Glandular Adenomas. Objectives 3/12/2012. Christopher Sonnier MD, FACE, ECNU. Review incidence rates. Review functionality concerns.

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1 Glandular Adenomas Christopher Sonnier MD, FACE, ECNU No Disclosures Related To This Discussion Objectives Review incidence rates. Review functionality concerns. Review determination of nonsurgical vs. surgical cases. 1

2 Why Be Concerned? Imaging volumes with Ultrasound, CT, MRI, PET, and other modalities have all increased finding more incidental glandular adenomas. e.g. the term Incidentalomas was coined. Prevalence of all glandular adenomas increases with age. The largest population group in the country is >60 years of age with continued growth predicted for at least another two decades. Pituitary 2

3 3

4 Pituitary Adenomas Incidence by autopsy series 14% Incidence by imaging series 23% Microadenoma (< 10 mm) Common accounts for 99% of cases 30% with no clinical history Macroadenoma (> 10 mm) Rare accounts for 1% of cases Usually symptomatic JCEM 2006:91; Clev Clin J of Med 2008:75: Pituitary Adenomas Microadenoma (< 10 mm) 10% grow over time Macroadenoma (> 10 mm) 20% grow over time Main concern with growth is always related to optic chiasm impingement. JCEM 2011:96; Pituitary Hormone Producing Adenomas Medical >90% of cases Non-Functioning (most produce low levels of Gonadotropins) Prolactinoma Surgical <10% of cases Acromegaly (Growth Hormone) Cushing s Disease (ACTH) TSH related (rare) Endocrine Society 2011 Guideline: Pituitary Incidentaloma Medicine 1999:78; JCEM 2011:96;

5 Other Pituitary Findings Of Note Empty Sella Syndrome 10% have hormone deficiency. Meningioma Typically does not effect function but can cause mass effect. Craniopharyngiomas Typically requires surgery and leads to panhypopituitarism. Pituitary cysts Benign process. Medicine 1999:78; Thyroid 5

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7 Thyroid Adenoma Incidence ranges from 25-50% in general population. Occurs more frequently in persons > 60 years of age. Well studied that physical exam findings are incorrect 50% of the time considering this high incidence rate. JCEM 2002:87; NEJM 2004:351; Recommended Screening A TSH level is the only recommended screening test to assess thyroid status when a nodule is found. Normal range for TSH by 3 rd generation testing is uiu/ml. If the result is outside of the normal range, all that can be said at that point is that the TSH is abnormal pending further evaluation. FNA biopsy should not be attempted without TSH data or in setting of abnormally low TSH until determination of possible toxic nodule is made. Thyroid 2006:16;1-33 Revised, Thyroid 2009:19; Thyroid Disease Spectrum Subclinical Hyperthyroidism TSH IU/mL Overt Hyperthyroidism TSH <0.007 IU/mL Mild Thyroid Failure TSH IU/mL Euthyroid TSH IU/mL Overt Hypothyroidism TSH >30.0 IU/mL 7

8 Functional Thyroid Nodule More common in regions with low iodine intake. Accounts for less than 5% of thyrotoxicosis cases in iodine-sufficient areas. Cancer incidence < 2%. Evolution from sporadic diffuse goiter to toxic nodular goiter is gradual. Thyrotropin receptor mutations and TSH mutations have been found in some patients with toxic nodular goiter. Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed Treatment of Toxic Nodule Beta-Blockers symptomatic treatment to counteract effect of elevated thyroid hormone levels on target organs. Anti-thyroid medications reduce thyroid hormone synthesis and peripheral conversion. Radioactive Iodine (I 131) definitive ablative therapy. Potassium Iodide blocks release of hormones from the thyroid. Surgery depends on many factors usually size of the lesion. Thyroid 2011:21; Non-Functional Thyroid Nodules Account for more than 95% of cases in iodine-sufficient areas. Cancer incidence ranges from 5-20% depending on data source. General incidence rate felt to be 10-15% of all patients with nodules. 80% Papillary, 14% Follicular, 3% Medullary, and 2% Anaplastic Papillary and Follicular cancer rates are on the rise. JCEM 2006:91; NEJM 2005:352;

9 Updated Thyroid Nodule Guidelines 2006 Key Concepts Cold nodules are no longer a concern, so nuclear medicine uptakes and scans no longer indicated just for finding of thyroid nodule. Use of Synthroid to suppress growth of nodules or goiter is no longer considered valid and this practice should be discontinued. Thyroid 2006:16;1-33 Revised, Thyroid 2009:19; Updated Thyroid Nodule Guidelines 2006 Key Concepts High resolution real-time ultrasound (US) has become the cornerstone imaging modality for management of thyroid nodules. US features and size determine need for fine needle aspiration (FNA). Patients need consistent long term follow up preferably by thyroidologist in same location for accurate comparison purposes. Thyroid 2006:16;1-33 Revised, Thyroid 2009:19; Parathyroid 9

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11 Parathyroid Hormone Producing Adenoma Primary hyperparathyroidism Declining incidence estimated to be 4 cases per 100,000 patient-years in Recent unpublished data from 2010 estimated to be 2 cases per 100,000 patient-years. Compared to incidence estimated to be 15 cases per 100,000 patient-years prior to Ann Intern Med 1997:126; Parathyroid Hormone Producing Adenoma Common Causes Sporadic Inherited primary hyperparathyroidism Uncommon Causes MEN 1 MEN 2 a Very rarely cancerous Nat Rev Cancer 2005:5; Asymptomatic Primary Hyperparathyroidism Most patients are now in this category. Commonly exacerbated by HCTZ use or Vitamin D deficient state. Most patients are just followed long term after full lab evaluation has confirmed diagnosis. Revised NIH guidelines from 2008 used as definitive source to determine if surgery indicated. Age being the key factor. Endo Practice 2009:15;

12 Adrenal 12

13 Adrenal Adenomas Incidence by autopsy series 2-10% Incidence by imaging series 5% 15% are bilateral <5% are cancer Endo Practice 2008:14; NEJM 2007:356:

14 Adrenal Hormone Producing Adenomas Cushing s Syndrome Incidence 5-45% (Likely 10-25%) Pheochromocytoma Incidence 2-20% (Rule of 10 s) Hyperaldosteronism (Conn s Syndrome) Incidence 1-20% (Likely 1-5%) Subclinical Cushing s Incidence 5-10% Endo Practice 2008:14; NEJM 2007:356: Endocrine News Sept 2009 Adrenal Adenomas Well defined algorithm for the evaluation and management of patients. Outlines approach to long term follow up of the subclinical and non-functioning lesions. Key point is to at least rule out pheochromocytoma for all cases especially before intervention is attempted. Developed by Dr. Young, Division of Endocrinology, Diabetes, Metabolism, Nutrition, and Internal Medicine, Mayo Clinic, Rochester, MN. NEJM 2007:356: Pancreas 14

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16 Pancreatic Hormone Producing Adenomas Rare incidence 4 cases per 1 million patient-years. Pancreatic cancer accounts for 6% of all cancer deaths per year about 40,000 patients per year. JCEM 2005:90; NCI 2010 Data Set 16

17 Pancreatic Hormone Producing Adenomas Insulinoma Gastrinoma (Zollinger-Ellison Syndrome) Glucagonoma VIPoma Insulinomas Most common type and presents with symptoms of hypoglycemia. Mostly sporadic but is associated with MEN 1. Mostly benign but can be malignant. Endocrine Society 2009 Guideline: Evaluation and Management of Adult Hypoglycemia Disorders JCEM 2005:90; JCEM 2009:94; Determination of Nonsurgical vs. Surgical Cases 17

18 What Needs To Be Done For The Patient? All cases need complete hormone evaluation at baseline after any glandular adenoma is found. Majority of cases will need long term imaging and possible lab follow-up over time. Pituitary Cases 85-90% managed medically 10-15% are surgical Non-prolactin functional adenomas Roughly < 10% of all cases Macroadenomas with chiasm impingement 1% of all cases Prolactinomas with apoplexy No firm data but small % of all prolactinomas JCEM 2006:91; Clev Clin J of Med 2008:75: Medicine 1999:78; Thyroid Cases Overall rate of surgery < 50% of all cases and declining. Less endemic goiter leading to less obstructive complaints. Low rate of toxic nodules requiring surgery. Improved US imaging for long term follow-up of non-functional nodules. Improved FNA diagnostics to aid in long term follow-up. J Endocrinol Invest 1997:20; Thyroid 2006:16;1-33 Revised, Thyroid 2009:19;

19 Parathyroid Cases Surgery is based on guidelines which outline importance of specific clinical findings most importantly age. Localization by imaging also key as less common to do exploratory neck surgery. High resolution US is replacing nuclear medicine parathyroid scan. Endo Practice 2009:15; Adrenal Cases Most functional lesions need to be removed to offer clinical improvement. Subclinical conditions can be followed with labs. Surgery is based on factors such as age and comorbid conditions. Largest proportion are just followed over time. NEJM 2007:356: Pancreas Cases These are rare conditions. All require laboratory confirmation as first step. Confirmation of source by imaging is needed to direct surgery. Intraoperative US is the most helpful. Most require surgery to offer cure of condition. Gastrinoma is exception and can be medically managed. JCEM 2005:90; JCEM 2009:94;

20 End Conclusions All glandular adenomas need complete hormonal evaluation at the time the adenoma is found before any intervention in form of biopsy or surgery is attempted. Most cases are nonsurgical and require long term medical follow-up, preferably by an endocrinologist. High resolution US is becoming the main image modality for a good portion of glandular adenomas. 20

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