Transcript Discuss the pathogenesis and imaging approach of

Discuss the pathogenesis and
imaging approach of acromegaly
and gigantism
Frans Naude
Outline
• Definition
• Pathogenesis
• Imaging of side-effects of increased growth
hormone production
• Imaging approach for pituitary microadenoma
Pathogenesis of acromegaly and
gigantism
• Def :A disorder due to excessive secretion of
pituitary growth hormone, characterized by
progressive enlargement of the head and
face, hands and feet, and thorax.
Microadenomas
• GH-secreting tumors are the second most
common type of functioning pituitary
adenoma.
• Somatotroph cell adenomas may be quite
large by the time they come to clinical
attention because the manifestations of
excessive GH may be subtle
Gigantism
• If a somatotrophic adenoma appears in children
before the epiphyses have closed, the elevated
levels of GH (and IGF-1) result in gigantism.
• This is characterized by a generalized increase in
body size with disproportionately long arms and
legs
• In most instances gigantism is also accompanied
by evidence of acromegaly. These changes
develop for decades before being recognized,
hence the opportunity for the adenomas to reach
substantial size
Acromegaly
• increased levels of GH are present after closure of the
epiphyses.
• growth is most conspicuous in:
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skin and soft tissues;
viscera (thyroid, heart, liver, and adrenals);
bones of the face, hands, and feet.
Bone density may be increased (hyperostosis) in both the spine
and the hips.
– Enlargement of the jaw results in protrusion (prognathism), with
broadening of the lower face
– hands and feet are enlarged with broad, sausage-like fingers
– Increased risk colon polyps ( increased risk for colon cancer has
not been determined)
Other disturbances
• GH excess is also correlated with a variety of
other disturbances:
– gonadal dysfunction,
– diabetes mellitus,
– generalized muscle weakness,
– arthritis,
– hypertension, congestive heart failure
– increased risk of gastrointestinal cancers.
Diagnosis of pituitary GH excess
• relies on documentation of elevated serum
GH and IGF-1 levels.
• failure to suppress GH production in response
to an oral load of glucose is one of the most
sensitive tests for acromegaly.
Imaging of effects of excess GH
• X-ray ( skelet, soft tissue)
• CT
• U/S : organomegly (thyroid, heart, liver, and adrenals)
Skull
• Thickening of the cranial bones and increased
density.
• The diplo' may be obliterated.
• Sella turcica, which houses the pituitary gland,
may or may not be enlarged.
• Paranasal sinuses become enlarged
• Mastoid cells become over pneumatized.
• Prognathous jaw, one of the obvious clinical
features of this condition, is apparent on the
lateral view of the facial bones.
• The skull shows the large sella turcica (arrow), the
large frontal sinuses, and the prognathic mandible.
Hands
• Heads of the metacarpals are enlarged + irregular bony
thickening along the margins, simulating osteophytes
• Increase in the size of the sesamoid at the
metacarpophalangeal joint of the thumb may be helpful.
Values of the sesamoid index (determined by the height and
width of this ossicle measured in millimeters) greater than 30
in women and greater than 40 in men suggest acromegaly;
(cant be used alone)
• distal phalanges; bases enlarge and the terminal tufts form
spur-like projections
• joint spaces widen as a result of hypertrophy of articular
cartilage
• hypertrophy of the soft tissues may also occur, leading to the
development of square, spade-shaped fingers.
• PA radiograph of the hands shows in a patient with acromegaly
shows the wide MCP cartilage spaces.
• distal phalanges have a spade-like appearance.
• Over grown tufts and
spur like projections
Feet – heel pad thickness
• Lateral view allows an important measurement to
be made: the heel-pad thickness.
• This index is determined by the distance from
the posteroinferior surface of the os calcaneus to
the nearest skin surface.
Reference range:
• Normal 70 kg person
< 22 mm.
• For each additional 11kg of body weight, 1 mm can be added
to the basic value;
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90kg person
<24mm
• If the heel-pad thickness is greater than the established
normal value, then acromegaly is a strong possibility
• The lateral radiograph of the heel shows a
thick fat pad.
Phenytoin (Dilantin)
• has been associated with calvarial thickening
and enlargement of the heel pad, similar to
the changes occurring in acromegaly
Imaging of arthritis and metabolic bone disease,P267
Acromegaly
• May result in secondary OA possibly related to
overgrowth of cartilage with inadequate nutrition of
the thickened cartilage or its poor quality.
• Knees, hips, and shoulders are affected most often
• At first, the cartilage spaces are noted to be unusually
thick
– MCP cartilage space >3 mm in males
>2 mm in females
– hip cartilage spaces >6 mm
• Later cartilage space narrowing occurs as secondary
arthritis develops
• Osteophytes may be very large
Imaging of arthritis and metabolic bone disease p131
• Oblique radiograph of the shoulder in patient with acromegaly shows
severe cartilage space narrowing and large osteophytes.
• Several intra-articular bodies (arrow) are noted within the joint recesses.
Spine
• Enlarged vertebral bodies
• Posterior scalloping
• Central-lateral lumbosacral spinal stenosis
Radiology: Volume 239: Number 2—May 2006
Monitoring of acromegaly
• Biochem: GH , IGF-1 (general pituitary fx after
surgery)
• MRI
– microadenoma dx
– 3–4 months after surgery :establish a baseline for
future follow-up.
– medical therapy should be assessed by MRI 3–6
months after starting therapy
• Echocariography
• Colonoscopy – at least 1 baseline
Imaging of microadenoma
Typical pituitary MR imaging protocol includes:
• high-resolution imaging of the sella and
parasellar regions at 3-mm thickness, before and
after contrast with fat suppression.
• Dynamic T1-weighted imaging may be
performed when a pituitary adenoma is
suspected based on clinical parameters.
Gadolinium contrast dose: 0,1 ml/kg
• High-resolution T2- weighted sequences are also
usually performed.
MRI evaluation includes:
• assist in the identification of tumor size (2mm)
,
• invasiveness,
• proximity to the optic chiasm,
• compression of surrounding structures
CT
• better than MR imaging for detecting
calcifications
• complementary to MR imaging if a primary
bony lesion is suspected
• Precontrast T1 images, the lesion may be
slightly hypointense to the remainder of
pituitary.
Gadolinium
• Adenomas and normal pituitary tissue have
different patterns of uptake and washout
following administration of intravenous
contrast;
• due to the lower vascularity of adenomas
compared with normal pituitary
Principle of enhancement
• Adenomas hypoenhance relative to normal
tissue during the first 60 seconds following
contrast administration.
• Thereafter, adenomas may retain contrast
more than surrounding pituitary and may thus
be hyperintense on delayed imaging
Radiol Clin N Am 49 (2011) 549–571: imaging of the pituitary
Exception
• Some adenomas have direct arterial supply
• Some peripheral adenomas not surrounded by
pseudocapsule
Most useful sequences are
• coronal T1 precontrast,
• 30- to 50-second dynamic post-contrast
images,
• conventional postcontrast images.
Ectopic GH
Ectopic GHRH producing tumors may arise from:
• Bronchial and pancreatic neuroendocrine
tumors,
• pheochromocytomas,
• pulmonary endocrine carcinomas,
• rarely thymic carcinod
Total body scintigraphy
with radiolabled somatostatin
• localize the tumor
• demonstrate somatostatin receptor
expression by the tumor which may respond
favorably to somatostatin analogue therapy
• Arteriovenous gradient of plasma GH over
tumour bed
• Normalization after removal of tumour
Treatment Primary
• Removal of GH adenoma – neurosurgery
• Medical
– somatostatin ligands – suppress GH production
and reduce adenoma size
– GH antagonist
– Dopamine antagonist
Treatment of comorbidities
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Arthropathy
hypertension
obstructive sleep apnea (OSA),
diabetes,
cardiomyopathy,
colon polyps,
goiter,
headache
Summary
Musculoskeletal imaging p255
References
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Orthopedic imaging: a practical approach, Chapter 30
Imaging of arthritis and metabolic bone disease p131
Radiol Clin N Am 49 (2011) 549–571: imaging of the pituitary
Musculoskeletal imaging, Klaus Bohndorf, Herwig Imhof
Guidelines for Acromegaly Management: An Update.J Clin Endocrinol Metab, May 2009, 94(5):1509–1517
Current diagnosis of acromegaly. Rev Endocr Metab Disord (2008) 9:13–19