Endocrine Disorders

Learning Objectives Pituitary Adenoma Acromegaly/gigantism Cushing’s disease Discuss epidemiology, causes, clinical manifestations, lab results, complications, treatment, and lifestyle modifications for both disease states

Major Endocrine Glands 1 – Pineal gland 2 – Pituitary gland 3 – Thyroid gland 4 – Thymus 5 – Adrenal gland 6 – Pancreas 7 – Ovary 8 – Testes There are a lot of places where things can go wrong. We are going to focus on the pituitary gland today

Pituitary adenoma A pituitary adenoma is an abnormal growth in the pituitary gland. Problems occur when: Overproduction of a certain hormone – Acromegaly and Cushing’s disease Other pituitary cells growing larger and pressing on cells causing pituitary cells to not make as much hormone. They can press on nearby structures in the brain such as the optic nerve

Types of Pituitary Tumors MRI From St. John’s Health Center http://www.youtube.com/watch?v=fY7p1bhg1P0&list=PLwWS6c78u0byN9EdQEIX772eV9ApAEigl Endocrine Inactive – Does not secrete any hormones Endocrine Active – Does secrete hormones

Related Tumors MRI From St. John’s Health Center http://www.youtube.com/watch?v=fY7p1bhg1P0&list=PLwWS6c78u0byN9EdQEIX772eV9ApAEigl Pituitary adenoma is contained within the sella turcica, but not contained within the pituitary gland

Taken from Brigham and Women’s Hospital, Sashank Prasad, MD

Pituitary adenoma Mass Effects: Onset may be gradual due to tumor growth or sudden due to tumor bleeding (apoplexy) Loss of peripheral vision, blurry vision Fronto-orbital headache Hypopituitarism (pituitary gland failure) Fatigue, weight gain, depression, decreased libido, impotence, infertility, loss of menses

Endonasal Pituitary Adenoma Removal http://www.youtube.com/watch?v=fY7p1bhg1P0&list=PLwWS6c78u0byN9EdQEIX772eV9ApAEigl&feature=player_detailpage#t=336

Acromegaly/gigantism Overview: Caused by excessive and extended growth hormone secretion → ↑ IGF → causes growth changes Due to a benign tumor in the anterior pituitary Timing is important! Gigantism before fusion of epiphyseal plates Acromegaly after fusion

“It’s not my fault being the biggest and the strongest “It’s not my fault being the biggest and the strongest. I don’t even exercise” – Fezzik, The Princess Bride

Acromegaly/Gigantism Causes: Proliferation of somatotroph cells in anterior pituitary Benign tumor Increased GH stimulates increased IGF-1 in liver IGF-1 causes growth of tissues and metabolic abnormalities

Acromegaly/Gigantism Epidemiology: Prevalence – 70/1,000,000 Incidence – 3-4/1,000,000 per year Neither disorder has strong genetic ties, although some genetic diseases can predispose to gigantism Carney Complex, Multiple Endocrine Neoplasia

Acromegaly/Gigantism Clinical Manifestations: Opthalmological Vision blurring Pulmonary Sleep Apnea, Orthopnea Dermatological Thickening of skin and hair Hyperhydrosis (sweating) Muskuloskeletal Skeletal growth and thickening, especially hand and foot Widening of jaw and overbite Joint pain Abnormally heavy brow and prominent forehead Husky voice due to larynx thickening

Acromegaly may occur at any time, commonly presenting between the ages of 30 and 50.

Acromegaly/Gigantism Diagnostic Testing: IGF-1 levels Growth Hormone levels Pulsatile secretion – one high value is not indicative Glucose tolerance test (glucose should suppress GH) Brain MRI to visualize adenoma Other Testing: Pituitary hormone levels to assess tumor effect TSH, FSH, LH, ACTH, Prolactin

Acromegaly/Gigantism Complications: Cardiovascular Cardiomyopathy, CHF Valve dysfunction Arrhythmia Hypertension Atherosclerosis Pulmonary Sleep apnea Metabolic Impaired glucose tolerance Impaired lipid metabolism

Metabolic Effects

Acromegaly/Gigantism Treatment: Goal is to lower levels of IGF-1, increase life expectancy Physical Therapy Surgery Remove tumor Medication Somatostatin analogues GH receptor antagonists Dopamine agonists Radiation Therapy Gamma knife

Cushing’s Disease Overview Caused by an extended increase in levels of ACTH, stimulating the adrenal glands to produce too much cortisol (a glucocorticoid) Caused by a benign pituitary tumor “Stress hormone” – Affects many organ systems, leading to metabolic, cardiovascular, and immune dysfunction

Cushing’s Disease Causes: All symptoms caused by prolonged exposure to high levels of cortisol Cushing’s Syndrome includes many causes most commonly iatrogenic ACTH-independent Cushing’s Disease is caused by pituitary adenoma ACTH-dependent

Cushing’s Disease Epidemiology: Prevalence – 13/1,000,000 Incidence – 2/1,000,000 per year 8x more common in women than men Most common in ages 20-40 years

Cushing’s Disease Clinical Manifestation

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Cushing’s Disease Diagnostic Testing: Urinary Free Cortisol Not specific unless 3x normal values Dexamethasone suppression test Negative feedback test – should be negative in pituitary adenoma ACTH levels Determine if adrenal or pituitary problem Overnight Cortisol levels Cortisol levels should fall throughout the day, lowest overnight MRI to visualize tumor

Cushing’s Disease Complications: Demineralization of bones causing osteoporosis May progress to bone pain and even osteonecrosis Generalized and sometimes extensive muscle weakness Often unable to rise from chair unassisted Cardiac hypertrophy, hypertension May lead to CHF if untreated Renal insufficiency Renal stones due to excretion of calcium

Cushing’s Disease Treatment: goal is to restore hormone balance and reverse Cushing’s Syndrome Surgery Removal of pituitary adenoma Removal of adrenal glands in refractory disease Medication Cortisol synthesis inhibitors (Ketoconazole) Glucocorticoid type II receptor antagonist (Mifepristone) Radiation Gamma knife Lifestyle modification High protein diet for those with muscle wasting Regular exercise Clean and inspect all wounds

Any Questions?