Pamela U Freda

Columbia University, New York, New York, United States

Are you Pamela U Freda?

Claim your profile

Publications (76)435.61 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Context Glucocorticoid (GC) exposure increases food intake, but the mechanisms in humans are not known. Investigation of appetite and food craving has not been done in patients with chronic GC exposure due to Cushing’s disease (CD), either before or after treatment, and could provide insight into mechanisms of food intake and obesity in these patients. Purpose To examine whether surgical remission of CD changes appetite (prospective consumption, hunger, satisfaction, and fullness) and food cravings (sweet, salty, fatty, and savory); and to identify predictors of appetite and craving in CD remission. Methods 30 CD patients, mean age 40.0 years (range 17–70), mean BMI 32.3 ± 6.4, were prospectively studied before and at a mean of 17.4 mo. after remission. At each visit fasting and post-test meal (50 % carbohydrate, 35 % protein, 15 % fat) appetite and craving scores were assessed. Results Remission decreased prospective consumption, sweet and savory craving (p < 0.05), but did not change hunger, satisfaction, fullness, or fat craving, despite decreases in BMI and fat mass. In CD remission, serum cortisol predicted lower satisfaction and fullness, and masses of abdominal fat depots predicted higher hunger and consumption (p < 0.05). Conclusions Chronic GC exposure in CD patients may stimulate the drive to eat by enhancing craving, rather than regulating the sensation of hunger. Continued alterations in appetite regulation due to abdominal fat mass and circulating cortisol could play a role in the cardiovascular and metabolic risk that has been reported in CD patients despite remission.
    No preview · Article · Oct 2015 · Pituitary

  • No preview · Article · Oct 2015 · Endocrine Practice
  • [Show abstract] [Hide abstract]
    ABSTRACT: GH and IGF-I have important roles in maintenance of substrate metabolism and body composition. However, when in excess in acromegaly, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) deposition. To examine the effect of surgery for acromegaly on AT distribution and ectopic lipid deposition in liver and muscle. Prospective study before and up to 2 years after pituitary surgery. Academic pituitary center. 23 newly diagnosed, untreated acromegaly patients. Adipose tissue mass of visceral (VAT), subcutaneous (SAT) and inter-muscular (IMAT) and skeletal muscle (SM) compartments by whole-body MRI; intrahepatic (IHL) and intramyocellular (IMCL) lipid by proton magnetic resonance spectroscopy ((1)HMRS), serum endocrine, metabolic and CV risk markers. VAT and SAT mass were lower than predicted in active acromegaly, but increased after surgery in males and females along with lowering of GH, IGF-1 and insulin resistance. VAT and SAT increased to a greater extent in men than women. SM mass decreased in men. IMAT was higher in active acromegaly and decreased in women after surgery. IHL increased, but IMCL did not change after surgery. Acromegaly may present a unique type of lipodystrophy characterized by a reduced storage of AT in central depots and a shift of excess lipid to IMAT. After surgery, this pattern partially reverses, but differentially in men and women. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use.
    No preview · Article · Jun 2015 · The Journal of Clinical Endocrinology and Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.
    No preview · Article · Apr 2015 · Pituitary
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To evaluate use of pegvisomant, a GH receptor antagonist, as monotherapy in ACROSTUDY, a global safety surveillance study set in 14 countries (373 sites).Methods: A descriptive analysis of safety, magnetic resonance imaging (MRI) reading and treatment outcomes in 710 subjects who received at least one pegvisomant dose as monotherapy during and up to 5 years follow-up in ACROSTUDY.Results: Subjects received 5.4 yr. (mean) of pegvisomant and were followed in ACROSTUDY 3.8 yr. (mean). A total of 1255 adverse events were reported in 345 subjects (48.6%). Serious adverse events were reported in 133 (18.7%) subjects including 22 deaths, none of which were attributed to pegvisomant use. Of 670 (94%) subjects with at least one liver function test reported in ACROSTUDY, 8 (1.2%) had reported increases in transaminases > 3X ULN. No liver failure was reported. Based on central MRI reading, 12 of 542 subjects (2.2%) had a confirmed increase or increase/decrease in tumor size. Injection-site reactions were reported in 2.3%. At 5 years of therapy, IGF-1 level was reported normal in 67.5% (mean dose 17.2 mg/day) and elevated in 29.9% (mean dose 19.8 mg/day). Subjects on 20 mg per day or more rose from 36% at 3 years to 41% at 5 years of therapy.Conclusions: ACROSTUDY data indicate that pegvisomant used as sole medical therapy is safe and effective medical treatment for acromegaly. The reported low incidence of pituitary tumor size increase and liver enzyme elevations are reassuring and support the positive benefit-risk of pegvisomant therapy.
    No preview · Article · Nov 2014 · Endocrine Practice
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Although epidemiological studies have found that GH and IGF-1 normalization reduce the excess mortality of active acromegaly to expected rates, cross-sectional data report some cardiovascular (CV) risk markers to be less favorable in remission than active acromegaly. Objective: The objective of the study was to test the hypothesis that remission of acromegaly after surgical therapy increases weight and adiposity and some CV risk markers and these changes are paralleled by a rise in ghrelin. Design: Forty-two adults with untreated, active acromegaly were studied prospectively. Changes in outcome measures from before to after surgery were assessed in 26 subjects achieving remission (normal IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery. Setting: The study was conducted at tertiary referral centers for pituitary tumors. Main Outcome Measures: Endocrine, metabolic, and CV risk parameters, anthropometrics, and body composition by dual-energy X-ray absorptiometry were measured. Results: Remission increased total ghrelin, body weight, waist circumference, C-reactive protein, homocysteine, high-density lipoprotein, and leptin and reduced systolic blood pressure, homeostasis model assessment, triglycerides, and lipoprotein (a) by 6 months and for 32 ± 4 months after surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1, and insulin and insulin resistance. Weight, waist circumference, and ghrelin did not increase significantly in the persistent active acromegaly group. Total body fat, trunk fat, and perentage total body fat increased by 1 year after surgery in 15 remission subjects: the increase in body fat correlated with the rise in total ghrelin. Conclusions: Although most markers of CV risk improve with acromegaly remission after surgery, some markers and adiposity increase and are paralleled by a rise in total ghrelin, suggesting that these changes may be related. Understanding the mechanisms and long-term implications of the changes that accompany treatment of acromegaly is important to optimizing management because some aspects of the postoperative profile associate with the increased metabolic and CV risk in other populations.
    No preview · Article · Aug 2014 · Journal of Clinical Endocrinology & Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Distinguishing between pituitary (Cushing's disease -CD) and ectopic causes (Ectopic ACTH syndrome -EAS) of ACTH-dependent Cushing's syndrome (CS), can be challenging. Inferior petrosal sinus sampling (IPSS) best discriminates between CD and occult EAS, but is a specialized procedure that is not widely available. Identifying adjunctive diagnostic tests may prove useful. In EAS, abnormal processing of the ACTH precursor proopiomelanocortin (POMC) and the accumulation of POMC-derived peptides might be expected and abnormal levels of other neuropeptides may be detected. Objective: To evaluate the diagnostic utility of POMC measurements for distinguishing between CD and occult EAS in patients referred for IPSS. To evaluate in parallel the diagnostic utility of another neuropeptide, agouti-related protein (AgRP), as we have observed a 10-fold elevation of AgRP in plasma in a patient with EAS from small cell lung cancer. Design and Participants: Plasma POMC and AgRP were measured in 38 CS patients presenting for IPSS, with either no pituitary lesion or a microadenoma on MRI, and in 38 healthy controls. Results: 27/38 patients had CD; 11/38 had EAS. Mean POMC was higher in EAS vs. CD (54.5±13.0 (SEM) vs. 17.2±1.5 fmol/ml; p<0.05). Mean AgRP was higher in EAS vs. CD (280±76 vs. 120±16 pg/ml; p=0.01). Although there was overlap in POMC and AgRP levels between the groups, POMC levels >36 fmol/ml (n=7) and AgRP levels >280 pg/ml (n=3) were specific for EAS. When used together, POMC >36 fmol/ml and/or AgRP >280 pg/ml detected 9/11 cases of EAS, indicating that elevations in these peptides have a high positive predictive value for occult EAS. Conclusions: Expanding upon previous observations of high POMC in EAS, this study specifically demonstrates elevated POMC levels can identify occult ectopic tumors. Elevations in AgRP also favor the diagnosis of EAS, suggesting AgRP should be further evaluated as a potential neuroendocrine tumor marker.
    No preview · Article · Jul 2014 · Journal of Clinical Endocrinology & Metabolism
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide LAR, many patients do not achieve biochemical control. Objective: To demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naïve patients with acromegaly. Design: Prospective, randomized, double blind. Setting: 84 sites; 27 countries. Patients: 358 patients with medically naïve acromegaly (GH>5μg/liter or GH nadir≥1μg/liter post-OGTT, and IGF-1>ULN). Patients either had prior pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on MRI. Interventions: Pasireotide LAR 40mg/28d (n=176) or octreotide LAR 20mg/28d (n=182) for 12 months. At months 3 and 7, titration to pasireotide LAR 60mg or octreotide LAR 30mg was permitted, but not mandatory, if GH≥2.5μg/liter and/or IGF-1>ULN. Main outcome measure: Proportion of patients in each treatment arm with biochemical control (GH<2.5μg/liter and normal IGF-1) at month 12. Results: Biochemical control was achieved by significantly more pasireotide LAR patients than octreotide LAR patients (31.3% versus 19.2%; P=0.007; 35.8% versus 20.9% when including patients with IGF-1 below the lower normal limit). In pasireotide LAR and octreotide LAR patients, respectively, 38.6% and 23.6% (P=0.002) achieved normal IGF-1, and 48.3% and 51.6% achieved GH<2.5μg/liter. 31.0% of pasireotide LAR and 22.2% of octreotide LAR patients who did not achieve biochemical control did not receive the recommended dose increase. Hyperglycemia-related adverse events were more common with pasireotide LAR (57.3% versus 21.7%). Conclusions: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.
    Full-text · Article · Jan 2014 · The Journal of Clinical Endocrinology and Metabolism
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cushing's Disease (CD) alters fat distribution, muscle mass, adipokine profile, and cardiovascular risk factors. It is not known whether remission entirely reverses these changes. Our objective was to determine whether the adverse body composition and cardiovascular risk profile in CD change after remission. Fourteen CD patients were studied prospectively: before surgery (active disease) and again postoperatively 6 months after discontinuing oral glucocorticoids (remission). Whole-body magnetic resonance imaging was used to examine lean and fat tissue distributions. Body composition (skeletal muscle and fat in the visceral, bone marrow, sc, and inter-muscular compartments) and cardiovascular risk factors (serum insulin, glucose, leptin, high-molecular-weight adiponectin, C-reactive protein, and lipid profile) were measured in active CD and remission (mean 20 months after surgery). Remission decreased visceral, pelvic bone marrow, sc (including trunk and limb sc), and total fat; waist circumference; and weight (P < 0.05). Remission altered fat distribution, resulting in decreased visceral/total fat (P = 0.04) and visceral fat/skeletal muscle ratios (P = 0.006). Remission decreased the absolute muscle mass (P = 0.015). Cardiovascular risk factors changed: insulin resistance, leptin, and total cholesterol decreased (P < 0.05), but adiponectin, C-reactive protein, and other lipid measures did not change. CD remission reduced nearly all fat depots and reverted fat to a distribution more consistent with favorable cardiovascular risk but decreased skeletal muscle. Remission improved some but not all cardiovascular risk markers. Remission from CD dramatically improves body composition abnormalities but may still be associated with persistent cardiovascular risk.
    No preview · Article · Mar 2012 · The Journal of Clinical Endocrinology and Metabolism

  • No preview · Conference Paper · Jan 2012
  • Pamela Freda · Laurence Katznelson · Mark Molitch

    No preview · Article · Apr 2011 · The Journal of Clinical Endocrinology and Metabolism
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim was to formulate practice guidelines for endocrine evaluation and treatment of pituitary incidentalomas. Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails and one in-person meeting. We recommend that patients with a pituitary incidentaloma undergo a complete history and physical examination, laboratory evaluations screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. We recommend that patients with incidentalomas not meeting criteria for surgical removal be followed with clinical assessments, neuroimaging (magnetic resonance imaging at 6 months for macroincidentalomas, 1 yr for a microincidentaloma, and thereafter progressively less frequently if unchanged in size), visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm (6 months and yearly), and endocrine testing for macroincidentalomas (6 months and yearly) after the initial evaluations. We recommend that patients with a pituitary incidentaloma be referred for surgery if they have a visual field deficit; signs of compression by the tumor leading to other visual abnormalities, such as ophthalmoplegia, or neurological compromise due to compression by the lesion; a lesion abutting the optic nerves or chiasm; pituitary apoplexy with visual disturbance; or if the incidentaloma is a hypersecreting tumor other than a prolactinoma.
    Preview · Article · Apr 2011 · The Journal of Clinical Endocrinology and Metabolism
  • Pamela U. Freda
    [Show abstract] [Hide abstract]
    ABSTRACT: Measurements of growth hormone (GH) and the GH-dependent peptide insulin-like growth factor-I (IGF-I) are essential for diagnosing and managing acromegaly. The IGF-I level can be easily measured as a single, random sample, and when done properly and compared to a well-characterized, age-adjusted normative database, elevation of the serum IGF-I level is a sensitive and specific indicator for the presence of acromegaly or persistent disease after therapy. The most common approach to GH assessment is to assess the degree of GH suppression after oral glucose administration (oral glucose tolerance test [OGTT]). Failure of GH to fall into the range expected for the healthy population, along with an elevated IGF-I, is confirmatory of active acromegaly. To distinguish active acromegaly from remission, an OGTT nadir GH cut-off of 1 μg/L has been found to be reliable for use with some GH assays, but this cut-off may be as low as 0.3 μg/L with others. Because GH assays are heterogeneous, uniform, clinically relevant GH criteria for acromegaly are difficult to establish. Caveats exist to the testing of GH or IGF-I and therefore the validity of reliance on the measurement of either of these alone remains controversial. In some settings, the acromegaly patient is monitored by the IGF-I level alone, and in others, a combined assessment is preferred, although discrepant results are not uncommon. This chapter reviews our current understanding of the value of GH and IGF-I measurements in the diagnosis and monitoring of acromegaly during therapy. KeywordsAcromegaly-Growth hormone-IGF-I
    No preview · Chapter · Dec 2010
  • Source
    Pamela U Freda · Jeffrey N Bruce
    [Show abstract] [Hide abstract]
    ABSTRACT: surgical resection of pituitary tumors is the treatment of choice for patients with hormone-secreting tumors or those that impair vision and other neurological functions. a recent study by grossman et al., however, found transsphenoidal surgery to be associated with increased mortality and morbidities in elderly patients, which suggests the need for careful individualized decision-making in this vulnerable population.
    Preview · Article · Nov 2010 · Nature Reviews Endocrinology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic hypercortisolemia due to Cushing's disease (CD) results in abnormal adipose tissue (AT) distribution. Whole-body magnetic resonance imaging (MRI) was used to examine lean and AT distribution in female patients with CD to further understand the role of glucocorticoid excess in the development of abnormal AT distribution and obesity. Cross-sectional and case-control study. Fifteen women with CD and 12 healthy controls. Mass of skeletal muscle (SM) and AT in the visceral (VAT), subcutaneous (SAT), and intermuscular (IMAT) compartments from whole-body MRI and serum levels of insulin, glucose, and leptin were measured. CD patients had leptin values that correlated to total AT (TAT) and SAT (P < 0.05) but not to VAT. CD patients had higher VAT/TAT ratios (P < 0.01) and lower SAT/TAT ratios (P < 0.05) compared to controls. TAT, VAT, and trunk SAT (TrSAT) were greater in CD patients (P < 0.01). SM was less in CD (P < 0.001) but IMAT was not different. TAT, VAT, trSAT, and the proportion of AT in the visceral depot were greater in CD although the proportion in the subcutaneous depot was less. SM was less but IMAT was not different. These findings have implications for understanding the role of cortisol in the abnormal AT distribution and metabolic risk seen in patients exposed to chronic excess glucocorticoids.
    Full-text · Article · Oct 2010 · Clinical Endocrinology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Only rarely do corticotroph pituitary tumors become invasive leading to symptoms caused by compression of cranial nerves and other local structures. When aggressive pituitary neuroendocrine tumors do develop, conventional treatment options are of limited success. A 50-year-old man developed a giant invasive corticotroph pituitary tumor 2 years after initial presentation. His tumor and symptoms failed to respond to maximal surgical, radio-surgical, radiation and medical therapy and a bilateral adrenalectomy was done. He subsequently developed rapid growth of his tumor leading to multiple cranial nerve deficits. He was administered salvage chemotherapy with capecitabine and temozolomide (CAPTEM), a novel oral chemotherapy regimen developed at our institution for treatment of neuroendocrine tumors. After two cycles of CAPTEM, his tumor markedly decreased in size and ACTH levels fell by almost 90%. Despite further decreases in ACTH levels, his tumor recurred after 5 months with increased avidity on PET scan suggesting a transformation to a more aggressive phenotype. Temozolomide had been reported to be effective against other pituitary tumors and this case adds to this literature demonstrating its use along with capecitabine (CAPTEM) against a corticotroph tumor. Further evaluation of the CAPTEM regimen in patients with pituitary neuroendocrine tumors which fail to respond to classic treatments is warranted.
    Full-text · Article · Dec 2009 · Pituitary
  • Martin Bidlingmaier · Pamela U Freda
    [Show abstract] [Hide abstract]
    ABSTRACT: Measuring the concentration of growth hormone (GH) in blood samples taken during dynamic tests represents the basis for diagnosis of growth hormone related disorders, namely growth hormone deficiency and growth hormone excess. Today, a wide spectrum of immunoassays are in use, enabling rapid and sensitive determination of growth hormone concentrations in routine diagnostics. From a clinical point of view several difficulties exist with the use and interpretation of GH assay results in the assessment of GH related disorders: Many physiological factors such as fat mass, age and gender influence the outcome of dynamic tests, overall leading to significant inter-individual differences in GH responses. However, in addition to the physiological variability, considerable variability exists in GH assay results obtained by different immunoassays. Unfortunately, all the new technical advances in the field of GH measurement techniques have not reduced this methodological variability. To a large extent, the actual values reported for the GH concentration in a sample depend on the method used by the respective laboratory. Obviously, such discrepancies limit the applicability of consensus guidelines on diagnosis and treatment in clinical practice. This review summarizes current practices for GH measurement with respect to the methods used, their limitations and the clinical consequences of the existing heterogeneity in GH immunoassay results.
    No preview · Article · Oct 2009 · Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society
  • Source
    Lowell Anthony · Pamela U Freda
    [Show abstract] [Hide abstract]
    ABSTRACT: Acromegaly is characterized by overproduction of growth hormone (GH) by the pituitary gland. GH stimulates the synthesis of insulin-like growth factor-I (IGF-I), and the somatic growth and metabolic dysfunction that characterize acromegaly are a consequence of elevated GH and IGF-I levels. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, slow-growing neoplasms that have usually metastasized by the time of diagnosis. The majority of GEP-NETs are carcinoid tumors whose syndrome is caused by the hypersecretion of biogenic amines, peptides and polypeptides responsible for the principal symptoms of diarrhea and flushing. The MEDLINE and EMBASE databases were searched for preclinical and clinical studies of octreotide (Sandostatin* ), a potent synthetic somatostatin analogue, in patients with acromegaly or GEP-NETs. This article reviews the 20 years of clinical experience with octreotide and the impact it has made in patients with acromegaly or GEP-NETs. Octreotide has proven to be an essential component in the management strategy of acromegaly and GEP-NETs over the past 20 years. The multiple beneficial effects of octreotide throughout the body, combined with its established safety profile (the most common adverse effects are injection-site pain and gastrointestinal events), have made it an appealing option for clinicians. The advent of the long-acting release (LAR) formulation of octreotide provided additional benefits to patients through monthly administration, while maintaining the efficacy and tolerability profile of the daily subcutaneous formulation. Octreotide is a potent synthetic somatostatin analogue that has become the mainstay of medical therapy for tumor control in neuroendocrine disorders such as acromegaly and GEP-NETs. The development of octreotide LAR offered a further advancement; less frequent dosing provided valuable benefits in quality of life to patients, with equivalent efficacy and tolerability. Moreover, recent results from the PROMID study have confirmed the antiproliferative effect of octreotide LAR in patients with well-differentiated metastatic GEP-NETs of the midgut. New therapeutic uses of octreotide are currently under investigation in a variety of clinical settings.
    Full-text · Article · Oct 2009 · Current Medical Research and Opinion
  • Jan Frystyk · Pamela Freda · David R Clemmons
    [Show abstract] [Hide abstract]
    ABSTRACT: For almost three decades, the measurement of circulating IGF-I has constituted a highly important biochemical tool in the management of GH disorders. In fact, in acromegaly the importance of circulating IGF-I has increased following the introduction of the GH receptor antagonist pegvisomant, as the use of this drug makes it impossible to use circulating GH as a monitor of disease activity. In addition, determination of circulating IGF-I constitutes a valuable scientific tool in various research areas, from epidemiological investigations through clinical trials and experimental studies. The multiple facets of IGF-I physiology and patho-physiology may explain why numerous endocrine laboratories have invested in IGF-I assays, by means of either in-house assays or commercial kits. However, despite its widespread use, the measurement of IGF-I is by no means trivial. On the contrary, the pronounced binding of IGF-I to the high-affinity IGF-binding proteins (IGFBPs) constitutes a notorious source of error, which has necessitated the development of methods that more or less successfully circumvent interference from the IGFBPs. Furthermore, there are some unsolved issues with the international standardization of the different IGF-I assays and there is no consensus regarding the procedures used when collecting and storing samples for measurement of circulating IGF-I. The aim of this review is to discuss the current state of the art of IGF-I immunoassays and to present the current analytical problems with IGF-I measurements. Finally, we would like to suggest an agenda that may be used when trying to produce internationally accepted uniform requirements for future IGF-I assays.
    No preview · Article · Oct 2009 · Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society
  • [Show abstract] [Hide abstract]
    ABSTRACT: GH and IGF-I are nitrogen retaining and anabolic, but the impact of long-term exposure to supraphysiological GH and IGF-I, either from endogenous overproduction in acromegaly or exogenous sources, on skeletal muscle (SM) mass is not clear. The objectives of the study were to assess SM mass by whole-body magnetic resonance imaging (MRI) in acromegaly and test the hypothesis that dual-energy x-ray absorptiometry (DXA) lean tissue mass-derived estimates of SM accurately estimate true SM mass. The design was a cross-sectional study in 27 acromegaly patients compared with predicted models developed in 315 nonacromegaly subjects and to matched controls. Mass of SM from whole-body MRI and lean tissue from DXA were measured. SM mass did not differ from predicted or control values in active acromegaly: 31.75 +/- 8.6 kg (acromegaly) vs. 33.06 +/- 8.9 kg (predicted); SM was 95.6 +/- 12.8% of predicted (range 66.7-122%) (P = 0.088). Lean tissue mass (DXA) was higher in acromegaly than controls: 65.91 +/- 15.2 vs. 58.73 +/- 13.5 kg (P < 0.0001). The difference between lean tissue mass (DXA) and SM in acromegaly patients was higher than that in controls (P < 0.0001) consistent with an enlarged non-SM lean compartment in acromegaly. SM mass predicted by DXA correlated highly with SM mass by MRI (r = 0.97, P < 0.0001). SM (MRI) to SM (DXA predicted) ratio was 1.018 (range 0.896-1.159), indicating high agreement of these measures of SM. SM mass in active acromegaly patients did not differ from predicted values. SM mass estimated from DXA agreed highly with SM by MRI, supporting the validity of the DXA model in assessing SM in acromegaly and other disorders of GH/IGF-I secretion.
    No preview · Article · Jun 2009 · The Journal of Clinical Endocrinology and Metabolism

Publication Stats

4k Citations
435.61 Total Impact Points


  • 1998-2015
    • Columbia University
      • • Department of Medicine
      • • College of Physicians and Surgeons
      New York, New York, United States
  • 1992-2010
    • CUNY Graduate Center
      New York, New York, United States
  • 2009
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 1998-2008
    • Icahn School of Medicine at Mount Sinai
      • Department of Neurosurgery
      Borough of Manhattan, New York, United States
  • 2005
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
    • Royal College of Physicians and Surgeons of Glasgow
      Glasgow, Scotland, United Kingdom
  • 2001-2003
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1999-2003
    • New York Medical College
      • Department of Medicine
      New York City, New York, United States
  • 2002
    • Devry College of New York, USA
      New York City, New York, United States