1. Endocrine Disorders

2. 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

3. 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

4. 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

5. Types of Pituitary Tumors
MRI From St. John’s Health Center
Endocrine Inactive – Does not secrete any hormones
Endocrine Active – Does secrete hormones

6. Related Tumors MRI From St. John’s Health Center
Pituitary adenoma is contained within the sella turcica, but not contained within the pituitary gland

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

8. 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

9. Endonasal Pituitary Adenoma Removal

10. 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

11. “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

12. 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

13. 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

14. 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

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

17. 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

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

19. Metabolic Effects

20. 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

21. 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

22. 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

23. 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 years

24. Cushing’s Disease
Clinical Manifestation

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26. 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

27. 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

28. 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

29. Any Questions?