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Diagnosis Of Acromegaly

* Symptoms due to local mass effects of the tumor
o Symptoms depend on the size of the intracranial tumor.
o Headaches and visual field defects are the most common symptoms. Visual
field defects depend on which part of the optic nerve pathway is
o The most common manifestation is a bitemporal hemianopsia due to
pressure on the optic chiasm.
o Tumor damage to the pituitary stalk might cause hyperprolactinemia due
to loss of inhibitory regulation of prolactin secretion by the
hypothalamus. Damage to normal pituitary tissue can cause deficiencies
of glucocorticoids, sex steroids, and thyroid hormone.
o Loss of end organ hormones is due to diminished anterior pituitary
secretion of corticotropin (ie, adrenocorticotropic hormone [ACTH]),
gonadotropins (eg, luteinizing hormone [LH], follicle-stimulating
hormone [FSH]), and thyrotropin (ie, thyroid-stimulating hormone [TSH]).
* Symptoms due to excess of GH/IGF-I
o Soft tissue swelling and enlargement of extremities
o Increase in ring and/or shoe size
o Hyperhidrosis
o Coarsening of facial features
o Prognathism
o Macroglossia
o Arthritis
o Increased incidence of obstructive sleep apnea
o Increased incidence of glucose intolerance or frank diabetes mellitus,
hypertension, and cardiovascular disease
o Hyperphosphatemia, hypercalcuria, and hypertriglyceridemia possible
o Increased incidence of congestive heart failure, which might be due to
uncontrolled hypertension or to an intrinsic form of cardiomyopathy
attributable to excess GH/IGF-I
o Increased incidence of colonic polyps and adenocarcinoma of the colon

* Typical facies of acromegaly
o Frontal bossing
o Thickening of the nose
o Macroglossia
o Prognathism
* Women can have mild hirsutism.
* The thyroid gland might be enlarged and typically manifests as multinodular
* Enlarged extremities with sausage-shaped fingers are signs of acromegaly.
* Skin is oily and has skin tags. Skin tags are possible markers for colonic

* Acromegaly can be either GHRH independent or GHRH dependent. Both forms cause
identical clinical syndromes.
* Most cases are GHRH independent. Elevated GH concentration suppresses GHRH
production by the hypothalamus.
o More than 95% of the GHRH-independent cases are due to a GH-secreting
pituitary tumor. The pituitary adenoma might be a macroadenoma (>1 cm)
or a microadenoma (<1 style="color: rgb(51, 102, 255);">Laboratory Studies
* Random GH measurements are often not diagnostic because of the episodic
secretion of GH, its short half-life, and the overlap between GH concentration
in acromegalic patients and healthy subjects.
* Because GH secretion is inhibited by glucose, measurement of glucose
nonsuppressibility might be useful. Two baseline GH levels are obtained prior
to ingestion of 75 or 100 g of oral glucose, and additional GH measurements
are made at 30, 60, 90, and 120 minutes following the oral glucose load.
o Patients with active acromegaly are unable to suppress GH concentration
below 2 ng/mL after a 75-g oral glucose load. With newer assays for GH
using the immunoradiometric assay (IRMA), a criterion of less than 1
mcg/L is used following oral glucose ingestion.
o A paradoxical rise in GH concentration is observed in 15-20% of patients
with acromegaly following oral glucose ingestion.
* Because IGF-I has a long half-life, its measurement is useful to gauge
integrated GH secretion, to screen for acromegaly, and to monitor the efficacy
of therapy.
o IGF-I concentrations vary with age. An assay in which reference ranges
have been stratified in such a manner is required.
o Starvation, obesity, and diabetes mellitus decrease IGF-I concentration.
o Pregnancy increases IGF-I concentration.
* Measurement of IGF-binding protein-3 (IGFBP-3), the main binding protein for
circulating IGF, is increased in acromegaly and might be useful in the
diagnosis of acromegaly. Measurement may also be helpful in following the
activity of the disease during treatment.
* GHRH concentration can be obtained if clinically indicated.
o Levels of less than 300 pg/mL usually indicate an ectopic source of GHRH.
o In pituitary disease (GHRH independent), GHRH concentration is within
reference ranges or suppressed.
* Because up to 20% of GH-secreting pituitary adenomas cosecrete prolactin, the
prolactin level may also be elevated. However, as indicated above, a rise in
prolactin can be due to stalk compression as well as co-secretion from a
pituitary adenoma.
* Pituitary adenomas can be associated with deficiencies of other pituitary
hormones. Consider evaluation of the adrenal, thyroid, and gonadal axes.
Imaging Studies: CLICK HERE
* Because of the relatively high incidence of nonfunctioning, incidentally
discovered pituitary adenomas, obtain imaging studies only after a firm
biochemical diagnosis of acromegaly.
* Because GH-secreting pituitary adenoma is the most common cause, perform
imaging of the sella turcica first.
o MRI is more sensitive than CT scan.
o MRI provides detailed information about surrounding structures such as
the optic chiasm and cavernous sinuses.
* If the MRI findings of the sella are negative, appropriate studies to localize
tumors causing ectopic secretion of GH or GHRH can be obtained.
o CT scan of the abdomen/pelvis evaluates for pancreatic, adrenal, or
ovarian tumors secreting GH/GHRH.
o Chest CT scanning evaluates for bronchogenic carcinoma secreting GH/GHRH. FOLLOW PART 2

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