Setting: office
CC: “I’m sleepy all day long, and my wife says I snore.”
VS: R: 12 breaths/minute; BP: 158/98 mm Hg; PR: 78 beats/minute; T: 97.8°F
HPI: A 48-year-old man with hypertension and diabetes comes to the office because he has daytime somnolence and his wife complains that he snores. He is also here for routine management of diabetes and hypertension.
ROS:
Shoe, hat, and ring size started increasing over the last 1 to 2 years
Body odor
Erectile dysfunction
PMHX:
Diabetes and hypertension
Medications:
Lisinopril
Metformin
PE:
General appearance: soft, sweaty, mushy handshake; rather unattractive
HEENT: large nose, lips, and jaw; teeth widely spaced
Cardiovascular: 3/6 pansystolic murmur radiating to axilla
Initial Orders:
HbA1c
CHEM-7
Lipid panel
What is the best initial test?
a. Insulinlike growth factor (IGF)
b. GH
c. MRI head
d. Glucose suppression test
Answer a. Insulinlike growth factor (IGF)
IGF has a longer half-life than GH. Because GH has a shorter half-life, elevated levels are harder to detect. Never start with a scan of the head in endocrinology. Do the MRI of the brain only after the disorder has been biochemically confirmed.
IGF is protein bound, giving it a long half-life.
When is GH release maximal?
a. On waking
b. 30 minutes before waking
c. Middle of the night
d. Before sleep
Answer c. Middle of the night
Deep sleep is the stimulant for the normal diurnal variation in GH level. Cortisol level increases 30 minutes before waking.
Move the clock forward 1 week.
Laboratory Test Results:
HbA1c: 7.2%
CHEM-7: glucose 145 mg/dL; BUN and creatinine: normal
Lipid panel: elevated LDL and triglycerides
IGF: markedly elevated
Acromegaly grows sweat glands!
Growth Hormone Mechanisms
• Acts as antiinsulin
• Raises serum glucose
• Raises free fatty acid level
Acromegaly causes hypertension.
You increase the dose of metformin and discuss possibly adding a second oral hypoglycemic agent to get the HbA1c concentration under 7%. You inform the patient that both his diabetes and hypertension may be from acromegaly, but you need to confirm the etiology.
Orders:
Glucose suppression test
IGF causes obstructive sleep apnea by growing neck tissues.
Erectile Dysfunction Etiology
• Diabetes
• Hypertension
• Vascular disease
• Associated with sleep apnea
IGF and GH fail to suppress with glucose loading. This is a failure of the normal feedback inhibition mechanism. You order an MRI and ask the patient to return to discuss the results. The patient comes back the following week and you inform him that the scan does show a pituitary lesion, and transsphenoidal surgery is needed to remove it. You also tell him that his diabetes may resolve when you remove the lesion.
If GH is an antiinsulin that raises glucose and free fatty acid levels, why does it produce another hormone call insulinlike growth factor? What is insulinlike about it?
a. Effect on hormone sensitive lipase
b. Effect on protein synthesis
c. Effect on lipids
Answer b. Effect on protein synthesis
GH is an antiinsulin in terms of its glucose and lipid effect. GH stimulates production of IGF at the liver and skeletal muscle. IGF is insulinlike, not GH. IGF increases protein synthesis, amino acid uptake into cells, and DNA synthesis.
Both IGF and insulin use a tyrosine kinase receptor.
The patient is frightened by the idea of “brain surgery” and does not come back to see you for a year. Order an “Interval History.” His erectile disfunction, body odor, and sleep apnea have all worsened. In addition, his numbness and tingling in the first three fingers of both hands have worsened by use. He has become immobile because of knee pain.
Physical Examination:
Facial features coarsened
Knees enlarged and abnormally shaped
New 3/6 pansystolic murmur radiating to the axilla
Uncontrolled IGF leads to misshapen joints and arthropathy.
IGF expand proteins abnormally.
Orders:
Glucose, HbA1c, lipids
Repeat MRI of head
Echocardiogram
What is the mechanism of the carpal tunnel syndrome?
a. Abnormal protein growth in the canal
b. Sodium alteration
c. Potassium alteration
Answer a. Abnormal protein growth in the canal
Acromegaly results in a protein expansion in the canal that the median nerve travels through. This compresses the nerve. Carpal tunnel syndrome is the most common neuropathy in acromegaly.
One week later the patient returns. He is becoming short of breath with exertion. His test results show that his glucose level is 195 mg/dL; his HbA1c concentration is 8.4%; his MRI shows an enlarging pituitary lesion; and his echocardiogram shows moderate mitral regurgitation with an ejection fraction of 32%.
Mechanism of Cardiomyopathy
• IGF causes abnormal cardiac shape.
• Hypertension, diabetes and hyperlipidemia cause coronary disease.
What cancer should you test the patient for?
a. Colon
b. Lung
c. Prostate
d. Gastric
Answer a. Colon
IGF leads to excess colonic polyp formation. This increases the risk of colon cancer.
Which of the following will most likely resolve after removing the pituitary gland?
a. Hyperlipidemia
b. Carpal tunnel
c. Cardiomyopathy
d. Joint abnormality
Answer a. Hyperlipidemia
Because the high lipid level results from the antiinsulin effect of GH, it will likely resolve after the GH is decreased. The other problems are from a permanent growth of protein and will not “resorb” after the GH and IGF levels drop. You have to remove the pituitary gland before these problems advance.
The most common cause of death from acromegaly is cardiomyopathy from coronary disease.
A month later you are seeing the patient at a follow-up appointment after the removal of his pituitary gland. He has been started on thyroid hormone replacement and prednisone.
Additional therapies to lower GH and IGF levels:
• Pegvisomant
• Octreotide (somatostatin)
• Cabergoline
Pegvisomant is a direct GH receptor antagonist.
Move the clock forward another 2 to 4 weeks. Recheck glucose and HbA1c levels because the patient may have a decreased need for diabetes medication. Treat the mitral regurgitation with ACE inhibitors as you would for any person with mitral regurgitation.