Pamela U Freda

Mount Sinai School of Medicine, Manhattan, NY, United States

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Publications (65)366.17 Total impact

  • [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.
    The Journal of clinical endocrinology and metabolism. 08/2014;
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    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.
    The Journal of clinical endocrinology and metabolism. 07/2014;
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    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.
    The Journal of Clinical Endocrinology and Metabolism 03/2012; 97(5):1702-11. · 6.31 Impact Factor
  • The Journal of Clinical Endocrinology and Metabolism 04/2011; 96(4):35A-6A. · 6.31 Impact Factor
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    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.
    The Journal of Clinical Endocrinology and Metabolism 04/2011; 96(4):894-904. · 6.31 Impact Factor
  • Pamela U. Freda
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    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
    12/2010: pages 253-270;
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    Pamela U Freda, Jeffrey N Bruce
    Nature Reviews Endocrinology 11/2010; 6(11):606-8. · 11.03 Impact Factor
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    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.
    Clinical Endocrinology 10/2010; 73(4):469-75. · 3.40 Impact Factor
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    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.
    Pituitary 12/2009; 14(4):418-24. · 2.67 Impact Factor
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    Lowell Anthony, Pamela U Freda
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    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.
    Current Medical Research and Opinion 10/2009; 25(12):2989-99. · 2.37 Impact Factor
  • Jan Frystyk, Pamela Freda, David R Clemmons
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    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.
    Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 10/2009; 20(1):8-18. · 2.35 Impact Factor
  • Martin Bidlingmaier, Pamela U Freda
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    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.
    Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 10/2009; 20(1):19-25. · 2.35 Impact Factor
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    ABSTRACT: Traditionally, acromegaly evaded diagnosis until in its clinically obvious later stages when treatment is more difficult. Over the last 25 years diagnostic tests have improved, but whether clinical disease detection also improved was unknown, so we tested if disease severity at diagnosis had changed from 1981 to 2006. Data on 324 consecutive acromegaly patients presenting from 1981 to 2006 at two New York City hospitals were collected by retrospective review (n = 324) and by interview (n = 200). The main complaint, acromegaly associated comorbidities, signs, symptoms, healthcare providers visited, preoperative GH and IGF-I levels and pituitary tumour size at diagnosis were compared in patients presenting in the earlier vs. later halves of the time period. Times from symptom onset to diagnosis were 5.9 year (early) vs. 5.2 year (late; P = NS). At diagnosis, 96% of early and late groups had facial feature changes and/or hand/foot enlargement. Comorbidities included hypertension 37% (early) vs. 36% (late), carpal tunnel syndrome (24%vs. 24%), sleep apnoea (13%vs. 29%; P < 0.01), osteoarthritis (25%vs. 23%) and diabetes mellitus (18%vs. 15%); each patient had 1.2 (early) vs. 1.3 (late; P = 0.53) comorbidities. Groups were similar in signs, symptoms, tumour size, GH and IGF-I. Clinical, biochemical and tumour size characteristics at diagnosis of acromegaly patients were unchanged from 1981 to 2006. Most patients still have marked manifestations of acromegaly at diagnosis, suggesting that acromegaly remains clinically under-recognized. Healthcare professionals should more commonly consider acromegaly, which can lead to earlier diagnosis and better treatment outcome.
    Clinical Endocrinology 06/2009; 72(2):203-8. · 3.40 Impact Factor
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    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.
    The Journal of Clinical Endocrinology and Metabolism 06/2009; 94(8):2880-6. · 6.31 Impact Factor
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    ABSTRACT: Giant pituitary adenomas of excessive size, fibrous consistency or unfavorable geometric configuration may be unresectable through conventional operative approaches. We present our select case series for operative resection and long-term follow-up for these unusual tumors, employing both a staged procedure and a combined transsphenoidal-transcranial above and below approach. A retrospective chart review was performed on patients operated via the staged, and combined approaches by the senior author (J.N.B.). Preoperative characteristics and postoperative outcomes were reviewed. A detailed description of the operative technique and perioperative management is provided. Between 1993 and 1996, two patients harboring giant pituitary adenomas underwent an intentionally staged resection, and between 1997 and 2006, nine patients harboring giant pituitary adenomas underwent surgery via a single-stage above and below approach. Nine patients (82%) presented with non-secreting adenomas and two patients (18%) presented with prolactinomas refractory to medical management. Gross total resection was achieved in six patients (55%), near total resection in 1 (9%), and subtotal removal in 4 (36%). Seven patients (64%) experienced visual improvement postoperatively and no major complications occurred. Long-term follow-up averaged 51.6 months. Panhypopituitarism was observed in four patients, partial hypopituitarism in four, persistent DI in two, and persistent SIADH in one. The addition of a transcranial component to the transsphenoidal approach offers additional visualization of critical neurovascular structures during giant pituitary adenoma resection. Complications rates are similar to other series in which complex pituitary adenomas are resected by other means. The above and below approach is both safe and effective and the immediate and long-term advantages of a single-stage approach justify its utility in this select group of patients.
    Pituitary 03/2009; 12(3):217-25. · 2.67 Impact Factor
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    Pamela U Freda
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    ABSTRACT: Monitoring of a patient with acromegaly requires periodic evaluation of levels of GH and IGF-1, the biochemical markers of this disease. Although the results of these two tests are usually concordant, they can be discrepant and how to proceed when they are can be a challenging clinical problem. In some cases, IGF-1 levels are normal yet GH suppression after oral glucose is abnormal; this pattern may be due to persistent GH dysregulation despite remission. In other cases, IGF-1 levels are elevated yet GH suppression appears to be normal; this pattern may be observed if the cutoff for GH suppression is inappropriately high for the GH assay being used. Various conditions known to alter GH and IGF-1 including malnutrition, thyroid disease and oestrogen use as well as the potential for methodological or normative data issues with the GH and IGF-1 assays should be considered in the interpretation of discrepant results. When a known cause of the discrepancy other than acromegaly is not identified, a clinical decision about the patient's therapy needs to be made. We adjust treatment in most patients whose results are discrepant based on the IGF-1 level, continuing current treatment if it is persistently normal or modifying this if it is elevated. The clinical picture of the patient, however, also needs to be incorporated into this decision. All patients should have continued periodic surveillance of both GH and IGF-1 levels.
    Clinical Endocrinology 03/2009; 71(2):166-70. · 3.40 Impact Factor
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    ABSTRACT: There is currently no medical therapy for Cushing's disease that targets the pituitary adenoma. Availability of such a medical therapy would be a valuable therapeutic option for the management of this disorder. Our objective was to evaluate the short-term efficacy of the novel multireceptor ligand somatostatin analog pasireotide in patients with de novo, persistent, or recurrent Cushing's disease. We conducted a phase II, proof-of-concept, open-label, single-arm, 15-d multicenter study. Thirty-nine patients with either de novo Cushing's disease who were candidates for pituitary surgery or with persistent or recurrent Cushing's disease after surgery without having received prior pituitary irradiation. Intervention: Patients self-administered sc pasireotide 600 microg twice daily for 15 d. Normalization of urinary free cortisol (UFC) levels after 15 d treatment was the main outcome measure. Of the 29 patients in the primary efficacy analysis, 22 (76%) showed a reduction in UFC levels, of whom five (17%) had normal UFC levels (responders), after 15 d of treatment with pasireotide. Serum cortisol levels and plasma ACTH levels were also reduced. Steady-state plasma concentrations of pasireotide were achieved within 5 d of treatment. Responders appeared to have higher pasireotide exposure than nonresponders. Pasireotide produced a decrease in UFC levels in 76% of patients with Cushing's disease during the treatment period of 15 d, with direct effects on ACTH release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.
    Journal of Clinical Endocrinology &amp Metabolism 11/2008; 94(1):115-22. · 6.43 Impact Factor
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    ABSTRACT: Few data are available on the selective use of bilateral inferior petrosal sinus sampling (BIPSS) in the presurgical evaluation of patients with ACTH-dependent Cushing's syndrome, so we investigated whether its use only in patients without a clear adenoma on magnetic resonance imaging and/or inconsistent biochemical testing affected remission and long-term outcome after surgery in patients with Cushing's disease (CD). This was a retrospective review of patients treated for CD by one pituitary neurosurgeon at tertiary medical centers in New York City. A total of 193 consecutive adult patients who underwent initial transsphenoidal surgery (TS) for presumed CD between 1987 and 2005 were included. We examined preoperative pituitary imaging and biochemical data, results of BIPSS and surgical pathology, and outcome based on biochemical tests after initial TS and long term after subsequent therapies. Remission rate after the first TS was 80.8% overall, 79.1% in the BIPSS group (n = 105), and 83.0% in the No-BIPSS group (n = 88). Recurrences occurred in 13.5% after the first TS at a mean of 4.8 +/- 3.5 yr (range, 0.7-12.4 yr) with no difference between BIPSS and No-BIPSS groups. Long-term remission was achieved after surgeries and radiotherapy in 85% (86.7% of BIPSS group, 83.0% of No-BIPSS group). CD was ultimately confirmed in all but one patient in each group. Selective use of BIPSS in the preoperative evaluation of patients with presumed CD did not lead to misdiagnosis in the No-BIPSS group or adversely affect remission rates or long-term outcome.
    Journal of Clinical Endocrinology &amp Metabolism 10/2008; 93(12):4624-32. · 6.43 Impact Factor
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    ABSTRACT: GH and IGF-I are important regulators of metabolism and body composition. In acromegaly, a state of GH and IGF-I excess, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) distribution. Our objective was to test the hypothesis that in acromegaly whole-body AT mass is less and to examine for the first time the relationship between GH/IGF-I excess and intermuscular AT (IMAT), an AT depot associated with insulin resistance in other populations. We conducted a cross-sectional study in 24 adults with active acromegaly compared with predicted models developed in 315 healthy non-acromegaly subjects. Mass of AT in the visceral AT (VAT), sc AT (SAT), and IMAT compartments from whole-body magnetic resonance imaging and serum levels of GH, IGF-I, insulin, and glucose were measured. VAT and SAT were less in active acromegaly (P < 0.0001); these were 68.2 +/- 27% and 79.5 +/- 15% of predicted values, respectively. By contrast, IMAT was greater (P = 0.0052) by 185.6 +/- 84% of predicted. VAT/trunk AT ratios were inversely related to IGF-I levels (r = 0.544; P = 0.0054). Acromegaly subjects were insulin resistant. VAT and SAT, most markedly VAT, are less in acromegaly. The proportion of trunk AT that is VAT is less with greater disease activity. IMAT is greater in acromegaly, a novel finding, which suggests that increased AT in muscle could be associated with GH-induced insulin resistance. 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.
    Journal of Clinical Endocrinology &amp Metabolism 06/2008; 93(6):2334-43. · 6.43 Impact Factor
  • John C Ausiello, Jeffrey N Bruce, Pamela U Freda
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    ABSTRACT: While most transsphenoidal pituitary surgery is accomplished without complication, monitoring is required postoperatively for a set of disorders that are specific to this surgery. Postoperative assessments are tailored to the early and later postoperative periods. In the early period, which spans the first few weeks after surgery, both monitoring of anterior and posterior pituitary function and managing neurosurgical issues are the focus of care. Potential disruption of pituitary-adrenal function is covered with perioperative glucocorticoids. Various strategies exist for ensuring the integrity of this axis, but typically this is done by measuring a morning cortisol on the 2nd or 3rd postoperative days. Patients with levels <10 microg/l should continue therapy with reassessment in the later postoperative period. Monitoring for water imbalances, which are due to deficiency or excess of ADH (DI or SIADH, respectively), is accomplished by continuous accounting of fluid intake, urine output and specific gravities coupled with daily serum electrolyte measurements. DI is characterized by excess volumes of inappropriately dilute urine, which can lead to hypernatremia. Most patients maintain adequate fluid intake and euvolemia, but desmopressin therapy is required for some. SIADH, which peaks in incidence on 7th postoperative day, presents with hyponatremia that can be severe and symptomatic. Management consists of fluid restriction. Neurosurgical monitoring is primarily for disturbances in vision or neurological function, and although uncommon, for CSF leak and infections such as meningitis. In the later postoperative period, the adrenal, thyroid and gonadal axes are assessed. New persistent hypopituitarism is rare when transsphenoidal surgery is performed by an experienced surgeon. Various strategies are available for assessing each axis and for providing replacement therapy in patients with deficiencies. Long term monitoring with assessments of visual, neurological and pituitary function coupled with pituitary imaging is necessary for all patients who have undergone surgery, irrespective of the hormone status of their tumors.
    Pituitary 04/2008; 11(4):391-401. · 2.67 Impact Factor

Publication Stats

2k Citations
366.17 Total Impact Points

Institutions

  • 2008–2012
    • Mount Sinai School of Medicine
      • Department of Medicine
      Manhattan, NY, United States
  • 2002–2011
    • Devry College of New York, USA
      New York City, New York, United States
  • 2010
    • New York University
      • Department of Medicine
      New York City, NY, United States
  • 2001–2010
    • Columbia University
      • • Department of Medicine
      • • College of Physicians and Surgeons
      New York City, NY, United States
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2009
    • Louisiana State University Health Sciences Center New Orleans
      New Orleans, Louisiana, United States
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
    • New York Presbyterian Hospital
      • Department of Neurological Surgery
      New York City, New York, United States
  • 2005
    • 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
  • 1995–2003
    • New York Medical College
      • Department of Medicine
      New York City, New York, United States