Reference no: EM133572329

Case Study #1

Pooja is a 42-year-old sales executive. She travels constantly and prides herself on being energetic and surpassing sales projections each quarter. Three years ago, she developed irregular menses, and she then she completely stopped menstruating. Over the past two years, she has begun to feel increasingly fatigued, has difficulty rushing the length of the airport terminals, and is bothered by frequent headaches. She has always had a firm handshake, but lately has noticed that her wedding ring is excessively tight. Pooja is also frustrated that she has recently had to replace her entire shoe collection because her shoe size has increased from 7.5 to 9, with a need for increased width as well. Additionally, she has noticed increased perspiration, even when she is not exerting herself, and increased spacing between her teeth. Concerned about her progressive cosmetic changes and her lack of menses, Pooja turns to Google for information and comes across a condition called acromegaly.

Struck by the uncanny resemblances between her complaints and those she has read about on Google,Pooja goes to see her doctor for further evaluation. A serum insulin-like growth factor (IGF-1) level is significantly elevated after correction for Pooja's age and sex, and her serum growth hormone (GH) level is 10 ng/mL (normal <1 ng/mL) after an oral glucose load of 75 mg. A magnetic resonance imaging (MRI) study of her head reveals a pituitary adenoma with a maximal diameter of 1.5 cm. These findings are consistent with a diagnosis of acromegaly due to a GH-secreting adenoma. Pooja receives a transsphenoidal pituitary surgery. Despite tolerating the surgery well, Pooja's postoperative IGF-1 and GH levels remain elevated. Based on the continue elevations in serum GH and IGF-1, Pooja's endocrinologist recommends medical treatment with a depot ocreotide injections. After 6 months of depot ocreotide injections, Pooja's GH and IGF-1 levels remain elevated and Pooja is frustrated by the lack of improvement. However, she does feel that she has more energy than before, and her menses have resumed. Pooja's endocrinologist recommends treatment with pegvisomant as an alternative medical approach. Pooja begins daily injections with pegvisomant and six months later, her IGF-1 level is in normal range. She resumes her normal life and continues to receive yearly head MRI and liver function test.

Questions:

1. Why did Pooja develop enlarged extremities rather than an increase in height in response to her elevated GH levels?

2. What was the likely cause of Pooja's amenorrhea?

3. Describe the relationship between GH and IGF-1 and the metabolic effects of both hormones

4. Why were serum levels of IGF-1 a more appropriate screening test for acromegaly than GH levels?

5. What is the purpose of the oral glucose load given to Pooja prior to measuring her plasma GH levels?

6. How do ocreotide and pegvisomant act to lower GH levels?

Case Study #2

A physician examined Tarek, a 66-year-old man, because he displayed symptoms of Parkinson's disease: resting tremor, muscle rigidity, and bradykinesia (slowness in the initiation and continuation of movement). This made it difficult for Tarek to perform daily tasks such as getting dressed, bathing, and many other activities. Further physical examination and a thorough history, together with an MRI to rule out alternative possibilities, confirmed the diagnosis. The physician placed Tarek on a dopamine agonist that can cross the blood-brain barrier and said that this could be supplemented later by levodopa, a monoamine oxidase inhibitor (MAOI), anticholinergics, and other medications.

Parkinson's disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain, with concomitant loss of their projections to the dorsal striatum along the nigrostriatal pathway. This loss in dopaminergic neurotransmission results in the involuntary motor control; the primary manifestation of Parkinson's disease. Dopamine is derived from L-dopa (levodopa) and is a monoamine degraded within presynaptic axons by the enzyme monoamine oxidase (MAO). Dopaminergic neurons produce effects that are antagonized by ACh released by other neurons that synapse in the striatum. A drug must be able to cross the blood-brain barrier to be effective in treating neurological disorders such as Parkinson's disease.

Questions

1. What are the monoamines and what are some examples?
2. What is the blood-brain barrier?
3. How would a dopamine agonist, levodopa, and an MAOI benefit Tarek with his Parkinson's disease?
4. What is an anticholinergic drug, and how would such a drug benefit Tarek?
5. Aside from voluntary motor control, name one other function served by dopamine in the brain and the associated brain region.

6. Parkinson's disease is also associated with the accumulation of Lewy bodies in the brain. What are Lewy bodies and how do they contribute to the pathophysiology of Parkinson's disease?

Case Study #3

Balun is an 81-year-old man with a history of hypertension treated with a diuretic and ACE inhibitor. He had broken two toes and, as a result, had spent two months resting more than usual in his easy chair. When he stood up from bed in the morning, or stood up from his easy chair, he became very dizzy and light-headed. His partner remarked that he also became disoriented and confused, and he saw a physician after an episode in which he fainted. When questioned, Balun mentioned that he sweated during those episodes, but did not notice undue sweatiness at other times or dryness of his mouth, nor did he have difficulties with his digestion or urination that were different from those occurring before the dizziness episodes. Balun stated that he felt weak and stood carefully after meals but did not have the extreme dizziness that occurred upon standing from bed. The physician measured Balun's blood pressure and pulse in a supine position, and a half-hour later, in the tilted and upright positions. His supine measurements were within the normal range, but a few minutes after standing his systolic pressure fell by 24 mm Hg, his diastolic pressure fell by 10 mm Hg, and his pulse increased. Balun didn't have problems moving his eyes to follow an object, had normal pupillary reflexes, and seemed aware with reasonably good memory.

Balun is elderly, is taking drugs that act to lower blood pressure, and had been especially inactive for an extended period. His blood pressure dropped significantly upon standing, despite an increased heart rate. His remarks suggest that his blood pressure may have also decreased somewhat after a meal. He seemed mentally aware and competent when he saw the physician, with normal control of his extrinsic eye muscles and a normal pupillary reflex. Although he was unable to maintain adequate blood pressure upon standing, he seemed to have normal autonomic control of his bladder, gastrointestinal system, sweat glands, and salivary secretions. There was no history of heart disease or signs of cardiovascular problems, other than his previously well-controlled hypertension.

Questions 

1. How do diuretics and ACE inhibitors act to lower blood pressure?
2. What is the mechanism that causes heart rate to increase upon standing?
3. How does eating influence blood flow around the body?
4. How does the autonomic system affect blood pressure?
5. What is the most likely explanation for Balun's symptoms?

Case Study #4

Lee is a 49-year-old woman who had been feeling weak and easily fatigued for several months, during which time her appetite had diminished and she had lost weight. She also experienced vague limb pain and felt stiff in the morning for an hour or more. Although this brought her concern, she didn't report her symptoms until she noticed that some of the joints in her hands and her wrists were swollen and reddish, and that her joints started to hurt when she moved them after inactivity. The physician noticed that the affected joints were the same on both sides of the body and noted subcutaneous nodules associated with some of the affected joints. She further observed swelling around the knee and ankle joints and mentioned that Lee's skeletal muscles appeared somewhat atrophied. The physician ordered X-rays, a blood test for rheumatoid factors, a complete blood cell count, and an erythrocyte sedimentation rate test.

Lee displayed synovitis of several joints in the wrists, hands, knees, and ankles that was present on both the right and left sides of her body. She had weakness, muscle atrophy, and other systemic symptoms that could be related to proinflammatory cytokines-particularly tumor necrosis factor (TNF), interleukin-1, and interleukin-6-released from the inflamed synovial joints. Her X-rays confirmed the involvement of the same joints on both sides of her body. Her erythrocyte sedimentation rate, a nonspecific measure of inflammation, was abnormally fast; she also had a mild anemia (low red blood cell count) known as normochromic normocytic anemia, which is often seen in people with joint inflammations. Her test for rheumatoid factors, which are IgM antibodies that target the Fc portion of IgG antibodies, was abnormally elevated. The physician told Lee that she was prescribing rest and physical therapy and recommend aspirin until Lee mentioned that she had a history of gastritis. The physician said that she would instead prescribe an NSAID that was a selective COX-2 inhibitor. She stated that glucocorticoid drugs may be needed later.

Questions

1. What is the Fc portion and the Fab portion of an antibody?

2. What is normochromic normocytic anemia? Given this form of anemia, what is the potential cause of anemia in Lee's case?

3. Briefly describe the type II and type II isoforms of the cyclooxygenase enzyme.

4. What is an NSAID and why did the physician prescribe a selective COX-2 inhibitor when learning of Lee's history with gastritis?

5. What are glucocorticoids, and why might they be of value in treating inflammatory diseases?

6. Following the rheumatoid factor blood test, Lee's physician decides to run a cyclic citrullinated peptide (CCP) assay. Why is this a good choice and what is the CCP assay measuring?