonadal function was restored in all hypogonadal men and in 75% of premenopausal women with amenorrhea. Tumor size decreased in 11 of the 15 patients. Side effects were minimal. Of the 5 patients who had experienced side effects in prior dopamine agonists, 4 had none on cabergoline, and the fifth had milder symptoms. During two further years of follow up, the improvement in PRL levels, gonadal function, and tumor size has persisted during cabergoline administration, and three patients have experienced a further decline in PRL and/or tumor size. This study demonstrates the effectiveness and minimal side effects of once-weekly cabergoline for treatment of macroprolactinomas.

Adenoma↗
PubMed1995

The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa.

To study the effects of prolonged anorexia nervosa on bone density (BD) and to determine whether estrogen administration prevents bone loss in women with this disorder, 48 amenorrheic women with anorexia nervosa (mean age, 23.7 yr) were randomized to receive estrogen and progestin replacement (n = 22) or no replacement (n = 26). Clinical variables, biochemical indices, and spinal trabecular BD were measured every 6 months for a mean of 1.5 yr. Initial mean BD (130 +/- 27 mg K2HPO4/cm3, +/- 1 SD) was significantly (P < 0.001) less than normal (176 +/- 26 mg K2HPO4/cm3) and less than 2 SD below normal in 21 of the 48 women. Forty-four women completed the study (19 in the estrogen group and 25 in the control group). The mean duration of follow-up was comparable in the estrogen-treated (1.57 +/- 0.89 yr) vs. the control group (1.41 +/- 0.69 yr). The estrogen-treated group had no significant change in BD compared with the control group; however, there was a 4.0% increase in mean BD in patients with an initial ideal body weight of less than 70% who were treated with estrogen. In contrast, control patients with comparably low initial weight had a 20.1 % decrease in BD. Women in the control group with spontaneous resumption of menses, all of whom had an initial percent ideal body weight of greater than 70%, had a 19.3% increase in bone mass. It is concluded that: 1) estrogen replacement cannot prevent progressive osteopenia in young women with anorexia nervosa; 2) a subset of patients may have improved BD with estrogen and progestin administration depending on initial body weight; and 3) recovery from anorexia nervosa is associated with significantly improved BD.

Adolescent↗
PubMed1994

Pathogenesis of pituitary Cushing's syndrome. Pituitary versus hypothalamic.

There has been a long-standing controversy as to whether Cushing's syndrome is primarily a hypothalamic disorder, with the pituitary simply responding to excess of CRH or other factors, or whether the defect lies at the level of the pituitary. Current data suggest that in nearly all cases, the tumor is clonal, implying a genetic defect at the level of the pituitary. The specific abnormalities underlying the development of corticotroph adenomas remain to be determined. It is certainly possible that the historical controversy has created an artificial dichotomy in our thinking about the pathogenesis of Cushing's syndrome and that hypothalamic factors may play a permissive role in the clonal expansion of a mutated pituitary cell. Finally, the finding of polyclonality in hyperplastic corticotroph tissue from a patient with an ectopic CRH-secreting tumor suggests there may be a more direct role for CRH in the pathogenesis of Cushing's syndrome in rare cases.

Adenoma↗