Endocrine Disorders

Learning ObjectivesPituitary Adenoma

Acromegaly/gigantism

Cushing’s disease

Discuss epidemiology, causes, clinical manifestations, lab results, complications, treatment, and lifestyle modifications for both disease states

Major Endocrine Glands1 – Pineal gland2 – Pituitary gland3 – Thyroid gland4 – Thymus5 – Adrenal gland6 – Pancreas7 – Ovary 8 – Testes

Pituitary adenomaA 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

Endocrine Inactive – Does not secrete any hormonesEndocrine Active – Does secrete hormones

Related Tumors

Pituitary adenomaMass Effects:

Onset may be gradual due to tumor growth or sudden due to tumor bleeding (apoplexy)

Loss of peripheral vision, blurry visionFronto-orbital headacheHypopituitarism (pituitary gland failure)

Fatigue, weight gain, depression, decreased libido, impotence, infertility, loss of menses

Endonasal Pituitary Adenoma Removalhttp://

www.youtube.com/watch?v=fY7p1bhg1P0&list=PLwWS6c78u0byN9EdQEIX772eV9ApAEigl&feature=player_detailpage#t=336

Acromegaly/gigantismOverview:

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. I don’t even exercise” – Fezzik, The Princess Bride

Acromegaly/GigantismCauses:

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/GigantismEpidemiology:

Prevalence – 70/1,000,000Incidence – 3-4/1,000,000 per yearNeither disorder has strong genetic ties,

although some genetic diseases can predispose to gigantism Carney Complex, Multiple Endocrine Neoplasia

Acromegaly/GigantismClinical 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/GigantismDiagnostic Testing:

IGF-1 levelsGrowth 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/GigantismComplications:

Cardiovascular Cardiomyopathy, CHF Valve dysfunction Arrhythmia Hypertension Atherosclerosis

Pulmonary Sleep apnea

Metabolic Impaired glucose tolerance Impaired lipid metabolism

Metabolic Effects

Acromegaly/GigantismTreatment: Goal is to lower levels of IGF-1,

increase life expectancyPhysical TherapySurgery

Remove tumorMedication

Somatostatin analogues GH receptor antagonists Dopamine agonists

Radiation Therapy Gamma knife

Cushing’s DiseaseOverview

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 DiseaseCauses:

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 DiseaseEpidemiology:

Prevalence – 13/1,000,000Incidence – 2/1,000,000 per year8x more common in women than menMost common in ages 20-40 years

Cushing’s DiseaseClinical Manifestation

Cushing’s DiseaseDiagnostic Testing:

Urinary Free Cortisol Not specific unless 3x normal values

Dexamethasone suppression test Negative feedback test – should be negative in

pituitary adenomaACTH levels

Determine if adrenal or pituitary problemOvernight Cortisol levels

Cortisol levels should fall throughout the day, lowest overnight

MRI to visualize tumor

Cushing’s DiseaseComplications:

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 DiseaseTreatment: goal is to restore hormone balance

and reverse Cushing’s SyndromeSurgery

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?