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:

– 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; • 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 scintigraphywith 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

• Arthropathy• hypertension• obstructive sleep apnea (OSA), • diabetes, • cardiomyopathy, • colon polyps, • goiter,• headache

Summary

Musculoskeletal imaging p255

References• 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