Monday, September 10, 2012

Pituitary MRI Imaging in Cats with Acromegaly


PAPER REVIEW

Magnetic Resonance Imaging Findings in 15 Acromegalic Cats
by Barbara Posch, Jane Dobson, Mike Herrtage
Veterinary Radiology & Ultrasound 2011;52:422–427.

Background
MRI imaging of a cat with acromegaly.
Note the large pituitary mass that has
expanded dorsally into the hypothalamus
In cats, chronic hypersecretion of growth hormone (GH) causes acromegaly, a disease characterized by insulin-resistant diabetes mellitus and progressive overgrowth of soft tissue, membranous bone, and viscera (1-3). Acromegaly has been considered rare in cats but it may be more common than suspected previously (4-6). In almost all cats, the cause of acromegaly is a GH-secreting pituitary tumor (1-7).

Definitive diagnosis of feline acromegaly can be difficult because of the gradual onset and subtle clinical signs and unavailability of a validated feline GH assay (2,3). Therefore, the diagnosis of acromegaly in cats is currently based upon a combination of clinical signs, the finding of high serum insulin-like growth factor-1 (IGF-1) concentrations, and the documentation of a pituitary mass on brain imaging (2-6).

The usefulness of  computed tomography (CT) and magnetic resonance imaging (MRI) in identifying a pituitary tumor and establishing a diagnosis of acromegaly in cats has been demonstrated in many reports (4,5,7). However, little information is available regarding MRI features of pituitary tumors in acromegalic cats.

Objectives
The purpose of this study by Posch et al (8) was to evaluate if pituitary abnormalities were present on MRI imaging in acromegalic cats and to determine if specific morphologic criteria can be established to aid in diagnosis.

Animals
Fifteen cats with acromegaly were included in this study.

Methods
Retrospective study. Inclusion criteria included the following: 1) high serum IGF-1 value (>100 ng/ml); 2) insulin-resistant diabetes mellitus (>1.5 U/kg per injection); 3) high serum fructosamine; 4) continued signs of diabetes (polyuria, polydipsia, polyphagia) despite insulin treatment; and 5) exclusion of other causes of insulin resistance.

MRI of the brain was performed using a 0.2 T scanner with a dual-phased array coil. T2-weighted  and pre- and post-contrast T1-weighted images were acquired in transverse and sagittal planes. Contrast-enhanced T1-weighted images were obtained following an intravenous bolus of 0.1 mmol/kg of gadobenate dimeglumine. Fluid attenuation inversion recovery (FLAIR) images were acquired in transverse plane in four cats.

The pituitary gland was measured on postcontrast T1-weighted images. Signal intensity was described relative to the normal cerebral cortical gray matter. Suprasellar extension, compression of the hypothalamus, dorsal displacement of the third ventricle were recorded.

Results
Enlargement of the pituitary gland with suprasellar extension was present in all 15 acromegalic cats. No characteristic signal patterns were identified on T1-weighted and T2-weighted sequences.

Contrast enhancement was nonuniform in all cats, as was suspected involvement of the adjacent hypothalamus. A mass effect on the cavernous sinus and third ventricle was present in 13 of the 15 cats. Mild peritumoral edema was present in four cats, and moderate edema in one cat. Transtentorial herniation was present in one cat.

Histopathology confirmed the presence of a pituitary adenoma in two cases.

Clinical conclusions
MRI is a useful modality to establish the diagnosis of acromegaly. Large pituitary masses were present in all cats but there was no consistent morphologic criterion. In most cats, the pituitary tumor had a heterogeneous appearance on both T1-weighted and T2-weighted images, with nonuniform contrast enhancement.

My Bottom Line:

Published reports of acromegaly in cats are relatively sparse but have been gradually increasing since the disease was first described 30 years ago (1,6). Although thought to be a rare disorder by most veterinarians, recent research suggests that the prevalence underlying acromegaly in cats with diabetes may actually be as high as 20 to 30% (4-6). This strongly suggests that this disorder is greatly underdiagnosed by practicing veterinarians today.

Because of the limited availability of a validated growth hormone assay in cats, measurement of IGF-1 is used as a screening test for acromegaly (2-5). For the practicing veterinarian, IGF-1 determinations are widely available and are performed by most commercial veterinary laboratories, in contrast to the limited availability of feline GH assays.

The basis for use of IGF-1 as a diagnostic test for acromegaly is that circulating GH activates the hepatic and peripheral tissue production of IGF-1, which is responsible for many of the actions normally attributable to GH itself. In fact, other than DM, most of the clinical features of acromegaly are not the result of a direct catabolic effect of GH excess, but rather result from an indirect anabolic effect of GH excess mediated through the production of the IGF-1 (e.g., overgrowth of soft tissue, bony enlargement, and organomegaly). Therefore circulating IGF-1 levels serve as a biomarker for assessing the peripheral biological effect of GH hypersecretion, which, at least in human patients, tends to correlate better with the severity of the acromegalic state than does random circulating GH determinations (9).

Although measurement of IGF-1 levels are useful in making a diagnosis of feline acromegaly, this is not a perfect diagnostic test. False-positive (and false-negative) results do occur, and high serum concentrations of serum IGF-1 is not uncommon in diabetic cats without acromegaly (10,11).  For that reason, the definitive diagnosis of acromegaly is best made by measuring a high IGF-1 combined with the finding of a pituitary mass with brain imaging (either MRI or CT).

It appears that MRI may be a more sensitive diagnostic test for this condition (2,3). However, virtually all cats with acromegaly have a clearly visible pituitary tumor on CT or MRI imaging. Therefore, at least clinically, it does not appear to make a large difference which imaging technique is chosen.

References:
  1. Peterson ME, Taylor RS, Greco DS, et al. Acromegaly in 14 cats. Journal of Veterinary Internal Medicine 1990;4:192–201.
  2. Niessen S, Peterson ME, Church DB. Acromegaly In: Mooney CT,Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;35-42.
  3. Peterson ME. Pituitary disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;610-625.
  4. Niessen SJ, Petrie G, Gaudiano F, et al. Feline acromegaly: an underdiagnosed endocrinopathy? Journal of Veterinary Internal Medicine 2007;21:899–905.
  5. Berg RI, Nelson RW, Feldman EC, et al. Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly. Journal of Veterinary Internal Medicine 2007;21:892–898.
  6. Peterson ME. Acromegaly in cats: are we only diagnosing the tip of the iceberg? Journal of Veterinary Internal Medicine 2007;21:889–891.
  7. Dunning MD, Lowrie CS, Bexfield NH, Dobson JM, Herrtage ME. Exogenous insulin treatment after hypofractionated radiotherapy in cats with diabetes mellitus and acromegaly. Journal of Veterinary Internal Medicine 2009;23:243–249.
  8. Melmed S. Acromegaly pathogenesis and treatment. Journal of Clinical Investigation 2009; 119:3189-3202.
  9. Posch B, Dobson J, Herrtage M. Magnetic resonance imaging findings in 15 acromegalic cats. Veterinary Radiology & Ultrasound 2011;52:422–427.
  10. Lewitt MS, Hazel SJ, Church DB, et al. Regulation of insulin- like growth factor-binding protein-3 ternary complex in feline diabetes mellitus. Journal of Endocrinology 2000;166:21–27.
  11. Reusch CE, Kley S, Casella M et al: Measurements of growth hormone and insulin-like growth factor 1 in cats with diabetes mellitus. Veterinary Record 2006;158:195-200.

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