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Beverly Hills, CA, United States

Carmichael J.D.,Pituitary Center
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2012

Purpose of review To discuss the multiple forms of hypophysitis, the various methods of classification, the recent findings in pituitary autoimmunity and novel methods of treating resistant or recurrent hypophysitis. (January 2010- December 2011). Recent findings Multiple novel presentations of hypophysitis have been described including cytotoxic T-lymphocyte antigen-4 antibody-related hypophysitis, an adverse event associated with a novel treatment for cancer, Food and Drug Administration approved for use in the treatment of metastatic melanoma. A rare, but newly described entity of immunoglobulin G4 related plasmacytic hypophysitis has been described and reviewed. Multiple investigations addressing the role of autoimmunity in the diagnosis and pathogenesis of hypophysitis have been reported with positive antipituitary antibodies found in patients with autoimmune hypophysitis, other autoimmune diseases, and nonimmune-related pituitary diseases. Several case series and case reports present new associations with concomitant diseases and novel therapy for cases requiring treatment when standard therapy fails or is contraindicated. Summary Hypophysitis is a rare disease with multiple subtypes. The description of hypophysitis related to cytotoxic T-lymphocyte antigen-4 antibody treatment is one of the first descriptions of hypophysitis triggered by medication. As the use of this novel treatment for cancer increases, so must our awareness of immune-related adverse effects and their treatment. Pituitary autoimmunity is a challenging field with multiple discoveries reported to help further our understanding of the disease and assist in diagnosis. Insufficient sensitivity and specificity of the currently reported methods prevents recommending measurement of antipituitary antibodies as standard of care in the diagnosis of hypophysitis. The treatment of hypophysitis remains controversial with recommendations ranging from hormonal replacement to newly described therapies such as azathioprine and radiation. Copyright © Lippincott Williams & Wilkins. Source


Lin E.,Massachusetts General Hospital | Bredella M.A.,Massachusetts General Hospital | Gerweck A.V.,Massachusetts General Hospital | Landa M.,Massachusetts General Hospital | And 3 more authors.
Clinical Endocrinology | Year: 2013

Objective We previously reported improved body composition and cardiovascular risk markers plus a small decrease in glucose tolerance with GH administration vs placebo for 6 months to abdominally obese premenopausal women. The objective of this study was to determine whether the effects of GH treatment on cardiovascular risk markers, body composition and glucose tolerance in obese women persist 6 months after GH withdrawal. Design and patients Fifty abdominally obese premenopausal women completed a trial of rhGH vs placebo for 6 months; thirty-nine women completed a subsequent 6-month withdrawal observation period. Measurements IGF-I, body composition by CT, 1H-MRS and DXA, serum cardiovascular risk markers, oral glucose tolerance test (OGTT). Results IGF-I standard deviation scores (SDS) within the GH group were -1·7 ± 0·1 (pretreatment),-0·1 ± 0·3 (after 6 months of GH) and -1·7 ± 0·1 (6 months post-GH withdrawal). Six months after GH withdrawal, total abdominal and subcutaneous adipose tissue, total fat, trunk fat, trunk/extremity fat, hsCRP, apoB, LDL, and tPA were higher than at the 6-month (GH discontinuation) timepoint (P ≤ 0·05). All body composition and cardiovascular risk markers that had improved with GH returned to baseline levels by 6 months after GH discontinuation, as did fasting and 2-h OGTT glucose levels. Conclusion The effects of GH administration to abdominally obese premenopausal women have a short time-course. The beneficial effects on body composition and cardiovascular risk markers, and the side effect of altered glucose tolerance returned to pretreatment levels after GH withdrawal. There was no suppression of endogenous IGF-I levels, which returned to baseline after GH withdrawal. © 2012 John Wiley & Sons Ltd. Source


Melmed S.,Cedars Sinai Medical Center | Melmed S.,Pituitary Center | Cook D.,Oregon Health And Science University | Schopohl J.,Medizinische Klinik Innenstadt | And 3 more authors.
Pituitary | Year: 2010

The study was designed to evaluate the long-term efficacy and safety of the 28-day prolonged-release Autogel formulation of the somatostatin analogue lanreotide (Lan-Autogel) in unselected patients with acromegaly. The study comprised four phases: washout; a double-blind comparison with placebo, at a single randomized dose (60, 90 or 120 mg) of Lan-Autogel; a single-blind, fixed-dose phase for four injections (placebo group was re-allocated to active treatment); and eight injections with doses tailored according to biochemical response. Serum samples were assessed for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, at weeks 4, 13, 14, 15, 16, 32 and 52. 108 patients were enrolled and 99 completed 52 weeks' treatment. Four weeks after the first injection, serum GH levels decreased by >50% from baseline in 63% of patients receiving Lan-Autogel compared with 0% receiving placebo (P < 0.001). After four injections, 72% of patients had a >50% reduction in GH levels; 49% patients achieved GH levels ≤ 2.5 ng/ml; 54% had normalized IGF-1; and 38% achieved the combined criterion of GH level ≤ 2.5 ng/ml and normalized IGF-1. The corresponding proportions by week 52 were 82, 54, 59 and 43%, respectively. In patients not requiring dose escalation to 120 mg, 85% achieved biochemical control (combined criterion). Treatment was well tolerated by all patients. In conclusion, Lan-Autogel was effective in controlling GH and IGF-1 hypersecretion in patients with acromegaly and showed a rapid onset of action. Source


Cuevas-Ramos D.,Pituitary Center | Carmichael J.D.,Pituitary Center | Cooper O.,Pituitary Center | Bonert V.S.,Pituitary Center | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: GH-secreting pituitary adenomas exhibit heterogeneous natural history ranging from small tumors to large aggressive adenomas. Objective: To rigorously classify an acromegaly patient cohort defined by clinical, radiological, histopathological, and outcome characteristics. Design: Cross-sectional study. Setting: Tertiary referral pituitary center. Patients: Subjectswereselected from a pituitarytumorresearch registry that includes 1178 patients with pituitary disease. Cluster analysis was performed on 338 acromegaly patients. Interventions: None. Main Outcome Measures: Biochemically active disease with elevated IGF-1 levels at follow-up. Results: Cluster analysis of all patients yielded 292 who were rigorously classified to three acromegaly types.Type1(50%)comprised older patients with the longest follow-upandmostfavorable outcomes, characterized by densely granulated, nonaggressive microadenomas and macroadenomas. Type 1 tumors extend to the sphenoid sinus more frequently than suprasellar extension (concave tumor image) and express abundant immunoreactive p21 and somatostatin receptor 2. Type 2 (19%) comprised noninvasive, densely or sparsely granulatedmacroadenomas,withoutsignificant extension (flattumor image), with intermediate biochemical outcome. Type 3 (31%) was characterized by sparsely granulated aggressive macroadenomas and comprised patients with adverse therapeutic outcomes, despite receiving more treatments. These tumors extend to both the sphenoid sinus and suprasellar regions with commonly encountered optic chiasm compression ("peanut" magnetic resonance image), with low tumor p21 and somatostatin receptor 2 expression. Conclusions: After validation, this classification may be useful to accurately identify acromegaly patients with distinctive patterns of disease aggressiveness and outcome, as well as to provide an accurate tool for selection criteria in clinical studies. © 2015 by the Endocrine Society. Source

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