Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Radiologic Features of
Acromegaly
Enyi Nwaneri
Harvard Medical School Year III
Gillian Lieberman, MD
March 2003
Our Patient
• ID/CC
A 29 year old Asian male visits his doctor because he
notices that his hands are getting bigger
• HPI
No major complaints except enlarging of hands, nose, jaw,
and feet over the past 2-3 years
• PE
Significant enlargement of hands and feet, broad nose,
enlargement of facial tissues, frontal bossing
• LABS
Growth Hormone: 18 ng/ml (nl 0-10 ng/ml)
IGF-I: 738 ng/ml (nl 114-492 ng/ml)
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
2
Diagnosis
ACROMEGALY
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
3
ACROMEGALY
• Clinical syndrome that results from excessive secretion of
growth hormone (GH) after fusion of the epiphyseal
growth plates
• Annual incidence is 3-4 per million people
• Incidence is equal in men and women
• Mean age at diagnosis is 40 to 45 years
• Most common cause is GH secreting adenoma of the
anterior pituitary
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
4
Clinical Manifestations
• Somatic effects due to excess GH and IGF-I which cause
stimulation of growth of skin, connective tissue, cartilage,
bone, viscera, and epithelial tissue
• Onset is insidious with slow progression
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From Motlitch ME. Clinical manifestations of acromegaly. Endocrinol
Metab Clin North Am 1992; 21(3): p 599.
5
Clinical Manifestations
• Acral and soft tissue overgrowth
• Articular overgrowth
• Enlarged viscera
• Cardiovascular disease
• Tumors
• Hypogonadism
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From http://www.library.uthscsa.edu/ms2/Pathology/Endocrine/
Labs/Lab%202/Lab%202.doc
From Melmed S. Clinical Manifestations of
Acromegaly. UpToDate 2003. 6
Anatomy and Relations of the Pituitary Gland
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From Netter F. The Ciba Collection, Vol. 4. R.R. Donnelley &
Sons Company. New York, 1965, p 6.
7
Relationship of the Pituitary Gland to the
Cavernous Sinus
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From Netter F. The Ciba Collection, Vol. 4. R.R. Donnelley & Sons
Company. New York, 1965, p 7.
8
Relationship of the Pituitary Gland to the
Sella Turcica
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From http://www.mythos.com/webmd/Content.aspx?
P=ENDOCC&E=6
Sella turcica
Pituitary
gland
Optic chiasm Mamillary body
9
Relationship of the Pituitary Adenoma to the
Sella Turcica
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From Netter F. The Ciba Collection, Vol 1(2). CIBA Pharmaceutical Company.
West Caldwell, NJ, 1986, p 122.
10
Imaging Modalities
• Plain Radiographs
• MRI
• Somatostatin Receptor Scintigraphy
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
11
Plain Radiographs
• No longer routinely used for diagnosis of
acromegaly
• Good for demonstrating wide variety of
radiologic changes of the skeleton in
patients with acromegaly
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
12
Plain Radiograph Features of
Skeletal Involvement
in Acromegaly
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
13
Companion Patient A
• 48 year old Italian woman presents to Mt. Auburn Hospital
in 1956 with chief complaint of headache, weight gain,
swollen hands, and changes in facial features
• Skull radiographs reveal an enlarged sella turcicaÆ
diagnosis of acromegaly made
• Refuses treatment for 15 years
• Finally presents to BI Hospital in 1971 for further work-up
and treatment of her acromegaly
• On exam noted to have thick, coarse skin, enlarged lips
and ears, separated teeth, macroglossia, marked
prognathism, frontal bossing, and enlarged hands and feet
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
14
Changes in Skin Thickness
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Courtesy of Ferris Hall, MD
Prominence of soft tissues of
the heel measuring 40 mm
Pathophysiologic
correlation: Excessive
growth hormone Æ
marked response by
collagen tissue Æ
connective tissue
hyperplasia Æ increased
thickness of skin (e.g.
heel pad)
Companion Patient AFindings:
15
Diagnostic Significance of
Thickened Heel Pad
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From Resnick D. Bone and Joint Disorders Vol. 3, 4th ed. W.B.
Saunders Company. Philadelphia, 2002, p 2010.
Measure shortest distance
between calcaneus and
plantar skin surface
Values greater than 23
mm in men and 21.5 mm
in women are suggestive
of acromegaly
Variation with body weight,
race somewhat limits
usefulness Æ development
of more sophisticated
calculations
Enthesal proliferation of bone
at insertion of Achilles tendon
and plantar aponeurosis
16
Differential Diagnosis of
Thickened Heel Pad
1) Acromegaly
2) Generalized edema (e.g. CHF, DVT, lymphedema)
3) Infection of soft tissues
4) Normal variant; genetic (especially Black and
Polynesian males)
5) Obesity
6) Trauma
7) Long-term phenytoin therapy
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
17
Abnormalities of the Skull
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Courtesy of Ferris Hall, MD
Companion Patient AFindings:
Thickened cranial
vault
Enlarged sella turcica
Prominence of the
occipital protuberance
Elongation and
projection of
mandible
Enlarged frontal
sinuses
18
Abnormalities of the Skull
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From Chew F. Radiologic manifestations in
the musculoskeletal system of miscellaneous
endocrine disorders. Radiologic Clinics of
North America 1991; 29(1): p 139.
From Resnick D. Bone and Joint Disorders Vol. 3,
4th ed. W.B. Saunders Company. Philadelphia,
2002, p 2010.
Findings:
Increased prominence of
mandible
Increased thickness of
clavaria
Enlarged frontal sinus
Enlarged supraorbital
ridge
19
Abnormalities of the Skull
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Pathophysiologic correlation:
Presence of pituitary neoplasm Æ sella
turcica abnormalities
Excess growth hormone Æ stimulation of
periosteal bone formation Æ mandibular
enlargement, thickening of cranial vault,
prominence of supraorbital ridges and
facial structures
20
Abnormalities of the Hand and Wrist
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Courtesy of Ferris Hall, MD
Companion Patient AFindings:
Widening of MCP joint spaces
Soft tissue thickening
Carpal cysts
Pathophysiologic correlation:
Excessive growth hormone Æ
increased chondrocytic activity Æ
proliferation of articular cartilage
(cartilage hypertrophy) Æ widening
of articular space
Carpal cysts result suggest bone
degeneration
Broadened phalangeal
tufts
21
Abnormalities of the Hand and Wrist
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
From Resnick D. Bone and Joint Disorders Vol. 3, 4th ed. W.B. Saunders
Company. Philadelphia, 2002, p 2012.
Findings:
Enlargement of terminal
phalangeal tuft (“spade-
like”)
Enlargement of terminal
phalangeal base
Soft tissue
thickening
Formation of pseudoforamina
Pathophysiologic correlation: Stimulation of periosteal bone formation Æ
enlargement of phalanges, phalangeal tufts especially
22
Abnormalities of the Foot
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Findings: Soft tissue enlargement, widening of
the MTP joints, prominence of terminal
phalangeal tufts and bases, pseudoforamina
From Resnick D. Bone and Joint Disorders Vol. 3, 4th ed. W.B. Saunders Company. Philadelphia, 2002, p 2015.
23
Differential Diagnosis of Phalangeal
Tuft Enlargement
1) Normal variant
Must take into account patient’s gender and
occupation
2) Acromegaly
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
24
Abnormalities of the Vertebral Column
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Findings: Increase in thoracic
vertebral body AP diameter
due to bone formation on
anterior aspect of vertebrae
Findings:
Increased
concavity on
posterior
aspect of
lumbar
vertebral
bodies
(scalloped
vertebrae)Æ
related to
excessive
resorption of
bone
From Resnick D. Bone and Joint Disorders
Vol. 3, 4th ed. W.B. Saunders Company.
Philadelphia, 2002, p 2016.
From Resnick D. Bone and Joint
Disorders Vol. 3, 4th ed. W.B.
Saunders Company.
Philadelphia, 2002, p 2016.
Companion
Patient A
Findings:
“…suggestion
of new bone
formation
involving the
anterior
aspects of the
vertebral
bodies.”
25
Companion Patient A
Noted on plain radiographs to have
degenerative disease in joints of shoulders,
fingers, wrists, knees
26
Articular Abnormalities
• Radiologic joint abnormalities seen most frequently in
knee, glenohumeral joint, and hip
• Two main categories: cartilage hypertrophy and
cartilaginous and bony degeneration
• Radiologic features of acromeglic degenerative changes
(joint space narrowing, cyst formation, osteophyte
formation) can be confused with primary degenerative
joint disease (osteoarthritis)
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
27
Acromegalic Arthropathy or
Osteoarthritis?
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
• If joint space is wide Æ Acromegaly
• If joint space is narrow Æ Differential diagnosis rests on
distribution of arthropathy
Acromegaly involves shoulders, elbows,
and MCP joints, which are unusual sites
for primary osteoarthritis
28
Additional Plain Radiograph
Features of Skeletal Involvement
• Abnormalities of the Thoracic Cage
May appear enlarged due to elongation and enlargement of the anterior
ribs (particularly first ribs) and medial clavicles
Prominence of costochondral junction (acromegalic rosary) due to GH
mediated reactivation of endochondral ossification
• Abnormalities of the Pelvis
Enlargement and “beaking” of pubis symphysis
Bony proliferation at ligament attachment sites (enthesopathy)
• Abnormalities of the Long Bones
Narrowing of diaphysis due to predominant bone resorption
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
29
Imaging Modalities
• Plain Radiographs
• MRI
• Somatostatin Receptor Scintigraphy
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
30
MRI
• Method of choice in detecting pituitary adenomas
• Can detect tumors as small as 2 mm in diameter
• Can accurately identify dimensions and anatomic extent of
tumor
• Compared to CT
Superior soft tissue contrast
More sensitive in defining the extrasellar extent of the
adenomas and in detecting cavernous sinus invasion
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
31
Any Role for CT?
• Postcontrast CT scans previously used for imaging of
adenoma and assessment of bone erosions or cavernous
sinus invasion
• Unable to detect small adenomas due to poor contrast
resolution and similar enhancing characteristics between
adenomas and normal pituitary gland
• Advantage over MRI Æ superior in demonstrating cortical
bone Æ critical in cases of pituitary adenomas causing
deformity or erosion of the sellar floor
• CT scans may be more useful than MRI in selected patients
in whom the bony anatomy of the floor of the sella turcica
needs to be visualized
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
32
Our Patient
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Findings: 5 mm x 11 mm x 10 mm low signal, non-enhancing
lesion in left side of pituitary consistent with adenoma
From BIDMC PACS From BIDMC PACS
33
Imaging Modalities
• Plain Radiographs
• MRI
• Somatostatin Receptor Scintigraphy
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
34
Somatostatin Receptor Scintigraphy
• Based on underlying principle that GH adenomas express
somatostatin receptors
• Radiolabeled octreotide is used as the detector allowing
somatostatin receptor positive tissues to be visualized
• Non-specific since somatostatin receptors are also widely
expressed by normal endocrine tissue Æ high incidence of
false positives
• Physiologic distribution of octreotide includes the digestive
tract Æ masking of abdominal tumors by normal octreotide
uptake in this region
• Implications for medical therapy Æ increased uptake on
octreotide scan predicts success of treatment with
somatostatin analogs
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
35
Companion Patient B
• 43 year old woman presents with clinical findings of
acromegaly
• Pituitary MRI was negative
• Underwent octreotide scan for further work-up of
possible pituitary adenoma
• Visualization done after 4 and 24 hours
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
36
Companion Patient B
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Initial 4 hour whole body image
Findings: Normal
activity involving the
kidneys, liver, and
spleen. Normal
accumulation in
bladder. No evidence
of focal abnormal
increased tracer
activity.
Courtesy of Kevin Donohoe, MD 37
Companion Patient B
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
24 hour whole body image Findings:
Normal uptake
visualized in
thyroid, kidneys,
liver spleen, and
non-specific GI
uptake
Focal increased
uptake at the
region of the
skull base
Courtesy of Kevin Donohoe, MD
38
Companion Patient B
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
Courtesy of Kevin Donohoe, MD
Left lateral view of head Findings:
Normal uptake
visualized in thyroid
Localized uptake at
base of skull
corresponding to
location of pituitary
fossa
Impression: Abnormal
uptake of octreotide in
region of the pituitary
fossa, suggestive of
adenoma
39
Our Patient
• On 12/4/02 underwent selective transsphenoidal surgical
resection of pituitary microadenoma
• Pathology of showed strong staining for growth hormone
• One day post-op GH level reduced to 2 ng/ml
• One month post-op reports improvement in hand swelling
• As of 1/29/03 GH levels reduced to less than 1 ng/ml and
IGF-I level was 250
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
40
References
• Chew F. Radiologic manifestations in the musculoskeletal system of miscellaneous
endocrine disorders. Radiologic Clinics of North America 1991; 29(1):135-147.
• Goldman AB. Some miscellaneous joint diseases. Seminars in Roentgenology 1982;
17(1):60-80.
• Hordon LD. Rheumatic and bone disorders associated with acromegaly. UpToDate
2003. www.uptodateonline.com
• Lieberman S, Bjorkengren A, Hoffman A. Rheumatological and skeletal changes in
acromegaly. Endocrinol Metab Clin North Am 1992; 21(3):615-630.
• Moran S, Patsalides A, Patronas N. A case of a hidden pituitary adenoma causing
acromegaly. EndoTrends 2002; 9(1) 1,9-13.
http://www.endocrinefellows.org/htmldocs/endotrends/v9i1.pdf
• Melmed S. Clinical manifestations of acromegaly. UpToDate 2003.
www.uptodateonline.com
• Melmed S. Diagnosis of acromegaly. UpToDate 2003. www.uptodateonline.com
• Melmed S. Treatment of acromegaly. UpToDate 2003. www.uptodateonline.com
• Motlitch ME. Clinical manifestations of acromegaly. Endocrinol Metab Clin North
Am 1992; 21(3):597.
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
41
References Cont.
• Netter F. The Ciba Collection, Vol. 4. R.R. Donnelley & Sons Company. New York,
1965.
• Netter F. The Ciba Collection, Vol 1(2). CIBA Pharmaceutical Company. West
Caldwell, NJ, 1986, p 122.
• Resnick D. Bone and Joint Disorders, Vol. 3, 4th ed. W.B. Saunders Company.
Philadelphia, 2002.
• Snyder P. Causes, presentation, and evaluation of sellar masses. UpToDate 2003.
www.uptodateonline.com
• Staple TW, Melson GL, Evens RG. Miscellaneous soft tissue lesions of the
extremities. Seminars in Roentgenology 1973; 8(1):117-127.
• Subbarao K, Jacobson HG. Systemic disorders affecting the thoracic cage.
Radiologic Clinics of North America 1984; 22(3):497-517.
• http://www.library.uthscsa.edu/ms2/Pathology/Endocrine/Labs.
• http://www.mythos.com/webmd/Content.aspx?P=ENDOCC&E=6
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
42
Special Thanks
Ferris Hall, MD
Kevin Donohoe, MD
Eric Niendorf, MD
Daniel Saurborn, MD
Robert Silver, MD
Gillian Lieberman, MD
Pamela Lepkowski
Larry Barbaras and Cara Lyn D’amour
Enyi Nwaneri, HMS III
Gillian Lieberman, MD
43
Radiologic Features of Acromegaly
Our Patient
Diagnosis
ACROMEGALY
Clinical Manifestations
Clinical Manifestations
Anatomy and Relations of the Pituitary Gland
Relationship of the Pituitary Gland to the Cavernous Sinus
Relationship of the Pituitary Gland to the Sella Turcica
Relationship of the Pituitary Adenoma to the Sella Turcica
Imaging Modalities
Plain Radiographs
Plain Radiograph Features of Skeletal Involvement�in Acromegaly
Companion Patient A
Changes in Skin Thickness�
Diagnostic Significance of Thickened Heel Pad
Differential Diagnosis of Thickened Heel Pad
Abnormalities of the Skull
Abnormalities of the Skull
Abnormalities of the Skull
Abnormalities of the Hand and Wrist
Abnormalities of the Hand and Wrist
Abnormalities of the Foot
Differential Diagnosis of Phalangeal Tuft Enlargement
Abnormalities of the Vertebral Column
Companion Patient A
Articular Abnormalities
Acromegalic Arthropathy or Osteoarthritis?
Additional Plain Radiograph Features of Skeletal Involvement
Imaging Modalities
MRI
Any Role for CT?
Our Patient
Imaging Modalities
Somatostatin Receptor Scintigraphy
Companion Patient B
Companion Patient B
Companion Patient B
Companion Patient B
Our Patient
References
References Cont.
Special Thanks