38. Results of Transsphenoidal Surgery for Prolactinomas Soule SG et al. Clin Endo 1996;44:711 Swearingen B et al. Clin Neurosurg 1997;45:48 Hofle G et al. Exp Clin Endo Diabetes 1996;106:211 Turner HE et al. Eur J Endo 1999;140:43 Tyrrell JB et al. Neurosurgery 1999;44:254 Laws ER, Thapar K. Endo Clin N Amer 1999;28:119 10-40% 60-80% Long-Term Normalization 10-20% 10-20% Recurrence Rate 20-50% 80-90% PRL Normalization Macroadenomas Microadenomas
56. Enlargement Of Soft Tissue In Acromegaly Large Nose, Large Lips, Furrowed Brow, Increased Supraorbital Ridges, And Growth Of Skin Lesions
57.
58. Prevalence of Adenomatous Colonic Polyps in Acromegaly Delhougne et al., JCEM 1996;80:3223 0 5 10 15 20 25 30 35 40 Total <55 >55 Men Women % with Polyps Acromegaly (n=103) Controls (n-138)
64. Cox model predicted survival Long-Term Mortality After Transsphenoidal Surgery Years after surgery Normal IGF-I Elevated IGF-I 0.8 0.4 0.2 1.0 0.6 Patient in remission Patient not in remission 0 5 10 15 20 Swearingen, B. et al. J Clin Endocrinol Metab 1998;83:3419
65.
66. Effects of Gamma Knife Radiotherapy in Acromegaly Landolt et al., J Neurosurg 1998;88:1002
67.
68. Efficacy of Somatostatin Analogues In Treatment of Acromegaly Newman, Endocrinol Metab Clin N Amer 1999;28:171 Freda, J Clin Endocrinol Metab 2002;87:3013 11% 5% 17% (33/194) 48% (199/417) Lanreotide 35% 8% 43% (22/51) 66% (204/309) Octreotide LAR 21% 25% 46% (53/116) 53% (220/417) Octreotide SC 20-50% Shrinkage <20% Shrinkage Total with Shrinkage (%) IGF-I Normalization Somatostatin Agonist
69.
70. Mechanism of GH Binding And Signal Transduction IGF-I Dimerization GH has two binding sites, each of which binds identical cell surface receptor When both sites bind, dimerizing the receptors, signal transduction occurs
71. Growth Hormone Receptor Antagonist: Pegvisomant Site-1 Binding to GH Receptor Enhanced Site-2 binding disrupted Functional Dimerization Prevented; Signal Transduction and IGF-I Production Do Not Occur
72. Percentage of Patients Achieving a Normal Serum IGF-I with Pegvisomant 20 40 60 80 100 placebo 10 mg 15 mg 20 mg % * * * * P <0.0001 v. placebo 54 7 89 81 Trainer et al NEJM 2000:342;1171-1177
82. ACTH Levels In Cushing’s Disease Compared To The Normal Range 70 18 81 Cushing's Disease Adrenal Tumor Ectopic ACTH 0 150 100 50 200 250 300 500 700 900 1000-2000 2000-4000 4000-12000 Plasma ACTH Concentrations at 900 Plasma ACTH (ng/l) Trainer, PJ in Besser/Thorner, eds. Clinical Endocrinology ,3rd Ed., 1999:Mosby-Wolfe, pg. 8.7.
83.
84.
85.
86.
87. Understanding Dexamethasone Testing Mini-Dexamethasone 1 mg at 11pm & Measure Serum Cortisol At 8am Screening Test For Cushing’s Syndrome Low Dose Dexamethasone 0.5 mg Every 6 Hours For 48 Hours Measuring Urine Free Cortisol & Serum Cortisol Before & After DEX High Dose Dexamethasone 2.0 mg Every 6 Hours For 48 Hrs Measuring Urine Free Cortisol & Serum Cortisol Before & After DEX = Stimulation = Inhibition ACTH Cortisol Cortisol CRH
88.
89.
90.
91.
92.
93. Treatment of Cushing’s Disease With Ketoconazole Pre Post Pre Post Percent Normalized 94% 100% Pre Post Pre Post 0 200 400 600 800 1000 1200 1400 1600 Urinary Free Cortisol (nmol/24h) Sonino et al Tabarin et al
94.
95.
96. Hypothalamic-Pituitary-Thyroid Axis TR Heart Liver Bone CNS Target Tissues TRH Hypothalamus Pituitary T 4 T 3 T 4 T 3 Liver, Muscle T 4 T 3 TSH Thyroid Gland
97.
98.
99. TSH-Secreting Adenoma vs RTH Normal No suppression Response to T 3 suppression No Yes High subunit No Yes Lesion on MRI Yes No Familial cases RTH TSH-oma Feature
100.
101. Ablative Treatment For TSH-Secreting Pituitary Adenomas Beck-Peccoz & Persani, 2002 32 36 32 Total (192) 23 42 35 Surgery + XRT (57) 17 50 33 Irradiation (6) 34 33 33 Surgery (129) Unchanged (%) Improved (%) Cured (%) Treatment (No. of Pts.)
102.
103.
104.
105.
106.
107.
108.
109. Natural History of Untreated Pituitary Incidentalomas *5 Of These 39 Had Tumor Enlargement Secondary To Hemorrhage Into The Tumor Reinecke et al., JAMA 1990;263:2772 Donovan & Corenblum, Arch Int Med 1995;155:181 Nishizawa et al., Neurosurgery 1998;43:1344 Feldkamp et al., Clin Endocrinol 1999;51:109 Eguchi et al., Prog 6 th Intl Pit Congress, 1999 Sanno et al., Eur J Endocrinol 2003;149:123 0.6 – 12 0.6 - 15.0 Yrs Followed 197 113 No Change 23 9 Decreased 39* (15%) 10 (8%) Enlarged 259 132 Total Macroadenomas Microadenomas
110. Flow Diagram for Pituitary Incidentalomas Evaluation of Pituitary Function Hyperfunctioning Clinically Nonfunctioning Prolactinoma Other < 1 cm > 1 cm Dopamine Surgery Visual Fields Agonist R/O Pituitary Hypofunction Repeat MRI at Repeat MRI at 1, 2, 5 yrs 0.5, 1, 2, 5 yrs No Change Tumor Growth Abnl Fields No Further Surgery Studies (?)
